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Chapter 3

Physico chemical properties

Section-I

Acoustical properties

Section-I Acoustical properties

Department of Chemistry, Saurashtra University, Rajkot-360005 82

INTRODUCTION

In general waves, having frequency above the range audible to the human ear are

known as Ultrasound. The actual range of ultrasounds lies above 20 KHz.

In 21st century, ultrasonic dependant devices are a handy tool in various industries

such as cement1-3, paper4-5, glass6-9, soap10-14, petrochemicals15-17, plastic18-19, steel20,

dairy21, liquor22 etc, because of it’s non destructive nature and accurate measuring. In

industries, it could be used in various processes like dyeing23, cleaning24, repairing of

cracks25, design26, food processing27, bleaching28, deacidification29, extraction30-31,

viscosity reduction32, electroplating33, powder compression34, wastewater treatment

effluents35 etc.

Latest development in sonography is used in medical treatment36-38. Mainly, it is

used for the diagnosis of diseases in the body organs like thyroid39, abdoman40, kidneys41,

urinary tracts42 etc. Boucaud et al. have performed the skin permeation study of caffeine

across human and rat.43.Various uses of ultrasonics has been reported for diagnosis as

well as treatment of cancer44-46 and other tumours47,48

Further, in medicine, the ultrasonic method is combined with other technique to

give more elaborate diagnosis49-51. It is also useful in forensic science52,53. Zhou et al.

have used the ultrasonic waves in biomedical applications54, while Song et al. have

studied genetic transformation55 by using this techniqur55. Nowadays, in nanotechnology

also, ultrasounds waves have been used56-59. The studies in some liquid crystals have also

been done by Ayachit et al60.

In synthetic organic chemistry, a lot of interest has been generated on the use of

ultrasound radiations because of its compatible features like less reaction time, higher

percentage of yield, lower reaction temperature, avoidance of phase transfer catalysis

etc61-66. It is a pollution free green chemistry approach for synthesis of organic materials.

Sono chemistry is also useful in the isomerisation of carbon-carbon double bond67,

crystallization68,69, solvent extraction70 etc.

The ultrasonic measurements have also been used to study molecular interactions

in various pure liquids71-73, liquid mixtures74-77 and solutions of organic and inorganic

compounds78-80, polymers81, amino acids82, drugs83,84 etc. The thermodynamic parameters

calculated through ultrasonic velocity measurements can give idea about intermolecular

attraction between molecules (solute-solute or solute-solvent)85.



In our laboratory, the ultrasonic studies of some compounds like Schiff bases86,

benzodiazepines87, dihydropyrimidines88 etc. have been studied in different solvents.

In the present section, ultrasonic studies of tetrahydropyrimidine derivatives have

been studied in N, N dimethylformamide and tetrahydrofuran solutions of various

concentrations at 303.15 K with a view to understand molecular interactions in these

solutions.



EXPERIMENTAL

The selected solvents, DMF and THF for the present study were distilled by the

reported procedure89. The synthesized tetrahydropyrimidine derivatives (PAB 101-PAB

110) were recrystalized before use.

The densities, viscosities and ultrasonic velocities of pure solvents and solutions

of tetrahydropyrimidine derivatives of different concentrations were measured at 303.15

K by using pyknometer, an Ubbelohde suspended level viscometer and single frequency

ultrasonic interferometer operating at 2 MHz, with the uncertainties of 0.0001 g/cm3, +

0.06 % and 0.01% respectively.

Density measurements:

The weight of distilled water, pure solvents and solutions of synthesized

compounds were measured by using pyknometer. The densities (ρ) were evaluated by

using following equation:

3 wt. of solvent or solution density of waterρ g cm =

wt. of water … (3.1.1)

Viscosity Measurements:

To determine the viscosity of solution, Ubbelohde viscometer90 was used, which

obeys Stoke’s low91. The measured quantity of the distilled water / solvent / solution was

placed in the viscometer, which was suspended in a thermostat at 303.15 K. The digital

stopwatch, with an accuracy of + 0.01 sec was used to determine flow time of solutions.

Using the flow times (t) and known viscosity of standard water sample, the viscosity of

solvent (η1) and solutions (η2) were determined according to equation:

1 1 1

2 2 2

t

t

... (3.1.2)

Sound velocity measurement:

Ultrasonic interferometer, (Mittal Enterprise, New Delhi, Model No.F-81)

working at frequency of 2 MHz was used to determine sound velocity.

The solvent / solution were filled in the measuring cell with quartz crystal and

then micrometer was fixed. The circulation of water from the thermostat at 303.15 K was

started and test solvent / solution in the cell is allowed to thermally equilibrate. The

micrometer was rotated very slowly so as to obtain a maximum or minimum of anode

current (n). A number of maximum reading of anode current were counted. The total



distance (d) travelled by the micrometer for n=10, was read. The wave length (λ) was

determined by the equation:

2d

n ... (3.1.3)

and sound velocity (U) of solvent and solutions were calculated by the equation:

U F ... (3.1.4)

where F is the frequency, which is equal to 2 x 106 Hertz.



RESULTS AND DISCUSSION

Table 3.1.1 shows the experimental data of density (ρ), viscosity (η) and sound

velocity (U) of pure solvents and solutions of PAB compounds in DMF and THF

solutions at 303.15 K.

From these experimental data, various acoustical parameters like specific acoustical

impedance (Z), isentropic compressibility (κs), inter molecular free length (Lf), molar

compressibility (W), Rao’s molar sound function (Rm), Vander Waals constant (b),

relaxation strength (r), relative association (RA), internal pressure (π ), apparent molar

compressibility (k) etc., were evaluated using the following equations:

1. Specific acoustical impedance:

Specific acoustical impedance (Z) can be calculated as:

Z U ... (3.1.5)

2. Isentropic compressibility:

Isentropic compressibility ( s ) can be evaluated by the equation92

2

1s U

… (3.1.6)

3. Intermolecular free path length:

Jacobson93 proposed an equation to calculate the intermolecular free path length

(Lf), which is given below:1 2

f j sL K … (3.1.7)

where KJ is Jacobson constant (=2.0965 X 10-6)

4. Molar compressibility:

Molar compressibility (W) can be calculated by the following equation94

1 7s

MW

… (3.1.8)

The apparent molecular weight (M) of the solution can be calculated according to

following equation:

1 1 2 2M M W M W … (3.1.9)

where W1 and W2 are weight fractions of solvent and solute respectively. M1 and M2 are

the molecular weights of the solvent and compounds respectively.



Table 3.1.1: The density (ρ), ultrasonic velocity (U) and viscosity (η) of PAB

compounds in DMF and THF at 303.15 K.

Conc.M

Densityρ

g.cm-3

VelocityU. 10-5

cm.s-1

Viscosityη.103

poise

Densityρ

g.cm-3

VelocityU. 10-5

cm.s-1

Viscosityη.103

poise

DMF THF

PAB-101

0.00 0.9304 1.4416 7.8072 0.8911 1.2852 5.5154

0.01 0.9323 1.4440 7.9519 0.9162 1.2868 5.7508

0.02 0.9326 1.4468 8.0492 0.9168 1.2892 5.8281

0.04 0.9331 1.4528 8.1727 0.9176 1.2916 5.9027

0.06 0.9338 1.4556 8.2948 0.9188 1.2944 5.9571

0.08 0.9342 1.4572 8.3970 0.9196 1.2976 6.0003

0.10 0.9353 1.4588 8.5466 0.9202 1.3016 6.0825PAB-102

0.01 0.9330 1.4424 8.3932 0.9164 1.2888 5.7943

0.02 0.9333 1.4436 8.4676 0.9168 1.2908 5.9093

0.04 0.9338 1.4448 8.5515 0.9179 1.2924 5.9597

0.06 0.9340 1.4464 8.6868 0.9184 1.2952 6.0174

0.08 0.9351 1.4480 8.7645 0.9188 1.2984 6.1145

0.10 0.9370 1.4488 8.8553 0.9194 1.3028 6.1293

PAB-1030.01 0.9359 1.4416 7.1965 0.9160 1.2876 5.6805

0.02 0.9365 1.4428 7.2834 0.9177 1.2896 5.7614

0.04 0.9370 1.4444 7.3801 0.9186 1.2916 5.8214

0.06 0.9376 1.4464 7.5084 0.9196 1.2936 5.8730

0.08 0.9380 1.4488 7.6104 0.9205 1.2948 5.9277

0.10 0.9384 1.4516 7.7034 0.9215 1.2960 6.0181

PAB-1040.01 0.9359 1.4428 8.3009 0.9132 1.2876 5.6329

0.02 0.9365 1.4444 8.3918 0.9147 1.2888 5.7024

0.04 0.9370 1.4464 8.4869 0.9167 1.2900 5.7623

0.06 0.9376 1.4492 8.6158 0.9186 1.2912 5.8361

0.08 0.9380 1.4524 8.7194 0.9195 1.2928 5.8985

0.10 0.9384 1.4540 8.8229 0.9206 1.2948 5.9772PAB-105

0.01 0.9330 1.4540 8.0501 0.9133 1.2864 5.6734

0.02 0.9340 1.4564 8.1538 0.9144 1.2876 5.7104

0.04 0.9341 1.4592 8.2583 0.9169 1.2896 5.7326

0.06 0.9346 1.4620 8.2917 0.9187 1.2904 5.7707

0.08 0.9355 1.4648 8.3560 0.9199 1.2924 5.8490

0.10 0.9356 1.4680 8.4511 0.9224 1.2936 5.9011

….. Continue



….. ContinueConc.

MDensity

ρg.cm-3

VelocityU. 10-5

cm.s-1

Viscosityη.103

poise

Densityρ

g.cm-3

VelocityU. 10-5

cm.s-1

Viscosityη.103

poise

DMF THF

PAB-106

0.00 0.9304 1.4416 7.8072 0.8911 1.2852 5.5154

0.01 0.9356 1.4528 8.2097 0.9124 1.2892 5.7657

0.02 0.9372 1.4548 8.2882 0.9134 1.2904 5.7945

0.04 0.9386 1.4564 8.3225 0.9152 1.2916 5.8137

0.06 0.9388 1.4588 8.3990 0.9164 1.2932 5.8376

0.08 0.9391 1.4604 8.5292 0.9169 1.2940 5.8528

0.10 0.9395 1.4628 8.5672 0.9189 1.2956 5.8814PAB-107

0.01 0.9347 1.4468 8.1715 0.9185 1.2924 5.6602

0.02 0.9348 1.4480 8.1942 0.9187 1.2936 5.7478

0.04 0.9350 1.4496 8.2044 0.9188 1.2944 5.8028

0.06 0.9351 1.4508 8.2229 0.9198 1.2960 5.8333

0.08 0.9354 1.4524 8.2415 0.9211 1.2972 5.8969

0.10 0.9359 1.4536 8.2580 0.9223 1.2988 5.9461

PAB-108

0.01 0.9339 1.4444 8.2362 0.9134 1.2904 5.8559

0.02 0.9350 1.4476 8.2691 0.9153 1.2920 5.9171

0.04 0.9365 1.4504 8.2990 0.9156 1.2936 5.9470

0.06 0.9374 1.4552 8.3269 0.9181 1.2956 6.0038

0.08 0.9383 1.4568 8.3546 0.9197 1.2968 6.0647

0.10 0.9393 1.4604 8.3875 0.9213 1.2980 6.0899PAB-109

0.01 0.9339 1.4544 8.0771 0.9138 1.2888 5.7141

0.02 0.9349 1.4564 8.1165 0.9148 1.2900 5.7952

0.04 0.9360 1.4584 8.1850 0.9155 1.2912 5.9022

0.06 0.9366 1.4600 8.2839 0.9164 1.2928 5.9793

0.08 0.9378 1.4612 8.3498 0.9179 1.2944 6.0377

0.10 0.9387 1.4632 8.5351 0.9192 1.2960 6.1267PAB-110

0.01 0.9329 1.4468 8.1762 0.9126 1.2892 5.6894

0.02 0.9333 1.4520 8.2571 0.9128 1.2904 5.7681

0.04 0.9334 1.4544 8.3245 0.9158 1.2920 5.8487

0.06 0.9359 1.4560 8.4070 0.9178 1.2936 5.8854

0.08 0.9363 1.4580 8.4717 0.9189 1.2944 5.9362

0.10 0.9371 1.4596 8.5343 0.9214 1.2956 6.0433



5. Rao’s molar sound function:

Rao’s molar sound function (Rm) can be evaluated by an equation given by

Bagchi et al.95

1 3m

MR U

… ... (3.1.10)

6. Van der Waals Constant:

Van der Waals constant (b) can be calculated as follows96

2

21 1 1

3

M RT MUb

MU RT

... (3.1.11)

where R is the gas constant (=8.3143 JK-1 mol-1) and T is the absolute temperature.

7. Relaxation Strength:

The relaxation strength (r) can be calculated as follows97

2

1rUU

… (3.1.12)

where U = 1.6 x 105 cm .sec-1.

8. Relative Association (RA):

1 3

0

0A

UR

U

… (3.1.13)

where U, 0U and ρ , 0ρ are ultrasonic velocities and densities of solution and solvent

respectively.

9. Apparent Molar Compressibility (k):

The apparent molar compressibility ( K ) of the solutions was calculated by the

following equation:



0 00 2

0 0

1000s s sK

M

c

... (3.1.14)

where ρ0 and 0s are density and isentropic compressibility of pure solvent respectively, c

is the concentration of the solution and M2 is the molecular weight of the compound.

10. Solvation number:

0

2

1

1 100

s

sn

M XS

M X

… (3.1.15)

where X is the number of grams of solute in 100 gm of the solution. M1 and M2 are the

molecular weights of solvent and solute respectively.

Some of the calculated acoustical parameters are given in Tables 3.1.2 and 3.1.3

for all the compounds in DMF and THF solutions respectively. Figures 3.1.1 and 3.1.2

show the variation of ultrasound velocity (U) with concentration in DMF and THF

respectively. It is observed that overall ultrasonic velocity (U) increases non linearly with

concentration for all the compounds in both the solvents. The velocity depends on

intermolecular free length ( Lf ). Comparison of ultrasonic velocity and intermolecular

free length (Tables 3.1.2 and 3.1.3) shows these two parameters are inversely related. The

decrease in the free length causes velocity to increase or vice versa. As evident from

Tables 3.1.2 and 3.1.3, Lf decrease continuously which is due to strong interaction

between solvents and compound molecules. This causes velocity to increase.

This is further supported by isentropic compressibility ( κs ) and relaxation

strength (r). The isentropic compressibility ( κs ) of the solutions in both the solvents is

also found to decrease with increase of concentration, as shown in Figures 3.1.3 and

3.1.4.

This phenomenon can be explained by assuming that the solvated molecules fully

compressed by the electrical forces of the ions98

. The compressibility of the solution is

mainly due to the free solvent molecules. Due to solute-solvent interactions in the system,

compressibility of the solution decreases with the increase in solute concentration. This is

further confirmed by decrease of relaxation strength (r) and increase in specific

impedance (Z) values (as reported in Tables 3.1.2 and 3.1.3).

Section-I

Department of Chemistry, Saurashtra University, Rajkot

Figure 3.1.1: The variation of

concentration in

1.440

1.445

1.450

1.455

1.460

1.465

1.470

0

U.1

0-5

(cm

.s-1

)

PAB-101

1.440

1.445

1.450

1.455

1.460

1.465

0

U.1

0-5

(cm

.s-1

)

PAB-

I Acoustical properties

Department of Chemistry, Saurashtra University, Rajkot-360005

ariation of ultrasonic velocity (U) of PAB compounds

concentration in DMF at 303.15 K.

0.02 0.04 0.06 0.08

Concentration (M)

101 PAB-102 PAB-103 PAB-104

0.02 0.04 0.06 0.08

Concentration (M)

-106 PAB-107 PAB-108 PAB-109


91

) of PAB compounds with

0.1

PAB-105

0.1

PAB-110

Section-I



concentration

1.284

1.288

1.292

1.296

1.300

1.304

0

U.1

0-5

(cm

.s)-1

PAB-101

1.288

1.290

1.292

1.294

1.296

1.298

1.300

0

U.1

0-5

(cm

.s-1

)

PAB-106



ariation of ultrasonic velocity (U) of PAB compounds

concentration in THF at 303.15 K.

0.02 0.04 0.06 0.08

Concentration (M)

101 PAB-102 PAB-103 PAB-104

0.02 0.04 0.06 0.08

Concentration (M)

106 PAB-107 PAB-108 PAB-109


92

compounds with

0.1

PAB-105

0.1

PAB-110



Table 3.1.2: Some acoustical parameters of PAB compounds in DMF at 303.15 K.

Conc.M

Z .10-5

g.cm-2

Lf

Ao

Rm.10-3

cm-8/3.s-1/3

bcm3.mol-1 r RA

PAB-101

0.00 1.3413 1.5077 4.1191 78.5558 0.1882 1.00000.01 1.3462 1.5037 4.1314 78.7470 0.1855 1.00150.02 1.3493 1.5005 4.1512 79.0724 0.1823 1.00120.04 1.3556 1.4939 4.1914 79.7287 0.1755 1.00030.06 1.3593 1.4905 4.2277 80.3668 0.1724 1.00050.08 1.3613 1.4886 4.2645 81.0369 0.1705 1.00040.10 1.3644 1.4860 4.2973 81.6305 0.1687 1.0013

PAB-102

0.01 1.3458 1.5048 4.1328 78.8017 0.1873 1.00260.02 1.3473 1.5033 4.1569 79.2408 0.1859 1.00270.04 1.3492 1.5016 4.2045 80.1260 0.1846 1.00290.06 1.3509 1.4998 4.2539 81.0362 0.1828 1.00280.08 1.3540 1.4973 4.2989 81.8632 0.1810 1.00360.10 1.3575 1.4949 4.3390 82.6115 0.1801 1.0054

PAB-103

0.01 1.3492 1.5033 4.1213 78.5982 0.1882 1.00590.02 1.3512 1.5015 4.1459 79.0451 0.1868 1.00630.04 1.3534 1.4995 4.1979 80.0059 0.1850 1.00650.06 1.3561 1.4970 4.2499 80.9609 0.1828 1.00660.08 1.3589 1.4941 4.3028 81.9230 0.1801 1.00650.10 1.3622 1.4909 4.3562 82.8860 0.1769 1.0063

PAB-104

0.01 1.3503 1.5020 4.1225 78.7303 0.1868 1.00390.02 1.3527 1.4998 4.1474 79.1701 0.1850 1.00440.04 1.3553 1.4974 4.1998 80.1523 0.1828 1.00420.06 1.3587 1.4941 4.2527 81.1342 0.1796 1.00390.08 1.3623 1.4904 4.3064 82.1305 0.1760 1.00320.10 1.3644 1.4885 4.3586 82.9592 0.1742 1.0049

PAB-105

0.01 1.3565 1.4928 4.1418 78.7637 0.1742 0.99990.02 1.3603 1.4895 4.1618 79.0998 0.1714 1.00040.04 1.3630 1.4866 4.2085 79.9372 0.1683 0.99990.06 1.3664 1.4833 4.2533 80.7351 0.1651 0.99980.08 1.3703 1.4798 4.2962 81.4975 0.1619 1.00010.10 1.3735 1.4765 4.3431 82.3289 0.1582 0.9995

Continue…..



….. Continue

Conc.M

Z .10-5

g.cm-2

Lf

Ao

Rm.10-3

cm-8/3.s-1/3

bcm3.mol-1 r RA

PAB-106

0.00 1.3413 1.5077 4.1322 78.5558 0.1882 1.00000.01 1.3592 1.4919 4.1521 78.6023 0.1755 1.00300.02 1.3634 1.4886 4.1978 78.9452 0.1733 1.00420.04 1.3669 1.4859 4.2493 79.7839 0.1714 1.00540.06 1.3695 1.4832 4.2997 80.7187 0.1687 1.00510.08 1.3715 1.4814 4.3505 81.6472 0.1669 1.00500.10 1.3743 1.4786 4.1322 82.5651 0.1641 1.0049

PAB-107

0.01 1.3524 1.4988 4.1341 78.7475 0.1823 1.00350.02 1.3536 1.4975 4.1641 79.2968 0.1810 1.00330.04 1.3553 1.4957 4.2234 80.3958 0.1792 1.00310.06 1.3566 1.4944 4.2825 81.4985 0.1778 1.00290.08 1.3586 1.4925 4.3408 82.5776 0.1760 1.00290.10 1.3604 1.4908 4.3979 83.6416 0.1746 1.0031

PAB-108

0.01 1.3490 1.5019 4.1357 78.8206 0.1850 1.00320.02 1.3536 1.4977 4.1633 79.2882 0.1814 1.00360.04 1.3584 1.4936 4.2179 80.2768 0.1783 1.00460.06 1.3642 1.4880 4.2771 81.3138 0.1728 1.00440.08 1.3669 1.4857 4.3331 82.3494 0.1710 1.00500.10 1.3717 1.4812 4.3906 83.3725 0.1669 1.0052

PAB-109

0.01 1.3583 1.4916 4.1321 78.5709 0.1737 1.00080.02 1.3616 1.4888 4.1458 78.7968 0.1714 1.00140.04 1.3651 1.4858 4.1751 79.3173 0.1692 1.00220.06 1.3674 1.4838 4.2066 79.8866 0.1673 1.00240.08 1.3703 1.4816 4.2347 80.3978 0.1660 1.00340.10 1.3735 1.4789 4.2649 80.9331 0.1637 1.0039

PAB-110

0.01 1.3497 1.5003 4.1351 78.7655 0.1823 1.00150.02 1.3552 1.4946 4.1602 79.1487 0.1764 1.00070.04 1.3576 1.4920 4.2058 79.9740 0.1737 1.00030.06 1.3627 1.4884 4.2400 80.5940 0.1719 1.00260.08 1.3651 1.4860 4.2837 81.3880 0.1696 1.00260.10 1.3678 1.4838 4.3252 82.1465 0.1678 1.0031



Table 3.1.3: Some acoustical parameters of PAB compounds in THF at 303.15 K.

Conc.M

Z .10-5

g.cm-2

Lf

Ao

Rm.10-3

cm-8/3.s-1/3

bcm3.mol-1 r RA

PAB-101

0.00 1.1452 1.7281 4.0775 80.7969 0.3548 1.00000.01 1.1790 1.7021 3.9860 78.9496 0.3532 1.02770.02 1.1819 1.6984 4.0044 79.2653 0.3508 1.02780.04 1.1852 1.6945 4.0402 79.9241 0.3483 1.02800.06 1.1893 1.6897 4.0745 80.5461 0.3455 1.02860.08 1.1933 1.6848 4.1111 81.2013 0.3423 1.02870.10 1.1977 1.6791 4.1493 81.8726 0.3382 1.0283

PAB-102

0.01 1.1810 1.6993 3.9932 79.0521 0.3512 1.02740.02 1.1834 1.6963 4.0180 79.5028 0.3492 1.02730.04 1.1863 1.6932 4.0637 80.3741 0.3475 1.02810.06 1.1895 1.6891 4.1132 81.2933 0.3447 1.02800.08 1.1930 1.6845 4.1635 82.2207 0.3415 1.02760.10 1.1978 1.6783 4.2142 83.1281 0.3370 1.0271

PAB-103

0.01 1.1795 1.7012 3.9957 79.1257 0.3524 1.02730.02 1.1835 1.6970 4.0169 79.5058 0.3504 1.02870.04 1.1865 1.6936 4.0680 80.4756 0.3483 1.02920.06 1.1896 1.6901 4.1188 81.4377 0.3463 1.02970.08 1.1918 1.6877 4.1688 82.4004 0.3451 1.03040.10 1.1943 1.6852 4.2179 83.3466 0.3439 1.0312

PAB-104

0.01 1.1759 1.7038 4.0080 79.3708 0.3524 1.02420.02 1.1788 1.7009 4.0296 79.7726 0.3512 1.02550.04 1.1825 1.6975 4.0753 80.6530 0.3500 1.02740.06 1.1860 1.6941 4.1210 81.5316 0.3488 1.02920.08 1.1887 1.6912 4.1713 82.4936 0.3471 1.02980.10 1.1919 1.6876 4.2212 83.4371 0.3451 1.0305

PAB-105

0.01 1.1749 1.7053 4.0020 79.2762 0.3536 1.02460.02 1.1774 1.7027 4.0209 79.6251 0.3524 1.02550.04 1.1824 1.6978 4.0565 80.2886 0.3504 1.02780.06 1.1855 1.6951 4.0938 81.0111 0.3496 1.02960.08 1.1889 1.6913 4.1347 81.7775 0.3475 1.03040.10 1.1933 1.6874 4.1682 82.4151 0.3463 1.0329

Continue…..



….. Continue

Conc.M

Z .10-5

g.cm-2

Lf

Ao

Rm.10-3

cm-8/3.s-1/3

bcm3.mol-1 r RA

PAB-106

0.00 1.1452 1.7281 4.0775 80.7969 0.3548 1.00000.01 1.1762 1.7025 4.0123 79.4216 0.3508 1.02280.02 1.1786 1.7000 4.0349 79.8448 0.3496 1.02360.04 1.1821 1.6967 4.0791 80.6943 0.3483 1.02530.06 1.1851 1.6935 4.1263 81.5945 0.3467 1.02630.08 1.1865 1.6920 4.1758 82.5557 0.3459 1.02660.10 1.1905 1.6881 4.2190 83.3769 0.3443 1.0284

PAB-107

0.01 1.1871 1.6926 3.9925 78.9643 0.3475 1.02890.02 1.1884 1.6909 4.0224 79.5322 0.3463 1.02870.04 1.1893 1.6898 4.0813 80.6798 0.3455 1.02860.06 1.1921 1.6867 4.1367 81.7414 0.3439 1.02930.08 1.1948 1.6840 4.1903 82.7752 0.3427 1.03050.10 1.1979 1.6808 4.2444 83.8089 0.3411 1.0314

PAB-108

0.01 1.1786 1.7000 4.0134 79.4199 0.3496 1.02360.02 1.1826 1.6961 4.0362 79.8383 0.3479 1.02540.04 1.1844 1.6937 4.0962 80.9904 0.3463 1.02520.06 1.1895 1.6888 4.1457 81.9283 0.3443 1.02760.08 1.1926 1.6858 4.1990 82.9546 0.3431 1.02900.10 1.1959 1.6827 4.2510 83.9570 0.3419 1.0305

PAB-109

0.01 1.1777 1.7017 3.9965 79.1180 0.3512 1.02450.02 1.1801 1.6992 4.0096 79.3526 0.3500 1.02540.04 1.1821 1.6970 4.0407 79.9438 0.3488 1.02580.06 1.1847 1.6940 4.0713 80.5160 0.3471 1.02640.08 1.1881 1.6906 4.0990 81.0303 0.3455 1.02760.10 1.1912 1.6873 4.1274 81.5565 0.3439 1.0286

PAB-110

0.01 1.1765 1.7023 4.0079 79.3344 0.3508 1.02310.02 1.1778 1.7006 4.0307 79.7612 0.3496 1.02290.04 1.1832 1.6957 4.0632 80.3721 0.3479 1.02590.06 1.1872 1.6917 4.0999 81.0643 0.3463 1.02770.08 1.1895 1.6896 4.1395 81.8295 0.3455 1.02880.10 1.1937 1.6858 4.1731 82.4699 0.3443 1.0312

Section-I



with concentration in

4.95

5.00

5.05

5.10

5.15

5.20

0

ks.1

011

(cm

2 .d

yn-1

)

PAB-101

4.95

5.00

5.05

5.10

5.15

5.20

0

ks.1

011

(cm

2 .d

yn-1

)

PAB-106



ariation of isentropic compressibility (κs) of PAB compounds

with concentration in DMF at 303.15 K.

0.02 0.04 0.06 0.08

Concentration (M)

101 PAB-102 PAB-103 PAB-104

0.02 0.04 0.06 0.08

Concentration (M)

106 PAB-107 PAB-108 PAB-109


97

PAB compounds

0.1

PAB-105

0.1

PAB-110

Section-I



with concentration in THF

6.35

6.40

6.45

6.50

6.55

6.60

6.65

0

ks.1

011

(cm

2.d

yn-1

)

PAB-101

6.40

6.45

6.50

6.55

6.60

6.65

0

ks.1

011

(cm

2 .d

yn-1

)

PAB-106



ariation of isentropic compressibility (κs) of PAB compounds

with concentration in THF at 303.15 K.

0.02 0.04 0.06 0.08

Concentration (M)

101 PAB-102 PAB-103 PAB-104 PAB

0.02 0.04 0.06 0.08

Concentration (M)

106 PAB-107 PAB-108 PAB-109


98

compounds

0.1

PAB-105

0.1

PAB-110



Further, molar compressibility (W) is observed to increase linearly in both the

solvents for all the studied compounds as shown in Figures 3.1.5 and 3.1.6. The Rao’s

molar sound function (Rm) and Vander Waal’s constant (b) are also observed to increase

linearly (correlation coefficient 0.9920-0.9998) with concentration for all the compounds

in both the solvents. The linear increase of these parameters shows absence of complex

formation in these systems.

From the Tables 3.1.2 and 3.1.3, it is also observed that the relative association

also increases with concentration almost for all the compounds in both the solvents

suggesting thereby predominance of solute-solvent interactions in the studied systems.

The type of interactions in a solution can also be confirmed by the solvation

number, which is a measure of structure forming or structure breaking tendency of a

solute in a solution. Figures 3.1.7 and 3.1.8 show that for all the compounds, solvation

number (Sn) increases with concentration. Further, these Sn values are positive for all the

compounds in both the solvents. The positive Sn values suggest structure forming

tendency of compounds in solution. This further confirms that there exist strong solute-

solvent interactions in the studied solutions.

The isentropic compressibility of all the solutions was also fitted to the following

Bachem’s relation99:

0 3 2s s AC BC … (3.1.16)

From the plot of 0 /s s C verses √C, values of A and B were evaluated from

the intercept and slope respectively. 0s is the isentropic compressibility of pure solvent.

Further, the apparent molar compressibility (k) of the solutions is fitted to Gucker’s

relation100:

k = ok + Sk √C … (3.1.17)

From the plot of k verses √C, ok and Sk values are evaluated from the intercept

and slope. Sk is known as interaction parameter.

The apparent molar volumes ΦV of the solutions were calculated by the following

equation:

Φv = M/ρ-[1000(ρ-ρ0)/ρc]

... (3.1.18)

Section-I



with concentration in DMF

2.30

2.35

2.40

2.45

2.50

0 0.01

W.1

0-3

(cm

-1.d

yn-1

)

PAB

2.30

2.35

2.40

2.45

2.50

0

W.1

0-3

(cm

-1.d

yn-1

)

PAB-



ariation of molar compressibility (W) of PAB compounds

with concentration in DMF at 303.15 K.

0.02 0.03 0.04 0.05 0.06 0.07 0.08

Concentration (M)

PAB-101 PAB-102 PAB-103 PAB-104

0.02 0.04 0.06 0.08

Concentration (M)

-106 PAB-107 PAB-108 PAB-109


100

PAB compounds

0.08 0.09 0.1

PAB-105

0.1

PAB-110

Section-I



with concentration in THF

2.20

2.25

2.30

2.35

2.40

0

W.1

0-3

(cm

-1.d

yn-1

)

PAB-

2.20

2.25

2.30

2.35

2.40

0

W.1

0-3

(cm

-1.d

yn-1

)

PAB



ariation of molar compressibility (W) of PAB compounds

with concentration in THF at 303.15 K.

0.02 0.04 0.06 0.08

Concentration (M)

-101 PAB-102 PAB-103 PAB-104

0.02 0.04 0.06 0.08

Concentration (M)

PAB-106 PAB-107 PAB-108 PAB-109


101

PAB compounds

0.1

PAB-105

0.1

PAB-110

Section-I


Figure 3.1.7: The Variation of

concentration in DMF

0.00

1.00

2.00

3.00

4.00

5.00

6.00

0

Sn

PAB-101

0.00

1.00

2.00

3.00

4.00

5.00

0

Sn

PAB-106



Variation of solvation number (Sn) of PAB compounds

concentration in DMF at 303.15 K.

