research article synthesis and biological evaluation of...

Research ArticleSynthesis and Biological Evaluation ofNew Hydrazone Derivatives of Quinoline and Their Cu(II) andZn(II) Complexes against Mycobacterium tuberculosis

Mustapha C Mandewale1 Bapu Thorat1 Dnyaneshwar Shelke1 and Ramesh Yamgar2

1PG and Research Centre Department of Chemistry Government of Maharashtra Ismail Yusuf College of ArtsScience and Commerce Jogeshwari (East) Mumbai 400 060 India2Department of Chemistry Chikitsak Samuharsquos Patkar-Varde College of Arts Science and Commerce Goregaon (West)Mumbai 400 062 India

Correspondence should be addressed to Mustapha C Mandewale iycmustaphagmailcom

Received 21 July 2015 Revised 16 September 2015 Accepted 28 September 2015

Academic Editor Viktor Brabec

Copyright copy 2015 Mustapha C Mandewale et alThis is an open access article distributed under theCreativeCommonsAttributionLicense which permits unrestricted use distribution and reproduction in anymedium provided the originalwork is properly cited

A new series of quinoline hydrazone derivatives and their metal complexes have been synthesized and their biological propertieshave been evaluated against Mycobacterium tuberculosis (H37 RV strain) Most of the newly synthesized compounds displayed100 inhibitory activity at a concentration of 625ndash25120583gmL against Mycobacterium tuberculosis Fluorescence properties of allthe synthesized compounds have been studied

1 Introduction

The tuberculosis also known as TB and ldquowhite plaquerdquois caused by infection with different species of bacteriaincluding Mycobacterium tuberculosis Mycobacteriumafricanum Mycobacterium bovis Mycobacterium capraeMycobacterium canettii Mycobacterium pinnipedii andMycobacterium microti Other factors that have also contrib-uted include population expansion poor case detection andslow cure rates in developing countries active transmissionin overcrowded hospitals drug abuse and homelessnessSuccessful treatment of fully susceptible TB depends oncombination of drugs and duration of therapy cost anddrugrsquos side effects Treatment failure is due to multiple factorsincluding incomplete or short duration therapy and resultsin persistence of the disease mainly due to emergence of drugresistance Primary resistance occurs when the resultingMycobacterium tuberculosis strain is transmitted to a newhost and it causes tuberculosis that is already resistant to thedrugs used for treatment of previous host [1 2]

Major factors associated with drug resistance develop-ment include nonadherence to therapy due tomultiple factorssuch as high cost of drugs long duration of therapy and

combination of multiple drugs used in treatment regimensand drug related coinfection with HIV adverse reactionsprior history of treatment and treatment failures with anti-tuberculosis (anti-TB) drugs [3ndash6] Simultaneous treatmentof HIV-tuberculosis coinfection may lead to malabsorptionand suboptimal therapeutic blood levels of Rifampin (RMP)and Isoniazid (INH) that facilitate the development of drugresistant TB and multiple drug resistant tuberculosis (MDR-TB) The malabsorption of antituberculosis drugs may alsooccur in patients having some other diseases in association[7 8]

The treatment of tuberculosis involves first-line drugsincluding Streptomycin Isoniazid (INH) Rifampin (RMP)Ethambutol and Pyrazinamide The second-line treat-ments of tuberculosis involve the application of p-aminos-alicylic acid Ethionamide Cycloserine Azithromycin Clar-ithromycin and Fluoroquinolones However the main com-plication associated with TB therapy is the poor assent withthe long duration of the treatment and mainly with thedrugs used to treat MDR-TB that are increasing resistanceexpensive relatively ineffective and having long duration oftreatment The Isoniazid is one of the commonly used and

Hindawi Publishing CorporationBioinorganic Chemistry and ApplicationsVolume 2015 Article ID 153015 14 pageshttpdxdoiorg1011552015153015

2 Bioinorganic Chemistry and Applications

effective antitubercular drugs but recently because of theappearance ofMTB resistant strainsmany attempts have beenmade to explain the mechanism of interaction of this drugand the origin of drug resistance and research its novelnewdrugs for the treatment of tuberculosis Therefore it is stilla challenge for the researchers to develop drugs of moreefficiency more effective with less toxicity to treat signs andsymptoms of tuberculosis

On the side the various pharmacological properties ofquinoline and their derivatives attracted great attention in thelast few decades because of their vast occurrence in naturalproducts and drugs [9] A large number of efforts have beenmade to develop quinoline-based compounds as importantantitubercular agent which is active on different clinicallyapproved therapeutic targets showing excellent therapeuticpotency in the past decade The literature survey showsthat 5 to 6 membered heterocyclic compounds containinga quinoline ring in a linear fashion were found to exhibitstrong anticancer and antimicrobial activities [10 11] Variousderivatives of quinoline have been employed in the synthe-sis of antifungal antihypertensive and antibacterial drugsRecently interest in the study of Schiff base hydrazones hasbeen increasing because of their antitumour antitubercularand antimicrobial activities Schiff base hydrazones play animportant role in inorganic chemistry as they easily form sta-ble coordination complexes with most transition series metalionsThe developments in the field of bioinorganic chemistryhave increased the interest in hydrazone complexes becauseit has been known that many of these complexes may act aslead for biologically important species [12ndash16]

