infrared spectroscopic studies of some oxidative products ......in vitro studies showed that the...

International Journal of Chemistry; 2013[03] ISSN 2306-6415

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Infrared Spectroscopic Studies of Some Oxidative Products of Primaquine

S.N.Sinha1*

, V.K.Dua2 and H.Venkatakrishna-Bhatt

1

1National Institute of Occupational Health (NIOH), Meghani Nagar, Ahmedabad 380016, Gujarat.

2Malaria Research Centre, Hardwar, Uttaranchal.

Email: [email protected]

Abstract: Infrared spectroscopy was used for the structure elucidation of five new compounds isolated

from the oxidation of primaquine (P). In vitro studies showed that the compounds P1 and P2 have four

times more gametocytocidal activity than primaquine. On the basis of the group frequencies, nature of

peaks, mode of vibration like stretching, bending and splitting of spectral lines the structure of P1 , P2 , P3

, P4 and P5 (Table I) were proposed.

Full Text:

PRIMAQUINE, an 8-aminoquinoline, is the clinical drug of choice for the radical cure of relapsing

malaria1. It is restricted in usage due to its side effects in patients with deficient glucose-6-phosphate

dehydrogenase (G6PD)2. Though several primaquine analogues were synthesized by chemical

3-6

oxidation method7 and screened for antimalarial activity, but found unequal to primaquine. We found two

out of five isolated compounds, showing better gametocytocidal activity than primaquine. Structure of

primaquine derivatives was widely worked out by FTIR. The hydroxy-derivatives of primaquine8-11

and

its IR spectral analyses of N-acetate12

were reported. An attempt has been made here, to correlate between

IR spectral data and the structural features of the five compounds.

The IR spectra were recorded as 4 cm-1

resolution with 8 scan average. A combination of Bio-Gel column

chromatography with reversed-phase high performance liquid was used for semi preparative isolation of

five compounds formed by per-oxydisulphate oxidation of primaquine7. Their structural characterization

was done by IR spectroscopy. The IR spectrum of the P1 compound is given in Figure l. The IR spectrum

of compound P1 showed typical bands at 3435 cm-1

and assigned to stretching vibration of N-H and a

group of bands in the region 1600 due to different modes of C-H/C=C bonds including one 1540 cm-1

indicative of the presence of aromatic nucleus. The bands at 1371 and that 1279 are assigned to methoxy

(-0CH3) and bending N-H modes respectively. The bands at 1109 cm-1

shows the presence of aromatics

substituted12

C-N. These assignments are based on the standard frequencies of primaquine10

. It was

worthy to point out that the IR assignments of wave frequencies, nature of peaks, mode of vibration and

splitting of spectral lines in compound code P1 were identical to primaquine12

.



The IR spectrum of the compound code P2 is shown in Figure 2 which is fairly similar to that of P1 and so

the assignments of different bands/peaks. The IR spectra of compound P3 and P4 are given in Figure 3 and

4 respectively which is very similar to that of hydroxy derivatives of primaquine7. The sharp band at 1634

due to bending triode of OH further supports the presence of OH group. The bands at 620 cm-1

(29.1%),

592 cm-1

(62.93%) and 560 cm-1

(63.3%) could be assigned to substituted benzene ring. It may be pointed

out that the spectral characteristics of this compound (P3) were similar to that of 5-hydroxy 6-demethoxy

primaquine8-10

.

The assignment of different peaks observed in case of P4were based on the analogy to compounds P3 and

primaquine whose IR spectra was discussed earlier. The IR spectrum of compound P4 is given in Figure

4. The IR spectrum of P5 compound is given in Figure 5. The assignment of different peaks observed in

case of P5 were based on the analogies to compound 6-methoxy-5, 8-di-(4’-amino-l’-methylbutylamino)-

quinoline (P1) and primaquine whose IR, spectra have already discussed. A strong band at 3435 cm-1

(3.15%) could be assigned to stretching vibration of –NH2 group similar to 6-methoxy-5, 8 di-(4’-amino-

l’ –methylburylamino)-quinoline P1. The broad band at 1621 cm-1

(25.48%) and a sharp band at 1520 cm-1

(38.18%) may be due to C=C skeleton to aromatic nucleus was confirmed. It may be noted that the nature

of peak at 6121 cm-1

was different with respect to primaquine, while similar to aliphatic compound N-

butyl amine as reported earlier13

. Therefore these peaks may be assigned due to NH2 bending vibration.