0.02 0.04 0.06 0.08

Concentration (M)

101 PAB-102 PAB-103 PAB-104

0.02 0.04 0.06 0.08

Concentrtaion (M)

106 PAB-107 PAB-108 PAB-109


102

PAB compounds with

0.1

PAB-105

0.1

PAB-110

Section-I


Figure 3.1.8: The Variation of

concentration in THF

0.00

0.50

1.00

1.50

2.00

2.50

0

Sn

PAB-

0.00

0.50

1.00

1.50

2.00

2.50

0

Sn

PAB-106



Variation of solvation number (Sn) of PAB compounds

concentration in THF at 303.15 K.

0.02 0.04 0.06 0.08

Concentration (M)

101 PAB-102 PAB-103 PAB-104

0.02 0.04 0.06 0.08

Concentration (M)

106 PAB-107 PAB-108 PAB-109


103

of PAB compounds with

0.1

PAB-105

0.1

PAB-110



and were fitted in the relation:

ΦV = ΦVo +Sv C ... (3.1.19)

From the plot of ΦV verses C, ΦVo and Sv values were calculated from the

intercept and slope respectively. Sv is the measure of solute-solvent interactions. All these

values are given in Table 3.1.4.

It is evident from Table 3.1.4 that in both DMF and THF solutions, A, ok, and Φ

V

o

values are negative whereas B, Sk and Sv values are positive. The lower or negative A, B,

ok confirms interaction between solvent and compound molecules. Further, negative

values of ΦV

oimplies electrostrictive solvation of ions(101,102) i.e., more compressibility in

solution. Table 3.1.4 shows that in comparison to DMF, for THF solutions, A, ok and Φ

V

o

are more negative whereas B, Sk and Sv values are more positive. This suggests that

compressibility is higher in THF than that in DMF solutions. Further, the positive and

higher values of interaction parameters Sk and Sv confirms the predominance of solute-

solvent interactions in studied systems.

Thus, it is concluded that in the studied systems, solute-solvent interactions

dominate in both DMF and THF solutions.



Table 3.1.4: The Bachem’s constants A and B, ok and Sk, ΦV

o and Sv of PAB

compounds in DMF and THF at 303.15 K.

Comp.

A X 1011

dyn-1. cm3

mol-1

B X 1011

dyn-1.cm-1/2

mol-3/2

ok X 108

dyn-1.mol-1

Sk X 108

dyn-1cm-3/2

mol-3/2

ΦVo

cm2 . mol-1

Sv

cm2.dm1/2

.mol-3/2

DMFPAB-101 -3.38 5.94 -3.38 9.26 -4.995 351.1

PAB-102 -2.69 7.70 -2.93 11.99 -116.3 2323

PAB-103 -2.01 3.08 -5.66 19.36 -170.2 1938

PAB-104 -1.96 2.26 -5.18 18.86 -236.9 3968

PAB-105 -6.01 12.62 -12.44 39.81 -42.87 710.2

PAB-106 -5.50 11.28 -10.94 33.21 -335.4 4085

PAB-107 -3.49 7.64 -9.31 35.37 -185.5 2787

PAB-108 -4.99 11.46 -5.26 15.64 -124.0 1194

PAB-109 -6.62 15.20 -11.08 35.28 -64.54 576.7

PAB-110 -7.82 27.49 -6.84 20.97 -93.23 1123

THF

PAB-101 -11.03 23.61 -19.13 47.96 -869.7 6694

PAB-102 -11.58 25.28 -19.69 50.61 -689.6 4731

PAB-103 -12.34 29.20 -20.51 54.37 -900.8 6919

PAB-104 -10.61 24.28 -17.94 46.93 -678.7 4498

PAB-105 -10.37 23.53 -17.71 45.45 -652.4 4048

PAB-106 -11.12 26.16 -17.96 47.63 -608.6 3997

PAB-107 -13.68 32.57 -21.73 57.42 -706.8 4597

PAB-108 -11.99 27.37 -18.61 47.47 -648.9 4119

PAB-109 -10.79 24.80 -17.98 46.32 -606.3 3885

PAB-110 -11.39 26.35 -18.31 47.13 -630.3 3937



REFERENCES

1. Niyogi, S.; Roy, P. and Roychaudhuri, M.; “Acousto-ultrasonic study on

hydration of portland cement.” Cera. Trans. (Adv. Cem. Mater.) 1991, 37-45.

2. Ranachowski, J. and Rejmund, F.; “Acoustic emission in thermomechanical

studies of Ceramics and cement Material.” Prace. Komi. Nau. Cera. 1994, 177-

186.

3. Ohtsu, M.; Shigeishi, M. and Munwam, M.; “Damage mechanics and fracture

mechanics of concrete by SiGMA.” J. Acou. Emis. 1998, 16(1-4), S 65-74.

4. Craver, J.; “Ultrasonic impedometric studies in the cellulose pulp water system.”

Trans. Symp. 1966, 1, 445-472.

5. Dion, J.; Garceau, J. and Morissette, J.; “Acousto-optical evaluation of fiber size

in wood pulp.” Proc. SPIE Int. Soc. Opt. Eng. 1986, 665, 361-365.

6. Moran, T.; Batra, N.; Bucholtz, F. and Thomas, R.; “Elastic properties of

manganese (II) oxide-alumina-silica glasses.” J. Ultra. Symp. Proc. 1974, 506-

508.

7. Berret, J.; Pelous, J.; Vacher, R.; Raychaudhuri, A. and Schmidt, M.; “Acoustic

properties and relationship with the low frequency light scattering in an optical

glass.” J. Non-Cryst. Solids. 1986, 87(1-2), 70-85.

8. Kezionis, A.; Orliukas, A.; Samulionis, V.; Jakubowski, W.; Bogusz, W. and B.

Wnetrzewski; “Electrical and ultrasonic properties of AgI, AgPO3 glasses.”

Lietuvos Fizikos Zurnalas. 1995, 35(3), 202-205.

9. Vasantharani, P.; Karthikeyani, K. and Vijayakumari; “Thermal expansion and

acoustical properties of zinc bismuth borate glasses.” Bull. Pure & App. Sci. 2007,

26D(2), 67-72.

10. Mehrotra, K. and Upadhyaya S.; “Acoustical studies of calcium soaps.” Acou.

Lett. 1987, 11(4), 66-71.

11. Mehrotra, K.; Shukla, R. and Chauhan M.; “Ultrasonic studies on neodymium

soap solutions.” Acustica. 1991, 75(1), 82-85.

12. Mehrotra, K. and Jain M.; “Ultrasonic measurements of chromium(III) soaps in

chloroform.” Acous. Lett. 1994, 18(3), 50-54.

13. Mehrotra, K. and Anis, M.; “Apparent molar volume and acoustic behaviour of

zirconyl soap solutions in benzene-chloroform mixture.” J. Ind. Chem. Soc. 1997,

74(9), 720-722.



14. Upadhyay, S.; Shukla, R. and Sharma, G.; “Acoustic behaviour of dysprosium

soaps in methanol.” Asi. J. Chem. 2007, 19(4), 2993-2998.

15. Botto, R.; “Applications of ultrasonic nebulization in the analysis of petroleum

and petrochemicals by inductively coupled plasma atomic emission spectrometry”

J. Anal. Atom. Spectro.1993, 8, 51-57.

16. Amani, M.; Najafi I. and Makarem, M.; “Application of ultrasound waves to

increase the efficiency of oxidative desulfurization process” Adv. Petro. Exp. Dev.

2011, 2(2) 63-69.

17. Pena, P.; Ivascan, L.; Georgescu, V. and Iacob.; “Investigations reffering to

Utilization of the ultrasonic devices to prevent depositions in oil refining plants.”

Chimie. 2005, 13, 113-120.

18. Anderson, B.; “Technical plan for nondestructive examination technology

development.” Avail. NTIS. Rep. 1982, 33.

19. Yan, J.; Li, D.; Dong, Z. and Zhen, Y.; “Analysis and measurement of acoustic

power in plastics ultrasonic welding process.” China Welding 1998, 7(2), 106-

111.

20. Meysam, A. and Mehdi, A.; “The application of Acoustic Emission technique to

plastic deformation of low carbon steel” Physics Procedia. 2010, 3(1), 795-801.

21. Kun, Y.; Jiaping, Lu.; Yuejie, Xie. and Jie, Sun.; “Application of ultrasound

technology in the dairy processing” Zhongguo Rupin Gongye. 2009, 37(11), 29-

32.

22. Zhanjun, Z. and Fuhua, W.; “Application of ultrasound techniques in traditional

liquor-making industry” Niangjiu. 2009, 36(4), 27-29.

23. McNeil, S. J. and McCall, R. A.; “Ultrasound for wooldyeing and finishing”

Ultra. Sonochem. 2011, 18(1), 401-406.

24. Foguel, M.; Uliana, C.; Tomaz, U.; Marques, O.; Yamanaka, H. and Ferreira, A.;

“Evaluation of the CDtrode cleaning constructed from gold recordable

CD/galvanoplasty tape” Ecletica Quimica. 2009, 34(2), 59-66.

25. Qian J.; “Method for cleaning parts of equipment in semiconductor device

fabrication” Chinese Pat. Appl. Patent No. CN 101439341, 2009, 9

26. Nanda, S.; Rao, R. and Anand, S.; “Use of factorial design in sonophoretic

transdermal delivery of propranolol HCL” Ind. Pharm. 2010, 9(98), 49-54.

http://www.sciencedirect.com/science/journal/13504177



27. Buyukkamaci, N.; Filibeli, A. and Erden, G.; “Effect of low frequency ultrasound

on anaerobic biodegradability of meat processing effluent”

Desalination. 2010, 259(13), 223-227.

28. Hong-xia, G.; Xiu-qiong, Guan.; Hong-ru, B. and Kui, Wang.; “Application of

ultrasound wave in bamboo pulp bleaching” Yinran Zhuji 2010, 27(2), 34-35.

29. Li, Xie.; Wei, Z.; Zifeng, L. and Xuhong, M.; “Study on the application of

ultrasonic in the esterification deacidification of high-acid crude oil” Shiyou

Lianzhi Yu Huagong 2010, 41(1), 6-10.

30. Juan, C.; Jose, G.; Antonio, Mulet.; Ligia, R. and Enrique, R.; “Ultrasonically

assisted antioxidant extraction from grape stalks and olive leaves” Procedia.

2010, 3(1), 147-152.

31. Mason, T.; Chemat, F. and Vinatoru, M.; “The Extraction of Natural Products

using Ultrasound or Microwaves” Curr. Org. Chem. 2011, 15(2), 237-247.

32. Weihua, Z.; Aixiang, W.; Chunfang, Zhang.; Xiaoping, L. and Pingfang, H.;

“Application of ultrasound in the viscosity reduction of vacuum residuum”

Huagong Jinzhan 2009, 28(11),1896-1900.

33. Chaowu, Z.; Fangyuan, Z.; Fen W.; Jun,Y. and Ling, X.; “Ultrasonic co-deposit

fabrication of Si-Ha nanopowder and mechanical performance of its Bio-cement”

Zhongguo Taoci Gongye 2010, 17(4), 23-27.

34. Levina, M.; Michael, H.; Rubinstein.; Ali, R. and Siahboomi, R.; “Principles and

application of ultrasound in pharmaceutical powder compression” Pharma. Res.

2000, 17(3), 257-265.

35. Isariebel, Q; Carine, J.; Ulises-Javier, J.; Anne-Marie, W. and Henri, D.;

“Sonolysis of levodopa and paracetamol in aqueous solutions” Ultra. Sonochem.

2009, 16(5), 610-616.

36. Hong, Y.; Xuemian, L.; Jiguang, L.; Yuantong, G. and Min, X.; “Application

value of ultrasonic measurement of intra-abdominal fat in assessment of

abdominal obesity” Hebei Yike Daxue Xuebao 2010, 31(1), 71-73.

37. Patil, M. and Onuora V.; “The value of ultrasound in the evaluation of patients

blunt scrotal trauma” Injury 1994, 25(3), 177-178.

38. Szenci, O.; Taverne, M.; Beckers, J.; Varga, J.; Börzsönyi, L.; Hanzen, C. and

Schekk, G.; “Evaluation of false ultrasonographic diagnoses in cows by

http://www.ingentaconnect.com/content/ben/coc;jsessionid=60jsfberqojs2.alice


Varga

Hanzen

Schekk



measuring plasma levels of bovine pregnancy-associated glycoprotein” Veterinary

Record 1998, 142, 304-306.

39. Perlmutter, G.; Goldberg, B. and Charkes, N.; “Ultrasound evaluation of the

thyroid” Seminars in Nuclear Medicine 1975, 5(4), 299-305.

40. Meizne, I. and Bar-Ziv, J.; “Prenatal ultrasonic diagnosis of anterior abdominal

wall defects” Eur. J. Obst. Gyn. Repro. Bio.1986, 22(4), 217-224.

41. Lovett, I.; Doust, B. and Orr, N.; “The Role of Ultrasound in the Diagnosis of

Parenchymal Disease in Transplanted Kidneys” Aust. Radio. 1988, 32(1), 104–

106.

42. Edward, S.; Amis, J.; John, J.; Cronan, M.; Richard, C.; Pfister, M.; Isabel, C. and

Yoder, M.; “Ultrasonic inaccuracies in diagnosing renal obstruction” Urology

1982, 19(1),101-105.

43. Boucaud, A.; Machet, L.; Arbeille, B.; Machet, M. C.; Sournac, M.; Mavon, A.;

Patat, F. and Vaillant, L.; “In vitro study of low-frequency ultrasound-enhanced

transdermal transport of fentanyl and caffeine across human and hairless rat skin”

Int. J. Pharma. 2001, 228(1-2), 69-77.

44. Annema, J.; Versteegh, M.; Veseliç, M.; Welker, L.; Mauad, T.; Sont, J.; Willems,

L. and Rabe, K.; “Endoscopic Ultrasound Added to Mediastinoscopy for

Preoperative Staging of Patients with Lung Cancer” JAMA 2005, 294(8), 931-936.

45. Nehmat, H.; Stefano, C.; Turner, R.; Cody, H. and Macaskill, P.; “Preoperative

Ultrasound-Guided Needle Biopsy of Axillary Nodes in Invasive Breast Cancer:

Meta-Analysis of Its Accuracy and Utility in Staging the Axilla” Annal. Surgery

2011, 254 (2), 243–251.

46. Husseini, G. and Pitt, W.; “Ultrasonic activated micellar drug delivery for cancer

treatment” J. Pharm. Sci. 2009, 98(3), 795-811.

47. Winkler, P. and Helmke, K.; “Ultrasonic diagnosis and follow-up of malignant

brain tumors in childhood A report of 4 cases and a review of the literature”

Pediatric Radiology 1985, 15(4), 215-219.

48. Tanaka, K.; Kazufumi M.; Ito, M. and Toshio Wagai, M.; “The Localization of

Brain Tumors by Ultrasonic Techniques” J. of Neurosur. 1965, 23(2), 135-147.

49. Hernandez, A.; Goldring, D.; Alexis, F.; Hartmann, J.; Charles Crawford, B. and

Reed, G.; “Measurement of blood pressure in infants and children by Doppler

ultrasonic technique” Pediatrics 1971, 48(5), 788-794.


http://www.sciencedirect.com/science?_ob=PublicationURL&_tockey=%23TOC%2313178%231975%23999949995%23639151%23FLP%23&_cdi=13178&_pubType=J&view=c&_auth=y&_acct=C000061812&_version=1&_urlVersion=0&_userid=3932454&md5=39855ac56a7c895787fe6d18226215e2




https://springerlink3.metapress.com/content/?Author=K.+Helmke

https://springerlink3.metapress.com/content/?Author=K.+Helmke

https://springerlink3.metapress.com/content/0301-0449/



50. Harvey, D.; Prince, J.; Bunton, J.; Parkinson, C. and Campbell, S.; “Abilities of

Children Who Were Small-for-Gestational-Age Babies” Pediatrics 1982, 69(3),

296-300.

51. Papanicolaou, N.; Pfister, R.; Young, H.; Yoder, I. and Herrin, J.; “Percutaneous

ultrasonic lithotripsy of symptomatic renal calculi in children” Pediatric

Radiology 1986,16(1), 13-16.

52. Uchigasaki, S.; Oesterhelweg, L.; Gehl, A.; Sperhake, J.; Püschel, K.; Oshida, S.;

Nemoto, N.; “Application of compact ultrasound imaging device to postmortem

diagnosis” For. Sci. Inter. 2004, 140(1), 33-41.

53. Uchigasaki, S.; Oesterhelweg, L.; Sperhake, J.; Püschel, K. and Oshida, S.;

“Application of ultrasonography to postmortem examination: Diagnosis of

pericardial tamponade” For. Sci. Inter. 2006, 162(1-3), 167-169.

54. Qifa Z.; Sienting, L.; Dawei, W. and Shung, K.; “Piezoelectric films for high

frequency ultrasonic transducers in biomedical applications” Prog. Mat. Sci.

2011, 56(2), 139-174.

55. Houhui, S.; Lu, Lin.; Wei, H. and Jian, Xu.; “Application of ultrasonic-mediated

genetic transformation of microorganism” Faming Zhuanli Shenging Chinese Pat.

Appl. 2010, Patent No CN 101875947 A 20101103.

56. Hong-zhi, W.; Zhi-xian, Z.; Rong-rong, Miao.; Su-wei, Y. and Wei-guo, Zhang.;

“Pulsed ultrasound enhances nanoparticle penetration into breast cancer

spheroids” Diandu Yu Jingshi 2010, 32(2),15-20.

57. Haijun, Z.; Hui, J.; Huangping, W.; Juan, Z.; Baoan, C. and Xuemei, W.;

“Ultrasound mediated drug-loaded nanoparticles crossing cell membranes as a

new strategy to reverse cancer multidrug resistance” J. Nanosci. Nanotech. 11(3)

2011, 1834-1840.

58. Yong, Li.; Xiao-ling, G. and Cha-fang, Q.; “Application of ultrasonic technology

in preparation and photocatalysis of nano-TiO2” Yinran Zhuji 2009, 26(9), 9-12.

59. Chaowu, Z.; Fangyuan, Z.; Fen, W.; Jun, Yang. and Ling, X.; “Ultrasonic co-

deposit fabrication of Si-Ha nanopowder and mechanicalperformance of its bio-

cement” Zhongguo Taoci Gongye 2010, 17(4), 23-27.

60. Ayachit, N.; Vasan, S.; Sannaningannavar, T. and Deshpande, D.;

“Thermodynamic and acoustical parameters of some nematic liquid crystals.” J.

Mol. Liq. 2007, 133(1-3), 134-138.

Pfister

https://springerlink3.metapress.com/content/?Author=H.+H.+Young

https://springerlink3.metapress.com/content/?Author=I.+C.+Yoder

https://springerlink3.metapress.com/content/?Author=J.+T.+Herrin




http://www.sciencedirect.com/science?_ob=PublicationURL&_tockey=%23TOC%235041%232004%23998599998%23489746%23FLA%23&_cdi=5041&_pubType=J&view=c&_auth=y&_acct=C000061812&_version=1&_urlVersion=0&_userid=3932454&md5=1525425bd2a1cde37acfda5c02cd1bac


http://www.ingentaconnect.com/content/asp/jnn



61. Ming Yang, H. and Yi Peng, G.; “Ultrasound-assisted third-liquid phase-transfer

catalyzed esterification of sodium salicylate in a continuous two-phase-flow

reactor” Ultra. Sonochem. 2010, 17(1), 239-245.

62. Katoh, R.;Yokoi, H.; Usuba, S.; Kakudate, Y. and Fujiwara, S.; “Sonochemical

polymerization of benzene derivatives: the site of the reaction.” Ultra. Sonochem.

1998, 5(2), 69-72.

63. Kruger, O.; Schulze, T. and Peters, D.; “Sonochemical treatment of natural ground

water at different high frequencies: preliminary results.” Ultra. Sonochem. 1999,

6(1-2), 123-128.

64. Zhao, Y.; Liao, X.; Hong, J. and Zhu, J.; “Synthesis of lead sulphide nanocrystals

via microwave and sonochemical methods” Mat. Chem. Phys. 2004, 87(1), 149-

153.

65. Mexiarová, M. and Kiripolský, T.; “The sonochemical arylation of active

methylene compounds.” Ultra. Sonochem. 2005, 12(5), 401-403.

66. Ming Yang, H. and Cheng Chiu, C.; “Ultrasound-assisted phase-transfer catalysis:

Benzoylation of sodium 4-acetylphenoxide by dual-site phase-transfer catalyst in

a tri-liquid system” Ultra. Sonochem. 2011, 18(1), 363-369.

67. Jun Hong, Y.; Yusheng, C. and Yi, P.; “Application of sonochemistry in the

isomerization of carbon-carbon double bonds” J. Poly. Sci. Part A

2010, 48(22), 5254-5257.

68. Suyog, A.; Ravindra, D.; Kakasaheb, M.; Anant, P. and Peter,Y.; “Ultrasound

assisted cocrystallization from solution (USSC) containing a non-congruently

soluble cocrystal component pair: Caffeine/maleic acid” Eur. J. Pharm. Sci.

2010, 41(5), 597-602.

69. Park, M. and Do Yeo, S.; “Antisolvent Crystallization of Roxithromycin and the

Effect of Ultrasound” Sep. Sci. Tech. 2010, 45, 1402–1410.

70. Shengdan, Y. and Dayou, F.; “Application of ultrasonic wave, microwave-assisted

extraction and their combined extraction technology for extracting effective

constituents from Chinese herbal medicine” Guangdong Huagong 2010,

37(2), 120-122.

71. Kim, M.; Kemp K. and Letcher, S.; “Ultrasonic measurement in liquid alkali

metals.” J. Acous. Soc. Am. 1971, 49(3), 706-712.


http://www.sciencedirect.com/science?_ob=PublicationURL&_hubEid=1-s2.0-S1350417709X00052&_cid=271548&_pubType=JL&view=c&_auth=y&_acct=C000228598&_version=1&_urlVersion=0&_userid=10&md5=ff071563145c14b10961da572c364f11




http://www.sciencedirect.com/science?_ob=PublicationURL&_hubEid=1-s2.0-S1350417710X00050&_cid=271548&_pubType=JL&view=c&_auth=y&_acct=C000228598&_version=1&_urlVersion=0&_userid=10&md5=29aa2ca51ab58b04a0f5a06d6f29ae90



72. Raman, S. and Tipnis, C.; “Ultrasonic studies in camphene solutions.” Ind. J. Pure

App. Phys. 1982, 20(1), 79-80.

73. Inoue, N.; Hasegawa, T. and Matsuzawa, K.; “Ultrasonic velocity measurement of

liquids in the frequency range 0.2-7 MHz using an improved ultrasonic

interferometer.” Acustica 1991, 74(2), 128-133.

74. Takagi, T.; “Ultrasonic velocity in binary mixtures under high pressures and their

thermodynamic properties.-Binary mixture for nitrobenzene-aniline.” Review

Phys. Chem. 1978, 48(1), 10-16.

75. Nath, J. and Dixit, A.; “Ultrasonic velocities in, and adiabatic compressibilities

for, binary liquid mixtures of acetone with benzene, toluene, p-xylene, and

mesitylene at 308.15 K.” J. Chem. Eng. Data. 1984 29(3), 320-321.

76. Ali, A.; Nain, A. and Kamil, M.; “Physical-chemical studies of non-aqueous

binary liquid mixtures at various temperatures.” Thermo. Chim. Acta, 1996, 274,

209-221.

77. Ezhil Raj, A.; Resmi, L.; Bena Jothy, V.; Jayachandran, M. and Sanjeeviraja, C.;

“Ultrasonic study on binary mixture containing dimethylformamide and methanol

over the entire miscibility range (0 < x < 1) at temperatures 303–323 K” Fluid

Phase Equi. 2009, 281(1), 78-86.

78. Pancholy, M. and Singal S.; “Ultrasonic studies in aqueous solutions of

electrolytes.” J. Sci. Ind. Res. 1962, 21B (2), 70-73.

79. Kim, W.; Yu, M.; Choi, I. and Kim, M.; “Measurement of ultrasonic relaxational

characteristics in aqueous solution of ZnCl2-DMF.” Ungyong Mulli 1998, 11(6),

675-682.

80. Laux, D.; Leveque, G. and Cereser, C.; “Ultrasonic properties of water/sorbitol

solutions.” Ultrasonics 2009, 49(2), 159-161.

81. Hassun, S.; Shihab, A. and Jassim, F.; “Studies on ultrasonic absorption and

visco-relaxation of poly (ethylene glycol) aqueous solutions.” Chin. J. Poly. Sci.

1989, 7(3), 270-279.

82. Srivastava, S. and Laxmi, S.; “Ultrasonic studies of amino acids” Z. Phys. Chem.

1970, 70, 219-223.

83. Sharma, P.; Chauhan, S.; Chauhan, M. and Syal, V.; “Ultrasonic velocity and

viscosity studies of tramacip and parvodex in binary mixtures of alcohol + water”

Ind. J. Pure Appl. Phys. 2008, 46 (12), 839-843.



84. Baluja, S.; Solanki, A. and Kachhadia, N.; “An ultrasonic study of some drugs in

solutions.” Russ. J. Phys. Chem. 2007, 81, 859-863.

85. Sasaki, K. and Arakawa, K.; “Ultrasonic and thermodynamic studies on the

aqueous solutions of tetramethylurea.” Bull. Chem. Soc. Jpn. 1973, 46(9), 2738-

2741.

86. S. Baluja; “Acoustical studies of some Schiff bases in 1,4-dioxane and

dimethylformamide at 318.15 K.” Chin. J. Chem. 2006, 24(10), 1327-1331.

87. Godvani, N.; Movaliya J. and Baluja, S.; “Acoustical studies of some derivatives

of 1,5-benzodiazepines at 298.15 K.” Russ. J. Phys. Chem. 2009, 83(13), 2223-

2229.

88. Gajera, R.; Bhalodia, R. and S. Baluja; “Synthesis and ultrasonic studies of some

dihydropyrimidines in different solvent at 298.15 K.” Int. J. Appl. Chem. 2009,

5(1), 47-55.

89. Riddick, J.; Bunger, W. and Sakano T.; “Organic solvents-Physical properties and

Methods for purification” 4th Edition, Techniques of Chemistry, Vol.II, Wiely,

New York 1986.

90. Ubbelhode, L.; “The simplest and most accurate viscometer and other apparatus

employing the hanging level.” J. Inst. Pet. 1933, 19, 376-420.

91. Robinson, R. and Stokes, R.; "Electrolyte Solutions", Butterworths Scientific

Publications, London; 1955.

92. Sastry, G.; Sastry, V. and Krishnamurty, B.; “Ultrasonic parameters in mixed salt

solutions.” Ind. J. Pure Appl. Phy. 1968, 6, 637-638.

93. Jacobson, B.; Nature (London), 1954, 173, 772-773.

94. Wada; Y.; “The relation between compressibility and molal volume of

organicliquids” J. Phy. Soc. Jpn. 1949, 4, 280-283.

95. Sendhilnathan, S.; Bagchi, S.; Nema, S. and Singh R.; “Ultrasonic and rheological

investigations of solid propellant binders” Euro. Poly. J. 1989, 25, 441-444.

96. Vigoureux, P.; “Ultrasonics”, Chapman and Hall, London 1952.

97. Johri G. K. and Misra R. C.; “Phase-transition study and ultrasonic investigations

in tert-butyl alcohol (TBA)” Ind. J. Phy. 1985, 59, 482-488.

98. Yawale, S.; Pakade, S. and Adagonkar, S.; “Solid state variable frequency pulser-

receiver system for ultrasonic measurements.” I. J. pure. App. Phy. 1995, 33, 638-

642.



99. Bachem, C.; Electrochem. 1935, 41,570.

100. F.T. Gucker (Jr.), Chem. Rev.1993, 64, 111.

101. Korey, V. B.; “Adiabatic compressibilities of some aqueous ionic solutions and

their variation with indicated liquid structure of the water” Phys. Rev. 1993, 64,

350-357.

102. Nikam, P. S and Hiray, R. A.; “Temperature and concentration dependence of

ultrasonic velocity and allied parameters of monochloro acetic acid in ethanol-

nitrobenzene mixtures” Ind. J. Pure appl. Phys. 1991, 29, 601-605.

Section-II

Solubility

Section-II Solubility


INTRODUCTION

The solubility of pharmaceuticals compounds is an important aspect of drug

development. The knowledge of an accurate solubility is needed for the design of

separation processes such as extractive crystallization or for the safe operation of different

processing units such as distillation columns, absorption units and extraction plants.

The extensive information on the thermodynamic properties of organic

compounds is needed not only their use in many industrial processes but also for the

advancement of theoretical developments through an understanding of the intermolecular

forces-solution structure-property relationship. Literature survey shows that many

researchers have studied the solubility of gases1, organic compounds2-4, amino acids5,6,

polymers7-9, ionic liquids10,11, inorganic compounds12-15, drugs16-19 etc.

In the field of pharmaceutical research, solubility is a key factor to concentrate20

as it is pivotal to determine the bio availability of drugs21. So, many researchers have

studied the solubility of various drugs like difloxacin22, clopidogril23, oxaprozin24,

bupivacaine25, aciclovir26, ibuprofen27 etc.

To study the solubility, various methods have been used such as HPLC28,

Differential Scanning Calorimetry29, 1H and 13P NMR30, laser monitoring observation

technique31 etc. Solubility of drugs can also be predicted by various theoretical methods32

like multiple linear regression33, general solubility equation34, group contribution

approach35 etc.

The dissolution of a solute in a solvent is accompanied by the heat change. If the

heat is absorbed, i.e., the solution is cooler, the enthalpy change (∆H) would be positive.

If the heat is evolved, solution is warmer and so enthalpy change would be negative.

Thus, the heat of solution is defined as the change in enthalpy, when one mole of

substance is dissolved in specified quantity of solvent at a given temperature. By using

the computation of solubility data, thermodynamics parameters of solution can also be

deduced36.

Our research group has actively engaged to study the solubility of various drug

APIs (Active Pharmaceutical Ingredients)37,38 and other bio active heterocyclic molecules 39,40.



In this chapter, solubility study of some tetrahydropyrimidine derivatives (PAB-

101 to PAB-110) have been done in various solvents such as methanol, ethanol, isopropyl

alcohol and tetrahydrofuran, at various temperatures (293.15 to 313.15K). Further, some

thermodynamic parameters such as dissolution enthalpy, Gibb’s energy of dissolution and

entropy have also been evaluated from the solubility data.



EXPERIMENTAL

All the synthesized compounds were recrystallized in chloroform. The solubility

of these synthesized compounds (PAB-101 to PAB-110) is determined in methanol,

ethanol, isopropyl alcohol and tetrahydrofuran. The choice of these solvents is due to

their different dielectric constants and solubility of compounds.

All these selected solvents were purified by fractional distillation and its purity

was checked by HPLC.

The gravimetric method41 was used to study the solubility. An excess mass of

compound was added to a known mass of solvent. The solution was warmed to a constant

temperature with continuous stirring. After, at least 3 hr the stirring was stopped and the

solution was kept at a constant temperature for 2 hr. A portion of this solution was filtered

and by a preheated injector, 5 ml of this clear solution was taken to pre weighted

measuring vial (m0). The vial was quickly and tightly closed and weighted (m1) to

determine the mass of the sample (m1- m0). To prevent dust contamination, the vial was

covered with a piece of filter paper. After completely dryness of vial mass, the vial was

reweighed (m2) to determine the mass of the constant residue solid (m2- m0). All the

weights were taken using electronic balance ( Mettler Toledo AB204-S, Switzerland)

with uncertainty of 0.0001 g. The procedure was repeated three times at each

temperature.




Using the weights of residues and solvents, the mole fraction solubility (x) of the

compound in the solution is determined by the equation:

2 0 1

2 0 1 1 2 2

( ) /

( ) / ( ) /

m m Mx

m m M m m M

… (3.2.1)

where M1 and M2 are the molar mass of compound and solvent respectively. For each

solvent, the experiment was repeated three times at each temperatures and an average

value is given in Tables 3.2.1 to 3.2.4 for all the selected solvents.