2 Experimental

The chemicals and solvents used in this work were ofanalytical grade and purchased from Merck and Sigma-Aldrich Chemicals The zinc chloride copper chloride andDMF (NN-dimethylformamide) were purchased from SDFine Chemicals

21 Synthesis of Schiff Base Hydrazones from 6-Fluoro-2-hydroxyquinoline-3-carbaldehyde 6-Fluoro-2-hydroxyquin-oline-3-carbaldehyde was synthesized by Vilsmeier-Haackreaction starting with 4-fluoroacetanilide as per reportedmethod [17 18]

6-Fluoro-2-hydroxyquinoline-3-carbaldehyde (0200 g00015 moles) was dissolved in 5mL ethanol and compounds1andash1e (00015 moles) were added A drop of glacial acetic acidwas added as a catalyst for the reactionThe reaction mixturewas refluxed for half an hour The reaction mixture wascooled in ice bath and precipitated product was filtered Theproduct was then dried in oven Structures of synthesizedhydrazone derivatives have been shown in Figure 10 andTable 1

211 Preparation of N1015840-[(E)-(6-Fluoro-2-hydroxyquinoline-3-yl)methylidene]pyridine-3-carbohydrazide [2a] MP 293ndash295∘C UV 120582max 383 nm MS [M + H] 31159 FTIR (KBrcmminus1) 3208 (phenolic -OH) 3073 (-N-H amide) 1660(azomethine -CH=N-) 1625 (C=O amide) 1425 (phenolic

C-O) 1294 (C-F quinoline) 1H NMR (300MHz DMSO-d6) 120575 735ndash742 (m 2H) 755 (s 1H) 775ndash778 (d 1H) 825ndash

828 (d 1H) 849 (s 1H) 869ndash875 (m 2H) 908 (s 1H)1209 (s 1H) 1216 (s 1H) 13C NMR (75MHz DMSO-d

6)

120575 16301 (-C=O amide) 16163 (-C-O phenolic) 15002 (-C-Fquinoline) 14875 14824 14726 14623 (-C=N- azomethine)13328 13099 13066 13050 12790 12663 12499 119431105 elemental analysis observed (calculated) C 6197(6193) H 366 (357) N 1820 (1806)

212 Preparation of N1015840-[(E)-(6-Fluoro-2-hydroxyquinoline-3-yl)methylidene]pyridine-4-carbohydrazide[2b] MPgt300∘CUV 120582max 388 nm MS [M minus H] 30927 FTIR (KBr cmminus1)3488 (phenolic -OH) 3153 (N-H amide) 3025 (aromatic C-H) 1650 (imine -CH=N-) 1630 (C=O amide) 1427 (phenolicC-O) 1288 (C-F quinoline) 1H NMR (300MHz DMSO-d6) 120575 732ndash745 (m 2H) 777ndash785 (m 3H) 850 (s 1H)

871 (m 2H) 877 (s 1H) 1213 (s 1H) 1226 (s 1H) 13CNMR (75MHz DMSO-d

6) 120575 1648 (-C=O amide) 16252 (-

C-O phenolic) 15232 (C-F quinoline) 15001 14726 14097(-C=N- azomethine) 13457 13102 13152 12743 1257111946 11821 1105 elemental analysis observed (calculated)C 6198 (6193) H 372 (357) N 1817 (1806)

213 Preparation of N1015840-[(E)-(6-Fluoro-2-hydroxyquinoline-3-yl)methylidene]-6-methylpyridine-3-carbohydrazide[2c] MPgt300∘C UV 120582max 385 nm MS [M + H] 32516 FTIR(KBr cmminus1) 3444 (phenolic -OH) 3228 (N-H amide) 2933(aromatic C-H) 2886 (aliphatic C-H) 1662 (imine -CH=N-)1628 (C=O amide) 1438 (phenolic C-O) 1234 (C-F quino-line) 1H NMR (300MHz DMSO-d

6) 120575 254 (s 3H) 736ndash

743 (m 3H) 776ndash779 (m 1H) 817ndash819 (m 1H) 849 (s 1H)870 (s 1H) 897 (s 1H) 1216 (s 2H) 13C NMR (75MHzDMSO-d

6) 120575 16331 (-C=O amide) 16040 (-C-O- phenolic)

15547 (-C-F quinoline) 15848 14794 14566 14129 (-C=N-azomethine) 13129 13106 13001 12869 12672 1252312208 11793 1124 2397 (-CH

3pyridine) elemental analysis

observed (calculated) C 6287 (6296) H 413 (404)N 1734 (1728)