The absence of proton NMR strong bands at 1130 cm-1

(11.9%) and 1119 (10.79%) cm-1

showed C-N

stretching vibration in R-NH-R type arrangement. The weak branches at 867 (77.63%) cm-1

, 815

(73.70%) cm-1

and 787 (73.09%) cm-1

were due to CH2 rocking vibration in –C- (CH2)n-C- type

arrangement. The sharp strong bands at 639 (58.79%) cm-1

showed the presence of –CH deformation14

. It

is worthy to point out that the assignment of IR wave frequencies, nature of peaks, mode of vibration of

P5 were identical to reported compound N-butyl amine (silver stein) and side chain of primaquine

respectively.

References:

1. Sinha, S.N. and Venkatakrishna-Bhatt, H., J.Med.Sci. 5, 27-35, 2001.

2. Clyde, D.F., Bull WHO, 1981, 59, 391-395.

3. Milhous, W.K., Robinson, B.L., Breuckner, R.P., Schuster, B.G. and Peters, W.,

Am.J.Trop.Med.Hyg., 1992, 47 Suppl., 89-96.

4. Jain, R., Gupta, R.C. and Anand, N., Indian J.Chem., 1994, 33, 792-794.

5. Lamontagne, M.P., Blumbergs, P. and Strube, R.E., J.Med.Chem., 1982, 25, 1094-1097.

6. Lamontagne, M.P., Markovae, A. and Khan, M.S., J.Med.Chem., 1982, 25, 964-968.

7. Brossi, A., Gessner, W., Hufford, C.D., Baker, J.K., Homo, F., Millet, P. and Landau, I., FEB.,

1987, 25, 77-81.

8. Dua, V.K., Sinha, S.N. and Sharma, V.P., J.Chromatography, B, 1998, 708, 316-320.

International Journal of Chemistry; 2013[0

9. Strother, A., Allahyari, R., Buchholz, J., Fraser, I.M. and Tilton, B.,

12, 35-44.

10. Allahyaqri, R., Strother, A., Fraser, I.M. and Verbiscar, A.J.,

11. Vivor, V.J. and Augusto, O.,

12. Clark;, A.M., Hufford, C.D. and McChesney, J.D.,

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13. Silverstein, R.M. and Bassler, G.C.,

Wiley International: 1976, Compound No.

14. Scheinmann, F., An introduction of spectroscopic methods for the identification of organic

compounds. Wiley International: 1979,

Table l-Structure of compounds formed from

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Strother, A., Allahyari, R., Buchholz, J., Fraser, I.M. and Tilton, B., Drug Metabol.Disp

Allahyaqri, R., Strother, A., Fraser, I.M. and Verbiscar, A.J., J.Med.Chem

J. and Augusto, O., J.Biol.Chem., 1992, 267, 6848-6854.

Clark;, A.M., Hufford, C.D. and McChesney, J.D., Antimicro.Agents Chemother.,

Silverstein, R.M. and Bassler, G.C., Spectrometric identification of organic compounds.

ernational: 1976, Compound No.5.12

An introduction of spectroscopic methods for the identification of organic

. Wiley International: 1979, 2.7.

Structure of compounds formed from the oxidation of primaquine by peroxidsulphate ion.

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Drug Metabol.Disp., 1984,

J.Med.Chem., 1984, 27, 407-410.

Antimicro.Agents Chemother., 1981, 19, 337-

Spectrometric identification of organic compounds. Eds.,

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the oxidation of primaquine by peroxidsulphate ion.


Table l-Structure of compounds formed from the oxidation of primaquine by peroxidsulphate ion (Continued).

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Structure of compounds formed from the oxidation of primaquine by peroxidsulphate ion (Continued).

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Structure of compounds formed from the oxidation of primaquine by peroxidsulphate ion (Continued).


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infrared spectroscopic studies of some oxidative products ......in vitro studies showed that the...

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