It is obvious from these tables that the solubility is much higher in THF in

comparison to alcohols. In the studied alcohols, maximum solubility is observed for

compound PAB-103 and minimum for PAB-104. However, in THF, maximum solubility

is observed for PAB-102 and minimum is observed for PAB-108.

The variation of solubility with temperature is also shown in Figures 3.2.1 to 3.2.4

for all the compounds in the studied solvents. It is evident from these figures that

solubility increases with temperature for all the compounds in the studied solvents.

Further, the temperature dependence of solubility in solvents is studied by the following

modified Apelblat equation42,43:

ln x = A + B/T + C lnT ... (3.2.2)

where x is the mass fraction solubility of compound, T is the absolute temperature and A,

B and C are the parameters. The values of these parameters are also given in Table 3.2.5.

Using these parameters, values of solubility (xc) were evaluated and are given in

Tables 3.2.1 to 3.2.4. Further, root-mean-square deviations (RMSD) were calculated by

equations (3.2.3) and are listed in Table 3.2.5.

1/ 22

1

( )

1

Nci i

i

x xRMSD

N

… (3.2.3)

where N is the number of experimental points and xci is the calculated solubility.

Using experimental data of solubility in different solvents, some thermodynamic

parameters such as dissolution enthalpy, Gibb’s energy of dissolution and entropy have

also been evaluated.



Table 3.2.1: The experimental mole fraction solubility (x) and calculated solubility

(xc) of tetrahydropyrimidine derivatives (PAB) in methanol at different

temperatures.

Temp.K

x. 103 xc.103 x. 103 xc.103

PAB-101 PAB-106

293.15 2.3355 2.4577 0.7946 0.7973

298.15 2.7406 2.8905 0.9063 0.9104

303.15 3.1486 3.2921 1.0281 1.0363

308.15 3.4323 3.6382 1.1783 1.1762

313.15 3.7212 3.9087 1.3229 1.3311

PAB-102 PAB-107

293.15 2.4890 2.5186 0.9903 0.9937

298.15 2.8392 2.8875 1.2376 1.2248

303.15 3.1960 3.2090 1.4849 1.5180

308.15 3.3958 3.4636 1.9204 1.8910

313.15 3.5996 3.6376 2.3533 2.3668

PAB-103 PAB-108

293.15 3.4381 3.2917 2.0302 2.1090

298.15 3.5237 3.3757 2.0928 2.1698

303.15 3.6168 3.4630 2.1296 2.2293

308.15 3.7144 3.5536 2.2177 2.2874

313.15 3.8097 3.6476 2.2491 2.3440

PAB-104 PAB-109

293.15 0.5055 0.5031 1.5909 1.5793

298.15 0.5303 0.5273 1.8949 1.8458

303.15 0.5517 0.5480 2.2075 2.2584

308.15 0.5666 0.5648 2.9960 2.8837

313.15 0.5814 0.5778 3.8391 3.8322

PAB-105 PAB-110

293.15 1.0337 1.0665 1.9735 2.0592

298.15 1.3007 1.3287 1.9931 2.0815

303.15 1.5713 1.6386 2.0126 2.0981

308.15 1.9606 2.0014 2.0180 2.1091

313.15 2.3465 2.4222 2.0262 2.1148

Section-II


Figure 3.2.1: The variation

compounds

0.000

0.001

0.002

0.003

0.004

0.005

290 295

X

0.000

0.001

0.002

0.003

0.004

0.005

290 295

x

II


The variation of mole fraction solubility x with temperature

in methanol.

295 300 305 310

Temperature (K)PAB-101 PAB-101PAB-102 PAB-102 PAB-103 PAB-103 PAB-104 PAB-104PAB-105 PAB-105

295 300 305 310Temperature (K)

PAB-106 PAB-106 PAB-107 PAB-107 PAB-108 PAB-108 PAB-109 PAB-109 PAB-110 PAB-110

Solubility

120

with temperature for PAB

315

315




(xc) of PAB compounds in ethanol at different temperatures.

Temp.K

x. 103 xc.103 x. 103 xc.103

PAB-101 PAB-106

293.15 1.3072 1.3675 1.7157 1.7662

298.15 1.7253 1.7821 1.7743 1.8425

303.15 2.1403 2.2514 1.8616 1.9161

308.15 2.6533 2.7623 1.9291 1.9868

313.15 3.1631 3.2974 1.9864 2.0544

PAB-102 PAB-107

293.15 1.3191 1.3927 1.0706 1.0732

298.15 1.6316 1.7115 1.1833 1.1824

303.15 1.9492 2.0714 1.2898 1.2944

308.15 2.3545 2.4713 1.4071 1.4088

313.15 2.7542 2.9088 1.5225 1.5246

PAB-103 PAB-108

293.15 3.5601 3.6655 2.6090 2.6237

298.15 3.6772 3.7842 2.6994 2.7162

303.15 3.7829 3.8939 2.7894 2.8019

308.15 3.8768 3.9943 2.8609 2.8806

313.15 3.9688 4.0855 2.9366 2.9523

PAB-104 PAB-109

293.15 0.5222 0.5126 3.8183 3.7898

298.15 0.5503 0.5377 3.8222 3.7936

303.15 0.5783 0.5727 3.8263 3.7975

308.15 0.6365 0.6189 3.8305 3.8015

313.15 0.6892 0.6779 3.8345 3.8055

PAB-105 PAB-110

293.15 1.8953 1.8748 2.6738 2.7602

298.15 2.0290 1.9972 2.9140 3.0049

303.15 2.1626 2.1501 3.1545 3.2617

308.15 2.3760 2.3375 3.4243 3.5307

313.15 2.5930 2.5647 3.6908 3.8118

Section-II



compounds in

0

0.001

0.002

0.003

0.004

0.005

290 295

X

0.0000

0.0010

0.0020

0.0030

0.0040

0.0050

290 295

X

II


of mole fraction solubility x with temperature

in ethanol.

295 300 305 310

Temperature (K)PAB-101 PAB-101PAB-102 PAB-102PAB-103 PAB-103 PAB-104 PAB-104 PAB-105 PAB-105



Solubility

122


315

315



Table 3.2.3: The experimental mole fraction solubility (x), calculated solubility (xc)

of PAB compounds in isopropyl alcohol at different temperatures.

Temp.K

x. 103 xc.103 x. 103 xc.103

PAB-101 PAB-106

293.15 1.7325 1.7150 0.8418 0.86832

298.15 1.9229 1.8878 0.8843 0.91518

303.15 2.1056 2.1047 0.9330 0.96217

308.15 2.4231 2.3745 0.9778 1.00919

313.15 2.7347 2.7086 1.0220 1.05614

PAB-102 PAB-107

293.15 4.0837 3.9834 0.4842 0.4755

298.15 4.1653 4.0677 0.5022 0.4877

303.15 4.2664 4.1609 0.5082 0.5022

308.15 4.3717 4.2633 0.5319 0.5190

313.15 4.4834 4.3747 0.5495 0.5381

PAB-103 PAB-108

293.15 5.6778 5.5748 2.3497 2.4000

298.15 5.7814 5.6824 2.4980 2.5408

303.15 5.8845 5.7716 2.6398 2.7074

308.15 5.9458 5.8431 2.8527 2.9024

313.15 6.0066 5.8971 3.0632 3.1289

PAB-104 PAB-109

293.15 0.4671 0.4867 3.6885 3.5707

298.15 0.5047 0.531 3.7480 3.6336

303.15 0.5485 0.5658 3.8282 3.7076

308.15 0.5599 0.5897 3.9217 3.7925

313.15 0.5777 0.6020 4.0137 3.8884

PAB-105 PAB-110

293.15 0.8224 0.7842 2.8864 2.8319

298.15 0.9502 0.8969 3.2916 3.2116

303.15 1.0775 1.0422 3.7028 3.6718

308.15 1.3089 1.2290 4.3595 4.2294

313.15 1.5383 1.4693 4.9881 4.9058

Section-II



compounds

0

0.001

0.002

0.003

0.004

0.005

0.006

0.007

290 295

X

0

0.001

0.002

0.003

0.004

0.005

0.006

290 295

X

II



compounds in isopropyl alcohol.


PAB-101 PAB-101PAB-102 PAB-102PAB-103 PAB-103 PAB-104 PAB-104 PAB-105 PAB-105



Solubility

124


315

315




(xc) PAB compounds in THF at different temperatures.

Temp.K

x. 103 xc.103 x. 103 xc.103

PAB-101 PAB-106

293.15 8.3590 8.7955 9.1415 9.4364

298.15 8.5903 9.0499 9.6052 9.9275

303.15 8.8212 9.2752 10.0701 10.3933

308.15 8.9873 9.4709 10.4860 10.8310

313.15 9.1530 9.6372 10.8784 11.2384

PAB-102 PAB-107

293.15 21.0426 21.9747 16.4174 16.5920

298.15 21.6805 22.6781 16.5749 16.7635

303.15 22.3133 23.2710 16.7336 16.9035

308.15 22.6998 23.7520 16.8228 17.0132

313.15 23.0872 24.1215 16.9100 17.0939

PAB-103 PAB-108

293.15 11.5150 12.1014 6.9170 7.1175

298.15 12.0429 12.6292 7.0822 7.2958

303.15 12.4813 13.1149 7.2556 7.4625

308.15 12.8859 13.5559 7.3964 7.6173

313.15 13.2852 13.9505 7.5377 7.7605

PAB-104 PAB-109

293.15 11.2591 10.9118 8.2134 8.1346

298.15 12.0687 11.5944 8.3264 8.2351

303.15 12.8938 12.6383 8.4152 8.3354

308.15 14.7346 14.1087 8.5199 8.4356

313.15 16.6013 6.1050 8.6250 8.5357

PAB-105 PAB-110

293.15 15.4735 14.7188 8.2966 8.5012

298.15 15.5848 14.8336 8.3941 8.6027

303.15 15.7250 14.9523 8.4921 8.6995

308.15 15.8547 15.0748 8.5743 8.7917

313.15 15.9845 15.2009 8.6642 8.8794

Section-II



compounds

0.000

0.005

0.010

0.015

0.020

0.025

0.030

290 295

x

0.004

0.006

0.008

0.010

0.012

0.014

0.016

0.018

290 295

X

II



compounds in tetrahydrofuran.


PAB-101 PAB-101PAB-102 PAB-102 PAB-103 PAB-103 PAB-104 PAB-104 PAB-105 PAB-105



Solubility

126


315

315



Table 3.2.5: Coefficient A, B and C of equation 3.2.2 and Root Mean Square Deviation (RMSD) of PAB compounds in different solvents.

Compounds A B C104

RMSDA B C

104

RMSD

Methanol Ethanol

PAB -101 650.84 -31438.39 -96.75 1.8415 549.75 -28520.52 -80.81 1.1085

PAB -102 646.2 -30853.69 -96.28 0.4859 209.6 -12614.36 -30.48 1.2683

PAB -103 -32.51 810.07 4.23 1.7254 50.54 -2954.79 -8.11 1.2482

PAB -104 167.46 -8436.42 -25.75 0.03281 -416.72 17374.83 61.59 0.1336

PAB -105 77.91 -7010.54 -10.71 0.58747 -307.87 12390.4 45.65 0.3104

PAB -106 -30.06 -956.71 4.61 0.0642 37.52 -2566.06 -6.18 0.6736

PAB -107 -296.33 9687.27 45.13 0.2404 74.26 -5022.78 -11.26 0.03062

PAB -108 6.57 -984.84 -1.65 0.9481 54.45 -3183.21 -8.72 0.1801

PAB -109 -1228.76 51705.93 184.12 0.6665 -6.72 35.48 0.18 0.32153

PAB -110 55.06 -2866.87 -9.06 0.9829 1.78 -1600.02 -0.39 1.1537

Isopropyl alcohol THF

PAB -101 -385.27 15320.36 57.5 0.3382 69.41 -3700.3 -10.83 5.1876

PAB -102 -63.21 2238.66 8.81 1.1646 110.84 -5535.32 -16.86 11.1337

PAB -103 65.65 -3414.52 -10.42 1.1795 84.02 -4542.43 -12.84 7.0374

PAB -104 498.18 -23647.46 -74.84 0.2674 -666.94 28375.61 99.57 5.1204

PAB -105 -488.72 19288.85 73.19 0.6454 -14.86 354.91 1.66 8.5917

PAB -106 14.48 -1732.03 -2.75 0.3414 76.09 -4322.34 -11.62 3.6875

PAB -107 -119.92 4584.6 17.01 0.1234 35.98 -1924.1 -5.9 2.0313

PAB -108 -204.98 7946.11 30.25 0.6277 29.24 -1878.37 -4.89 2.3829

PAB -109 -83.46 3180.31 11.79 1.3587 -9.9 42.6 0.87 0.9477

PAB -110 -294.36 10882.28 44.25 0.9219 3.03 -520.89 -1.06 2.3562



According to van’t Hoff analysis, the standard enthalpy change of solution is

obtained from the slope the ln x versus 1/T plot. However, in recent thermodynamic

treatments, some modifications have been introduced in the van’t Hoff equation to

diminish the propagation of errors and consequently to separate the chemical effects from

those due to statistical treatment used when enthalpy-entropy compensation plots are

developed42. For this reason, the mean harmonic temperature (Thm) is used in the van’t

Hoff analysis, which is calculated by modified van’t Hoff equation.

The enthalpy of solution (Hsol) was calculated by modified Van’t Hoff equation44

ln

1 1Sol

hm P

Hx

RT T

... (3.2.6)

where T is the experimental temperature and R is gas constant. Thm is the mean harmonic

temperature which is given as

1hm n

i

nT

T

... (3.2.7)

where n is the number of experimental temperatures. In the present case, the Thm value

obtained is only 302.99 K. The slope of the plot of ln x versus (1/T-1/Thm) gives the value

of Hsol.

The Gibbs energy change (Gsol) for the solubility process was then evaluated

from intercept of the above plot using following relation45:

ΔGsol = -RT. intercept ... (3.2.8)

Using these evaluated Hsol and Gsol values, the entropies of solutions Ssol were

obtained from equation

solsol

sol

hm

H - GS =

T ... (3.2.9)

All these thermodynamic parameters are given in Table 3.2.6.

It is evident from Table 3.2.6 that for all the compounds Hsol are Gsol values are

positive in all the studied solvents. However, Ssol values are negative for some



compounds. When stronger bonds are broken and weaker bonds are formed, energy is

consumed. So, Hsol becomes positive49. This indicates endothermic dissolution of

Table 3.2.6: The thermodynamic parameters of PAB compounds in different

solvents.

Comp.

code

ΔHsol

kcal.mol-1ΔGsol

kcal.mol-1ΔSsol

cal.mol-1.K-1

ΔHsol

kcal.mol-1ΔGsol

kcal.mol-1ΔSsol

cal.mol-1.K-1

Methanol Ethanol

PAB-101 17.7067 14.6103 10.2195 33.5886 15.5348 59.5864

PAB-102 14.0451 14.5599 -1.6992 28.0847 15.7363 40.7558

PAB-103 3.9370 14.1614 -33.7456 4.1288 14.0576 -32.7701

PAB-104 5.2536 18.9229 -45.1152 10.6622 18.7188 -26.5908

PAB-105 31.3184 16.2477 49.7409 11.9588 15.4164 -11.4118

PAB-106 19.5667 17.3308 7.3796 5.7525 15.8497 -33.3257

PAB-107 33.1166 16.3484 55.3432 13.4022 16.7691 -11.1125

PAB-108 4.0115 15.4794 -37.8496 4.5029 14.8269 -34.0745

PAB-109 33.8046 15.2149 61.3554 0.1621 14.0183 -45.7323

PAB-110 0.9562 15.6431 -48.4740 12.3061 14.5095 -7.2726

Isopropyl alcohol Tetrahydrofuran

PAB-101 14.5079 15.9555 -4.7775 3.4653 11.9275 -27.9297

PAB-102 9.6276 16.8749 -23.9196 3.5401 9.5949 -19.9839

PAB-103 3.3762 15.1796 -38.9569 5.4055 11.0532 -18.6401

PAB-104 5.7225 14.7992 -29.9576 14.8559 10.8570 13.1984

PAB-105 0.8234 14.5624 -45.3455 1.2529 10.4590 -30.3845

PAB-106 5.0308 14.1871 -30.2203 6.6562 11.5950 -16.3006

PAB-107 7.8177 14.3760 -21.6459 0.9869 10.3129 -30.7804

PAB-108 0.2333 13.8470 -44.9321 3.3846 12.4137 -29.8004

PAB-109 26.1558 12.0031 46.7110 1.4832 12.0258 -34.7957

PAB-110 32.1004 11.8142 66.9543 1.6478 12.0132 -34.2108



compounds. The endothermic effect in the dissolving process is perhaps because the

interactions between compound molecules and solvent molecules are more powerful than

those between the solvent molecules50. The positive value of Gsol indicates that the

dissolution process is not spontaneous49, 37. The entropy values are positive for some

compounds in some solvents whereas these values are negative in other solvents for few

compounds. The positive entropy indicates that dissolution process increases the

randomness in solution whereas negative entropy is due to more order in solutions51. This

depends on the functional groups present in the compound as well as on the solvent.

Different functional groups interact differently with the solvent, so randomness will be

different. It is observed that in tetrahydrofuran, entropy is negative for all the compounds

indicating thereby less randomness in this solvent. In alcohols, for some compounds,

randomness is more in methanol than in ethanol and isopropyl alcohol. So, entropy values

are positive for most of the compounds in methanol than other two alcohols.

Thus, it is concluded that for the studied compounds, dissolution process is not

completely enthalpy or entropy driven in the selected solvents.



REFERENCES

1. Weiss, R.; “Solubility of nitrogen, oxygen, and argon in water and seawater”

Deep-Sea Res. Oceano. Abs. 1970, 17, 721-735.

2. Buchowski, H.; Ufnalski, W. and Jodzewicz, W.; “Solubility and hydrogen

bonding, part III solubility of 4-nitro-5-methylphenol in binary solvents” Roczniki

Chemii, 1977, 51, 2223-2232.

3. Regosz, A.; Krzykowska, Z.; Weclawska, K. and Chmielewska, A.; “Solubility

and thermo-dynamics of aqueous solutions of benzodiazepines” Pharmazie 1990,

45, 867-868.

4. Zhou, X.; Wang, Z. and Gao, J.; “Solubility of anthracene in butanol/alkane

binary solvent” Meitan Zhuanhua, 1995, 18, 84-89.

5. Amend, J. and Helgeson, H.; “Solubilities of the common L-α -amino acids as a

function of temperature and solution pH” Pure Appl. Chem. 1997, 69, 935-942.

6. Gao, L.; Liu, H.; Cai, S.; Chai, Y.; Liu, L. and Wu Y.; “Solubility behavior of four

diastereo-meric salts and two amino acids in near-critical CO2” Yao. Xue. 2002,

37, 355-358.

7. Tuminello, W.; “Solubility of polyand its copolymers” Fluoropolymers 1999, 2,

137-143.

8. Nagarajan, R.; “Solubilization vs. microemulsification in block copolymer-oil-

water systems” Abstracts of Papers, 224th ACS National Meeting, Boston, August

2002, 18-22.

9. Minati, L. and Biffis, A.; “A polymer support with controllable solubility in

mutually immiscible solvents” Chemi. Comm. 2005, 8, 1034-1036.

10. Freire, M.; Neves, C.; Carvalho, P.; Gardas, R.; Fernandes, A.; Marrucho, I.;

Santos, L. and Coutinho; J.; “Mutual Solubilities of Water and Hydrophobic Ionic

Liquids” J. Phy. Chem. 2007, 111, 13082-13089.

11. Kerle, D.; Ludwig, R.; Geiger, A. and Paschek, D.; “Temperature dependence of

the solubility of carbon dioxide in imidazolium-based ionic liquids” J. Phy.

Chemi. 2009, 113, 12727-12735.

12. Kruchenko, V.; “Solubility of gypsum in aqueous solutions of lithium salts” Khim.

Reaktsii, Alma-Ata. 1983, 29, 8-14.



13. Zaitseva, I.; Sytnik, O.; Krasnoperova, A. and Bondarev N.; “Influence of

properties of nonaqueous solvents on the solubility of NH4Cl and thermody

namics of its solution” Russ. J. Gen. Chem. 2005, 75, 25-30.

14. Skriptun, I. and Zarubitski, O.; “Solubility of CrO3, MoO3 and WO3 oxides in

molten alkali” Ukra. Khimiche. Z. 2007, 73, 37-39.

15. Benezeth, P.; Dandurand, J. and Harrichoury, J.; “Solubility product of siderite

(FeCO3) as a function of temperature (25-250 oC)” Chemi. Geology 2009, 265, 3-

12.

16. Kim, C.; “Effects of drug solubility, drug loading, and polymer molecular weight

on drug release from polyox tablets” Drug Dev. Indu. Phar. 1998, 24, 645-651.

17. Li, J.; Masso, J. and Guertin, J.; “Prediction of drug solubility in an acrylate

adhesive based on the drug-polymer interaction parameter and drug solubility in

acetonitrile” J. Controlled Release. 2002, 83, 211-221.

18. Nti-Gyabaah, J. and Chiew, Y.; “Solubility of Lovastatin in ethyl acetate, propyl

acetate, isopropyl acetate, butyl acetate, sec-butyl acetate, isobutyl acetate, tert-

butyl acetate, and 2-butanone, between (285 and 313) K” J. Chem. Eng. Data.

2008, 53, 2060-2065.

19. Ali, S.; Mohammad, A.; William, E. and Abolghasem, J.; “Solubility if

Lamotrigine, Diazepam and Clonazepam in ethanol+water mixture at 298.15K” J.

Chem. Eng. Data. 2009, 54, 1107-1109.

20. Hughes, L.; Palmer, D.; Nigsch F. And Mitchell, J.; “Why Are Some Properties

More Difficult To Predict than Others? A Study of QSPR Models of Solubility,

Melting Point, and Log P” J. Chem. Inf. Model. 2008, 48, 220-232.

21. Muenster, U.; Pelzetter, C.; Backensfeld, T.; Ohm, A.; Kuhlmann, T.; Mueller, H.;

Lustig, K.; Keldenich, J.; Greschat, S.; Andreas, H.; Mark, G. and Gnoth, J.;

“Volume to dissolve applied dose (VDAD) and apparent dissolution rate (ADR):

Tools to predict in vivo bioavailability from orally applied drug suspensions” Eur.

J. Pharm. Bio. 2011, 78, 522–530.

22. Baluja, S.; Bhalodia, R.; Gajera, R.; Vekariya, N. and Bhatt, M.; “Solubility of

Difloxacin in Acetone, Methanol, and Ethanol from (293.15 to 313.15) K” J.

Chem. Eng. Data. 2009, 54, 1091–1093.

23. Song, L.; Minxu, Li. and Gong, J.; “Solubility of Clopidogrel Hydrogen Sulfate

(Form II) in Different Solvents” J. Chem. Eng. Data. 2010, 55, 4016–4018.



24. Maestrelli, F.; Cirri, M.; Mennini, N.; Zerrouk, N.; Mura, P.; “Improvement of

oxaprozin solubility and permeability by the combined use of cyclodextrin,

chitosan, and bile components” Eur. J. Pharm. Bio. 2011, 78, 385–393.

25. Jug, M.; Mennini, N.; Melani, F.; Maestrelli, F. and Mura, P.; “Phase solubility,

1H NMR and molecular modelling studies of bupivacaine hydrochloride

complexation with different cyclodextrin derivates” Chem.Phy.Lett. 2010, 500,

347–354.

26. Brandi,G.; Rossi, L.; Giuditta, F.; Schiavano, M. and Magnani, M.; “A new

homodimer of aciclovir as a prodrug with increased solubility and antiviral

activity” Int. J. Anti. Age. 2009, 34,177–180.

27. Avdeef, A.; “Solubility of sparingly-soluble ionizable drugs” Adv.Drug Del.Rev.

2007, 59, 568–590.

28. Hua Mu, T.; SzeTan, S. and Lin Xue, Y.; “The amino acid composition, solubility

and emulsifying properties of sweet potato protein” Food Chemistry 2009, 112,

1002–1005

29. Bala, I.; Bhardwaj, V.; Hariharan, S. and Ravi Kumar, M.; “Analytical methods

for assay of ellagic acid and its solubility studies” J. Pharm. Bio. Ana. 2006, 40

(1) 206–210.

30. Bustamanate, P.; Romero, S.; Pen, A.; Escalera, B. and Reillo, A.; “Enthalpy-

Entropy Compensation for the Solubility of Drugs in SolventMixtures:

Paracetamol, Acetanilide, and Nalidixic Acid in Dioxane–Water” J. Pharm. Sci.

1998, 87(12), 1590-1596.

31. Zhi, X.; Guo. and Sheng Wang, L.; “Solubilities of Phosphorus-Containing

Compounds in Selected Solvents” J. Chem. Eng. Data. 2010, 55, 4709–4720.

32. Qiang Liu, J.; Qian, C. and Zhi Chen, X.; “Solubilities of 2,4-Dinitro-L-

phenylalanine in Monosolvents at (273.15 to 368.15) K” J. Chem. Eng. Data.

2010, 55, 5302–5304.

33. Jorgensena, W. and Duffyb, E.; “Prediction of drug solubility from structure” Adv.

Drug Del. Rev. 2002, 54, 355–366.

34. Mitchell, B. and Jurs, Peter.; “Prediction of Aqueous Solubility of Organic

Compounds from Molecular Structure” J. Chem. Inf. Comput. Sci. 1998, 38, 489-

496.


http://www.sciencedirect.com/science/journal/07317085/40/1




35. Ran,Y. and Yalkowsky, S.; “Prediction of Drug Solubility by the General

Solubility Equation (GSE)” J. Chem. Inf. Comput. Sci. 2001, 41, 354-357.

36. Klopman, G. and Zhu, H.; “Estimation of the Aqueous Solubility of Organic

Molecules by the Group Contribution Approach” J. Chem. Inf. Comput. Sci. 2001,

41, 439-445.

37. Liang Zhang, C.; Zhao, F. and Wang, Y.; “Thermodynamics of the solubility of

sulfamethazine in methanol, ethanol,1-propanol, acetone, and chloroform from

293.15 to 333.15 K” J. Mol. Liq. 2011, 159, 170–172.

38. Baluja, S.; Bhalodia, R.; Bhatt, M.; Vekariya, N. and Gajera, R.; “Solubility of

Enrofloxacin Sodium in Various Solvents at Various Temperatures” J. Chem.

Eng. Data. 2008, 53, 2897–2899.

39. Baluja, S.; Gajera, R.; Bhalodia, R.; Vekariya, N. and Bhatt, M.; “Solubility of

Difloxacin in Acetone, Methanol and Ethanol from (293.15 to 313.15) K”. J.

Chem. Eng. Data. 2009, 54, 1091-1093.

40. Baluja, S.; Gajera, R. and Kulshreshtha, A.; “Solubility of biologically active

chalcones in 1, 4 - dioxane and N, N dimethyl formamide from (298.15 to 318.15)

K” J. Chem. Eng. Data. 2010, 55, 574–577.

41. Patel, A.; Vaghasiya, A.; Gajera, R.; and Baluja, S.; “Solubility of 5-amino

salicylic acid in different solvents at various temperatures” J. Chem. Eng. Data.

2010, 55, 1453-1455.

42. Zhu, M.; “Solubility and Density of the Disodium Salt Hemiheptahydrate of

Ceftriaxone in Water + Ethanol Mixtures” J. Chem. Eng. Data 2001, 46, 175-

176.

43. Apelblat, A. and Manzurola, E.; “Solubilities of o-acetylsalicylic, 4-aminosalic, 3,

5-di nitrosalicylic, and p-toluic acid, and magnesium DL-aspartate in water from

T= (278 to 348) K” J. Chem. Therm. 1999, 31, 85-91.

44. Gao, J.; Wang, Z.; Xu, D. and Zhang, R.; “Solubilities of triphenylphosphine in

ethanol, 2-propanol, acetone, benzene and toluene” J. Chem. Eng. Data. 2007,

52, 189-191.

45. Shalmashi, A. and Eliassi, A.; “Solubility of salicylic acid in water,ethanol,carbon

tetrachloride, ethyl acetate and xylene” J. Chem. Eng. Data. 2008, 53,199- 200.

46. Kong, M.; Shi, X.; Cao, Y. and Zhou, C.; “Solubility of imidacloprid in different

solvents.” J. Chem. Eng. Data 2008, 53, 199-200.



47. Glasstone, S.; “Thermodynamics for Chemist”, Litton Edu.Pub.,Inc.New York.

48. Krug, R.; Hunter, W. and Grieger, R.; “Enthalpy-entropy compensation. 2.

Separation of the chemical from the statistical effects” J. Phys. Chem. 1976, 80,

2341-2351.

49. Kalsi, P.; “Organic reactions and their mechanisms.”(2nd Edition), New Age

International (P) Limited 2004, 119.

50. Triana, M. T.; Reyes, A. C.; Jimenez-Kairuz, A. F.; Manzo, R. H.; Martinez, F.;

“Solution and mixing thermodynamics of propranolol and atenolol in aqueous

media”, J. Sol. Chem., 2009, 38, 73-81.

51. El-Bindary, A.; El-Sonbati, A.; El-Mosalamy, E. and Ahmed, R.; “Potentiometric

and thermodynamic studies of Azosulfonamide drugs X” Chem. Pap. 2003, 57,

255-258.

Section-III

Density and refractive index

Section-III Density and refractive index


INTRODUCTION

The ratio of the velocity of light in vacuum to its velocity in the given medium is

known as refractive index. The refractive index of a material is the most important

property of any optical system that uses refraction.

The refractive index is a characteristic property of a substance, which depends

upon temperature and the wavelength of the light used. It decreases with increasing

temperature and wavelength. So, it is used to determine the structure and identity of

unknown compounds. It also determines isotropic and anisotropic behaviour of the crystal

by the arrangement of atoms1. The number of atoms, groups, radicals and bonds present

in the compound can also be calculated by refractive index measurement. Generally,

refractive index is a unit less number. Most compounds have refractive index values

between 1.3000 and 1.7000, but some materials give negative refractive index values and

are known as meta materials. These materials were first demonstrated for microwave

frequencies2.

The refractive index of a material medium is an important optical parameter since

it exhibits the optical properties of the material. It is important parameter in the design of

a solid state laser3.

Properties like refractive index, viscosity and density of binary liquid mixtures

over the whole composition range are useful for a full understanding of their

thermodynamic as well as for practical chemical engineering purposes and is also useful

for the adequate design of industrial processes4,5 and for theoretical purposes6. Various

applications of refractive index in optical fibers and other fields have also been reported7-

15. It is used in various industries to control manufacturing processes such as

fermentation16, dyes17, canning and preservation of food18,19 and for the identification or

assaying of some solids, liquids or constituents of a solution. A very well known

application is to determine the thickness of film20-24. Thus, this property has been used to

study various substances.

Nowadays refractive index also found useful in research related to medical

science and biotechnology25,26. Recent years have seen a rapid increase of research

interests in determining the cell physical parameters such as size, shape and refractive

index of living cells as demanded by biological studies and cell-based drug screening27,28.



The refractive index method also permits the determination of the concentration

distribution of solutes under non-destructive circumstances29.

Literature survey shows that refractive index of various types of materials such as

ionic liquids30-35, oils36,37, amino acids38, proteins39, sugar40,41, liquid crystals42,43, optical

fibres44-46, detergent47, photo sensitive materials48, nanomaterials49,50, holographic

materials51, various gases52, other materials53,54 etc has been reported.

The refractive index plays a vital role in various branches of science. It plays a

crucial role in instruments related to chemistry. Refractive index (RI) detection has been

successfully applied to many analytical techniques including HPLC55,56 size exclusion

chromatography57 and CE58,59. RI based detectors60 are more attractive alternatives to

fluorescence and absorption methods.