214 Preparation of 2-[(7-Bromo-23-dihydro-1H-inden-4-yl)oxy]-N1015840-[(E)-(6-fluoro-2-hydroxyquinoline-3-yl)methylid-ene]acetohydrazide [2d] MP gt300∘C UV 120582max 382 nmMS [M +H] 45800 FTIR (KBr cmminus1) 3538 (phenolic -OH)3432 (N-H amide) 3002 (aromatic C-H) 2848 (aliphatic C-H) 1656 (imine -CH=N-) 1627 (C=O amide) 1425 (phenolicC-O) 1263 (C-F quinoline) 1HNMR (300MHz DMSO-d

6)

120575 285ndash297 (m 6H) 448 (s 2H) 724ndash747 (m 2H) 759ndash762 (m 1H) 774ndash781 (m 1H) 823 (s 1H) 842 (s 1H)851 (s 1H) 1182 (s 1H) 1213 (s 1H) 13C NMR (75MHzDMSO-d

6) 120575 16850 (-C=O amide) 16275 (C-O- phenolic)

15914 (C-F quinoline) 15580 15455 14626 14372 (-C=N-azomethine) 13514 13359 13179 13006 12743 1259312220 (-C-Br) 12093 11197 10995 6783 (-CH

2-O-) 2983

(CH2aliphatic) 2977 (CH

2aliphatic) 2578 (CH

2aliphatic)

elemental analysis observed (calculated) C 5550 (5504)H 369 (374) N 920 (917)

Bioinorganic Chemistry and Applications 3

Table 1 Structures of hydrazones 2andash2e (see Figure 10)

Entry Hydrazide (1) Hydrazone (2) Yield () Colour

a

N

O

NHNH2

N

NN

O

HF N

OH

84 Dark yellow

bN

O

NHNH2

N

NN

O

HF

N

OH

87 Yellow

c

N

O

NH2

H3C

NH

N

NN

O

HF N

OH

76 Faint yellow

d

O

Br

ONH2

NH

N

NN

O

HF

O

Br

OH

90 Pale yellow

e

OO

NH2

NH

N

N N

O

H

FO

OH

84 Pale yellow

215 Preparation of 2-(23-Dihydro-1H-inden-4-yloxy)-N1015840-[(E)-(6-fluoro-2-hydroxyquinoline-3-yl)methylidene]acetohy-drazide [2e] MP gt300∘C UV 120582max 381 nm MS [M + H]38044 FTIR (KBr cmminus1) 3193 (phenolic -OH) 3064 (N-H amide) 2950 (aromatic C-H) 2854 (aliphatic C-H) 1668(imine -CH=N-) 1625 (C=O amide) 1428 (phenolic C-O)1232 (C-F quinoline) 1HNMR (300MHz DMSO-d

6) 120575 199

(m 2H) 283 (m 4H) 465 (s 2H) 660ndash665 (m 1H) 682(m 1H) 705 (m 1H) 733ndash742 (m 2H) 760ndash762 (m 1H)822 (s 1H) 842 (s 1H) 1176 (s 1H) 1210 (s 1H) 13C NMR(75MHz DMSO-d

6) 120575 16840 (-C=O amide) 16296 (-C-

O- phenolic) 15981 (-C-F quinoline) 15490 14735 14695(-C=N- azomethine) 1375 13514 13099 1308 1306612790 12663 12501 11943 11372 1105 6686 3261 (CH

2

aliphatic) 2967 (CH2aliphatic) 2538 (CH

2aliphatic) ele-

mental analysis observed (calculated) C 6652 (6648)H 470 (478) N 1121 (1108)

22 Synthesis of Cu(II) and Zn(II) Complexes from 2andash2e Thesolution of metal salt [ZnCl

2 CuCl

2] dissolved in ethanol

was added gradually to a stirred ethanolic solution of theSchiff base hydrazones [2andash2e] in the molar ratio 1 2 Thereaction mixture was further stirred for 2ndash4 hr at 60∘CThenit was cooled in ice bath to ensure the complete precipitation

of the formed complexes The precipitated solid complexeswere filtered and washed four times with water Finallythe complexes were washed with diethyl ether and driedin vacuum desiccators over anhydrous CaCl

2 Structures of

synthesized complexes have been shown in Figure 11 andTable 2

3 Results and Discussion

All the synthesized hydrazone ligands 2andash2e and their Cu2+and Zn2+ complexes 3andash3j are stable at room temperatureand are nonhygroscopic in nature The metal complexesare insoluble in H

2O but are soluble in DMF The spectral

characterizations of synthesized compounds confirm thesuggested structures of the hydrazones as well as their metalcomplexes The elemental analysis physical properties andspectral data of the ligand and complexes are summarizedbelow

31 1H NMR Spectra 1H NMR spectra were recorded onVarian-NMR-Mercury 300MHz instrument The DMSO-d

6

was used as a solvent with TMS (tetramethylsilane) as aninternal standard The chemical shifts are expressed as 120575


Table 2 Proposed structures of Zn(II) and Cu(II) complexes from hydrazones 2andash2e (see Figure 11)

Entry Metal complex Yield() Colour

3a

NO

N NH

O

F

NO

O

F

Zn

N

N

H2O

NHN

OH2 92 Brightyellow

3b

NO

N

O

F

NO

O

F

Zn

N

N

H2O OH2

NH

NHN

90 Darkyellow

3c

NO

N

O

F

NO

O

F

Zn

N

N

NHN

H2O OH2

NH

93 Darkyellow

3d

NO

N NH

O

F

NO

O

F

Zn

O

O

Br

Br

H2O OH2

NHN

88 Shinyyellow


Table 2 Continued


3e

NO

N NH

O

F

NO

O

F

Zn

O

O

H2O OH2

NHN

92 Darkyellow

3f

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

90 Darkgreen

3g

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

87 Green

3h

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

89 Green


Table 2 Continued


3i

NO

N

O

F

NO

O

F

Cu

O

O

Br

Br

H2O OH2

NHN

NH

86 Green

3j

NO

N NH

O

F

NO

O

F

Cu

O

O

H2O OH2

NHN

91 Darkgreen

values (ppm) The 1H NMR spectra of the hydrazones 2andash2e were recorded in DMSO-d6 solvent over the range of0ndash16 ppm and shown in Table 3 The disappearance of thesinglet at 1023 ppm and appearance of new singlet peak inthe range of 859ndash908 ppm are assignable to the azomethineprotons which confirms the condensation of hydrazones 1andash1e and 6-fluoro-2-hydroxyquinoline Also a set of multipletsobserved in the range 660ndash840 ppm is ascribed to thearomatic protons in all the compoundsThe peak observed inthe range of 1176ndash1213 ppm in the hydrazones is attributableto the -OH of quinoline at 2nd position A sharp singlet at1210ndash1226 ppm observed in the hydrazones is due to -NH ofamide carbonyl

32 13C NMR Spectra In the 13C spectra azomethine carbonatom appeared most downfield as reported in literaturevalues in the hydrazones (2andash2e) it was observed in therange of 14097ndash14695 ppm shown in Table 4 The phenoliccarbon appears in the range of 16040ndash16275 ppm Theamidic carbon from hydrazide gives signal in the range of16301ndash16850 ppm The 13C spectral analysis confirms theformation of the hydrazone derivatives 2andash2e

33Mass Spectra The formation of imine is confirmed by thepresence of intense molecular ion peak in the mass spectraof hydrazone derivatives (2andash2e) Spectral evaluation predictsthe molecular weights of the desired hydrazone compounds

34 IR Spectra The infrared spectra were recorded on FTIR-7600 Lambda Scientific Pty Ltd using KBr pellets From

the interpretation of IR spectra we get valuable informationregarding the nature of functional group present in thehydrazone derivatives (2andash2e) and metal complexes (3andash3j)In the IR spectra of hydrazones the imine group (-HC=N-)and hydroxyl group show strong peak in the regions of1625ndash1630 cmminus1 and 3193ndash3538 cmminus1 respectively All metalcomplexes show broad peak in the region of 3200ndash3400 cmminus1due to coordinated water molecules

In order to study the bonding mode of hydrazone ligandto the centralmetal atom the IR spectra of the free hydrazoneswere compared with the spectra of the complexes Theimportant IR bands and their assignments are listed in Tables5 and 6

The phenolic -OH band appears at 3193ndash3588 cmminus1 whichdisappears in IR spectra of the metal complexes howevernew broad peak has been observed at 3200ndash3400 cmminus1 dueto coordinated water molecules which confirms the com-plexation of hydrazones with central metal atom throughphenolic -OH The IR spectra of all the metal complexesshow prominent band at about 501ndash599 cmminus1 due to 120592M-Nstretching The low frequency region of the spectra indicatedthe presence of two new medium intensity bands at about449ndash482 cmminus1 due to 120592M-O vibrations and at 501ndash599 cmminus1due to 120592M-N vibrations

35 Molar Conductivity Measurements From the mathemat-ical relation Λ119898 = 119870119862 the molar conductance of themetal complexes (Λ119898) can be calculated by dissolving inproper solvent where 119862 is the molar concentration of the


Table 3 1H NMR signals for hydrazones (2andash2e) and their assignments

Hydrazones Amidic -NHlowast- Phenolic -OHlowast Azomethine -CHlowast=N-2a 1216 1209 9082b 1226 1213 8772c 1211 1211 8972d 1213 1182 8512e 1210 1176 842

Table 4 13C NMR for hydrazones (2andash2e) and their assignments

Hydrazones -Clowast=O amide -Clowast-OH phenolic -ClowastH=N- azomethine2a 16301 16163 144632b 16480 16252 140972c 16531 16040 141292d 16850 16275 143722e 16840 16196 14695