Further, various workers studied refractive index in liquid mixtures60-75, but scanty

work has been reported for the solutions of organic76-78, inorganic79-84 and polymeric

materials85-89. Study of solutions for solute-solute and solute-solvent interactions is found

to be attractive for researchers90-94 and have been studied by the knowledge of refractive

index. Refractive index of some aliphatic alcohols with dioxane has also been reported by

Sherstneva and Koleboshin95. Refractive index of methyl isobutyl ketone + pentanols has

also been measured by Riggio et al.96. Aal-Wahaibi et al. have reported refractive index

of ternary system: isopropyl alcohol + cyclohexane + water97. Campos et al. 98 have

determined the refractive index of formamide + water system. Aminabhavi99 has

predicted refractive index of some binary solvent mixtures. Govindan et al100 have

measured of refractive index of liquids using fiber optic displacement sensors.

Iulian, et al101 have studied Refractive index for water-organic component

homogeneous liquid mixtures. The characterization of an organic nonlinear optical crystal

urea ninhydrin monohydrate was also studied by refractive index measurement102.

In the present section, the density and refractive index of synthesized

tetrahydropyrimidine were measured in N, N-dimethylformamide and tetrahydrofuran

solutions of different concentrations. Further, molar refraction have been evaluated. From

these data, the refractive index and density of compounds were determined



EXPERIMENTAL

The solvents N. N-dimethyformamide (DMF) and tetrahydrofuran (THF) were of

LR grade and are fractionally distilled by the reported method103

. All the studied

synthesized tetrahydropyrimidine derivatives were recrystalized from chloroform. For

each compound, a series of solutions of different concentrations were prepared in DMF

and THF solvents.

The density and refractive index of solutions were measured by using pyknometer

and Abbe refractometer respectively at constant temperature 303.15 K. The temperature

was maintained by circulating water through jacket around the prisms of refractometer

from an electronically controlled thermostatic water bath (NOVA NV-8550 E). The

uncertainty of temperature was ±0.1o C. Mettler Toledo AB204-S, Switzerland electronic

balance with uncertainty of 0.0001 g, was used for all the weights taken for density

measurements.

The experimental data of density and refractive index of solutions are given in

Table 3.3.1.




The density of solution (ρ12) is related to densities of the solvent, solute and their

weight fractions g1 and g2 according to the equation:

1 2

12 1 2

1 g g

… (3.3.1)

where ρ12 is the density of solution and ρ1 and ρ2 are the densities of solvent and solute

respectively. Table 3.3.1 shows the experimental values of densities and refractive index

for all the ten synthesized tetrahydropyrimidine in different solutions.

The slope of the plot of 1 121 g verses 2 1g g gives the density of these

compounds. The plot of 1 121 g verses 2 1g g is given in Figure 3.3.1 for PAB-101 in

DMF and THF respectively. The densities of all the synthesized compounds were

evaluated from the slope of such plots. The inverse of slope gives density of compound

(ρ2). Table 3.3.2 shows these calculated densities for all the compounds. Further, the

density of compounds were calculated by using the following equation (3.3.2),

A iKM N V … (3.3.2)

ρ indicates the density of the compound, K is packing fraction which is equal to 0.599 for

organic compounds, M is for molecular weight of the compound, NA is the Avogadro’s

number and ΔVi is the volume increment of the atoms and atomic groups present in the

compound. The density of all the studied compounds have been evaluated and reported in

Table 3.3.2. The calculated volume increment ΔVi for different atomic groups are given

in Table 3.3.3.

Comparison of densities evaluated from graphs and those calculated from eq.

(3.3.2) showed that calculated values are different from those evaluated graphically. For

the same compound, density in the two different solvents is different. This suggests that

one has to consider the role of solvent in the measurement of the physical parameters of

any solutions. It is because of the fact that, in every solution molecular interactions exists

which differs with different solvents. This is further confirmed by acoustical parameter

which is already discussed in Section I. Generally, intermolecular interactions do not

affect the density but due to the presence of different substituted groups in solutes,

interactions differ in different solvents which may cause change in volume thereby

affecting the density of solute in a particular solvent.



Table 3.3.1: The density (ρ12) and refractive index (n) of tetrrahydropyrimidine

derivatives in DMF and THF at 303.15 K.

Conc.(M)

DMF THF DMF THFρ12

(g.cm-3)n

ρ12

(g.cm-3)n

ρ12

(g.cm-3)n

ρ12

(g.cm-3)n

PAB-101 PAB-1060.00 0.9304 1.4171 0.8779 1.4032 0.9304 1.4171 0.8779 1.40320.01 0.9323 1.4237 0.8776 1.4038 0.9356 1.4260 0.8760 1.40410.02 0.9326 1.4246 0.8790 1.4047 0.9372 1.4262 0.8770 1.40580.04 0.9331 1.4260 0.8794 1.4056 0.9386 1.4268 0.8788 1.40790.06 0.9338 1.4275 0.8800 1.4069 0.9388 1.4272 0.8800 1.40940.08 0.9342 1.4289 0.8816 1.4081 0.9391 1.4280 0.8806 1.41000.10 0.9353 1.4304 0.8846 1.4093 0.9395 1.4288 0.8825 1.4114

PAB-102 PAB-1070.01 0.9330 1.4239 0.8790 1.4053 0.9347 1.4259 0.8820 1.40580.02 0.9333 1.4248 0.8804 1.4070 0.9348 1.4267 0.8823 1.40620.04 0.9338 1.4259 0.8815 1.4082 0.9350 1.4281 0.8829 1.40700.06 0.9340 1.4271 0.8820 1.4089 0.9351 1.4291 0.8835 1.40780.08 0.9351 1.4291 0.8824 1.4102 0.9354 1.4301 0.8847 1.40910.10 0.9370 1.4309 0.8830 1.4109 0.9359 1.4313 0.8860 1.4101

PAB-103 PAB-1080.01 0.9359 1.4243 0.8797 1.4045 0.9339 1.4268 0.8770 1.40420.02 0.9365 1.4248 0.8814 1.4049 0.9350 1.4272 0.8789 1.40620.04 0.9370 1.4255 0.8823 1.4052 0.9365 1.4279 0.8792 1.40760.06 0.9376 1.4269 0.8832 1.4057 0.9374 1.4287 0.8818 1.40970.08 0.9380 1.4281 0.8841 1.4063 0.9383 1.4291 0.8833 1.41120.10 0.9384 1.4289 0.8851 1.4077 0.9393 1.4298 0.8850 1.4128

PAB-104 PAB-1090.01 0.9343 1.4255 0.8769 1.4045 0.9339 1.4257 0.8774 1.40460.02 0.9351 1.4258 0.8783 1.4062 0.9349 1.4265 0.8785 1.40520.04 0.9354 1.4262 0.8803 1.4071 0.9360 1.4274 0.8792 1.40630.06 0.9356 1.4271 0.8822 1.4089 0.9366 1.4279 0.8800 1.40730.08 0.9357 1.4288 0.8831 1.4093 0.9378 1.4289 0.8815 1.40860.10 0.9376 1.4302 0.8842 1.4099 0.9387 1.4296 0.8828 1.4096

PAB-105 PAB-1100.01 0.9330 1.4251 0.8770 1.4048 0.9329 1.4259 0.8780 1.40490.02 0.9340 1.4249 0.8781 1.4052 0.9333 1.4265 0.8774 1.40590.04 0.9341 1.4251 0.8806 1.4062 0.9334 1.4272 0.8794 1.40790.06 0.9346 1.4262 0.8823 1.4073 0.9359 1.4292 0.8814 1.40980.08 0.9355 1.4279 0.8851 1.4092 0.9363 1.4301 0.8826 1.41080.10 0.9356 1.4290 0.8861 1.4094 0.9371 1.4314 0.8850 1.4122

Section-III


Figure 3.3.1: The variation of 1/g

THF at 303.15 K.

1.06

1.07

1.08

1.09

1.10

0.00

1/ρ

12g

1

1.12

1.14

1.16

1.18

0.00

1/ρ

12g

1

III Density and refractive index


1: The variation of 1/g1ρ12 with g2/g1 for PAB-101 in [A] DMF and [B]

at 303.15 K.

0.01 0.02

g2/g1

[A]

0.01 0.02

g2/g1

[B]


141

in [A] DMF and [B]

0.03

0.03



Table 3.3.2: Experimental and calculated densities of tetrahydropyrimidine

derivatives in DMF and THF solutions at 303.15 K.

Compound CodeDensity (g.cm-3) calculated from Fig. 3.5.1 Density (g.cm-3)

calculated fromEqn. 3.5.2DMF THF

PAB-101 1.1405 1.2143 1.3048PAB-102 1.1756 1.0845 1.2404

PAB-103 1.1962 1.1716 1.3865PAB-104 1.1545 1.2259 1.3865

PAB-105 1.1339 1.4478 1.3648

PAB-106 1.2918 1.1217 1.2840

PAB-107 1.0711 1.1360 1.5496

PAB-108 1.3046 1.2261 1.3191

PAB-109 1.3891 1.1574 1.5199PAB-110 1.2563 1.2663 1.3444



Table 3.3.3: Volume increments of some atoms and groups of atoms.

Atoms orAtomic group

VolumeIncrements (Ao)3

Atoms orAtomic group

VolumeIncrements (Ao)3

C

C

C

N1 37. 1 4. 10.2 N

C

C

C 1 37.1 37.

0.9

C

C

C

C. 1 54.

1 349.0

C N C1 28.1 37. 5.62

C

C

N

H1 00. 1 28.

1 48.

3.61C

O

H

HH

1 091 09. .

1 5.

26.3

C

C

C

F 11.40 C

C

C

O 11.65

C Cl

C

C

10.39 C Cl1 77.

19.35

C C N 15.9 O H 4.7

C F1 34.

9.2 Car O Cal1 37.1 5. 2.67

CH

C

C

1 4. 14.7 C O H1 37.

5.36

N

O

O

C 1 21.1 57.

7.46 C N 10.0

N

C

C

H 1.36.1.08

.8.3 N

H

H

C ..

6.38



Further, the molar refraction of a pure liquid (MRD) 1 can be calculated using the

Lorentz-Lorenz equation104:

2

21

1

1

n MMRD

n

… (3.3.3)

where n, M and ρ are refractive index , molecular weight and density of pure liquid

respectively.

For solutions, the following eq. (3.3.4) was used to determine molar refraction.

212 1 1 2 221212 12

1

1

n X M X MMRD

n

... (3.3.4)

where n12 and ρ12 are refractive index and density of solution respectively. X1 and X2 are

the mole fractions and M1 and M2 are the molecular weight of the solvent and solute

respectively.

The plots of (MRD) 12 verses concentration for all the studied compounds in DMF

and THF are given in Figures 3.3.2 and 3.3.3. It is evident from these figures that (MRD)

12 increases with the increase in concentration. From the values of the molar refraction of

solution and pure solvent, molar refraction of solid compounds were determined by

following equation:

1 212 1 2MRD X MRD X MRD … (3.3.5)

From the density and molar refraction data, the refractive indexes of all the

compounds were calculated from eq. (3.3.3). The molar refraction (MRD)2 and refractive

index of all the compounds are reported in Table 3.3.4 for 0.1 M solution.

Each solvent interacts differently with different functional groups, so that (MRD)2

and refractive index of compounds is different in each solvent, as shown in Table 3.3.4.

As discussed above, in different solvents intermolecular interactions are different, which

affect these parameters. In some solvents, aggregation or hydrogen bonding takes place

whereas in others, breakage of bonds takes place. The refractive index and molar

refraction depends not only upon atomic refraction but also upon single, double or triple

bonds. However, it is reported that bond refraction is more effective than atomic

refraction. Further, bond polarity also causes change in molar refraction. Thus, type of

solvent affects the refractive index and molar refraction of a solute.

Section-III


Figure 3.3.2: The plots of molar refraction (MRD)

tetrahydropyrimidine derivatives

19.50

20.00

20.50

21.00

0.00

(MRD

) 12

PAB

19.50

20.00

20.50

21.00

0.00

(MRD

) 12

PAB 106



2: The plots of molar refraction (MRD)12 against concentration of

tetrahydropyrimidine derivatives in DMF solutions at 303.15 K.

0.02 0.04 0.06 0.08

Concentration (M)

PAB-101 PAB-102 PAB-103 PAB-104

0.02 0.04 0.06 0.08Concentration (M)

PAB 106 PAB 107 PAB 108 PAB 109


145

against concentration of

in DMF solutions at 303.15 K.

0.08 0.10

PAB-105

0.10

PAB 110

Section-III


Figure 3.3.3: The plots of molar refraction (MRD)

tetrahydropyrimidine

20.00

20.50

21.00

0.00

(MRD

) 12

PAB-101

20.00

20.50

21.00

0

(MRD

) 12

PAB-106



3: The plots of molar refraction (MRD)12 against concentration of

tetrahydropyrimidine derivatives in THF solutions at 303.15 K.

0.02 0.04 0.06 0.08

Concentration (M)

101 PAB-102 PAB-103 PAB-104

0.02 0.04 0.06 0.08

Concentration (M)

106 PAB-107 PAB-108 PAB-109


146

against concentration of

solutions at 303.15 K.

0.10

PAB-105

0.1

PAB-110



Table 3.3.4: Calculated molar refraction and refractive index of 0.1 M solution of

tetrahydropyrimidine derivatives in DMF and THF at 303.15 K.

Compounds

SolventsDMF THF

(MRD)2 n (MRD)2 nPAB-101 114.6601 2.3786 73.0112 1.7662PAB-102 119.6821 2.2822 92.6678 1.7736PAB-103 107.8992 2.0531 73.1031 1.6026PAB-104 116.7910 2.1278 86.8397 1.7980PAB-105 115.3017 2.2076 74.4360 1.8980PAB-106 103.1046 2.1386 97.7948 1.8526PAB-107 129.9348 2.1108 86.1133 1.6762PAB-108 113.3016 2.2177 102.7612 1.9493PAB-109 98.7597 2.6587 76.6407 1.8134PAB-110 119.3591 2.5593 91.2837 2.0012



REFERENCES

1. Twieg, R.; He, M.; Sukhomlinova, F.; You, W.; Moerner, E.; Diaz-Garcia, M.;

Wright, D.; Casperson, J.; Wortmann, R.; Glania, C.; Kramer, P.; Lukaszuk, K.;

Matschiner, R.; Singer, K.; Ostoverkhov, V. and Petschek, R.; “Design and

optimization of chromophores for liquid crystal and photorefractive applications.”

Mat. Res. Soc. Symp. Proc. 1999, 561, 119-130.

2. Valentine, J.; Zhang, S.; Zentgraf, T.; Ulin-Avila, E.; Genov, D.; Bartal, G. and

Zhang, X.; “Three-dimensional optical metamaterial with a negative refractive

index” Nature 2008, 455, 376-379.

3. Singh, S.; “Refractive index measurement and its applications”, Phys. Scripta,

2002, 65, 167-180.

4. Heavens, O. S. and Ditchburn, R. W.;”Interferometry in Insight into optics”, John

Wiley and Sons Ltd. Chichester West Sussex UK, 1991, 193-202.

5. Angelis, D. M.; Nicole, D. S.;Ferraro, P.; Finizio, A. and Pierattini, G.;”Liquid

refractometer based on interferometric fringe projection” Optics Commu. 2000,

175, 315-321.

6. Frederick, W.; “Optical Properties of Solids”. Academic Press, New York, 1972,

49.

7. Meriaudeau, F.; Wig, A. G.; Passian, A. and Ferrell, T. L.; “New fiber optic

sensor: application to refractive index sensing” Proc. SPIE 1986, 4074, 354-364.

8. Banerjee, A.; Mukherjee, S.; Verma, R. K.; Jana, B.; Khan, T. K.; Chakroborty,

M.; Das, R.; Biswas, S.; Saxena, A.; Singh, V.; Hallen, R. M.; Rajput, R. S.;

Tewari, P.; Kumar, S.; Saxena, V.; Ghosh, A. K.; John, J. and Gupta, B. P.; “Fiber

optic sensing of liquid refractive index” Sensors and Actuators B-Chemical,

2007, 123, 594-605.

9. Buck J. A.; “Fundamentals of optical fibers” John Wiley and Sons Inc. New

Jersey, USA. 2004.

10. Chiu, M. H. and Wang, S. F.; “New-type fiber optical liquid refractometer,

Novel Optical Systems Design and Optimization VII.” Proc. SPIE 2004, 5524,

169-175.

http://adsabs.harvard.edu/cgi-bin/author_form?author=Meriaudeau,+F&fullauthor=Meriaudeau,%20Fabrice&charset=UTF-8&db_key=PHY

http://adsabs.harvard.edu/cgi-bin/author_form?author=Wig,+A&fullauthor=Wig,%20A.%20G.&charset=UTF-8&db_key=PHY

http://adsabs.harvard.edu/cgi-bin/author_form?author=Passian,+A&fullauthor=Passian,%20A.&charset=UTF-8&db_key=PHY

http://adsabs.harvard.edu/cgi-bin/author_form?author=Ferrell,+T&fullauthor=Ferrell,%20Trinidad%20L.&charset=UTF-8&db_key=PHY



11. Huang, X. F.; Chen, Z. M.; Shao, L. Y.; Cen, K. F.; Sheng, D. R.; Chen, J. and

Zhou, H.; “Design and characteristics of refractive index sensor based on

thinned and microstructure fiber Bragg grating” Appl. Optics 2008, 47, 504-511.

12. Kaur, H.; “Optical Fibre Refractive in Voltage and Strain Sensor Fabrication and

Application” Ph. D thesis, Victoria University, Australia. 2011.

13. Flavell, R. G. and Lane, J. A.; “The application of potential refractive index in

tropospheric wave propagation” J. Atmos. Terr. Phys.1962, 24, 47-56.

14. Petrin, A.; “Application of Media with Negative Refraction Index to

Electromagnetic Imaging. Fundamental Aspects”, Wave Propagation in Materials

for Modern Applications, ISBN: 978-953-7619-65-7.

15. Yang, S. Y.; Chieh, J. J.; Horng, H. E.; Hong, C. Y. and Yang, H. C.; “Origin and

applications of magnetically tunable refractive index of magnetic fluid films”

Appl. Phys. Lett. 2004, 84, 5204-5206.

16. Yuan, W.; Kong, L. and Bai, Z.; “Simultaneous determination of ethanol, sugar

and organic acids in Kluveromyces marxious broth by high performance liquid

chromatography-ultraviolet/refractive index detector” Fenxi Huaxue 2009, 37(6),

850-854.

17. Rekha, R. and Ramalingam, A.; “Nonlinear characteristic and optical limiting

effect of oil red azo dye in liquid and solid media” J. Modern Optics. 2009, 56(9),

1096-1102.

18. Kirchner, J. and Miller, J.; “Volatile water-soluble and oil constituents of valencia

orange juice” Canning and Storage Effects. 1957, 5(4), 283-291.

19. Patindol, J.; Gonzalez, B.; Wang, Y. and McClung, A.; “Starch fine structure and

physicochemical properties of specialty rice for canning” J Cereal Sci. 2007,

45(2), 209-218.

20. Diao, J. and Hess, D.; “Refractive index measurements of films with biaxial

symmetry-Determination of film thickness and refractive indices using polarized

transmission spectra in the transparent wavelength range” J. Phys. Chem. 2005,

109(26), 12819-12825.

21. Shabana, H.; “Determination of film thickness and refractive index by

interferometry” Polym. Testing 2004, 23(6), 695-702.

http://www.intechopen.com/books/wave-propagation-in-materials-for-modern-applications

http://www.intechopen.com/books/wave-propagation-in-materials-for-modern-applications



22. Nordman, O.; Nordman, N. and Peyghambarian, N.; “Electron beam induced

changes in the refractive index and film thickness of amorphous AsxS100 – x and

AsxSe100 – x films” J. Appl. Phy. 1998, 84(11), 6055-6058.

23. Nair, S. and Tsapatsis, M.; “Infrared reflectance measurements of zeolite film

thickness, refractive index and other characteristics” Micro. Meso. Mat. 2003,

58(2), 81-89.

24. Kensuke, M. and Akira, A.; “Silicone coated films with good heat resistance, and

high transparency and refractivity, and their manufacture.” Jap. Pat. Appl. 2009,

Patent no.: JP-2009148670

25. Zillies, J.; Zwiorek, K.; Winter, G. and Coester, C.; “Method for Quantifying the

PEGylation of Gelatin Nanoparticle Drug Carrier Systems Using Asymmetrical

Flow Field-Flow Fractionation and Refractive Index Detection” Anal. Chem.

2007, 79, 4574-4580.

26. Park, Y.; Diez-Silva, M.; Popescu, G.; Lykotrafitis, G.; Choi, W.; Feld, M. and

Suresh, S.; “Refractive index maps and membrane dynamics of human red blood

cells parasitized by Plasmodium falciparum” PNAS 2008, 105(37), 13730–13735.

27. Song, W.; Zhang, X.; Liu, A. and Lim, C.; “Refractive index measurement of

single living cells using on-chip Fabry-Perot cavity” App. Phys. Lett. 2006, 89,

203901-203903.

28. Kemper, D.; Carl, J.; Schnekenburger, I.; Bredebusch, M.; Schäfer, W.

Domschke. and von Bally, G.; “Self-interference digital holographic microscopy

for live cell imaging” J. Biomed. Opt. 2006, 11, 34005-34011.

29. Weng, L.; Lu, Y.; Shi, L.; Zhang, X.; Zhang, L.; Guo, X. and Xu, J.; “In Situ

Investigation of Drug Diffusion in Hydrogels by the Refractive Index Method”

Anal. Chem. 2004, 76, 2807-2812

30. Soriano, A.; Doma, B. and Hui Li, M.; “Measurements of the density and

refractive index for 1-n-butyl-3-methylimidazolium-based ionic liquids” J. Chem.

Thermo. 2009, 41, 301–307.

31. Mokhtarani, B.; Mojtahedi, M. M.; Mortaheb, H. R.; Mafi, M.; Yazdani, F. and

Sadeghian, F.; “Densities, refractive indices, and viscosities of the ionic liquids 1-

methyl-3-octylimidazolium tetrafluoroborate and 1-methyl-3-butyl imidazolium

perchlorate and their binary mixtures with ethanol at several temperatures” J.

Chem. Eng. Data. 2008, 53, 677−682.



32. Tariq, M.; Forte, P. A. S.; Gomes, M. F. C.; Lopes, J. N. C. and Rebelo, L. P. N.;

“Densities and refractive indices of imidazolium- and phosphonium-based ionic

liquids: Effect of temperature, alkyl chain length, and anion” J. Chem. Thermo.

2009, 41,790 −798.

33. Anouti, M.; Vigeant, A.; Jacquemin, J.; Brigouleix, C. and Lemordant, D.

“Volumetric properties, viscosity and refractive index of the protic ionic liquid,

pyrrolidinium octanoate, in molecular solvents” J. Chem. Thermo. 2010, 42, 834

−845.

34. Yu, Z.; Gao, H.; Wang, H. and Chen, L. “Densities, viscosities, and refractive

properties of the binary mixtures of the amino acid ionic liquid [bmim][Ala] with

methanol or benzylalcohol at T = (298.15 to 313.15) K. J. Chem. Eng. Data.

2011, 56, 2877 −2883.

35. Xu, Y.; Yao, J.; Wang, C. and Li, H.; “Density, Viscosity, and Refractive Index

Properties for the Binary Mixtures of n -Butylammonium Acetate Ionic Liquid +

Alkanols at Several Temperatures” J. Chem. Eng. Data. 2012, 57, 298-308.

36. Rhodes, F. and Goldsmith, H.; “Variation of Refractive Index of China Wood Oil

with Temperature.” Ind. Eng. Chem. 1923, 15, 786-795.

37. Mitsuhiro, F.; Tadashi, Y.; Satoshi, M. and Yasuhiro, O.; “Concentration

measurement of refrigerant/refrigeration oil mixture by refractive index.” Int. J.

Refrig. 2004, 27, 346-352.

38. Yu, Z.; Gao, H.; Wang, H. and Chen, L.; “Densities, Viscosities, and Refractive

Properties of the Binary Mixtures of the Amino Acid Ionic Liquid [bmim][Ala]

with Methanol or Benzylalcohol at T = (298.15 to 313.15) K” J. Chem. Eng. Data

2011, 56, 2877–2883.

39. Husband, F.; Garrood, M.; Mackie, A.; Burnett, G. and Wilde, P.; “Adsorbed

Protein Secondary and Tertiary Structures by Circular Dichroism and Infrared

Spectroscopy with Refractive Index Matched Emulsions” J. Agric. Food Chem.

2001, 49, 859-866.

40. Barroso, M.; Pineiro, M.; Silva, S. and Seixas d.; “Refractometry in determination

of sugar and Aspartame contents in commercial beverages.” Quimica 2003, 91,

61-65.

41. Riyazuddeen and Usmani M.; “Densities, Speeds of Sound, and Viscosities of (L-

Proline + Aqueous Glucose) and (L-Proline + Aqueous Sucrose) Solutions in the



Temperature Range (298.15 to 323.15) K” J. Chem. Eng. Data. 2011, 56, 3504–

3509.

42. Murakami, N. and Yoshimi, H.; “Liquid crystal cell substrate for liquid crystal

display device and refractive indices thereof.” Jpn. Kokai Tokkyo Koho. 2009, 26,

31-38.

43. Sim, J.; Baek, G.; Won, Y.; Park, Y.; Park, I. and Jeon, S.; “Optically anisotropic

films with controlled refractive index in the thickness direction for liquid crystal

displays.” Repub. Korean Kongkae Taeho Kongbo. 2009, 6, 26-31.

44. Abe, I.; De Goes, R.; Fabris, J.; Kalinowski, H.; Müller, M.; Fugihara, M.; Falate,

R.; Diesel, B.; Kamikawachi R. and Barbosa, C.; “Production and characterization

of refractive index gratings in high- birefringence fibre optics.“ Optics and

Lasers in Eng. 2003, 39(5-6), 537-548.

45. Michael, R.; Marle, J.; Vrensen, G. and Van den Berg, T.; “Changes in the

refractive index of lens fibre membranes during maturation – impact on lens

transparency” Exper. Eye Res. 2003, 77(1), 93-99.

46. Martincek, I.; Kacik, D.; Turek, I. and Peterka, P.; “The determination of the

refractive index profile in α-profile optical fibres by intermodal interference

investigation” Optik. Int. J. Light and Electron Optics 2004, 115(2), 86-88.

47. Strop P. and Brunger, A. T.; “Refractive index-based determination of detergent

concentration and its application to the study of membrane proteins” Protein Sci.

2005, 14(8), 2207–2211.

48. Lee, B.; Choi, J.; Choi, K.; Kang, D. and Lim, M.; “Photosensitive paste

composition, barrier ribs prepared using the composition and plasma display panel

comprising the barrier ribs.” Korean Pat. Appl. 2009, Patent no. KR 2009080756

49. Oosterbaan, D.; Vrindts, V.; Berson, S.; Guillerez, S.; Douheret, O.; Ruttens, B.;

D'Haen, J.; Adriaensens, P.; Manca, J.; Lutsen, L. and Vanderzande, D.; “Efficient

formation, isolation and characterization of poly(3-alkylthiophene) nanofibres:

probing order as a function of side-chain length.” J. Mat. Chem. 2009, 19(30),

5424-5435.

50. Yakuphanoglu, F.; Mehrotra, R.; Gupta, A. and Munoz, M.; “Nanofiber organic

semiconductors: The effects of nanosize on the electrical charge transport and

optical properties of bulk polyanilines.” J. Appl. Poly. Sci. 2009, 114(2), 794-799.



51. Belendez, A.; Belendez, T.; Neipp, C. and Pascual, I.; “Determination of the

refractive index and thickness of holographic silver halide materials by use of

polarized reflectances.” Appl Opt. 2002, 41(32), 6802-6808.

52. Clergent, Y.; Durou, C. and Laurens, M.; “Refractive Index Variations for Argon,

Nitrogen, and Carbon Dioxide at = 632.8 nm (He-Ne Laser Light) in the Range

288.15 K, T 323.15 K, 0 < p < 110 kPa.” J. Chem. Eng. Data. 1999, 44, 197-199.

53. Burokur, S.; Sellier, N.; Kante, A.; Lustrac, B. and De, A.; “Symmetry breaking in

metallic cut wire pairs metamaterials for negative refractive index” Appl. Phys.

Let. 2009, 94(20), 2011111-2011113.

54. Wang, J.; Hutchins, M.; Woo, K.; Matayabas, C. and Konish, T.; “Halogen-free,

radiation-curable, high refractive index materials” JCT Coatings Tech. 2009, 6,

44-49.

55. Bornhop, D. J. and Dovichi, N. J.; “Simple nanoliter refractive index detector”

Anal. Chem. 1986, 58, 504-505.

56. Peepliwal, A.; Bonde, C. and Bothara, K.; “A validated RP-HPLC method for

quantitative determination of related impurities of ursodeoxycholic acid (API) by

refractive index detection” J. Pharm. Bio. Ana. 2011, 54, 845–849.

57. Turner, C. E.; Williamson, D. A.; Stroud, P. A. and Talley, D. J.; “Evaluation and

comparison of commercially available Aloe vera L. products using size exclusion

chromatography with refractive index and multi-angle laser light scattering

detection” Inter. Immuno. 2004, 4, 1727–1737.

58. Bornhop, D. J. and Dovichi, N. J.; “Simultaneous laser-based refractive index and

absorbance determinations within micrometer diameter capillary tubes” Anal.

Chem.1987, 59, 1632-1636.

59. Bruno, A. E.; Krattiger, B.; Maystre, F. and Widmer, H. M.; “On-column laser-

based refractive index detector for capillary electrophoresis” Anal. Chem. 1991,

63, 2689-2697.

60. Burggraf, N.; Krattiger, B.; De Mello, A.; De Rooij, N. and Manz, A.;

“Holographic refractive index detector for application in microchip-based

separation systems” Analyst 1998, 123, 1443–1447.

61. Heric, E. L. and Brewer, J. G.; “Refraction in some ternary and Quaternary liquid

nonelectrolyte systems” J. Chem. Eng. Data. 1971, 16, 317-321.



62. Gee, N. and Freeman, G. R.; “Relative permittivities of 10 organic liquids as

function of temperature” J. Chem. Thermodyn. 1993, 25, 549-554.

63. Proutiere, A.; Megnassan, E. and Hucteau, H.; “Reply to Comment on "Refractive

Index and Density Variations in Pure Liquids. A New Theoretical Relation” J.

Phys. Chem. 1994, 98, 4769-4769.

64. Fornefeld-Schwarz, U. M. and Svejda, P.” Refractive index and relative

permittivities of liquid mixtures of γ-butyrolactone, γ-valerolactone, δ-

valerolactone, or ε-Caprolactone+benzene, toluene, or +ethylbenzene at 293.15 K

and 313.15 K and atmospheric pressure” J. Chem. Eng. Data. 1999, 44, 597-604.

65. Toti, U.; Kariduraganavar, M.; Aralaguppi, M. and Aminabhavi, T.; “Density,

Viscosity, Refractive Index, and Speed of Sound of Ternary Systems: Polystyrene

in 1,4-Dioxane + Tetrahydrofuran Mixtures at (298.15, 303.15, and 308.15) K.” J.

Chem. Eng. Data. 2000, 45, 920-925.

66. Gomez-Diaz, D.; Mejuto, J. and Navaza, J.; “Physicochemical Properties of

Liquid Mixtures. 1. Viscosity, Density, Surface Tension and Refractive Index of

Cyclohexane + 2,2,4-Trimethylpentane Binary Liquid Systems from 25 C to 50

C” J. Chem. Eng. Data. 2001, 46, 720-724.

67. Chen, S.; Lei, Q. and Fang, W.; “Density and Refractive Index at 298.15 K and

Vapor-Liquid Equilibria at 101.3 kPa for Four Binary Systems of Methanol, n-

Propanol, n-Butanol, or Isobutanol with N-Methylpiperazine” J. Chem. Eng. Data.

2002, 47, 811-815.

68. Pandey, J.; Jain, P. and Vyas, V.; “Speed of sound, viscosity, and refractive index

of multicomponent systems: analysis of experimental data from the Bertrand-

Acree-Burchfield equation” Can. J. Chem. 1994, 72, 2486-2492.