0

2

4

6

8

10

()

3j3i3f3c 3e3a 3g3b 3d 3hMetal complexes

ZnCu

Figure 1 Showing comparative of Zn and Cu contents in metalcomplexes 3andash3j

metal complex solutions [19] The metal complexes (3andash3j)were dissolved in DMF to prepare 10minus3M of their solutionsThe molar conductivities were measured at 25 plusmn 2∘C Thestudy shows negligible molar conductance values for metalcomplexes 3andash3j (290ndash730Ωminus1molminus1 cm2) indicating thatthe complexes are nonelectrolytesThe results are representedin Table 7

36 Elemental Analysis of Metal Complexes The quantitativeestimation of Cu(II) and Zn(II) has been done by complex-ometric titration with standard EDTA solution In a titrationan accurately known mass of metal complex is dissolved inan aqueous solution by chemical treatment such as acid-digestion of solid metal complex samples and diluted withhigh purity water to an accurately known volume Then anaccurately known volume of the aliquot is pipetted into atitration vessel and the analyte of interest is carefully titratedwith a standardized EDTA solution to the endpoint of thetitration [20] The observed results are represented in Table 8and Figure 1

From the experimental study it is clear that practicalobservations are in good agreement with the theoreticalvalues calculated for 1 2 ratio of metal ligand stoichiometryRegarding the above explanation of the results of variousspectroscopic details it may be concluded that the proposedgeometry for the transitionmetal complexes with general for-mula ML

2sdot2H2O is octahedral for Zn+2 and Cu+2 complexes

The probable structures are shown in Table 2

37 Structure Activity Relationship Study (SAR) The Cressetsoftware Forge is a molecular design and SAR (structureactivity relationship) interpretation tool that generates anduses molecular alignments as a way to make meaningfulcomparisons across chemical series The interaction betweena ligand and a protein involves electrostatic fields and surfaceproperties (eg hydrogen bonding and hydrophobic sur-faces) Two molecules which both bind to a common activesite tend to make similar interactions with the protein andhence have highly similar field properties

Accordingly using these properties to describemoleculesis a powerful tool for the medicinal chemist as it concentrateson the aspects of the molecules that are important forbiological activity In Forge molecules can be aligned byusing the fields of the molecules by using shape propertiesor by using a common substructure Using the fields givesa ldquoproteinrsquos viewrdquo of how the molecules would line up inthe active site generating ideas on how molecules withdifferent structures could interact with the same proteinUsing substructure or common shape properties shows howthe fields around a single chemical series vary with activityand in many cases these can be automatically examined togive a 3D structure active relationship (SAR) with predictivepower for new ideas for synthesis

371 Interpretation of Field Point Patterns Molecules beardifferent types of field points Larger field points representstronger points of potential interactionThroughout Cressetrsquossoftware the blue points are negative field points which like tointeract with positivesH-bond donors on a protein whereas


Table 5 FTIR bands for hydrazones (2andash2e) and their assignments

Compounds Phenolic 120592(OH)

Cmminus1Amide 120592

(C=O)Cmminus1

Imine 120592(C=N)

Cmminus1Phenolic 120592

(C-O)Cmminus1

120592(C-F)Cmminus1

2a 3208 1660 1625 1425 12942b 3488 1650 1630 1427 12882c 3444 1662 1628 1438 12342d 3538 1656 1627 1425 12632e 3193 1668 1625 1428 1232

Table 6 FTIR bands for metal complexes (3andash3j) and their assignments

ComplexLattice water120592(OH)


(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(M-N)Cmminus1

120592(M-O)Cmminus1

3a 3399 1650 1631 1376 574 4743b 3372 1646 1614 1369 590 4493c 3392 1652 1619 1380 599 4823d 3369 1650 1631 1376 599 4683e 3392 1621 1589 1425 592 4703f 3436 1665 1616 1380 597 4703g 3357 1610 1558 1375 501 4603h 3432 1658 1616 1386 566 4743i 3426 1658 1617 1382 530 4533j 3368 1663 1616 1380 599 472

Table 7 Molar conductance (Λ119898) of Cu(II) and Zn(II) complexes

Complexes Molar conductanceΛ119898 (Ωminus1molminus1 cm2)

Zn complexes

3a 363b 493c 323d 293e 53

Cu complexes

3f 7303g 4833h 6423i 4743j 332

red points are positive field points which like to interact withnegativesH-bond acceptors on a protein Similarly the yellowpoints are van der Waals surface field points which describepossible surfacevan der Waals interactions It can be seenthat ionic groups give rise to the strongest electrostatic fieldsHydrogen bonding groups also give strong electrostatic fieldsAromatic groups encode both electrostatic and hydrophobicfields Aliphatic groups such as the methyl or cyclopentylgroup give rise to hydrophobic and surface points but areessentially electrostatically neutral

To generate these fields we use XED (Extended ElectronDistribution) molecular mechanics force field which uses