69. Gomez-Diaz, D.; Mejuto, J.; Navaza, J. and Rodriguez-Alvarez, A.; “Effect of

Composition and Temperature upon Density, Viscosity, Surface Tension, and

Refractive Index of 2,2,4- Trimethylpentane + Cyclohexane + Decane Ternary

Liquid Systems.” J. Chem. Eng. Data. 2003, 48, 231-235.

70. Resa, J.; Gonzalez, C. and Juez, M.; “Density, refractive index and speed of sound

for mixtures of ethyl acetate with 2-butanol and 3-methyl-1-butanol. Vapor-liquid

equilibrium of the ethyl acetate + 3-methyl-1-butanol system.” Fluid Phase Equi.

2004, 217, 175-180.



71. Baluja, S.; Pandaya, N.; Kachhadia, N. and Solanki, A.; “Refractive index:

theoretical evaluation in binary liquid mixtures.” J. Ultra Sci. Phys. Sci. 2006, 18,

247-250.

72. Resa, J.; Gonzalez, C.; Diez, E.; Concha, R. and Iglesias, M.; “Mixing properties

of isopropyl acetate + aromatic hydrocarbons at 298.15 K: Density, refractive

index and isentropic compressibility.” Korean J. Chem. Eng. 2009, 21, 1015-

1025.

73. Mirjana, L.; Kijevcanin, I.; Radovic, B.; Djordjevi, C.; Aleksandat, Z.; Tasi, C.;

Slobodan, P. and Serbanovi, C.; “Experimental determination and modeling of

densities and refractive indices of the binary systems alcohol + dicyclohexylamine

at T = (288.15–323.15) K” Thermochim. Acta 2011, 525, 114– 128.

74. Berm C.; Salguero, U. and Gracia-Fadrique, J.; “Densities, Refractive Indices,

Speeds of Sound and Surface Tensions for Dilute Aqueous Solutions of 2-Methyl-

1-propanol, Cyclopentanone, Cyclohexanone, Cyclohexanol and Ethyl

Acetoacetate at 298.15 K” J. Chem. Eng. Data. 2011, 56, 3823–3829.

75. Taib, M. M.; Ziyada, A. K.; Wilfred, C. D. and Murugesan, T.; “Volumetric

properties and refractive indeces for binary mixtures of 1-propyronitrile-3-

hexylimidazolium bromide+ethanol at temperatures from 293.15 to 323.15 K” J.

Sol. Chem. 2012, 41, 100-111.

76. Benjamin, J. and Ernest, G.; “Molar refraction as an index of proton transfer: An

estimate of the acid strength of p-toluenesulfonic acid” J. Am. Chem. Soc. 1961,

83, 2956-2956.

77. Tanio, N. and Irie, M.; “Refractive index of organic photochromic dye-amorphous

polymer composites” Jap. J. Appl. Phys. 1994, 33, 3942-3946.

78. Liu, J.; Nakamura, Y.; Shibasaki, Y.; Ando, S. and Ueda, M.; “High Refractive

Index Polyimides Derived from 2,7-Bis(4-amino phenylenesulfanyl) thianthrene

and Aromatic Dianhydrides” Macromol. 2007, 40, 4614-4620.

79. Yakowitz, M. and Jorgensen, P.; “Refractive Index of Strontium Nitrate” Ind.

Eng. Chem. Anal. 1937, 9, 204-204.

80. Koutnik, V.; “Refractive index of inorganic pigments” Chem. Prumysl. 1964, 14,

604-606.



81. Upadhyay, R. K. and Bansal, R. R.; “Refractometry determination of formation

constant of gold, platinum, osmium and iridium complexes”, Ind. J. Chem., 1977,

15A, 756-757.

82. Sahai, R.; Singh, V. and verma, R.; “Differential refractometric and

conductometric studies on the charge transfer interactions of some metal β-

diketonates with iodine” J. Ind. Chem. Soc. 1982, 59(1), 46-51.

83. Sangwal, K. and Kucharczyk, W.; “Relationship between density and refractive

index of inorganic solids” J. Phys. D. Appl. Phys. 1987, 20, 522-525.

84. Taboada, M. E.; Veacuteliz, D. M.; Gallequillos, H. R. and Teoacutefilo, A.;

“Solubility, densities, viscosities, electrical conductivities and refractive index of

saturated solutions of potassium sulfate in water+1-propanol at 298.15, 308.15

and 318.15K” J. Chem. Eng. Data. 2002, 47(5), 1193-1196

85. Kalyanasundaram, S.; Stephan, A. M. and Gopalan, A.; “The Rao formulism and

refractometric studies on poly (methylmethacrylate) in dimethyl formamide”

Acustica 1999, 85, 136-138.

86. Ottani, S.; Vitalini, D.; Camelli, F. and Castellari, C.;”Densities, viscosities and

refractive index of poly(ethylene glycol) 200 and 400+cyclic ethers at 303.15K” J.

Chem. Eng. Data. 2002, 47(5), 1197-1204.

87. Assaid, I.; Bosc, D. and Hardy, I.; “Improvements of the Poly(vinyl cinnamate)

Photoresponse in Order to Induce High Refractive Index Variations” J. Phys.

Chem. B. 2004, 108, 2801-2806.

88. Lu, C.; Guan, C.; Liu, Y.; Cheng, Y. and Yang, B.; “PbS/Polymer Optical

Materials with High Refractive Index” Chem. Mater. 2005, 17, 2448-2454.

89. Mohsen, N.; Modarress, H. and Rasa, H.; “Measurement and Modeling of

Density, Kinematic Viscosity, and Refractive Index for Poly(ethylene Glycol)

Aqueous Solution at Different Temperatures” J. Chem. Eng. Data. 2005, 50,

1662-1666.

90. Aminabhavi, T. M.; Phayde, H. T. S.; Khinnavar, R. S. and Bindu, G.; “Density,

refractive index, speed of sound and viscosities of diethylene glycol dimethyl

ether + butyl acetate at 298.15, 303.15, 308.15, 313.15 and 218.15 K” J. Chem.

Eng. Data.1993, 38, 542-545.

91. Iglesias, M, Orge, B. And Tojoq, J.; “Refractive index, density and excess

property on mixing of the system acetone+methanol+water and



acetone+methanol+1-butanol at 298.15K” Fluid Phase Equi. 1996, 126(2), 203-

223.

92. Mariano, A.; Postigo, M.; Gonzalez-Salgado, D. and Roman, L.; “Densities,

speeds of sound, and refractive indices of the ternary mixtures (toluene + methyl

acetate + butyl acetate) and (toluene + methyl acetate + methyl heptanoate) at

298.15 K” J. Chem. Thermodyn. 2007, 39, 218–224.

93. Shyam, S.; Pradhan, P. and Roy, M.; “Solute–solvent and solvent–solvent

interactions of menthol in isopropyl alcohol and its binary mixtures with methyl

salicylate by volumetric, viscometric, interferometric and refractive index

techniques” Thermochim. Acta 2010, 499, 149–154.

94. Kurnia Kiki, A.; Taib, M.; Abdul Mutalib, M. and Murugesan, T.; “Densities,

refractive indices and excess molar volumes for binary mixtures of protic ionic

liquids with methanol at T=293.15 to 313.15 K” J. Mol. Liq. 2011, 159, 211–219.

95. Sherstneva, T. and Koleboshin, G.; “Physicochemical study of binary systems

containing dioxane and aliphatic alcohol” Zhu. Prikli Khimii 1972, 28(13), 53-56.

96. Riggio, R.; Martinez, H. and Solimo, H.; “Densities, viscosities, and refractive

indexes for the methyl isobutyl ketone + pentanols systems. Measurements and

correlations.” J. Chem. Eng. Data 1986, 31(2), 235-238.

97. Al-Wahaibi, Y.; Grattoni, C. and Muggeridge, A.; “Physical Properties (Density,

Viscosity, Surface Tension, Interfacial Tension, and Contact Angle) of the System

Isopropyl Alcohol + Cyclohexene + Water.” J. Chem. Eng. Data. 2007, 52(2),

548-552.

98. Campos, V.; Gomez, M. and Solimo, H.; “Density, viscosity, refractive index,

excess molar volume, viscosity, and refractive index deviations and their

correlations for the (formamide + water) system. Isobaric (vapour + liquid)

equilibrium at 2.5 kPa.” J. Chem. Eng. Data. 2008, 53(1), 211-216.

99. Aminabhavi, T. M.; “Predicting refractive index and density increment of binary

solvent mixtures”, J. Chem. Eng. Data. 1987, 32, 406-409.

100. Govindan G.; Gokul R. S. and Sastikumar D.; “Measurement of refractive index

of liquids using fiber optic displacement sensors” J. Am. Sci. 2009, 5(2), 13-17.

101. Iulian, O.; Iliuta, M.; Hamplea, L. and Lintes, G.; “Refractive index composition

calibration curves for water-organic component homogeneous liquid mixtures.”

Revista de Chim, 1995, 46(6), 591-593.



102. Uma Devi, T.; Lawrence, N.; R. Ramesh Babu, S.; Selvanayagam, H.; Stoeckli-

Evans and Ramamurthi, K.; “Characterization of a newly synthesized organic

nonlinear optical crystal: Urea ninhydrin monohydrate.” J. Crystal Growth 2009,

311(13), 3485-3490.

103. Riddick, J. A.; Bunger, W. B. and Sakano, T.; Organic Solvents: Physical

Properties and methods of purification, Fourth Edition., Techniques of Chemistry,

II, A Wiley-Interscience Publication, John Wiley, New York 1986.

104. Lorentz, H. A. And Lorentz,” Theory of Electronics”, Leipzig 1906.

Section-IV

Dissociation constants

Section-IV Dissociation constants


INTRODUCTION

In general, the term ionization constant means a constant, which is used to

measure the strength of acids and bases. It is often known as dissociation constant. The

knowledge of dissociation constant is a key parameter for understanding the chemical

interactions between the compounds of interest. It also provides useful information in

drug design studies, in explaining the biopharmaceutical properties of substances1,2, to

understand the absorption site of drug, distribution to various organs and excretion3-5 etc.

Further, it is also helpful in developing analytical methods, like HPLC6, in screening

salts, developing pre-clinical and clinical formulation7-9 .

In literature, various researchers have used several methods to determine the

dissociation constant like potentiometer10, pH metry11-14, capillary electrophoresis15,

kinetic exclusion assay16 , NMR methods17, polarography18, conductometry19-21,

ratiometry22-23, spectrophotometric24-25, interfacial FT-IR spectroscopy26, separation

methods (RP-HPLC)27, UV-visible spectroscopy28-29 etc . Krebs and Speakman30 have

reported the dissociation constant of some solvents. Danish et al. have determined the

dissociation constant of Zn2+ ions in live cells and tissues by using a photon microscopic

method31. Potentiometry is mostly used for the determination of dissociation constants of

acids32-33 because it is economical in time. Further, it can be used for acids of pKa range

from 2 to 11 units34. Kodo et al. have studied the ion-pair formation constants of some

salts and ether derivatives by potentiometry35. Jano et al36 have used potentiometric

titration to determine dissociation constants of polyprotic acids and bases. However, for

very low pKa values, this method does not give accurate results. In such cases, more

sensitive instruments should be used. Spectrophotometer method is considered to be an

ideal method. The determination of the dissociation constant of different systems by

spectrophotometric technique has been reported by various workers37-40. However, this

method is also found to be more time consuming. A number of workers41-44 has thus used

pH metry for the determination of dissociation constants of various compounds in various

solvents, to get the reliable results. However, there are certain difficulties in mixed

aqueous media and non aqueous media.

The dissociation constant of various types of substance such as complexes45-50,

amino acids51-52, various acids and their derivatives53-57, drugs58,-59, indicators60-61 etc.,

have been reported using different methods. Fedorov et al62 reported the dissociation

constants of micelle-solubilized compounds. Hayman and Tapuhi63 have determined the



dissociation constant of tri chloro acetic acids using distribution method. Meloun et al64-65

have determined dissociation constant of various drugs using spectroscopic and

potentiometric method.

Further, in last few years dissociation constant of various organic compounds66-73

have been studied by various workers. Azimi et al.74 have reported dissociation constant

of some newly Synthesized 1,2,4-Triazole Derivatives in Ethanol-Water Mixtures.

Bhagwatkar et al.75 have been reported pH metric studies of some synthesized ligands.

In this chapter, the dissociation constant of all synthesized tetrahydropyrimidine

derivatives (PAB101-110) are studied in dimethyl formamide-water mixture at 303.15 K

by Calvin Bjerrum pH titration technique.



EXPERIMENTAL

All solutions used for the titration are prepared using distilled water. Following

are the concentrations of the solutions used for the titration. The chemicals used were of

B.D.H Analar grade.

Solutions Concentration (M)

Nitric acid 1.0

Sodium hydroxide 0.5

Sodium nitrate 1.0

Ligand (in DMF) 0.1

Nitric acid and sodium hydroxide were standardized by titrating with 0.1 N

NaOH and 0.05 M succinic acid solution respectively.

The buffer solutions used for the calibration of pH meter were 0.05 M potassium

hydrogen phthalate and 0.01 M Borax buffer.

A Elico pH meter (Model No. Li 610) with combined electrode was used for the

pH determination. Before measurement, the pH meter was calibrated with buffer solution

of known pH.



Calvin Bjerrum pH titration:

The following sets of mixtures were prepared for titration:

(I) 2 ml HNO3 (1.0M) + 4 ml water + 30 ml DMF + 4.0 ml NaNO3 (1.0 M).

(ii) 2 ml HNO3 (0.1M) + 4 ml water + 28 ml DMF + 2.0 ml ligand solution (0.1M) +

4.0 ml NaNO3 (1.0 M).

Thus, total volumes (V0) in each set = 40.0 ml and DMF: Water ratio 60:40 (v/v).

The above mentioned solutions were allowed to attain a constant temperature (303.15 K)

and then titrated against standard NaOH solution (0.5 M) under an inert atmosphere of

nitrogen.



THEORY

In the present work out of ten synthesized compounds i.e., tetrahydropyrimidines,

eight are of HL type whereas two are of H2L type. For these, the equilibria are,

L H HL

In general, the synthesized tetrahydropyrimidines, are represented by LH j-1. The

equilibrium can be written as:

1j jLH H LH

The thermodynamic proton-ligand stability constant ( HjTK ) is given by:

1

jHj

j

LHTK

LH H

.... (3.4.1)

TKjH is reciprocal of the thermodynamic dissociation constant of the acid LHj

dissociating as:

1i iLH LH H

The overall thermodynamic proton-ligand stability constant jH is given by:

jH

j j

LHT

L H

… (3.4.2)

and it refers to the reaction:

jL JH LH

The stoichiometric proton-ligand stability constant is given by:

1

jHj

j

LHK

LH H

… (3.4.3)

and

jHj j

LH

L H

… (3.4.4)



These thermodynamic constants are difficult to determine because of the

existence of several complexes. So, an inert electrolyte is used to determine the stability

constant in a particular salt medium. Sodium nitrate is mostly preferred as supporting

electrolyte, because of very slight complexing tendency of nitrate ion. Generally, the

competition between nitrate ion and the ligand under study is minor importance. The

molar concentrations are used in place of activities.

For the determination of dissociation constants, Bjerrum76 introduced a relation for

the determination of Hn , which is defined as average number of hydrogen bound to each

ligand.

Hn = {K1H [H] + 2K1

H K2H [H]2 + .....JK1

H K2H [H] ... Kj

H [H]j} / {1 + K1H [H] + K1

H

K2H [H]2.....K1

HK2H.....Kj

H [H]j .... (3.4.5)

From equation (3.4.4), we can write

1

1

jHj

jH

jHj

j

j H

nH

: 0 1H … (3.4.6)

Equation (3.4.6) is called Bjerrum formation function of the system.

The determination of dissociation or formation constants from experimental data

comprises the following three steps: (i) evaluation of formation curve of the system (ii)

calculation of stoichiometric K`s of the system by direct solution of the formation

function and (iii) conversion of stoichiometric constants into thermodynamic constants.

When the system consists of a ligand, which is a conjugated base of a weak acid,

the pH-metric method introduced by Bjerrum has been widely used. This method is

known as "Bjerrum-Calvin pH titration technique". In this technique, by pH-meter, the

concentration of H+ ions is measured. Thus, a large amount of data can be obtained in a

short period of time. However, the Irving and Rossotti method77 is more popular because

it has some advantages. This method is valid for both pure water and for the mixed

solvents. In this method, the conversion of pH-meter reading in to stoichiometric

hydrogen ion concentration is not necessary and it is not necessary to know the

stoichiometric concentration of neutral salt added to maintain the ionic strength constant.



Due to these advantages, this method is used in the present work. In this method,

the pH-meter is standardized using an aqueous buffer. The pH (B) is measured for two

solutions: (1) A mixture containing a mineral acid, a chelating agent and a neutral

electrolyte to keep ionic strength constant and (2) A mixture same as above but without

the chelating agent, when titrated against an alkali solution.

After each addition of standard alkali, the pH meter reading (B) is noted using a

glass electrode-saturated calomel electrode combination. For both the titrations, same

initial volume of the mixture and same standard alkali is used. The titration curves

obtained in the above two titrations are designated as the reagent or ligand titration curve

and the acid titration curve respectively.

The possible hydrolysis reactions are ignored because (i) fresh reagent solutions

were used in pH titrations, (ii) titration times were within one hour, (iii) there were no

observable drifts with time in the meter readings and (iv)the concentrations of the mineral

acid or alkali in the solutions were small.

Usually, a pH-meter calibrated with an aqueous buffer is used for aqueous solutions

only. However, for the mixed aqueous media, especially aqueous dioxane solutions, van

Uitert and Haas78 gave a relation between the glass electrode reading B in dioxane-water

medium and the stoichiometric hydrogen ion concentration of the same in mixture of

varied composition and ionic strength. They reported the relation:

0log log log HH pH f U … (3.4.7)

where f is the activity coefficient of the hydrogen ions in the solvent mixture under

consideration at the same temperature and ionic strength, and 0HU is a correction factor

at zero ionic strength, which depends only on the solvent composition and temperature.

0HU is taken as unity in aqueous media. The meter reading in any aqueous dioxane

solution can, therefore, be converted into hydrogen ion concentration using equation

(3.4.7), provided that correction factor for the appropriate solvent, salt medium, and

temperature, has been determined.

Equation (3.4.7) can be written as:

01 log [ ] Hanti pH H fU ... (3.4.8)



0

1

log H

Hanti pH fU

... (3.4.9)

Substituting for [H+] in equation (3.4.5) we get,

Hn = (K1H/f U0

H)[1/antilog B] +....+ ((JK1H K2

H...KJH) /(f U0

H)J)[1/antilog pH]J

/(1+K1H/f U0

H))[1/antilog B]+..+ ((K1HK2

H...KJH)/(f U0

H)J)[1/antilogpH] ... (3.4.10)

0 .H Hj H jK fU pK ... (3.4.11)

0 .H Hj H jfU p ... (3.4.12)

The proton-ligand constant, pKjH can be obtained by the following methods:

1. Interpolation at half Hn values:

At the following Hn values, log K1 and log K2 can be determined:

10.5

log HK n … (3.4.13)

21.5

log HK n ... (3.4.14)

2. Midpoint slope method:

For H2L type ligands:

21 2[ ] 1K K L

or 1 2 1log 2K K pL …(3.4.15)

From the measured mid-point slope, D, the ratio K1/K2 can be calculated by eq.

(3.4.16):

1

2

4.606

2

DK

K

... (3.4.16)

The individual values of K1 and K2 were obtained by using K1/K2 values and

relation (3.4.15). This method is applicable only where K1/K2 lies between 103 and 10-2

and it uses only a very small portion of the formation curve in the region of mid point.




The titration curves obtained in the above two titrations are designated as the acid

titration curve and ligand or reagent titration curve respectively. The titration curves for

PAB-101 and PAB-110 are shown in Figure 3.4.1.

From these curves, the average number of protons associated with ligand ( Hn ) can

be calculated by Irving and Rossotti equation.

= − // /{( /) } … (3.4.17)

where Y is the number of displaceable protons per ligand molecule. V/ and V// are the

volume of alkali required at the same pH for both acid and ligand titration curves

respectively. V0 is the initial volume of the test solution. N0, E0 and T0L are the initial

concentration of the alkali, acid and ligand respectively. For PAB-108 and PAB-110,

value of Y is 2. Whereas for other compounds, Y is equal to one.

The calculated values of Hn for all the studied compounds are given in Table

3.4.1. It is evident from table that Hn values are in between zero and one for all the

system except PAB-108 and PAB-110 for which, the values of Hn extend over the range

from 0 to 2 indicating two dissociation steps. The 1HpK values at Hn = 0.5 were evaluated

for each systems except PAB-108 and PAB-110. For these two compounds, the 1HpK and

2HpK were calculated at Hn = 0.5 and Hn = 1.5 respectively. The general plots for the

variation of Hn with B of PAB-101 and PAB-110 are given in Figure 3.4.2.

Further, the log 1H Hn n values are plotted against B as shown in Figure 3.4.3.

The plots are straight lines from which 1log HpK values were calculated at several B

values, by the following equation.

log = + log … (3.4.18)

Section-IV


Figure 3.4.1: The plot of pH

[B] PAB-110

IV Dissociation constants


pH (B) against volume of NaOH for for [A] PAB

110 at 303.15 K.


168

[A] PAB-101 and



Table 3.4.1: The pH (B), pK1H and other terms for Tetrahydropyrimidine derivatives

at 303.15 K.

pH V/ V// V//-V/ log( / − ) pK1H/ pK2

H

PAB-1019.60 4.3577 5.2940 0.5463 0.3547 -0.3322 9.01819.70 4.3599 5.3122 0.5623 0.3944 -0.2898 9.15159.80 4.3610 5.3366 0.5856 0.4521 -0.2374 9.29329.90 4.3644 5.3610 0.6066 0.5040 -0.1978 9.4252

10.00 4.3682 5.3854 0.6272 0.5550 -0.1644 9.552610.10 4.3735 5.4103 0.6468 0.6034 -0.1368 9.675610.20 4.3785 5.4359 0.6674 0.6543 -0.1114 9.797210.30 4.3834 5.0715 0.6881 0.7054 -0.0889 9.916610.40 4.3892 5.0903 0.7011 0.7374 -0.0762 10.0278

Ave. pK1H =9.5397

PAB-10212.50 4.6677 5.3097 0.642 0.5810 -0.1492 12.065212.60 4.6925 5.3234 0.6309 0.5528 -0.1658 12.151512.70 4.7186 5.3372 0.6186 0.5216 -0.1857 12.235112.80 4.7415 5.3510 0.6095 0.4985 -0.2018 12.322012.90 4.7627 5.3648 0.6021 0.4796 -0.2157 12.410713.00 4.7751 5.3786 0.6035 0.4826 -0.2134 12.512613.10 4.7859 5.3924 0.6065 0.4896 -0.2082 12.6168

Ave. pK1H = 12.3306

PAB-1039.10 4.3399 4.5001 0.1602 0.6026 -0.5535 9.28079.20 4.3427 4.5161 0.1734 0.5699 -0.5678 9.32219.30 4.3449 4.5321 0.1872 0.5356 -0.5839 9.36209.40 4.3468 4.5481 0.2013 0.5007 -0.6017 9.40129.50 4.3544 4.5641 0.2097 0.4799 -0.6130 9.46519.60 4.3577 4.5801 0.2224 0.4485 -0.6314 9.51029.70 4.3599 4.5961 0.2362 0.4143 -0.6534 9.5496

Ave. pK1H = 9.4130

PAB 1049.20 4.3427 4.9230 0.5803 0.5605 -0.5721 9.30559.30 4.3449 4.9345 0.5896 0.5375 -0.5830 9.36529.40 4.3468 4.9460 0.5992 0.5137 -0.5949 9.42389.50 4.3544 4.9575 0.6031 0.5043 -0.5998 9.50759.60 4.3577 4.9690 0.6113 0.4841 -0.6107 9.57239.70 4.3599 4.9805 0.6206 0.4611 -0.6239 9.63239.80 4.3610 4.9920 0.631 0.4353 -0.6396 9.6870

Ave. pK1H = 9.4991



pH V/ V// V//-V/ log( / − ) pK1H/ pK2

H

PAB 1059.70 4.3599 4.5089 0.1490 0.6305 -0.5421 9.83219.80 4.3610 4.5268 0.1658 0.5889 -0.5594 9.85609.90 4.3644 4.5446 0.1802 0.5532 -0.5755 9.892810.00 4.3682 4.5625 0.1943 0.5183 -0.5925 9.931810.10 4.3735 4.5804 0.2069 0.4871 -0.6090 9.977610.20 4.3785 4.5982 0.2197 0.4554 -0.6272 10.022410.30 4.3834 4.6265 0.2431 0.3975 -0.6650 10.0194

Ave. pK1H = 9.9331

PAB-1069.60 4.3577 4.5165 0.1588 0.6062 -0.5520 9.78739.70 4.3599 4.5332 0.1733 0.5703 -0.5676 9.82299.80 4.3610 4.5501 0.1891 0.5311 -0.5861 9.85419.90 4.3644 4.5645 0.2001 0.5039 -0.6000 9.906710.00 4.3682 4.5900 0.2218 0.4501 -0.6305 9.913010.10 4.3735 4.6256 0.2521 0.3751 -0.6815 9.878310.20 4.3785 4.6513 0.2728 0.3238 -0.7242 9.8802

Ave. pK1H = 9.8632

PAB-10710.60 4.4062 4.9780 0.5718 0.4164 -0.6520 10.453410.70 4.4144 4.9980 0.5836 0.4454 -0.6333 10.604710.80 4.4234 5.0196 0.5962 0.4763 -0.6151 10.758810.90 4.4331 5.0413 0.6082 0.5057 -0.5991 10.909911.00 4.4439 5.0630 0.6191 0.5323 -0.5855 11.056211.10 4.4555 5.0848 0.6293 0.5571 -0.5736 11.199711.20 4.4667 5.1065 0.6398 0.5827 -0.5621 11.3450

Ave. pK1H = 10.9040

PAB-1083.30 3.7458 3.9046 0.1588 1.6007 0.5117 3.50433.40 3.7875 3.9316 0.1441 1.6380 0.5920 3.61433.50 3.8112 3.9586 0.1474 1.6299 0.5733 3.71223.60 3.8272 3.9857 0.1585 1.6022 0.5146 3.80473.70 3.8432 4.0136 0.1704 1.5725 0.4598 3.89663.80 3.8592 4.0560 0.1968 1.5064 0.3605 3.97793.90 3.8752 4.0864 0.2112 1.4705 0.3163 4.06754.00 3.8912 4.1227 0.2315 1.4198 0.2624 4.15224.10 3.9072 4.1591 0.2519 1.3689 0.2161 4.2364

Ave. pK1H = 3.8851

9.90 4.3644 4.9284 0.5640 0.6016 -0.1578 9.533710.00 4.3682 4.9468 0.5786 0.5655 -0.1726 9.595710.10 4.3735 4.9651 0.5916 0.5334 -0.1861 9.660810.20 4.3785 4.9835 0.6050 0.5004 -0.2005 9.723310.30 4.3834 5.0014 0.6180 0.4683 -0.2151 9.785410.40 4.3892 5.0157 0.6265 0.4475 -0.2249 9.859710.50 4.3972 5.0300 0.6328 0.4322 -0.2324 9.9403

Ave. pK2H = 9.7284



pH V/ V// V//-V/ log( / − ) pK1H/ pK2

H

PAB-10910.60 4.4062 4.5670 0.1608 0.6017 -0.5539 10.779110.70 4.4144 4.5853 0.1709 0.5767 -0.5647 10.834410.80 4.4234 4.6046 0.1812 0.5513 -0.5764 10.889510.90 4.4331 4.6276 0.1945 0.5185 -0.5924 10.932111.00 4.4439 4.6506 0.2067 0.4884 -0.6083 10.979911.10 4.4555 4.6736 0.2181 0.4603 -0.6243 11.031011.20 4.4667 4.6966 0.2299 0.4313 -0.6422 11.0799

Ave. pK1H = 10.9323

PAB-1103.40 3.7875 4.0363 0.2488 1.3750 0.2213 3.74243.50 3.8112 4.0452 0.2340 1.4125 0.2553 3.88103.60 3.8272 4.0532 0.2260 1.4328 0.2753 4.00243.70 3.8432 4.0607 0.2175 1.4543 0.2981 4.12573.80 3.8592 4.0695 0.2103 1.4726 0.3187 4.24593.90 3.8752 4.0757 0.2005 1.4973 0.3488 4.37404.00 3.8912 4.0832 0.1920 1.5188 0.3772 4.4992

Ave. pK1H = 4.1244

9.50 4.3544 4.9478 0.5934 0.5284 -0.4449 9.05519.60 4.3577 4.9545 0.5968 0.5200 -0.4542 9.14589.70 4.3599 4.9608 0.6009 0.5099 -0.4657 9.23439.80 4.3610 4.9651 0.6041 0.5020 -0.4748 9.32529.90 4.3644 4.9723 0.6079 0.4927 -0.4856 9.4144

10.00 4.3682 4.9815 0.6133 0.4795 -0.5012 9.498810.10 4.3735 4.9905 0.6170 0.4705 -0.5120 9.5880

Ave. pK2H = 9.3231

Section-IV


Figure 3.4.2: The plot of

0.3

0.4

0.5

0.6

0.7

0.8

9.4 9.6

nH



against B for PAB-101 and PAB-110 at 303.15 K.

9.8 10.0 10.2 10.4

B

[A]


172

at 303.15 K.

10.6



The average pK1H values are evaluated and given in Table 3.4.1 for all compounds.

Further, from Figure 3.4.2 (A), at Hn = 0.5, the pK1H values were evaluated for

PAB-1 –PAB-107 and PAB-109 and are given in Table 3.4.2. It is evident from Table

3.4.2 that for most of the compounds, the pK1H values calculated by average method and

half-integral method are in good agreement.

For PAB-108 and PAB-110, the proton-ligand constants were calculated by

solving equation 3.4.1. For all the points below Hn =1, the following equation was used

HH H1log pK = pH +log n n -1

… (3.4.19)

Whereas for the points above Hn =1, the equation used was:

Hlogp K = pH +log n -1 2 - n2 H H … (3.4.20)

From the various values of log pK1H (or log pK2

H), the average value was

calculated. The values of log pK1H and log pK2

H calculated by the two methods i.e., half-

integral method and average method are given in Table 3.4.2.

Comparison of pK1H values of studied compounds (except PAB-108 and PAB-

110, which are of H2L type) shows that, PAB-102 which is most basic which is followed

by PAB-109. PAB-103 is found to be most acidic. All the compounds have the same

central moiety but different side chains which affects the dissociation constant. PAB-102

contains cinnamaldehyde side chain which is found to increase the basic character of this

compound whereas in PAB-109, due to furfuladehyde side chain, basic character is

greater than other studied compounds but less than that of PAB-102. PAB-103 contains

chloro group at meta position and its acidic character is higher. However, PAB-104 also

contains chloro group but at para position and acidic character of this compound is

slightly decreased. This suggests that the position of groups also affects the dissociation.

In case of PAB-105, fluoro group is at para position which further decreases the acidic

character in comparison to p-chloro group (as in PAB-104). Other compounds show

intermediate acidic character.

PAB-108 and PAB-110 are of H2L type and both contain hydroxyl groups at para

positions. Comparison of pK1 and pK2 values of these two compounds shows slight

difference. However, significant variations in these pK1 values evaluated by average and



half-integral methods are also observed. Thus, it is difficult to compare the acidic

character of these two compounds. However, considering the pK2 values of these two

indicates the higher acidity of PAB-108, which may be due to presence of methoxy

group. Same characteristic behavior was also reported earlier79. Alteration of hydroxy

group with any other functional group can also change the dissociation of rate of the

compounds80.

From these results, it is concluded that different compounds exhibit different

dissociation constant which also depends upon the type of substituent group81. This is due

to inductive or mesomeric effect of functional groups.

Section-IV


Figure 3.4.3: The plot of log

against B for PAB

-0.40

-0.35

-0.30

-0.25

-0.20

-0.15

-0.10

-0.05

0.00

9.4 9.5lo

g(

nH/(

1-n

H)

-0.22

-0.21

-0.20

-0.19

-0.18

9.4 9.5

log

( n

H/(

2-n

H)



log (nH/(1-nH) against B for PAB-101 and log (

PAB-110

9.6 9.7 9.8 9.9 10.0 10.1 10.2

B

9.6 9.7 9.8 9.9 10.0 10.1

B


175

(nH /(2-nH) in

10.2 10.3

10.2



Table 3.4.2: The log pK1H and log pK2

H values for all the studied compounds

calculated by different methods.

Compounds

log pK1H log pK1

H / log pK2H

Half-

integral

method

Average

method

Half-integral

method

Average

method

PAB-101 9.88 9.54 PAB-107 10.90 10.90

PAB-102 12.78 12.33PAB-108

3.86 (nH=1.5)

10.2 (nH=0.5)

3.88 (nH=1.5)

9.73 (nH=0.5)PAB-103 9.40 9.41

PAB-104 9.50 9.50 PAB-109 10.96 10.93

PAB-105 9.94 9.93PAB-110

4.00 (nH=1.5)

9.8 (nH=0.5)

4.12 (nH=1.5)

9.32 (nH=0.5)PAB-106 9.84 9.86



References

1. Foulon, C.; Danel, C.; Vaccher, C.; Yous, S.; Bonte, J.; Goossens, J.;

“Determination of ionization constants of N-imidazole derivatives, aromatase

inhibitors, using capillary electrophoresis and influence of substituents on pKa

shifts” J. Chroma. A 2004, 1035, (1)131–136.

2. Poupaert, J.; Carato, P.; Colacino, E; “2(3H)-Benzoxazolone and bioisosters as

privileged scaffold in the design of pharmacological probes” Curr. Med. Chem

2005, 12 877–885.

3. Avdeef, A.; Box, K. J.; Comer, J. E. A.; Gilges, E.; Hadley, M.; Hibbert, C.;

Patterson, W.; Tam K.Y.; “pKa determination of water-insoluble drugs in organic

solvent-water mixtures” J. Pharm. Biomed. Anal. 1999, 20, 631-641.

4. Shargel, L.; Andrew BC, Y.; “Applied Biopharmaceutics and Pharmacokinetics,

4th Edition, Appleton and Lange, 1999.

5. Poole, S. K.; Patel S.; Dehring, K.; Workman, H. and Poole, Colin F.;

“Determination of acid dissociation constants by capillary electrophoresis” J.

Chrom. A, 2004, 1037, 445–454.

6. Venkatesh, G.; Ramanathan, S.; Mansor, S. M.; Nair, N. K.; Abdul Sattar, M.;

Croft, S. L. and Navaratnam, L.; “Development and validation of RP-HPLC-UV

method for simultaneous determination of buparvaquone, atenolol, propranolol,

quinidine and verapamil: A tool for the standardization of rat in situ intestinal

permeability studies” J. Pharm. Bio. Ana. 2007, 43(4), 1546-1551.

7. TonyTong, W. Q. and Whitesell, G.; “In Situ Salt Screening-A Useful Technique

for Discovery Support and Preformulation Studies” Pharm. Dev. Technol., 1998,

3, 215-223.

8. Lee, Y.; Zocharski, P. and Samas, B.; “An intravenous formulation decision tree for

discovery compound formulation development” Int. J. Pharm. 2003, 253, 111-119.

9. Basavaraj, S.; Sihorkar, V.; Shantha Kumar, T. R.; Sundaramurthi, P.; Srinivas, N.

R.; Venkatesh, P.; Ramesh, M. and Kumar Singh, S.; “Bioavailability

Enhancement of Poorly Water Soluble and Weakly Acidic New Chemical Entity

with 2-Hydroxy Propyl-β-Cyclodextrin: Selection of Meglumine, a Polyhydroxy

Base, as a Novel Ternary Component” Pharm. Dev. Technol., 2006, 11, 443-451.

10. Dawsan, H. M.; Hall, G. V. and Key, A.; “Acid and salt effects in catalysed

reactions. Part XVII. The variation of the catalytic activity of an acid with its



concentration, and the determination of ionisation constants” J. Chem. Soc. 1928,

2844-2853.

11. Dey, B.; Coates, J.; Duckworth, P.; Lincoln, S. and Wainwright, K.; “pH-metric

studies on the acid dissociation constants of a macrocyclic ligand and the apparent

formation constants of some transition metal complexes of the ligand” Science

1993, 17(2), 57-65.

12. Fan, J.; Shen, X. and Jianji, W.; “Determination of acids-base dissociation

constants of glycine in ethanol-water mixed” Fenxi. Shiyanshi 1997, 16(2), 66-70.

13. Saraswathi, K.; Babu, S. S. and Sunandamma, Y.; “pH-metric method for ligand

dissociation constants of mercaptotriazoles and their reactions” Asian. J. Chem.

2000, 12(1), 313-314.

14. Maharramov, A.; Babayeva, G.; Gasanov, V.; Chyraqov, F.; Sadikhova, N. and

Allakhverdiyev, M.; “Determination of dissociation constants of (2-imino-4-

oxothiazolidin-5-yl) acetic acid and stability constnants of its complexes with

some metals” Sakartvelos Mec. 2008, 34(2), 175-178.

15. Mercier, J. P.; Morin, Ph. and Tambute, D.; “Determination of weak (2.0-2.5)

dissociation constants of non-UV absorbing solutes by capillary electrophoresis”

Chromatographia 1998, 48, 529-534.

16. Winzor, D.; “Specific allowance for antibody bivalence in the determination of

dissociation constants by kinetic exclusion assay” Anal. Bio. 2011, 414, 273–277.

17. Fielding, L.; “NMR methods for the determination of protein-ligand dissociation

constants” Prog. In NMR Spect. 2007, 51, 219-242.

18. Delahay, P. and Vielstich, W.; “Kinetics of the dissociation of weak acids and

bases. Application of polarography and voltammetry at constant current” J. Am.

Chem. Soc. 1955, 77, 4955-4958.

19. Dauphin, J.; Chatonier, D.; Couquelet, J.; Payard, M. and Picard, M.; “Application

of conductimetry to the study of dissociation constants of 2-chromo Necarboxylic

acid and its sodium salt” Labo-Pharma – Prob. Tech. 1970, 18, 58-59.

20. Funasaki, N.; “The dissociation constants of acid-base indicators on the micellar

surface of dodecyldimethylamine oxide” J. Colloid Inter. Sci. 1977, 60, 54-59.

21. Levitt, L.; “Determination of the dissociation constant and limiting equivalent

conductance of a weak electrolyte from conductance measurements on the weak

electrolyte” Anal. Chim. Acta. 1981, 125, 219-220.



22. Tanaka, H.; Aritsuka, K.; Tachibana, T.; Chuman, H. and Dasgupta, P. K.;

“Determination of dissociation constants of weak acids by feedback-based flow

ratiometry,” Anal. Chim. Acta. 2003, 499, 199-204.

23. Tanaka, H.; Tachibana, T.; Oda, R. and Dasgupta, P.; “Determination of acid

dissociation constants based on continuous titration by feedback-based flow

ratiometry,” Talanta 2004, 64, 1169-1174.

24. Sıdır, Y. G.; Sıdır, I. and Berber, H.; “Spectroscopic Determination of Acid

Dissociation Constants of N-Substituted-6-acylbenzothiazolone Derivatives” J.

Phys. Chem. A 2011, 115, 5112–5117.

25. Ogretir, C.; Demirayak, S. and Duran, M.; “Spectroscopic Determination and

Evaluation of Acidity Constants for Some Drug Precursor 2-Amino-4-(3- or 4-

substituted phenyl) Thiazole Derivatives” J. Chem. Eng. Data. 2010, 55, 1137–

1142.

26. Lachenwitzer, A.; Li, N. and Lipkowski, J.; “Determination of the acid

dissociation constant for bisulfate adsorbed at the Pt(111) electrode by

subtractively normalized interfacial Fourier transform infrared spectroscopy” J.

Electroanal. Chem. 2002, 532, 85-98.

27. Uhrova, M.; Miksik, Z. and Bellini, D.; “Determination of dissociation constants

by separation method (HPLC and CE). Theoretical background and guidelines for

application”, Process Control Quality, 1997, 10, 151-167.

28. Bogolitsyn, K. G.; Kosyakov, D. S.; Gorbova, N. S.; Aizenshtadt, A. M. and

Shorina, N. V.; “The acidity and salvation of ligninrelated phenols in water-1,4-

dioxane mixtures” Russ. J. Phys. Chem. A. 2008, 82, 237-241.

29. Blano, S. E.; Almandoz, M. C. and Ferretti, F. H.; “Determination of overlapping

pKa values of recorcinol using UV-visible spectroscopy and DFT methods”

Spectrochem. Acta. A 2005, 61, 93-102.

30. Krebs, H. A. and Speakman, J. C.; “Dissociation constant, Solubility and the pH

value of the solvent J. Chem. Soc. 1945, 593-595.

31. Danish, I. A.; Lim, C. S.; Shun Tian, Y. S.; Han, J. H.; Kang, M. Y. and Cho, B.

R.; “Two-Photon Probes for Zn2+ Ions with Various Dissociation Constants.

Detection of Zn2+ Ions in Live Cells and Tissues by Two-Photon Microscopy”

Chem. Asian J. 2011, 6, 1234 – 1240.



32. Sue, K.; Morita, T.; Totsuka, K.; Takebayashi, Y.; Yoda, S.; Furuya, T. and Hiaki,

T.; “Determination of Dissociation Constants of Hexanoic, Heptanoic, and

Benzoic Acids to 673 K and 30 MPa by Potentiometric pH Measurements” J.

Chem. Eng. Data 2010, 55, 4823–4826.

33. Meloun, M.; Ferencíkova, Z.; Netolicka, L. and Pekarek, T.; “Thermodynamic

Dissociation Constants of Alendronate and Ibandronate by Regression Analysis of

Potentiometric Data” J. Chem. Eng. Data 2011, 56, 3848–3854.

34. Albert, A. and Serjeant, E. P.; “Ionization Constants of Acids and Bases”,

Methuen and Co., Ltd. 1962, 69-92.

35. Kudo, Y.; Takeuchi, S.; Kobayashi, Y.; Katsuta, S. and Takeda, Y.”

“Potentiometric determination of ion-pair formation constants for cadmium,

calcium salts, and cadmium-18-crown-6 ether derivative complexes with a

sulphate ion in water”. J. Chem. Eng. Data 2007, 52(5), 1747-1752.

36. Jano, I.; Hardcastle, J.; Jano, L.; Bates, K. and McCreary, H.; “General equation

for determining the dissociation constants of polyprotic acids and bases from

additive properties Part IV. Application to potentiometric titration” Anal. Chim.

Acta. 2001, 428, 309–321.

37. Pryszczewska, M. and Lipiec, T.; “Spectrophotometric determination of the

dissociation constant of a complex compound” Roczniki Chemii. 1955, 29, 985-

992.

38. Ernst, Z. L. and Menashi, J.; “Spectrophotometric determination of the

dissociation constants of some substituted salicylic acids” Trans. Farad. Soc.

1963, 59, 230-240.

39. Hewala, I. I.; el-Yazbi, F. A.; Awad, A. and Wahbi, A. M.; “Determination of

dissociation constants of some pharmaceutical compounds using derivative

spectrophotometry” J. Clin. Pharm. Thera. 1992, 17, 233-239.

40. Kadar, M. Biro, A.; Toth, K.; Vermes, B. and Huszthy, P.; “Spectrophotometric

determination of the dissociation constants of crown ethers with grafted acridone

unit in methanol based on Benesi-Hildebrand evaluation” Spectrochim. Acta, Part

A: Mol. Biomol. Spect. 2005, 62, 1032-1038.

41. Unal, G.; Yeloglu, I.; Anilanmert, B. and Narin, I.; “pKa Constant of Varenicline”

J. Chem. Eng. Data 2012, 57, 14 – 17.



42. Kamps, A. P. and Maurer, G.; “Dissociation Constant of N-Methyldiethanolamine

in Aqueous Solution at Temperatures from 278 K to 368 K” J. Chem. Eng. Data

1996, 41, 1505-1513.

43. Taha, M. and Fazary, A.; “Thermodynamics of the second-stage dissociation of 2-

[N-(2-hydroxyethyl)- N -methylaminomethyl]-propenoic acid (HEMPA) in water

at different ionic strength and different solvent mixtures” J. Chem. Thermo. 2005,

37, 43–48.

44. Evagelou, V.; Tsantili-Kakoulidou A.; Koupparis, M.; “Determination of the

dissociation constants of the cephalosporins cefepime and cefpirome using UV

spectrometry and pH potentiometry” J. Pharm. Bio. Ana. 2003, 31(6), 1119-1128.

45. Hagenmuller, P.; “New method of determination of the dissociation constant of a

complex in solution” Compt. rend. 1950, 230, 2190-2192.

46. Vasil'ev, V.; “Effect of ionic strength on the dissociation constants of complex

compounds” Zhur. Neorga. Khim. 1962, 7, 1788-1794.

47. Patel, C. and Patel, R.; “Acid dissociation constants of some 3-substituted 2-

hydroxy-5-methylacetophenones and the formation constants of their metal

complexes” J. Ind. Chem. Soc. 1975, 52, 312-314.

48. Morrison, J. F. and Cleland, W. W.; “A kinetic method for determining

dissociation constants for metal complexes of adenosine 5'-triphosphate and

adenosine 5'-diphosphate” Biochem. 1980, 19, 3127-3131.

49. Piran, U. and Riordan, W. J.; “Dissociation rate constant of the biotin-streptavidin

complex” J. Immuno. Methods. 1990, 133, 141-143.

50. Rózga, M.; Kłoniecki, M.; Dadlez, M. and Bal, W.; “A Direct Determination of

dissociation Constant for the Cu(II) Complex of Amyloid β 1−40 Peptide” Chem.

Res. Toxico. 2010, 23 (2), 336–340.

51. Zuskova, I.; Novotna, A.; Vcelakova, K. and Gas, B.; “Determination of limiting

mobilities and dissociation constants of 21 amino acids by capillary zone

electrophoresis at very low pH” J. Chromato. B. 2006, 841, 129-134.

52. Nagai, H.; Kuwabara, K.; Carta, G.; “Temperature Dependence of the

Dissociation Constants of Several Amino Acids” J. Chem. Eng. Data. 2008, 53,

619–627.

http://www.sciencedirect.com.jerome.stjohns.edu:81/science/article/pii/S0731708502006532





53. Leyda, J. P.; Lamb, D. J. and Harris, L. E.; “Distribution coefficients and

dissociation constants of a series of barbituric acid derivatives” J. Am. Pharm.

Asso. Sci. Edi. 1960, 49, 581-583.

54. Dang, U.; Nguyen, T. and Vuong, D.; “Determination of dissociation constant of

monoprotic acids from pH data by simplex algorithm” Tap Chi Phan Tich Hoa, Ly

Va Sinh Hoc. 2002, 7, 31-36.

55. Delphay, P. and Vielstich, W.; “Kinetics of the dissociation of weak acids and

bases-application of polarography and voltammetry at constant current” Phy.

Inorg. Chem. 1955, 77, 4955-4958.

56. Poe, M.; “Acidic dissociation constants of folic acid, dihydrofolic acid, and

methotrexate” J. Bio. Chem. 1977, 252, 3724-3728.

57. Brockman, F. G.; Kilpatrick, M.; “The Thermodynamic Dissociation Constant of

Benzoic Acid from Conductance Measurements” J. Am. Chem. Soc. 1934, 56(7),

1483–1486.

58. Oumada, F. Z.; Rafols, C.; Roses, M. and Bosch, E.; “Chromatographic

determination of aqueous dissociation constant of some water-insoluble

antiinflamatory drugs” J. Pharm. Sci. 2002, 91(4), 991-999.

59. Şanli, S.; Şanli, N. and Alsancak, G.; “Determination of Protonation Constants of

Some Tetracycline Antibiotics by Potentiometry and LC Methods in Water and

Acetonitrile-Water Binary Mixtures” J. Braz. Chem. Soc. 2009, 20(5), 939-946.

60. Srour, R. K. and McDonald, L. M.; “Determination of the Acidity Constants of

Methyl Red and Phenol Red Indicators in Binary Methanol - and Ethanol-Water

Mixtures” J. Chem. Eng. Data 2008, 53, 116–127.

61. Funasaki. N.; “The dissociation constants of acid-base indicators on the micellar

surface of dodecyldimethylamine oxide” J. Colloid Interface Sci. 1977, 60, 54-59.

62. Fedorov, S.; Kudryavtseva, L.; Bel'skii, V.; Ivanov, B.; “Determination of the

dissociation constants of micelle-solubilized compounds, Kolloidnyi Zhur” 1986,

48, 199-201.

63. Hayman, B. and Tapuhi, E.; “The Dissociation Constants of Dim and

Trichloroacetic Acids Measured by a Distribution Method” J. Chem. Eng. Data

1977, 22(1), 22-24.

http://www.jbc.org/search?author1=M+Poe&sortspec=date&submit=Submit





64. Melouna, M.; Ferenciková, Z. and Vrána, A.; “Determination of the

thermodynamic dissociation constant of capecitabine using spectrophotometric

and potentiometric titration data” J. Chem. Thermo. 2011, 43, 930–937.

65. Meloun, M.; Syrovy, T. and Vrana, A.; “The thermodynamic dissociation

constants of losartan, paracetamol, phenylephrine and quinine by the regression

analysis of spectrophotometric data” Anal. Chim. Acta 2005, 533, 97–110.

66. Solinova, V.; Kasicka, V.; Koval, D.; Cesnek, M. and Holy, A.; “Determination of

acid-base dissociation constants of amino- and guanidinopurine nucleotide

analogs and related compounds by capillary zone electrophoresis”

Electrophoresis. 2006, 27, 1006-1019.

67. Issam, J.; James, H.; Jano, L.; Bates, K. and McCreary, H.; “General equation for

determining the dissociation constants of polyprotic acids and bases from additive

properties Part IV. Application to potentiometric titration” Anal. Chim. Acta 2001,

428, 309–321.

68. Kulig, K.; Rybicka, K. and Malawska, B.; “Application of RP-TLC technique for

the determination of dissociation constants of 1-substituted pyrrolidin-2-one

derivatives” Biomed. Chroma. 2008, 22, 1225-1229.

69. Yagil, G.; “The protein dissociation constant of Pyrrole, Indole and related

compounds” Tetrahedron 1967, 23, 2855-2861.

70. Bartolini, M.; Bertucci, C.; Gotti, R.; Tumiatti, V.; Cavalli, A.; Recanatini, M. and

Andrisano, V.; “Determination of the dissociationconstants (pKa) of basic

acetylcholinesterase inhibitors by reversed-phase liquid chromatography” J.

Chrom. 2002, 958(1–2), 59–67.

71. Hwan Urn, I.; Ju Hong, Y.; and Sook Kwon, D.; “Acid dissociation constants of

phenols and reaction mechanism for the reactions of substituted phenyl benzoates

with phenoxide anions in absolute ethanol” Tetrahedron 1997, 53(14), 5073-5082.

72. Belikov, V.; Belokon, Y.; Dolgaya, M. and Mawtinkova, N.; “The kinetics and

mechanism of mannich base dissociation in aqueous buffers” Tetrahedron 1970,

26, 1199-1216.

73. Tamura, H. and Furuichi, R.; “Determination of the dissociation constants of

surface hydroxyl groups: application to the characterization of metal oxides”

Nipp. Kinz. Gakk. Kai. 1988, 27, 158-164.






74. Azimi, G.; Khoobi, A.; Zamani, K. and Zolgharnein, J.; “Multiwavelength

Spectrophotometric Determination of Acidity Constants of Newly Synthesized

1,2,4-Triazole Derivatives in Ethanol-Water Mixtures” J. Chem. Eng. Data 2008,

53, 1862–1866.

75. Bhagwatkar, R.; Tayade, D.; Pund, D.; Rathod, D. and Bhagwatkar, N.; “pH

Metric Studies of Interaction of Synthesized Ligands 2-amino-4-hydroxy-6-

methylpyrimidine and 1-(4-hydroxy-6-methylpyrimidino)-3 -phenylthiocarbamide

with Cu(II), Cd(II), Cr(II), Cations At 0.1 M Ionic Strength” I. J. Chem. 3(1),

2011, 36-41.

76. Bjerrum, J. and Hease, P. “Metal Ammine Formation in aqueous solution” 1941.

77. Irving, H. M. and Rossoti, H. S.; “The calculation of formation curves of metal

complexes from pH titration curves in mixed solvents” J. Chem. Soc. 1954, 10,

2904-2910.

78. Uitert, L. and Hass, C.; “A Method for Determining Thermodynamic Equilibrium

Constants in Mixed So1vents” J. Am. Chem. Soc. 1953, 75, 451-455.

79. Ephraim, J.; Alegret, S.; Mathuthu, A.; Bicking, M.; Malcolm, R. and Marinsky,

J.; “A unified physicochemical description of the protonation and metal ion

complexation equilibria of natural organic acids (humic and fulvic acids). 2.

Influence of polyelectrolyte properties and functional group heterogeneity on the

protonation equilibria of fulvic acid.” Environ. Sci. Technol. 1986, 20(4), 354–

366.

80. Yoda, A.; “Structure-Activity Relationships of Cardiotonic Steroids for the

Inhibition of Sodium- and Potassium-Dependent Adenosine Triphosphatase I.

Dissociation Rate Constants of Various Enzyme-Cardiac Glycoside Complexes

Formed in the Presence of Magnesium and Phosphate.” Mol. Pharmacol. 1973,

9(1), 51-60.

81. El-Sonbati, A.; El-Bindary, A.; Shoair, A. and Younes, R.; “Stereochemistry of

new nitrogen containing heterocyclic aldehyde. vii. potentiometric,

conductometric and thermodynamic studies of novel quinoline azodyes and their

metal complexes with some transition metals.” Chem. Pharma. Bull. 2001, 49(10),

1308-1313.

Section-V

Thermal properties

Section-V Thermal properties


INTRODUTION

Thermal analysis has been proved to be a key method in the study and

characterization of various materials and finds wide applications in industrial and

research fields. Among the several instruments and technique, thermal analysis has grown

rapidly in recent years. This increasing importance is due to the advancement of thermal

analysis technology, relative low cost of the equipment and time required to achieve the

desired results.

For the complete development of a new drug, thermal analysis has many

applications1,2. The information obtained regarding the compounds under study is useful

for the initial chemical research phase3. In the chemical research phase, thermal analysis

plays an important role. The purity of the compound, the compound’s ability to be able to

exist in various crystalline forms as well as to characterize polymorphs and other forms of

solid state should be investigated. It also makes possible to determine optimum conditions

of storage of drugs and to define the parameters of technological processes, which can be

used without loss of specific physicochemical properties of a drug 4-5

Apart from its traditional use in investigations of chemical reactions, temperature

programmed decompositions, reaction kinetics and mechanism, determination of material

purity etc. can also be studied. This technique is also used in pharmaceutical science6,7,

forensic science8, archeology9,10 etc. Various thermal methods have been used in

analyzing and characterizing a wide variety of materials like coals, rocks and minerals11,12

petroleum coke13, hydrocarbon sludge from petrochemical plants14,15, hydrogen storage

materials16, catalysis17,18, dyes19,20, fertilizers21,22, nuclear fuel23,24, vitamin25, honey26,

tobacco27 and edible oil28 and even rocks from moon.

Literature survey shows that various workers have studied thermal properties of

various drugs29-34 and organic compounds35-37. Bei et al.38 have reported the thermal

decomposition kinetic of 5-flourouracil from thermogravimetric analysis. Vora et al39

studied thermal stability of folic acid. Quan et al40 have reported thermal data of 4-

Dimethylaminopyridine. Thermal behavior of cobalt(II) 5-chloro-piridylamides

complexes have been studied by Lima et al41. Thermal decomposition studies of triazole

and 1-methyl-3,4,5-trinitropyrazole have been reported by Sasidharan et al42 and Ravi et

al43 respectively.



Differential scanning calorimetry (DSC) has been extensively used for material

characterization in a wide variety of research areas, including food science,

pharmaceutics, material science, biochemistry, and physics, due to a number of

significant advantages, such as ease of sample preparation, applicability to solid and

liquid samples, fast analysis time, and a broad temperature range44. DSC provides both

quantitative and qualitative thermal and physical material property information (e.g.,

phase transition, glass transition, cold crystallization, polymorphism, and purity) as a

function of time and temperature. Because every change in structure (transition) either

absorbs or releases heat, DSC is the universal detector for measuring structural changes45.

Various researchers have reported the calorimetric study of drugs46-48. Lee et al.49,50 have

shown that the loss of crystalline structure in sucrose, glucose, and fructose is due to the

kinetic process of thermal decomposition, dehydration, and chemical reactions. Thermo

physical study of several barbituric acid derivatives was done by differential scanning

calorimetry51.

Both calorimetry and thermogravimetry can also be used in the evaluation of

compound stability52-56 Predicting stability or instability at a very early stage of product

development, such as immediately after the initial synthesis process, provides valuable

information.

In the present study, thermal analysis of some new synthesized

tetrahydropyrimidine derivatives has been done by DSC and TGA techniques.



THEORY

From TGA curves, various kinetic parameters can be evaluated by several

methods. In all these methods, it is assumed that thermal and diffusion barriers are

negligible because small quantity of material is used. The shape of any TGA curve

depends on the nature of apparatus and the way in which it is used. Further, Arrhenius

equation is valid in all these methods.

The kinetic treatments are generally based on the relationship of the type:

dC/dt = K f (C) ... (3.5.1)

where C is the degree of conversion, t is time and K is rate constant. f(C) is a temperature

independent function of C.

The constant K is assumed to have the Arrhenius form:

K = A e -E/RT ... (3.5.2)

C can also be defined as:

C = 1-(W/ W0) ... (3.5.3)

where W0 and W are the initial weight at t=0 and weight at any time t of the material.

Equation (3.5.3) can be written as:

(W/W0) = (1-C) ... (3.5.4)

W/ W0 is known as residual weight fraction.

Thus, the rate of conversion is,

dC/dt = - (1/ W0) (dW/dt) ... (3.5.5)

For homogeneous kinetics, the conversion is assumed to be of the form:

f (C) = (1-C)n ... (3.5.6)

where n is the order of the reaction.

Substituting the values from equation (3.5.2) and (3.5.6) in equation (3.5.1) gives:

dC/ dt = A e -E/RT (1-C)n

or dC/dt = (A/β) e -E/RT (1-C)n ... (3.5.7)

where A is the frequency factor, β is the rate of heating and E is the energy of activation.



Various methods for single and multiple heating rates have been reported. The

methods of single heating rate are as follows:

1. Freeman-Carroll57 and Anderson-Freeman Method58:

At a single heating rate, Freeman and Carroll gave the following relation to

analysis TGA data :

ln (dC/dt)/ln (1-C) = n-E/R [(1/T/(△ln(1-C)] ... (3.5.8)

A plot of left hand side against (1/T)/( △ln(1-C)) gives a straight line with a slope

equal to -E/R and the intercept is equal to n.

Above equation (3.5.8) is modified by Anderson and Freeman in the following

form:

(△ln[dC/dt]) = n (△ln(1-C)) - E/R△(1/T) ... (3.5.9)

The plot of (△ln[dC/dt]) against (△ln(1-C)) for equal intervals of △(1/T) gives a

straight line with slope equal to n and intercept -E/R△(1/T).

2. Horowitz and Metzger method59 :

In this method, the value of energy of activation E can be determined from a

single TG curve by the relation:

ln [ln(1-C)-1] = (E/RTs

2) θ ... (3.5.10)

where θ = T-Ts. Ts is the temperature at which the rate of decomposition is maximum.

The frequency factor A and entropy change △S can be determined by the following equations:

ln E - ln (RTs2) = ln A - ln β - E/RTs ... (3.5.11)

A = (kbT / h) e△S/R ... (3.5.12)

where kb is Boltzmann constant and h is Planck’s constant.



EXPERIMENTAL

Thermo gravimetric analysis (TGA) and Differential Scanning Calorimetry (DSC)

measurements were made on the instrument “Pyris-1, Perkin Elmer Thermal Analysis” at

the heating rate of 10C /min in nitrogen atmosphere for all the tetrahydropyrimidine

derivatives.




The TGA thermo grams of PAB-101 and PAB-109 are given in Figure 3.5.1.

Various thermal properties such as initial decomposition temperature (IDT), the

decomposition temperature range and the maximum degradation along with the

percentage weight loss are reported in Table 3.5.1.

For all the compounds, degradation is single step process. Out of ten compounds,

PAB-102 is most unstable which is followed by PAB-103. PAB-107 is the most stable

compound which is followed by PAB-106. All the studied compounds have the same

central moiety but substitution groups are different. Thus, substitution affects the thermal

stability of a compound. PAB-102 contains cinnamaldehyde as substitution to aromatic

ring. Thus, cinnamaldehyde makes the compound unstable whereas chloro group at meta

position (as in PAB-103) makes it a little bit less stable. However, the presence of nitro

group at meta position increases the stability as is the case for PAB-107. Whereas

presence of methoxy group at para position decreases the stability slightly. Further, it is

observed that the position of group affect the stability as observed in case of PAB-103

and PAB-104. Both these compounds contain chloro group. In PAB-103, it is at meta

position whereas in PAB-104, it is at para position. It is observed that when chloro group

is at meta position, it decreases the stability in comparison to that at para position. Both

methoxy and hydroxyl groups when present alone at para position increases the stability

as observed in PAB-106 and PAB-110. However, when both groups are present together

as in PAB-108, stability is reduced. Further, it is observed that although PAB-102 is most

unstable, weight loss is minimum for this compound whereas for PAB-1-1, it is

maximum. The variation in thermal decomposition may also be due to some

intermolecular interactions (structural as well as electronic).

Further, various kinetic parameters, such as order of the degradation (n), energy of

activation (E), frequency factor (A) and entropy change (ΔS) have also been calculated

from the thermograms and are reported in Table 3.5.2. The order of reaction (n) varies

from 0.64 to 8.09. The value of n is minimum for PAB-104 and maximum for PAB-103.

The energy of activation (E) is highest for PAB-105 containing fluoro group at

para position and minimum for PAB-103 which is containing chloro group at meta

position. The frequency factor (A) is also highest for PAB-105 but minimum for PAB-

107. Further, change in entropy (ΔS0) for all these reactions were also calculated by

Section-V


Figure 3.5.1: The TGA graphs of PAB

V Thermal properties


The TGA graphs of PAB-101 and PAB-109

Thermal properties

191



Table 3.5.1: TGA data for synthesized tetrahydropyrimidine derivatives.

Comp. Code

Amount(mg.)

InitialDecomp.Temp.(°C)

Decomp.Range (°C)

% Wt.loss

Residual wt.loss

(mg.)

Max.Degrad.Temp. (°C)

Transition

PAB-101 2.297 110.00 110-250 99.02 2.275 168.08 EndoPAB-102 5.104 70.00 70-296.50 49.72 2.538 191.49 EndoPAB-103 2.497 80.00 80-190 88.76 2.217 164.67 EndoPAB-104 1.741 140.00 140-230 93.72 1.632 181.74 EndoPAB-105 2.160 110.00 110-230 99.85 2.157 172.27 EndoPAB-106 2.938 150.00 150-246.20 71.26 2.094 209.00 EndoPAB-107 3.127 153.51 153-296.30 88.43 2.766 247.22 EndoPAB-108 1.071 90.00 90-246.80 81.37 0.872 210.00 EndoPAB-109 2.969 100.00 100-240 92.72 2.753 166.72 EndoPAB-110 1.903 145.45 145.45-246.70 87.17 1.659 213.18 Endo

Table 3.5.2: The kinetic parameters of tetrahydropyrimidine derivatives

Comp.code

n E(kJ)

A(Sec-1)

ΔSo

(J-1)

PAB-101 2.89 418.46 4.47X1049 855.48PAB-102 2.79 434.24 7.52X1048 840.22PAB-103 8.09 251.64 7.88X1029 477.38PAB-104 0.64 529.69 9.75X1060 1072.28PAB-105 1.78 535.92 1.09X1063 1111.64PAB-106 5.14 460.97 9.85X1049 861.30PAB-107 3.29 253.15 1.34X1025 384.64PAB-108 1.32 480.17 9.59X1051 899.36PAB-109 4.44 401.11 5.06X1047 818.24PAB-110 2.44 490.65 5.91X1052 914.42

Section-V


Figure 3.5.2: The DSC graphs of PAB

V Thermal properties


igure 3.5.2: The DSC graphs of PAB-101 and PAB-109

Thermal properties

193



Table 3.5.3: The melting temperature (0C) of tetrahydropyrimidine derivatives by

DSC and open capillary methods.