Table 8 Percentage content of Zn and Cu inmetal complexes 3andash3j

Zn(II) complexes Zn content observed (calculated)3a 921 (908)3b 896 (908)3c 863 (874)3d 632 (644)3e 780 (762)Cu(II) complexes Cu content observed (calculated)3f 873 (885)3g 893 (885)3h 864 (852)3i 631 (627)3j 740 (742)

off-atom sites to more accurately describe the electron distri-bution in a molecule as opposed to other force fields wherecharges are placed at the atomic nuclei only

For SAR study we have selected ciprofloxacin as refer-ence compound as it shows strong antitubercular activityagainst Mycobacterium tuberculosis The bactericidal actionof ciprofloxacin results from inhibition of the enzymestopoisomerase II (DNA-gyrase) and topoisomerase IV whichare required for bacterial DNA replication transcriptionrepair strand supercoiling repair and recombination Bykeeping in mind two molecules which both bind to acommon active site of receptor and tend to make similarinteractions with the protein and hence have highly similar


Ciprofloxacin 2a 2b

2e2d2c

Figure 2 Showing different electrostatic regions of products 2andash2e

Ciprofloxacin 2a 2b

2c 2d 2e

12

Figure 3 Showing point charges of products 2andash2e

field properties we have compared the field properties ofthe ciprofloxacin with synthesized hydrazone derivatives 2andash2e This comparison strengthens the correlation between thetheoretical and observed activities of the target compoundsWe have calculated structure activity score of compounds2andash2e compared with ciprofloxacin The structure activityscore for 2a is 0556 for 2b is 0536 for 2c is 0536 for 2d is0505 and for 2e is 0526 All hydrazones have comparablepositive field regions but their negative field regions arelargely different from that of ciprofloxacin (Figures 2ndash4)Thisdifference in the field regions affects the activity Compounds2b and 2e show least negative field regions and are close tothat of ciprofloxacin and hence show greater activity againstMycobacterium tuberculosis

38 Biological Assay

381 Antitubercular Studies The antitubercular activity ofthe hydrazone ligands and their metal complexes was testedagainst Mycobacterium tuberculosis (H37 RV strain) ATCCnumber 27294 to findout their potency as antimicrobial agentby MIC method (minimum inhibitory concentration)

382 Microbiological Method The antibacterial activity ofhydrazones and their metal complexes was tested againstMycobacterium tuberculosis using Microplate Alamar BlueAssay (MABA) (Figure 1) [21] This methodology is nontoxicand reagents used are thermally stable It also shows good


Ciprofloxacin

2d

2b

2e

2c

2a

Figure 4 Hydrophobic regions for products 2andash2e

correlation with proportional and BACTEC radiometricmethod and reproducible results

To minimize the evaporation of medium in the test wellsduring incubation 200120583L of sterile deionized water wasadded to all outer perimeter wells of sterile 96-well plateThe 96-well plate received 100 120583L of the Middlebrook 7H9broth and serial dilution of compounds was made directlyon plate The concentration of the test sample was preparedbetween 100 and 08 120583gmL rangesThese plates were coveredand sealed with paraffin and incubated at 37∘C for five daysThen in the next step 25120583L of freshly prepared 1 1 mixture ofAlamar Blue Reagent Tween 10 and Tween 80 was addedto the plate and incubated for 24 hrs in incubator A bluecolor in thewell indicates bacterial growthwhereas pink colorshows growth of bacteria From this experiment the MIC canbe defined as lowest drug concentration which prevented thecolor change from blue to pink (Figure 1)

383 In Vitro Antimicrobial Activity When we compareMIC values of hydrazone and its complexes it indicates thatmetal complexes exhibit higher antimicrobial activity thanthe free hydrazone ligands and the same is represented fromthe results given in Table 9

There was moderate to good antibacterial activityobserved against Mycobacterium tuberculosis (H37 RVstrain) It was in the range ofMIC values of 625ndash2500 120583gmLconcentration compared to standard antibiotic ciprofloxacinhaving MIC of 312 120583gmL Pyrazinamide having MIC of312 120583gmL and Streptomycin having MIC of 625 120583gmLThese observations may be because of presence of active

Table 9 Showing comparative antituberculosis screening results byMIC method

Test samples Sample concentrationin 120583gmL (MIC)

Hydrazones

2a 502b 252c 502d 502e 25

Zn complexes

3a 253b 253c 1253d 253e 125

Cu complexes

3f 6253g 1253h 6253i 1253j 25

pharmacophore present in the molecular structure of thehydrazone and metal complexes like fluorine substitutedheterocyclic ring of quinoline moiety pyridine heterocyclicring imine double bond between carbon and nitrogen andwell positioned hydroxyl group These structural scaffoldsmight interfere in the mechanism of cell multiplication and