Comp. Code

PAB-101

PAB-102

PAB-103

PAB-104

PAB-105

PAB-106

PAB-107

PAB-108

PAB-109

PAB-110

DSC 140.00 113.29 153.75 163.51 129.04 116.48 105.77 132.94 71.60 177.94

Opencapillary 142 114 154 164 129 116 106 132 72 178

equation (3.5.12) and are reported in Tables 3.5.2. The entropy change (ΔS0) is found to

be positive for all ten compounds which indicate that the transition state is less ordered

than the original compound60.

Figure 3.5.2 shows DSC of PAB-101 and PAB-109. From DSC, melting points of

all the compounds are determined and are given in Table 3.5.3 along with melting points

determined by open capillary method. There is good agreement between the values

evaluated from DSC and those determined by open capillary method.

Thus, it is concluded that for the studied compounds, degradation is single step

process with different order of reaction. The thermal stability depends upon the type of

substituent present.



REFERENCES

1. D. Giron, “Application of thermal analysis in the pharmaceutical industry” J.

Pharm. Biomed. Anal. 1986, 4(6), 755-770.

2. D. Giron, “Thermal Analysis of Drugs and Drug Products” Encyclopedia of

Pharmaceutical Technology, Third Edition, 2006.

3. Hardy, M. J.; Charsley E. L. and Warrington, S. B.; Thermal analysis-techniques

and applications, The Royal Society of Chemistry, Cambridge 1992, 180–197.

4. Rubinstein M. H.; “Pharmaceutical technology: drug stability.” Chichester: Ellis

Horwood; 1989.

5. Brittain H G.; “Physical characterization of pharmaceutical solids.” New York:

Marcel Dekker, Inc.; 1995.

6. Neill, O.; Michael, A. and Gaisford, S.; “Application and use of isothermal

calorimetry in pharmaceutical development” Inter. J. Pharm. 2011, 417(1-2), 83-

93.

7. Lizarraga, E.; Zabaleta, C. and Palop, J.; “Thermal stability and decomposition of

pharmaceutical compounds” J. Therm. Anal. Calori. 2007, 89(3) 783–792.

8. Raja, S., Thomas, P.; Stuart, B.; Guerbois, J. and O'Brien, C.; “The estimation of

pig bone age for forensic application using thermogravimetric analysis.” J. Therm.

Anal. Calori. 2009, 98(1), 173-176.

9. Cavallaro G.; Donato, I.; Lazzara G. and Milioto S.; “A comparative

thermogravimetric study of waterlogged archaeological and sound woods” J

Therm. Anal. Calori. 2011, 104, 451-457.

10. Deviese, T.; Colombini, M.; Regert, M.; Stuart, B. and Guerbois, J.; “TGMS

analysis of archaeological bone from burials of the late Roman period” J. Therm.

Anal. Calori. 2010, 99, 811–813.

11. Kodle, K.; Andrade, P.; Valenca, J. and Souza, D.; “Study on the composition of

mineral scales in oil wells” J. Petro. Sci. Eng. 2012, 81, 1-6.

12. Srivastava, Y.; Neloy, K. and Ingle, S.; “Characterization of clay minerals in the

sediments of Schirmacher Oasis, East Antarctica: their origin and climatological

implications.” Curr. Sci., 2011, 100(3), 363-372.

13. Jess, A. and Andresen, A.; “Influence of mass transfer on thermogravimetric

analysis of combustionand gasification reactivity of coke” Fuel 2010, 89 1541–

1548.



14. Remmler, M.; Kopinke, F. and Stottm, E.; “Thermoanalytical methods for

characterizing hydrocarbon-sludge-soil mixtures.” Thermochim. Acta. 1995, 263,

101-112.

15. Lapuerta, M.; Ballesteros, R. and Rodriguez-Fernandez, J; “Thermogravimetric

analysis of diesel particulate matter.” Meas. Sci. Technol. 2007, 18, 650–658.

16. Kamruddin, M.; Dash, A.; Tyagi, S. and Baldev, A.; “Thermogravimetry-evolved

gas analysis–mass spectrometry system for materials research.” Bull. Mater. Sci.

2003, 26(4), 449–460.

17. Youssef, T. and Mekewi, M.; “Thermal stability eminence of PMMA prepared in

presence of photosynthesized ruthenium carbonyl Schiff base as a catalyst.” J.

Appl. Poly. Sci. 2009, 114(3), 1503-1510.

18. Babenko, V.; Pakhomov, N. and Buyanov, R.; “Study of thermal stability of

aluminum-chromium catalysts for a single-stage process of butane

dehydrogenation.” Kataliz v Promyshlennosti 2009, 1, 13-19.

19. Bindhu, C. and Harilal, S.; “Effect of the excitation source on the quantum-yield

measurements of Rhodamine B laser dye studied using thermal technique”.Anal.

Sci. 2001, 17, 141-144.

20. Long, J.; Wang, H. and Chen, X.; “Study of the inclusion action of cyclodextrin

on cationic dyes” Fan. Xue. 2002, 23, 33-35.

21. Chen, J.; Tsai, H. and Lin, Y.; “Evaluation of the suitability of three analysis

methods for determining organic matter contents in fertilizers” Nongye Huaxue Yu

Shipin Kexue, 2004, 42,116-124.

22. Kolesnikov, V. and Moskalenko, L.; “Thermal analysis studies of modification

transformations of a fertilizer obtained from ammonium nitrate” Khimiche.

Promy. Sego. 2006, 7, 18-21.

23. Sugama, H.; Okamoto, M. and Wakatani, M.; “Transport analysis based on K-β

anomalous transport model,” AIP Conf. Proc. 1994, 284, 509-525.

24. De Luca, F.; Galli, P.; Gorini, G.; Jacchia, A.; Mantica, P.; Deliyanakis, N.; Erba,

M. and L. Porte; “Sawtooth heat pulse propagation in tokamaks. Ballistic response

and Fourier analysis” Nucl. Fus. 1996, 36, 909-916.

25. Moura, T.; Gaudy, D.; Jacob, M. and Terol, A.; Pauvert, B. and Chauvet, A.;

“Vitamin C spray drying: study of the thermal constraint” Drug Develop. Ind.

Pharm. 1996, 22, 393 – 400.



26. Maria, L.; Cristiane, B.; Jivaldo, R.; Lígia, B. and Roy, E.; “Optimization of

Thermogravimetric Analysis of Ash Content in Honey” J. Brazil. Chem. Soc.

2004, 15(6), 797-802.

27. Li, G.; Lv, Y.; Ma, G.; Jian, S. and Tan, H.; “Thermogravimetric investigation on

co-combustion characteristics of tobacco residue and high-ash anthracite coal”

Bio. Tech. 2011, 102(20), 9783-9787.

28. Heda, L.; Sharma, R.; Tank, P. and Sherwani, M.; “Thermogravimetric analysis of

copper (II) soaps derived from edible oils.” J. Lipid Sci. Tech. 2008, 40(1), 6-9.

29. Refat, M. and Mohamed G.; “Ti(IV), Cr(III), Mn(II), and Ni(II) Complexes of the

Norfloxacin Antibiotic Drug: Spectroscopic and Thermal Characterizations” J.

Chem. Eng. Data. 2010, 55, 3239–3246.

30. Szynkaruk, P.; Wesolowski, M. and Malgorzata, S.; “Principal component

analysis of thermal decomposition of magnesium salts used as drugs” J. Therm.

Anal. Calori. 2010, 101, 505–512.

31. Oliveira, A.; Maria Irene, Y.; Gomes, E.; Wagner da Nova, M.; Cristina Duarte,

V. and Gerson Antonio, P.; “Thermal analysis applied to simvastatin

characterization in pharmaceutical formulations” Quimica Nova 2010, 33(8),

1653-1657.

32. Seiman, C.; Vlase, T.; Vlase, G.; Seiman, D.; Albu, P. and Doca, N.; “Thermal

analysis study of amlodipine as pure compound and in binary mixture” J. Therm.

Anal. Calori. 2011, 105, 677-683.

33. Rocasoares, M.; Sobrinho, J.; Ramos, K.; Alves,L.; Lopes, P.; Corriea, L.; Souza,

F.; Macedo, O. and Neto, P.; “Thermal characterization of antimicrobial drug

ornidazole and is compatibility in a solid pharmaceutical product” J. Therm. Anal.

Calori. 2011, 104(1), 307-313.

34. Duda-Seiman, C.; Vlase, T.; Vlase, G.; Duda-Seiman, D.; Albu, P. and Doca, N.;

“Thermal analysis study of amlodipine as pure compound and in binary mixture”

J. Therm. Anal. Calori. 2011, 105, 677–683.

35. Sun, Y.; “Determination of purity of crystallized organic compounds by thermal

analysis technology” Guan. Huag. 2002, 31, 29-31.

36. Chafik, T.; Zaitan, H.; Harti, S.; Darir, A. and Achak, O.; “Determination of the

heat of adsorption and desorption of a volatile organic compound under dynamic



conditions using Fourier-transform infrared spectroscopy” Spectro. Lett. 2007, 40,

763-775.

37. Leboeuf, E. and Zhang, L.; “Thermal analysis for advanced characterization of

natural nonliving organic materials” Biophys. Chem. Pro. Environ. Sys. 2009, 2,

783-836.

38. Bei, Y.; Qing-yang, L.; Gui-bin, Q. and Yuan-jun, D.; “Thermal decomposition

kinetics of 5-fluorouracil from thermogravimetric analysis” Korean J. Chem. Eng.

2008, 25(5), 980-981.

39. Vora, A.; Riga, A.; Dollimore, D. and Alexander, K. S.; “Thermal stability of folic

acid” Thermochim. Acta 2002, 392–393, 209–220.

40. Quan, S.; Zhi-Cheng, T.; You-Ying, D.; Tong, B.; Yan-Sheng, L. and Shao-Xu,

W.; “Thermal Analysis and Calorimetric Study of 4-Dimethylaminopyridine” J.

Chem. Eng. Data 2007, 52 (3), 941–947.

41. Lima, Cicero B. A.; José, G. P.; De Oliveira, S, F.; Arakaki, Luiza N. H.; Fonseca,

M, G.; Airoldi, C.; “Synthesis, characterization and thermal behavior of cobalt(II)

5-chloro-piridylamides complexes” Thermochim. Acta 2003, 407, 117–120.

42. Sasidharan, N.; Hariharanath, B. Rajendran, A. G.; “Thermal decomposition

studies on energetic triazole derivatives” Thermochim. Acta 2011, 520, 139–144

43. Ravi, P. Gore, G, M.; Sikder, A, K. and Tewari, S, P.; “Thermal decomposition

kinetics of 1-methyl-3,4,5-trinitropyrazole” Thermochim. Acta 2012, 528, 53–57.

44. Verdonck, E. and Schaap, K.; “L. C. A discussion of the principles and

application of modulated temperature DSC (MTDSC)”. Int. J. Pharm. 1999, 192,

3–20.

45. Danley, R.; Caulfield, P. and Aubuchon, S.; “A rapid-scanning differential

scanning calorimeter. Am. Lab. 2008, 40, 9–11.

46. Carvalho, T.; Matias, A.; Braga, L.; Evangelista, S. and Prado, A.; “Calorimetric

studies of removal of nonsteroidal anti-inflammatory drugs diclofenac and

dipyrone from water” J. Therm. Anal. Calori. 2011, 106(2), 475-481.

47. Raut, D.; Sakharkar, D.; Bodke, P. and Mahajan, D.; “Determination of traces of

amorphous carvidilol content in carvedilol drug substance and drug product using

modulated differential scanning calorimetry” Pharma. Lett. 2011, 3(4), 1-12.


http://www.sciencedirect.com/science/journal/00406031/392




http://www.sciencedirect.com/science/journal/00406031/528



48. Keswani, N. and Kishore, N.; “Calorimetric and spectroscopic studies on

theinteraction of anticancer drug mitoxantrone with human serum albumin” J.

Chem. Thermo. 2011, 43(9), 1406-1413.

49. Lee, J.; Thomas, L. and Schmidt, S.; “Investigation of the heating rate dependency

associated with the loss of crystalline structure in sucrose, glucose, and fructose

using a thermal analysis approach (part I)” J. Agric. Food Chem. 2011, 59, 684–

701.

50. Lee, J.; Thomas, L.; Jerrell, J.; Feng, H.; Cadwallader, K. and Schmidt, S.;

“Investigation of thermal decomposition as the kinetic process that causes the loss

of crystalline structure in sucrose using a chemical analysis approach (part II).” J.

Agri. Food Chem. 2011, 59, 702–712.

51. Temprado, M.; Roux, M. V.; Ros, F.; Notario, R.; Segura, M. and Chickos, J. S.;

“Thermophysical Study of Several Barbituric Acid Derivatives by Differential

Scanning Calorimetry (DSC)” J. Chem. Eng. Data 2011, 56 (2), 263–268.

52. Ford, L. and Timmins, P.; “Pharmaceutical Thermal Analysis. Techniques and

applications. Ellis Horwood, Chichester 1989. 180-200.

53. Wesolowski, M.; and Konarski, T.; General remarks on the thermal

decomposition of some drugs. J. Thermal Anal. 43 (1995) 279-289.

54. Cheng, Y.; Huang, Y.; Alexander, K.; Dollimore, D.; “A thermal analysis study of

methyl salicylate”, Thermochim. Acta, 367–368 (2001) 23.-28

55. Thompson, K.; “Pharmaceutical applications of calorimetric measurements in the

new millennium”, Thermochim. Acta, 355 (2000) 83-87.

56. Lizarraga, E.; Zabaleta, C.; Palop, J.; “Thermal decomposition and stability of

quinoline compounds using thermogravimetry and differential scanning

calorimetry”, Thermochim. Acta. 2005, 427(1-2), 171-174.

57. Freeman, E. S. and Carroll, B.; “The application of thermoanalytical techniques to

reaction kinetics.The thermogravimetric evaluation of the kinetics of the

decomposition of calcium oxalate monohydrate” J. Phys. Chem. 1958, 62, 394-

397.

58. Anderson, D. A. and Freeman, E. S.; “Kinetics of the thermal degradation of

polystyrene and polyethylene” J. Poly. Sci. 1961, 54, 253-260.

59. Horowitz H. H. and Metzger, G.; “A New Analysis of Thermogravimetric Traces”

Anal. Chem.1963, 35(10), 1464-1468.



60. Mishra, A. P.; Tiwari, V.; Singhal, R. and Gautam, S. K.; “Synthesis,

characterization, thermal decomposition and kinetic parameters of Ni (II) and

Cu(II) terephthalate-8Hg complexes.” Ind. J. Chem. 2002, 41A(10), 2092-2095.

Section-VI

Conductance

Section-VI Conductance


INTRODUCTION

The ability of a material to conduct electric current is known as conductivity.

Conductivity is the inverse of resistivity which is determined from the voltage and current

values according to Ohm's law1. In electrolytic solutions, concentration of solution,

charge on ions, mobility of ions etc., plays vital role to determine its conductance. Thus

the conductance behavior alters with concentration of strong or weak electrolytes.

By taking the importance of synthesized organic compounds in view, it is quiet

necessary to give the conductance profile of solutions of these compounds, because

conductivity measurement has widespread use in industrial applications that involve the

detection of contaminants in water and concentration measurements 2. It is also used to

determine the dissociation constant and limiting equivalent conductance of weak

electrolytes3, electro osmotic flow4, for studying conformational changes in poly

electrolytes in aqueous solutions5, etc. Baghalha and Papangelakis6, have developed

conductivity meter which is useful at high temperature and high concentration, which

found too useful in industrial process. Conductance determination is also a handed tool

for determination of nutrients in food stuffs7.

Further, knowledge of conductivity is useful to various biological processes8-11

such as determination of ascorbic acid in vitamin C tablet12, carbon in uranium carbide

and its solution in nitric acid13, enzymatic degradation of microbial biofilm14, dye-

surfactant ion pair formation in aqueous solutions15 etc. The antibiotic residues in bovin

kidneys have also been detected by conductometry16. Literature survey shows that

conductance of various inorganic and organic compounds have been measured in

aqueous17-25 and non aqueous solvents26-31. Liu et al32 have measured conductance of

macro cyclic Schiff base metal complexes in methanol. Morita et al reported ionic

conductance of polymeric electrolytes and of polymeric composite solid electrolytes33. In

aqueous solutions, conductance of antidepressant drug and surfactant was reported by

Kabir-ud-Din et al and coworkers34. The conductance measurement of pyrazinamide in

aqueous solution in presence and absence of additives at 308.15 K have also been

reported35. Some workers36-38 have studied conductance of chloro acetic acid and tartaric

acid. Yecid et al reported conductance of potassium sulphate in water-1-propanol systems

at different temperatures39. The conductance of binary mixtures of some ionic liquids



have also been studied40,41. Bester-Rogac42 has reported conductometric data of salicylate,

naproxen, diclofenac and ibuprofen in dilute aqueous solutions.

In our laboratory, conductance of some synthetic compounds43-45 has also been

studied.

Thus, in the present section conductance of all the synthesized tetrahydro

pyrimidine was measured in DMF and THF solutions at 303.15 K, over a wide range of

concentration.



EXPERIMENTAL

The solvents DMF and THF were purified by fractionally distillation by the

method reported in the literature46

.

The solutions of different concentrations were prepared for each compound in

DMF and THF and the conductance of each solution was measured by using Elico

Conductivity Meter (Model No.CM 180) at 303.15 K.

At 303.15 K, the cell constant was determined by measuring the conductance of

0.01N KCl solution and its value was found to be 0.89 cm-1.

The measured conductance was corrected by subtracting the conductance of pure

solvent.




The measured conductance (k) of each solution after correction was used to

determine the specific conductance (κ), which is then used for the calculation of

equivalent conductance (λc).

The equations used for calculating specific conductance (κ) and equivalent

conductance (λc) are:

k … (3.6.1)

1000c C

… (3.6.2)

where θ is the cell constant and c is the concentration (g.equi./lit.) of solution. The cell

constant θ was 0.89 cm-1.

The equivalent conductance values of tetrahydropyrimidine derivatives in both

DMF and THF solutions are reported in Tables 3.6.1 and 3.6.2 along with measured

conductance (k).

It is observed that conductance is lower in THF solutions than that in DMF

solutions. The lower conductivities of THF solutions may be due to greater electro

relaxation effect owing to the higher permittivity of THF, which contributes inter ionic

repulsions to a larger extent.

Figures 3.6.1 and 3.6.2 show the variation of conductance with concentration for

all the compounds in DMF and THF solutions respectively. It is observed that for all the

compounds, conductance increases nonlinearly with concentration. However, at lower

concentrations, variation is linear.

The equivalent conductance (λc) is plotted against √C for all compounds in both

the solvents as shown in Figures 3.6.3 and 3.6.4. In DMF solutions (as shown in Figure

3.6.3), equivalent conductance increases with dilution. For most of the compounds,

compounds, the nature of graph shows weak electrolytic behavior in DMF solutions.

For weak electrolytes, it is difficult to determine λ0. However, in some solutions,

λ0 values are evaluated by extrapolation method. For compounds PAB-101, PAB-102 and

PAB-104, λ0 value cannot be evaluated by extrapolation.



Figure 3.6.4 shows that in THF solutions, for PAB-103 and PAB-109, equivalent

conductance increases with dilution in the beginning but after √C =0.15, it starts

decreasing. Similar behavior was observed by other workers47 in DMSO solutions. The

reason is not clear. For other compounds, equivalent conductance increases with dilution

In this case also; most of the compounds, exhibit weak electrolytic nature. The λ0 value

was evaluated by extrapolation except for compounds PAB-103, PAB-105, PAB-108 and

PAB-109.

These λ0 values are compared with those determined by an alternate procedure

using the following equation47:

0 0 ck k c c … (3.6.3)

where k and k0 are the electrolytic conductivity of the solutions and solvent respectively.

c is the equivalent concentration and the function Φ(c) denotes the effect of interionic

interactions.

The limiting conductivity can be evaluated accurately from the limiting slope of

smaller linear portions of the curve of k verses c, provided other derivatives (dk0/dc) and

d[cΦ(c)]/dc in differential form of equation (3.6.3) are neglected as compared to λ0, which

can be determined from differential form of equation (3.6.3) is

0

0

cd cdkdk

dc dc dc

… (3.6.4)

These λ0 values are reported in Table 3.6.3 along with those determined by

extrapolation.

From Table 3.6.3.it is observed that in both the solvents, calculated values of

limiting equivalent conductance (λ0) are in fair agreement with those evaluated

graphically suggesting thereby that equation 3.6.3 can be used for the studied systems.



Table 3.6.1: The conductance (k) and equivalent conductance (C) of tetrahydropyrimidine derivatives in DMF at 303.15 K.

Conc. (gm/lit)

k.105

()-1C

(cm2/.equiv.)k.105

()-1C

(cm2/.equiv.)k.105

()-1C

(cm2/.equiv.)k.105

()-1C

(cm2/.equiv.)k.105

()-1C

(cm2/.equiv.)PAB-101 PAB-102 PAB-103 PAB-104 PAB-105

0.000 0.50 - 0.50 - 0.50 - 0.50 - 0.50 -

0.001 1.00 4.6000 1.10 5.5200 0.98 4.4160 1.19 6.3480 0.84 3.15560.002 1.36 3.9560 1.50 4.6000 1.39 4.0940 1.69 5.4740 1.02 2.39200.004 1.88 3.1740 1.90 3.2200 1.91 3.2430 2.05 3.5650 1.47 2.23100.006 2.42 2.9440 2.50 3.0667 2.47 3.0207 2.56 3.1587 1.84 2.05470.008 2.89 2.7485 3.00 2.8750 3.06 2.9440 3.09 2.9785 2.34 2.11600.010 3.38 2.6496 3.50 2.7600 3.32 2.5944 3.72 2.9624 2.63 1.95960.020 5.52 2.3092 5.60 2.3460 5.50 2.3000 6.32 2.6772 4.08 1.64680.040 9.64 2.1022 9.70 2.1160 9.50 2.0700 10.60 2.3230 8.30 1.79400.060 12.30 1.8093 13.00 1.9167 12.70 1.8707 15.80 2.3460 9.94 1.44750.080 15.80 1.7595 16.50 1.8400 16.80 1.8745 18.60 2.0815 12.20 1.34550.100 17.30 1.5456 18.90 1.6928 18.80 1.6836 20.30 1.8216 14.10 1.2512

PAB-106 PAB-107 PAB-108 PAB-109 PAB-110

0.001 0.69 3.8364 0.95 4.2136 0.96 4.2412 0.98 4.4712 0.78 2.63120.002 0.97 3.2154 1.31 3.7260 1.39 4.0940 1.41 4.1860 0.98 2.24020.004 1.51 2.8405 1.90 3.2200 2.10 3.6800 2.19 3.8870 1.39 2.04700.006 2.01 2.6603 2.37 2.8673 2.69 3.3580 2.79 3.5113 1.81 2.00870.008 2.44 2.4898 2.81 2.6565 3.29 3.2085 3.20 3.1050 2.20 1.94930.010 2.95 2.4610 3.19 2.4748 3.68 2.9256 3.89 3.1188 2.57 1.90440.020 5.09 2.2149 5.23 2.1758 6.69 2.8474 6.54 2.7784 4.20 1.70200.040 9.60 2.1448 9.61 2.0953 12.30 2.7140 12.40 2.7370 6.82 1.45360.060 14.10 2.1198 14.10 2.0853 16.20 2.4073 16.70 2.4840 9.11 1.38000.080 16.80 1.9027 17.50 1.9550 18.70 2.0930 19.50 2.1850 13.10 1.4490

0.100 20.40 1.8515 20.30 1.8188 20.80 1.8685 21.40 1.9228 16.40 1.4628



Table 3.6.2: The conductance (k) and equivalent conductance (C) of tetrahydropyrimidine derivatives in THF at 303.15 K.

Conc.(gm/lit)

k.106

()-1C

(cm2/.equiv.)k.106

()-1C

(cm2/.equiv.)k.106

()-1C

(cm2/.equiv.)k.106

()-1C

(cm2/.equiv.)k.106

()-1C

(cm2/.equiv.)PAB-101 PAB-102 PAB-103 PAB-104 PAB-105

0.000 0.17 - 0.17 - 0.17 - 0.17 - 0.17 -

0.001 0.37 0.1780 0.37 0.1780 0.24 0.0623 0.38 0.1869 0.31 0.1246

0.002 0.55 0.1691 0.53 0.1602 0.31 0.0623 0.59 0.1856 0.45 0.1233

0.004 0.91 0.1647 0.86 0.1535 0.42 0.0556 0.97 0.1769 0.72 0.12170.006 1.26 0.1617 1.18 0.1498 0.50 0.0490 1.23 0.1577 0.83 0.09790.008 1.58 0.1569 1.48 0.1457 0.64 0.0523 1.51 0.1491 0.94 0.08540.010 1.82 0.1469 1.79 0.1442 0.80 0.0561 1.66 0.1329 1.03 0.07680.020 3.01 0.1264 2.99 0.1255 1.80 0.0725 2.64 0.1100 1.51 0.05980.040 3.99 0.0850 4.55 0.0975 2.78 0.0581 3.93 0.0837 2.69 0.05610.060 4.21 0.0599 5.47 0.0786 3.40 0.0479 4.25 0.0605 3.41 0.04810.080 4.38 0.0468 6.71 0.0728 4.20 0.0448 4.96 0.0533 4.28 0.04570.100 4.66 0.0400 7.57 0.0659 5.42 0.0467 5.54 0.0478 5.06 0.0435

PAB-106 PAB-107 PAB-108 PAB-109 PAB-110

0.001 0.24 0.0623 0.31 0.1246 0.23 0.0534 0.22 0.0445 0.24 0.0623

0.002 0.30 0.0579 0.44 0.1215 0.30 0.0579 0.30 0.0579 0.30 0.0579

0.004 0.42 0.0556 0.68 0.1128 0.34 0.0378 0.52 0.0779 0.42 0.05560.006 0.50 0.0490 0.85 0.1003 0.40 0.0341 0.80 0.0935 0.50 0.04900.008 0.60 0.0478 0.97 0.0884 0.43 0.0289 1.14 0.1079 0.62 0.05010.010 0.64 0.0418 1.10 0.0828 0.50 0.0294 1.40 0.1095 0.70 0.04720.020 1.10 0.0414 1.61 0.0641 0.72 0.0245 3.10 0.1304 1.02 0.03780.040 1.62 0.0323 2.21 0.0455 1.10 0.0207 4.90 0.1052 1.72 0.03450.060 2.10 0.0286 2.85 0.0398 1.50 0.0197 6.50 0.0939 2.30 0.03160.080 2.44 0.0253 3.43 0.0363 1.74 0.0175 7.29 0.0792 2.72 0.02840.100 2.80 0.0234 3.53 0.0299 2.02 0.0165 8.40 0.0732 3.02 0.0254

Section-VI

Department of Chemistry, Saurashtra University,

Figure 3.6.1: The variation of conductance with concentration for

tetrahydropyri

0.0

5.0

10.0

15.0

20.0

25.0

0

co

nd

uc

tan

ce10

5(m

ho

)

PAB-

0.0

5.0

10.0

15.0

20.0

25.0

0

con

du

ctan

ce10

5(m

ho

)

PAB

VI Conductance


The variation of conductance with concentration for

tetrahydropyrimidine derivatives in DMF at 303.15 K.

0.02 0.04 0.06 0.08

Concentration (M)

[A]

-101 PAB-102 PAB-103 PAB-104

0.02 0.04 0.06 0.08

Concentration (M)

[B]

PAB-106 PAB-107 PAB-108 PAB-109

Conductance

208

The variation of conductance with concentration for

.15 K.

0.1

PAB-105

0.1

PAB-110

Section-VI



tetrahydropyrimidine derivatives

0.0

0.2

0.4

0.6

0.8

1.0

-1.53E-1

con

du

cta

nce

105

(mh

o)

PAB-101

0.0

0.2

0.4

0.6

0.8

1.0

0

Co

nd

uct

ance

105 m

ho

PAB 106

VI Conductance


The variation of conductance with concentration

tetrahydropyrimidine derivatives in THF at 303.15 K.

0.02 0.04 0.06 0.08

Concentraction (M)

[A]

101 PAB-102 PAB-103 PAB-104

0.02 0.04 0.06 0.08

Concentration (M)

[B]

PAB 106 PAB 107 PAB 108 PAB 109

Conductance

209

conductance with concentration for

.15 K.

0.1

PAB-105

0.1

PAB 110

Section-VI


Figure 3.6.3: The variation of equivalent conductance tetrahydropyrimidine derivatives

VI Conductance


The variation of equivalent conductance with √C for etrahydropyrimidine derivatives in DMF at 303.15 K.

Conductance

210

for



Figure 3.6.4: The variation of equivalent conductance with √C for tetrahydropyrimidine derivatives in THF at 303.15 K.



Table 3.6.3: The limiting equivalent conductance (λ0) of tetrahydropyrimidine derivatives in DMF and THF at 303.15 K.

CompoundCode

λ0

mho.cm2.equi.-1

from graph

λ0103

mho.cm2.equi.-1

from eq. (3.4.4)

λ0

mho.cm2.equi.-1

from graph

λ0103

mho.cm2.equi.-1

from eq. (3.4.4)DMF THF

PAB-101 - 4.874 0.205 0.197PAB-102 - 5.811 0.200 0.190PAB-103 5.950 4.904 - 0.050PAB-104 - 6.648 0.184 0.220PAB-105 4.250 3.081 - 0.198PAB-106 5.550 3.918 0.049 0.072PAB-107 5.650 4.575 0.158 0.161PAB-108 4.950 4.520 - 0.063PAB-109 5.550 4.789 - 0.075PAB-110 3.250 2.792 0.070 0.069



REFERENCES

1. Eutech Instruments - A leader in the field of electrochemical instrumentation,

1997

2. Application data sheet, “Theory and application of conductivity” ADS43

018/rev. B, August 2004

3. Levitt, L. S.; “Determination of the dissociation constant and limiting equivalent

conductance of a weak electrolyte from conductance measurements on the weak

electrolyte” Anal. Chim. Acta. 1981, 125, 219-220.

4. Tang, L. and Huber, C. O.; “Electroosmotic flow and injection: application to

conductometry” Talanta 1994, 41(10), 1791-1795.

5. Kargov, S. I. and Davydova, O. V.; “Application of conductometry for studying

conformational changes in polyelectrolytes in aqueous solutions” Russ. J. Phys.

Chem. 2005, 79, S81-S85.

6. Baghalha, M. and Papangelakis, V. G.; “High-Temperature Conductivity

Measurements for Industrial Applications” Ind. Eng. Chem. Res. 2000, 39, 3640-

3645.

7. Law, W. S.; Kubán, P.; Zhao, J. H.; Yau Li, S. F. and Hauser, P. C.;

“Determination of vitamin C and preservatives in beverages by conventional

capillary electrophoresis and microchip electrophoresis with capacitively coupled

contactless conductivity detection” Electrophoresis 2005, 26, 4648–4655.

8. Berezovskaia, G. E. and Korytnyi, V. S.; “Role of polarization processes near

electrodes during the measurement of the electrical conductivity of biological

objects.” Biofizika 1968, 13(3), 524-528.

9. De, L. J.; Berard, A. and Grabowski, B.; “Hybrid paraconductors: a new class of

components obtained by bionic synthesis, Application to analog memories and to

conductors of biological processes” Elec. Ther. 1977, 14(1), 19-25.

10. Vybornova, I. I.; Goltsov, A. N.; Yepifanov, S. Y.; Kadantsev, V. N. and

Krasilnikov, P. M.; “Modeling of mechanisms of influence of thermal and

anthropogenic chemical factors on the functioning of biological membranes.” Fiz.

Cheloveka 1994, 20(6), 124-136.

11. Canizares, P.; Beteta, A.; Saez, C.; Rodriguez, L. and Rodrigo, M. A.; “Use of

electrochemical technology to increase the quality of the effluents of bio-oxidation

processes. A case studied” Chemosphere 2008, 72(7), 1080-1085.



12. Grudpan, K.; Kamfoo, K. and Jakmunee, J.; “Flow injection spectrophotometric

orconductometric determination of ascorbic acid in a vitamin C tablet using

permanganate or ammonia” Talanta 1999, 49(5),1023-1026.

13. Ahmed, M. K.; Geetha, R.; Pandey, N. K.; Murugesan, S.; Koganti, S. B.; Saha,

B.; Sahoo, P. and Sundararajan, M. K.; “Conductometric determination of carbon

in uranium carbide and its solution in nitric acid” Talanta 2000, 52(5), 885-892.

14. Johansen, C.; Bredtved, B. K. and Moller, S.; “Use of conductance measurements

for determination of enzymatic degradation of microbial biofilm” Methods in

Enzymology 1999, 310, 353-361.

15. Bracko, S. and Span, J.; “Conductometric investigation of dyesurfactant ion pair

formation in aqueous solution” Dyes and Pigments 2000, 45(2), 97-102.

16. Myllyniemi, A. L.; Sipila, H.; Nuotio, L.; Niemi, A. A. and Honkanen, B. T.; “An

indirect conductimetric screening method for the detection of antibiotic residues in

bovine kidneys” Analyst 2002, 127(9), 1247-1251.

17. Apelblat, A.; “An analysis of the conductances of aqueous malonic acid.” J. Mol.

Liq. 1997, 73-74, 49-59.

18. Syal, V. K.; Chauhan, S. and Gupta, P. K.; “Conductance and viscosity studies of

some univalent electrolytes in water, dimethyl sulfoxide and water + dimethyl

sulfoxide mixtures at different temperatures.” J. Ind. Chem. Soc. 2002, 79(11),

860-865.

19. Naderi, A.; Claesson, P. M.; Bergstroem, M.; and Dedinaite, A.; “Trapped

nonequilibrium states in aqueous solutions of oppositely charged polyelectrolytes

and surfactants: effects of mixing protocol and salt concentration.” Phy. Eng. Asp.

2005, 253(1-3), 83-93.

20. Stasiewicz, W. A.; Szejgis, A.; Chmielewska, A. and Bald, A.; “Conductance

studies of NaBPh4, NBu4I, NaI, NaCl, NaBr, NaClO4 and the limiting ionic

conductance in water + propan-1-ol mixtures at 298.15 K” J. Mol. Liq. 2007,

130(1–3), 34-37.

21. Shcherbakov, V. V.; Artemkina, Y. M. and Ponamareva, T. N.; “Electric

conductivity of concentrated aqueous solutions of propionic acid, sodium

propionate and their mixtures.” Russ. J. Elec. 2008, 44(10), 1185-1190.

http://www.sciencedirect.com/science/article/pii/S0167732206001383





22. Shekaari, H. and Mousavi, S. S.; “Conductometric studies of aqueous ionic

liquids, 1-alkyl-3-methylimidazolium halide, solutions at T = 298.15–328.15 K”

Fluid. Phase Equi. 2009, 2862, 120-126.

23. Shekaari, H. and Jebali, F.;”Densities and electrical conductances of amino

acids + ionic liquid ([HMIm]Br) + H2O mixtures at 298.15 K” Fluid. Phase Equi.

2010, 295(1), 68-75.

24. Yan, Z.; Li, W.; Zhang, Q.; Wang, X. and Wang, J.; “Effect of sodium caproate

on the volumetric and conductometric properties of glycyl-L-glutamine and L-

alanyl-L-glutamine in aqueous solution at 298.15 K” Fluid. Phase Equi. 2011,

301(2), 156-162.

25. Chen, Y. J.; Xuan, X. P.; Zhang, H. H. and Zhuo K. L.; “Conductivities of 1-

alkyl-3-methylimidazolium chloride ionic liquids in monosaccharide + water

solutions at 298.15 K” Fluid Phase Equi. 2012, 316, 164-171.

26. Ghasemi, J. and Shamsipur, M.; “Conductance study of some transition and heavy

metal complexes with 1,10-diaza-18-crown-6 in binary acetonitrile dimethyl

sulfoxide mixtures.” J. Sol. Chem. 1996, 25(5), 485-504.

27. Jauhar, S. P. and Sandhu, S.; “Conductance and viscosity measurements of some

1:1 electrolytes in dimethylformamide + methanol mixtures at 25, 30 and 40°C.”

Ind. J. Chem. 2000, 39(4), 392-399.

28. Ozeroglu, C. and Sarac, A.; “Potentiometric and conductometric measurements of

dicarboxylic acids in non-aqueous solvents.”Asian J. Chem. 2006, 18(3), 1808-

1814.

29. Arjomandi, J. and Holze, R.; “In situ characterization of N-methylpyrrole and

(Nmethylpyrrole-cyclodextrin) polymers on gold electrodes in aqueous and non

aqueous solution.” Syn. Met. 2007, 157(24), 1021-1028.

30. Rounaghi, G. H.; Mohajeri, M.; Soruri, F. and Mohamadzadeh Kakhki, R.;

“Solvent Influence upon Complex Formation between Dibenzo-18-crown-6 with

the Y3+ Metal Cation in Pure and Binary Mixed Organic Solvents” J. Chem. Eng.

Data. 2011, 56 (6), 2836–2840.

31. Boruń, A. and Bald, A.; “Conductometric Studies of 1-Ethyl-3-

methylimidazolium Tetrafluoroborate and 1-Butyl-3-methylimidazolium

Tetrafluoroborate in N,N-Dimethylformamide at Temperatures from (283.15 to

318.15) K” J. Chem. Eng. Data. 2012, 57(2), 475–481.











http://pubs.acs.org/doi/abs/10.1021/je101341y?prevSearch=conductometric&searchHistoryKey=

http://pubs.acs.org/doi/abs/10.1021/je101341y?prevSearch=conductometric&searchHistoryKey=



32. Liu, J.; Masuda, Y. and Sekido, E. “A conductance study of macrocyclic Schiff

base metal (II) complexes in methanol.” Bull. Chem. Soc. Jap. 1990, 63, 2516-

2520.

33. Morita, M.; Fujisaki, T.; Yoshimoto, N. and Ishikawa, M.; “Ionic conductance

behavior of polymeric composite solid electrolytes containing lithium aluminate”

Electrochim. Acta 2001, 46, 1565-1569.

34. Kabir-ud-Din, A. A.; Mohammed, D. A.; Naqvi, A. Z. and Akram, M.;

“Conductometric study of antidepre ssant drug-cationic surfactant mixed micelles

in aqueous solution, Colloids and Surfaces.” Biointerfaces 2008, 64, 65-69.

35. Taher, A.; Mohsin, M. and Farooqui , M.;“Density, viscosity and conductance

measurement of pyrazinamide in aqueous solution in presence and absence of

additives at 308.15 K.” J. Ind. Chem. Soc. 2011, 88 (7), 959-962.

36. Niazi, M. S. K.; “Conductivities and Thermodynamic Dissociation Constants for

Chloroacetic Acid in Binary Mixed Solvent Systems at 298.15 K.” J. Chem. Eng.

Data 1993, 38, 527-530.

37. Bhat, I, J. and Shetty, K. M.; “Ion Association and Solvation of Sulfathiazole

Sodium in Aqueous and Partial Aqueous Media J. Chem. Eng. Data 2010, 55,

4721–4724.

38. Bhat, I, J. and Shivakumar, H. R.; “Conductometric studies on the solvation

bahaviour of tartaric acid in various solvent mixtures” J. Mol. Liq. 2004, 111,

101–108.

39. Yecid, P. J.; Taboada, M. E.; Flores, E. K. and Galleguillos, H. R.; “Density,

Viscosity, and Electrical Conductivity in the Potassium Sulfate + Water + 1-

Propanol System at Different Temperatures.” J. Chem. Eng. Data 2009, 54,

1932-1934.

40. Ren, R.; Zuo, Y.; Zhou, Q.; Zhang, H. and Zhang, S.; “Density, Excess Molar

Volume and Conductivity of Binary Mixtures of the Ionic Liquid 1,2-Dimethyl-3-

hexylimidazolium Bis(trifluoromethylsulfonyl)imide and Di methyl Carbonate” J.

Chem. Eng. Data 2011, 56(1), 27–30.

41. Fox, E. T.; Weaver, J. E. and Henderson, W. A.; “Tuning Binary Ionic Liquid

Mixtures: Linking Alkyl Chain Length to Phase Behavior and Ionic Conductivity”

J. Phys. Chem. C, 2012, 116 (8), 5270–5274.



42. Bester-Rogac, M.; “Nonsteriodal Anti-Inflammatory Drugs Ion Mobility: A

Conductometric Study of Salicylate, Naproxen, Diclofenac and Ibuprofen Dilute

Aqueous Solutions. Acta Chim. Slov., 2009, 56, 70–77.

43. Baluja, S.; “Physicochemical studies of some Schiff bases derived from 6

ethylbenzene-1,3-diol.” E- J. Chem. 2004, 1, 199-205.

44. Baluja, S.; Kasundra, P. and Vekariya, N.; “Physicochemical studies of some

azomethines of 5-amino isophthalic acid in solutions of DMF and DMSO at

308.15 K.” Int. J. Chem. Sci. 2009, 7, 533-538.

45. Baluja, S.; Patel, A. and Movalia, J.; “A study of physicochemical properties of

some azomethines of vanillin”, Ife J. Sci., 2011, IV, 46-53.

46. Riddick, J. A., Bunger, W. B. and Sakano, T.; Organic Solvents-Physical

Properties and Methods of Purification, Fourth Edition., Techniques of

Chemistry, II, A Wiley-Interscience Publication, John Wiley, New York (1986).

47. Singh, M. and Prasad, B. B.; Electrolytic conductivity of the N-chloranil- and N-

xylylene-based polyelectrolytes in dimethylformamide and dimethyl sulfoxide, J.

Chem. Eng. Data, 1996, 41, 409.

http://pubs.acs.org/doi/abs/10.1021/je9501907?prevSearch=M.%2BSingh%2Band%2BB.%2BB.%2BPrasad&searchHistoryKey=

http://pubs.acs.org/doi/abs/10.1021/je9501907?prevSearch=M.%2BSingh%2Band%2BB.%2BB.%2BPrasad&searchHistoryKey=

Section-VII

Partition coefficient

Section-VII Partition coefficient


INTRODUCTION

General explanation of the partition coefficient or distribution coefficient is the

ratio of concentrations of a substance in the two phases of a mixture of two immiscible

solvents at equilibrium1. These coefficients have been a measure of differential solubility

of the substance between two solvents of different polarity. Partition coefficient finds

enormous applications in the various fields of general science research2, medical science3,

research related to environment4, 5 as well as industry6. Klooster et al have made very

delicious research by checking air-liquid partition coefficient of aroma volatiles in

different ice cream flavors7. So, partition coefficient also a matter of interest in food

industries too.

Literature survey shows that partition study of compound creates high interest in

medicinal or pharmaceutical chemistry research because in pharmacokinetics, the

distribution coefficient has a strong influence on ADME properties (Absorption,

Distribution, Metabolism, and Excretion) of the drug8. Whereas in Pharmacodynamics,

the hydrophobic effect is the major driving force for the binding drugs to their receptor

targets9, 10. Partition coefficient is a most crucial parameter of QSAR and QSPR study11-

13.

The knowledge of solubility and the octanol-water partition coefficient of a drug

is important in drug discovery, development, and manufacturing14-17. Latest technology

has made this study easy and versatile. Specifically UV-visible spectroscopy18-22 and gas

chromatography are sophisticated tools to study partition function23-25. Reiner et al. have

used HPLC for determination of partition coefficient26 in phenols. Leithner et al. have

studied the brain-blood partition phenomenon by using MRI27. Ward et al. have compared

different chromatographic methods for estimating octanol-water partition coefficient28.

The distribution between water and an immiscible nonpolar solvent is

acknowledged as a useful measure for the hydrophobicity of a substance. Hydrophobicity

is the association of non-polar groups or molecules in an aqueous environment which

arises from the tendency of water to exclude non-polar molecules. n-Octanol and water

are widely accepted as the best two-phase system to study partition coefficient between

biomass and water. Relationships between the partition coefficient of this system and

bioconcentration29-32, soil sorption33-35 and toxicity36-38 for fish have also been found.

Literature survey shows that various workers have studied partition coefficient of drugs39,

organic compounds40-42, aminoacids43, and flavanoids44.

http://en.wikipedia.org/wiki/Concentration

http://en.wikipedia.org/wiki/Immiscible

http://en.wikipedia.org/wiki/Solvent

http://en.wikipedia.org/wiki/Partition_equilibrium

http://en.wikipedia.org/wiki/Partition_coefficient#cite_note-Leo-0

http://en.wikipedia.org/wiki/Solubility

http://en.wikipedia.org/wiki/ADME

http://en.wikipedia.org/wiki/Distribution_(pharmacology)

http://en.wikipedia.org/wiki/Metabolism



In the present study, partition coefficients of synthesized tetrahydropyrimidine

derivatives (PAB-101-PAB-110) have been studied in n-Octanol-water system by UV

spectroscopy at different pH.



EXPERIMENTAL

n-Octanol is of analytical grade. The purity of solvent was checked by GC and

found to be 99.8%. Distilled water was used throughout for all experiments.

Preparation of standard solution:-

10 mg sample was dissolved in n-octanol to give 100 ml solution of 100

ppm. This solution was known as standard solution. Suitable dilutions were made from

this standard solution (2 g to 20 g).

Measurement:-

For the solution of each compound in octanol, absorbance (OD) was

measured at different wavelengths (λ) using UV spectrophotometer (Shimadzu, UV-1700,

Pharmaspec) to determine λmax. Solutions of different concentrations were prepared in

octanol for each compound and absorbance was measured at respective λmax to get

calibration curve.

A known amount of the compound under investigation was dissolved in n-octanol

at a concentration not higher than 20 g. Equal volumes of this solution and water is

mixed in oven dried stoppered flask and the mixture was stirred for 24 hrs. at room

temperature. After 24 hrs, the solution was transferred into 60 ml of separating funnel and

allowed to stand in order to separate the aqueous and organic layers. The organic layer

will be upper one while lower will be aqueous. The organic layer was then analyzed by

UV spectrophotometer. Using calibration curve, the concentration of compounds in

organic layer was then evaluated.

In the present study, partition coefficients of tetra hydropyrimidines have been

studied in n-octanol-water system by UV spectroscopy at different pH. The partition

coefficient is highly influenced by pH. So, in the present study, a wide range of pH (0.84

to 8.0) is selected. For 0.84 pH, 0.1 N HCl was taken whereas for 6.0, 7.4 and 8.0,

phosphate buffer was used. These values of pH are selected due to their existence in

human body. As HCl exists in gastric juice in stomach45, 0.1 N HCl is taken. Blood46 has

7.4 pH, so the study is done at pH 7.4. Further, the middle and upper range of body pH is

6.0 and 8.0 respectively, so study was done at these all pH also.



THEORY

Partition coefficient (P) is defined as the ratio of the compounds in organic phase

to that present in the aqueous phase. i.e.,47

org

aq

CP

C …(3.7.1)

where Corg and Caq are concentration of solute in organic and aqueous phases respectively.

In the present case, concentrations were determined by UV measurement so,

equation (3.5.1) written as48:

E

E E

BP

B A

… (3.7.2)

where BE= Absorbance before extraction and AE=Absorbance after extraction.

From equation (3.5.2) log P were calculated for each set of experiment.




The log P values for the studied compounds at different pH are given in Table

3.7.2. The log P value depends upon the hydrophilic and hydrophobic character of

compounds and has inverse relation with hydrophilicity of compounds.

Table 3.7.2 shows that log P varies with pH. However, no regular pattern

is observed. The variation of log P with pH for all the studied compounds is also shown in

Figure 3.7.2. It is clear from Figure 3.7.2 that PAB-110 shows maximum hydrophobicity

almost in all pH. It is followed by PAB-106. PAB-107 is found to have minimum log P

for almost all pH range in comparison to other compounds suggesting thereby its highly

hydrophilic character. Further, for all the compounds, log P values are higher for 0.1 N

HCl i.e., at minimum pH.

All the studied compounds have the same central moiety but different side chains

i.e, substituents, as shown in Table 3.7.1. Thus the hydrophobic or hydrophilic character

of a compound depends not only on pH but also on substituent. As reported in Table

3.7.1, PAB-110 has hydroxy group at para position whereas PAB-108 has methoxy group

at para position. Thus, the presence of hydroxy group increases the hydrophobicity (as in

PAB-110) in comparison to methoxy (as in PAB-106). However, when both methoxy

and hydroxyl groups are present (as in the case of PAB-108), hydrophobic character is in

between PAB-106 and PAB-110). It means lower hydrophobicity. From this observation

one can assumes that if -OCH3 and –OH both are present in the same compound, it

increases the polar (hydrophilic) character in the solution due to presence of two

electronegative oxygen atoms. Thus, the substitution in compound plays a major role in

the nature of solution.

Further, the position of functional group is also important in the hydrophobic-

hydrophilic character of the compound. In PAB-104, chloro group is present at the para

position which gives least log P while for PAB-103, log P values are quite high in

comparison to PAB-104 although it also has chloro group but at meta position. Other

noticeable matter in this study is that PAB-104 and PAB-105 shows almost same

behavior. PAB-104 contains chloro group at para position whereas PAB-105 contains

fluoro group at para position. This suggests that at the same position, effect due to the

presence of difference halogens is negligible.



Overall observation shows that all compounds exhibit higher hydrophobic

character in acidic pH. In some compounds, higher hydrophobic character is also

observed in water. At higher basic solutions, almost all compounds show higher

hydrophilic character.

Figure 3.7.1: General structure of tetrahydropyrimidine derivatives

Where R=side chain

Table 3.7.1: Different side chains present in tetrahydropyrimidine derivatives

Table 3.7.2: log P values for tetrahydropyrimidine derivatives

CompoundsCode

Max absorptionWavelength (nm)

log PWater 0.1N HCl 6.0 pH 7.4 pH 8.0 pH

PAB-101 308 0.1636 0.4223 0.1741 0.1415 0.1153

PAB-102 350 0.4658 0.8044 0.6443 0.5445 0.2190

PAB-103 230 0.1504 1.1841 0.9550 0.5790 0.0989

PAB-104 318 0.1320 0.5506 0.1699 0.1818 0.0647

PAB-105 314 0.1135 0.5509 0.2452 0.1341 0.1722

PAB-106 350 0.8314 1.2556 0.9315 0.8771 0.7994

PAB-107 292 0.1449 0.2152 0.1063 0.1388 0.1637

PAB-108 382 0.7814 0.9327 0.8402 0.7244 0.5553

PAB-109 342 0.6210 0.6617 0.5689 0.5607 0.4537

PAB-110 360 1.0009 1.0283 0.9333 0.8618 0.7948

Code R Code RPAB-101 C6H5- PAB-106 4-OCH3-C6H4-PAB-102 C6H4-CH=CH- PAB-107 3-NO2-C6H4-

PAB-103 3-Cl-C6H4- PAB-108 4-OH-3-OCH3-C6H4-PAB-104 4-Cl-C6H4- PAB-109 4(α-C4H3O)-PAB-105 4-F-C6H4- PAB-110 4-OH-C6H4-

N

HN

R

NH2

CN

H2N

Section-VII


Figure 3.7.2: log P values for tetrahydropyrimidine

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

PAB 101 PAB 102 PAB 103

log

P

VII Partition coefficient

y, Saurashtra University, Rajkot-360005 224

etrahydropyrimidine derivatives.

PAB 103 PAB 104 PAB 105 PAB 106 PAB 107 PAB 108

Compounds

Water 0.1N HCl 6.0 pH 7.4 pH 8.0 pH

PAB 108 PAB 109 PAB 110

8.0 pH



REFERENCES

1. Leo, A.; Hansch, C. and Elkins, D.; “Partition coefficients and their uses” Chem.

Rev. 1971, 71 (6), 525–616.

2. Wolf, E.; Riccomagno, E.; De Pater, J.; Deelman, B. and Koten, G.; “Parallel

Synthesis and Study of Fluorous Biphasic Partition Coefficients of 1H,1H,2H,2H-

Perfluoroalkylsilyl Derivatives of Triphenylphosphine: A Statistical Approach” J.

Comb. Chem. 2004, 6, 363-374.

3. Engel, L.; Alexander, J.; Carter, P.; Elliott, J. and Weester, M.; “Relations

between Phase Composition and Partition Coefficients for Some Neutral Steroids

A Nomographic Approach” Anal.Chem. 1954, 26(4), 639-641.

4. Miller, M.; and Waslk, S.; Huang, G.; Shlu, T. and Mackay, D.; “Relationships

between Octanol-Water Partition Coefficient and Aqueous Solubility” Environ.

Sci. Technol. 1985, 19(6), 522-529.

5. Wenhung, H.; Fuhlin, T. and Chiou, C.; “Partition Coefficients of Organic

Contaminants with Carbohydrates” Environ. Sci. Technol. 2010, 44, 5430–5436.

6. Lidgate, D.; Brandl, M,; holper, M.; Abubakari, A. and Wu, X.; “Influence of

Ferrous Sulfate on the Solubility, Partition Coefficient, and Stability of

Mycophenolic Acid and the Ester Mycophenolate Mofetil” Drug. Dev. Ind.

Pharm. 2002, 28(10), 1275-1283.

7. Klooster J.; Ciledruaux, C. and Vreeker, R.; “AirLiquid Partition Coefficients of

Aroma Volatiles in Frozen Sugar Solutions” J. Agri. Food Chem. 2005, 53, 4503-

4509.

8. Kubinyi, H.; “Nonlinear dependence of biological activity on hydrophobic

character: the bilinear model” Farmaco Sci. 1979, 34 (3), 248–276.

9. Eisenberg, D. and McLachlan, A.; “Solvation energy in protein folding and

binding” Nature 1986, 319, 199–203.

10. Miyamoto, S. and Kollman, P.; “What determines the strength of noncovalent

association of ligands to proteins in aqueous solution?” Proc. Natl. Acad. Sci.

1993, 90(18), 8402–8406.

11. Dashtbozorgi , Z. and Golmohammadi, H.; “Prediction of air to liver partition

coefficient for volatile organic compounds using QSAR approaches” Eur J. Med.

Chem. 2010, 45, 2182–2190.



12. Posa, M.; Pilipovi, A.; Lali, M. and Popovi, J.; “Determination and importance of

temperature dependence of retention coefficient (RPHPLC) in QSAR model of

nitrazepams partition coefficient in bile acid micelles” Talanta 2011, 83, 1634–

1642.

13. Toropov, A.; Toropova, A.; Raska, I. and Benfenati, E.; “QSPR modeling of

octanol/water partition coefficient of antineoplastic agents by balance of

correlations” Eur. J. Med. Chem. 2010, 45,1639–1647.

14. Modarresi, H.; Conte, E.; Abildskov, J.; Gani, R. and Crafts, P.; “Model-based

calculation of solid solubility for solvent selection” A review. Ind. Eng. Chem.

Res. 2008, 47, 5234–5242.

15. Constable, D.;Jimenez-Gonzalez, C. and Henderson, R.; “Perspective on solvent

use in the pharmaceutical industry” Org. Process; Res. Dev. 2007, 11, 133–137.

16. Chieh-Ming, H.; Shu, Wang.; Shiang-Tai, L. and Stanley S,; “A Predictive Model

for the Solubility and Octanol-Water Partition Coefficient of Pharmaceuticals” J.

Chem. Eng. Data. 2011, 56(4), 936-945.

17. Jorgensen, W.; “The many roles of computation in drug discovery” Science 2004,

303, 1813–1818.

18. Lin H.; Xiaoying, L.; Mugan, Ding.; Xiaofen,Ye.; Jingmin, L.; Jiahui, G.;

Zhitang, L. and Guohui, L.; “Determination of equilibrium solubility and apparent

oil/water partition coefficient of silymarin” Guangdong Yaoxueyuan Xuebao

2011, 27(5), 445-449.

19. Xiuxia, L.; Lin, H.; Li, Chen.; Weiang, W.; Ruibiao, S. and Xiaoying, L.;

“Determination of equilibrium solubility and oil-water partition coefficient of

scutellarin” Guangdong Yaoxueyuan Xuebao 2011, 27(1), 1-4.

20. Ming-ming, W.; “Determination of the oil-water partition coefficient of

hymecromone by UV spectrophotometry” Anhui Nongye Kexue 2010, 38(22),

11985-11986.

21. Song, G.; Han, L.; Fang, F.; Zhiqiang, H.; Guifeng D. and Xiang, L,;

“Determination of the partition coefficient and its significance of telmisartan”

Yaowu Fenxi Zazhi 2007, 27(11), 1704-1706.

22. Lavinia, U.; Szabadai, Z.; Vlaia, V. and Miclea, L.; “Spectrophotometric

determination of piroxicam partitioning coefficient in paraffin oil/water binary



system for different pH values of the aqueous phase” Farmacia 2005, 53(1), 112-

119.

23. Acree, W.; Baker, G.; Mutelet, F.; and Moise, J.; “Partition Coefficients of

Organic Compounds in Four New Tetraalkylammonium

Bis(trifluoromethylsulfonyl)imide Ionic Liquids Using Inverse Gas

Chromatography” J. Chem. Eng. Data. 2011, 56, 3688–3697.

24. Mutelet, F.; Laure Revelli, A.; Jaubert, J.; Sprunger, L.; Acree, W. and Baker, G.;

“Partition Coefficients of Organic Compounds in New Imidazolium and

Tetralkylammonium Based Ionic Liquids Using Inverse Gas Chromatography” J.

Chem. Eng. Data. 2010, 55, 234–242.

25. Revelli, A.; Mutelet, F. and Jaubert, J.; “Partition coefficients of organic

compounds in new imidazolium based ionic liquids using inverse gas

chromatography” J. Chrom. A, 2009, 1216, 4775–4786.

26. Reiner, G.; Labuckas, D. and Garcia, D.; “Lipophilicity of some GABAergic

phenols and related compounds determined by HPLC and partition coefficients in

different systems” J. Pharma. Biomed. Ana. 2009, 49, 686–691.

27. Leithner C.; Muller, S.; Fuchtemeier, M.; Lindauer, U.; Dirnagl U. and Royl, G.;

“Determination of the brain–blood partition coefficient for water in mice using

MRI” J. Cerebral. Meta. 2010, 30, 1821–1824.

28. Ward, R.; Davies, J.; Hodges, G. and Roberts, D.; “Applications of immobilised

artificial membrane chromatography to quaternary alkylammonium sulfobetaines

and comparison of chromatographic methods for estimating the octanol–water

partition coefficient” J. Chrom. A, 2003, 1007, 67–75.

29. Zaroogian, G.; Heltshe, J. and Johnson, M.; “Estimation of bioconcentration in

marine species using structure-activity models” Environ. Toxi. Chem. 1985, 4(1),

3-12.

30. Nishihara, T.; Saito, S. and Matsuo, M.; “Mechanism in bioconcentration of

organic chemicals in fish and its structure-activity relationship” Japan. J. Toxi.

Enviro. Health 1993, 39(6), 494-508.

31. Dimitrov, S.; Mekenyan, O. and Walker, J.; “Non-linear modeling of

bioconcentration using partition coefficients for narcotic chemicals” SAR and

QSAR Enviro. Res. 2002, 13(1), 177-184.



32. Yang, Z. and Zeng, E.; “Comment on Bioconcentration Factor Hydrophobicity

Cutoff: An Artificial Phenomenon Reconstructed” Enviro. Sci. Tech. 2008,

42(24), 9449-9450.

33. Wallace, A. and Procopiou, J.; “A statistical analysis of crop responses to nitrogen

and phosphorus fertilizers in Greece.” Comm. Soil Sci. Plant Anal. 1982, 13(1), 7-

19.

34. Girvin, D. and Scott, A.; “Polychlorinated biphenyl sorption by soils:

measurement of soil-water partition coefficients at equilibrium” Chemosphere,

1997, 35(9), 2007-2025.

35. Franco, A. and Trapp, S.; “Estimation of the soil-water partition coefficient

normalized to organic carbon for ionizable organic chemicals” Enviro. Toxi.

Chem. 2008, 27(10), 1995-2004.

36. Zaroogian, G.; Heltshe, J. and Johnson, M.; “Estimation of toxicity to marine

species with structure-activity models developed to estimate toxicity to freshwater

fish” Aquatic Toxicol. 1985, 6(4), 251-270,

37. Saito, H.; Koyasu, J.; Shigeoka, T. and Tomita, I.; “Cytotoxicity of chlorophenols

to goldfish GFS cells with the MTT and LDH assays” Toxicology in Vitro, 1994,

8(5), 1107-1112.

38. Hay et al.; Jones, R.; Beaumont, K. and Kemp, M. “Modulation of the Partition

Coefficient between Octanol and Buffer at pH 7.4” Drug Metab Dispos. 2009, 37,

1864-1870.

39. Perillo, M.; “Determination of the membrane-buffer partition coefficient of

flunitrazepam, a lipophilic drug” J. Neuro. Meth. 1991, 36(2–3), 203–208.

40. Hilal, S.; Karickhoff, S. and Carreira, L.; “Prediction of the Solubility, Activity

Coefficient and Liquid/Liquid Partition Coefficient of Organic Compounds”

QSAR & Combi. 2004, 23(9),709–720.

41. Rich, P. and Harper, R.; “Partition coefficients of quinones and hydroquinones

and their relation to biochemical reactivity” Febs Lett. 1990, 269(1), 139–144.

42. Yamagami, C.; Takao, N. and Fujita, T.; “Partition coefficients of diazines” Prog.

Clin. Bio.Res. 1989, 291, 83-86

43. Libby, M. and Richard, D.; “Measurement and Correlation of Partition

Coefficients of Polar Amino Acids” Mole. Pharma.1981, 20 (3) 602-608.

http://www.sciencedirect.com/science/article/pii/0165027091900463

http://www.sciencedirect.com/science/article/pii/0165027091900463



http://onlinelibrary.wiley.com/doi/10.1002/qsar.v23:9/issuetoc




44. Joseph, A.; Rothwell, A.; Day, J. and Michael R.; “Experimental Determination of

Octanol−Water Partition Coefficients of Quercetin and Related Flavonoids” J.

Agric. Food Chem., 2005, 53(11), 4355–4360.

45. Pelfrêne, A.; Waterlot, C. and Douay, F.; “In vitro digestion and DGT techniques

for estimating cadmium and lead bioavailability in contaminated soils: Influence

of gastric juice pH” Sci. Enviro. 2011, 409, 5076– 5085.

46. Janjuaa, N.; Siddiqa, A.; Yaquba, A.; Sabahat,S.; Qureshi, R. and Haque S.;

“Spectrophotometric analysis of flavonoid–DNA binding interactions at

physiological conditions” Spectrochim. Acta Part A 2009, 74, 1135–1137.

47. Sawyer, Heniman and Beebe.; “Chemistry Experiments for Instrumental

Analysis” Willy 1984.

48. Jayshree, B.; Sahu, R.; Murthy.; M. and Venugopala, K.; “Synthesis determination

of partition coefficient and antimicrobial activity of triazole thiadiazinyl

bromocoumarin derivatives” Mat. Sci. Res. Ind. 2005, 3(2), 187-190.

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