HydrophilicHydrophobic

10nmmycolic acids60ndash90 carbon atoms

Arabinogalactan

Peptidoglycan

5nmcytoplasmic membrane

Figure 5 Schematic diagram of mycobacterium cell wall

hence stop further growth of Mycobacterium tuberculosisAll the studied samples are showing different potency dueto the effective barrier of an outer cell wall membrane ofMycobacterium tuberculosis for entry of external substanceslike test compounds under this studyThe schematic diagramof mycobacterial cell wall is represented in Figure 5

Metal complexes showed greater activity as comparedwith hydrazone ligand This may be probably because of thegreater lipophilic character of the complexes This increasedactivity of the metal complexes can be explained on thebasis of coordination theory [22] According to Overtonersquosconcept of cell permeability only lipid soluble materialsfavour the passage of the lipid membrane that surrounds thecell Therefore the extent of lipid solubility of a molecule isan important factor which controls the antimicrobial activityAccording to the molecular theory of coordination of metalorbital overlap with ligand orbitals this reduces the positivecharge on themetal ion by accepting the electrons fromdonorgroups of the hydrazone ligand [23 24]Thus the donation ofthe electrons from ligand to metal also favours the increaseddelocalization of the 120587-electrons through entire coordinatingrings This results in increased lipophilicity of the metalcomplexes Therefore the enhanced lipophilicity facilitatesthe passage of the complexes across the lipid cell membraneof the bacteria and hence it can block the metal bindingsites on different enzymes of bacteria [25] Also these metalcomplexes disturb the respiration process of the cell andthereby prevent the synthesis of proteins If the synthesis ofproteins is blocked then formation of bacterial cell wall is notpossible and hence finally it results in cell death and thereforerestricts further growth of the bacteria [26] According toone more possible mechanism these complexes might beinteracting with the DNA gyrase enzyme which is essentialfor DNAmultiplication step The DNA gyrase is inhibited by

metal complexes which alter the multiplication of bacterialcells ultimately resulting in death of the bacteria [27 28]

However in case of test samples 3f and 3h complexesshowed good activity up to MIC value of 65120583gmL and3c 3e 3g and 3i complexes showed activity up to MICvalue of 125 120583gmL This could be due to coordination ofcentral metal atom to form a specific complex with cellwall protein and ultimately interfering in cell wall synthesisof Mycobacterium tuberculosis during cell mitosis phase ofmultiplication The observed results of the test compoundsindicate the future potential for the development of metalcoordination complexes to solve the limitations due to cur-rently available antituberculosis agents to treat multiple drugresistant tuberculosis

39 Fluorescence Study The UV-Visible absorption spectrawere recorded with UV spectrophotometer model ShimadzuUV-1800The path length of the measurements was 1 cmThefluorescence study was done on a Spectrofluorophotometermodel Shimadzu RF-5301pc having 1 cm path length Theconcentration 200 ppm of ligand and metal complexes whichwas in DMF (NN-dimethylformamide) was prepared forstudy Figures 6ndash9 show absorption as well as emissionspectraThe instrumental results are summarized in Table 10

All the ligands in UV-Visible spectra exhibit bandsaround 381ndash388 nm The broad intense band around 280 nmin the ligands can be assigned to intraligand n-plowast transitionassociated with the azomethine linkage This band experi-ences red shift in all the complexesThe bands at around 390ndash408 nm are attributed to the ligand to metal charge transfertransitions

The emission spectra of compounds 2andash2e showed emis-sion band in the range of 451ndash459 nm and compounds3andash3j showed emission band in the range of 456ndash485 nm


2a2b2c

2d2e

0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity

320 370 420270Wavelength (nm)

Figure 6 Electronic spectra of hydrazones (2andash2e)

3a3b3c3d3e

3f3g3h3i3j


0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity

Figure 7 Electronic spectra of metal complexes (3andash3j)

Compounds 3a 3b 3c and 3j showed higher emissionintensity Complex formation of hydrazones induces markedhyperchromic and bathochromic shifts The Zn(II) com-plexes showed intense fluorescent properties as compared toCu(II) complexes and their parent ligands

4 Conclusions

To assess the antimycobacterial activity potential of this classof compounds some of the compounds synthesized werechecked againstMycobacterium tuberculosis (H37 RV strain)ATCC number 27294 All the compounds were screened forantituberculosis activities and results are worthy of furtherinvestigationsThe incorporation of Zn2+ andCu2+ effectivelyincreases the conformational rigidity of the hydrazones and

2a2b2c

2d2e


0

50

100

150

200

250

300

350

400

450

Fluo

resc

ence

inte

nsity

minus50

Figure 8 Fluorescence spectra of hydrazones (2andash2e)

0

100

200

300

400

500

600

700

800

900Fl

uore

scen

ce in

tens

ity


3a3b3c3d3e

3f3g3h3i3j

Figure 9 Fluorescence spectra of metal complexes (3andash3j)

enhances the fluorescence intensities of the complex whichshows that it is good material in photochemical applicationsof these complexes

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgments

The authors thank Principal Head of Department of Chem-istry Government ofMaharashtra Ismail Yusuf Arts Scienceand Commerce College for providing research and library


N

FH

O

EtOH

N

NN R

O

H

FR

N

O

NH H

H

6-Fluoro-2-hydroxyquinoline-3-carbaldehyde

OHΔ

OH

(2andash2e)(1andash1e)

+

Figure 10

N

NN R

O

H

F

+

RefluxEtOH

NO

NR

O

F

NO

OR

F

MOH

M = Cu(II) Zn(II)

MCl2 H2O OH2

NH

NHN

(2andash2e)

(3andash3j)

Figure 11

Table 10 The absorption and emission wavelength with intensity

Compound Absorption 120582max(intensity)

Emission 120582max(intensity)

2a 383 (173) 456 (20011)2b 388 (237) 452 (22203)2c 385 (142) 459 (20363)2d 382 (278) 458 (11040)2e 381 (165) 451 (40014)3a 405 (149) 479 (79191)3b 408 (063) 485 (65431)3c 405 (275) 485 (76640)3d 391 (150) 466 (45399)3e 392 (169) 464 (40944)3f 401 (099) 473 (13856)3g 402 (069) 464 (28408)3h 394 (107) 460 (35955)3i 399 (034) 466 (44655)3j 390 (187) 456 (70406)

facilities The authors also thank Dr Kishore Bhat of Gov-ernmental Dental College Belgaum for facilitating anti-TBassays and providing the procedure for the same

References

[1] WHO ldquoWHOHTMTB2008393rdquo World Health Organiza-tion Report 2008 WHO Geneva Switzerland 2008

[2] T R Frieden T R Sterling S S Munsiff C JWatt and C DyeldquoTuberculosisrdquoTheLancet vol 362 no 9387 pp 887ndash899 2003

[3] American Thoracic Society CDC Infectious Disease Society ofAmerica ldquoTreatment of tuberculosisrdquo MMWR Morbidity andMortality Weekly Report vol 52 pp 1ndash77 2003

[4] M Palaci R Dietze D J Hadad et al ldquoCavitary diseaseand quantitative sputum bacillary load in cases of pulmonarytuberculosisrdquo Journal of ClinicalMicrobiology vol 45 no 12 pp4064ndash4066 2007

[5] World Health Organization Anti-Tuberculosis Drug Resistancein the World Fourth Global Report WHOHTMTB2008394World Health Organization (WHO) Geneva Switzerland2008

[6] F Drobniewski Y Balabanova M Ruddy et al ldquoRifampin andmultidrug-resistant tuberculosis in Russian civilians and prisoninmates dominance of the Beijing strain familyrdquo EmergingInfectious Diseases vol 8 no 11 pp 1320ndash1326 2002

[7] M E Kimerling P Phillips P Patterson M Hall C ARobinson and N E Dunlap ldquoLow serum antimycobacterialdrug levels in non-HIV-infected tuberculosis patientsrdquo Chestvol 113 no 5 pp 1178ndash1183 1998

[8] EMokaddas S AhmadA T Abal andA S Al-Shami ldquoMolec-ular fingerprinting reveals familial transmission of rifampin-resistant tuberculosis in Kuwaitrdquo Annals of Saudi Medicine vol25 no 2 pp 150ndash153 2005


[9] J Toth G Blasko A Dancso L Toke and M Nyerges ldquoSyn-thesis of new quinoline derivativesrdquo Synthetic Communicationsvol 36 no 23 pp 3581ndash3589 2006

[10] D S Lamani K R Venugopala Reddy H S Bhojya NaikA Savyasachi and H R Naik ldquoSynthesis and DNA bindingstudies of novel heterocyclic substituted quinoline schiff basesa potent antimicrobial agentrdquo Nucleosides Nucleotides andNucleic Acids vol 27 no 10-11 pp 1197ndash1210 2008

[11] P Rodrıguez-Loaiza A Quintero R Rodrıguez-Sotres J DSolano and A Lira-Rocha ldquoSynthesis and evaluation of 9-anilinothiazolo[54-b]quinoline derivatives as potential antitu-moralsrdquo European Journal of Medicinal Chemistry vol 39 no 1pp 5ndash10 2004

[12] R S Yamgar Y R Nivid S Nalawade M Mandewale RG Atram and S S Sawant ldquoNovel zinc(II) complexes ofheterocyclic ligands as antimicrobial agents synthesis charac-terisation and antimicrobial studiesrdquo Bioinorganic Chemistryand Applications vol 2014 Article ID 276598 10 pages 2014

[13] C Jayabalakrishnan and K Natarajan ldquoSynthesis characteriza-tion and biological activities of ruthenium(II) carbonyl com-plexes containing bifunctional tridentate Schiff basesrdquo Synthesisand Reactivity in Inorganic and Metal-Organic Chemistry vol31 no 6 pp 983ndash995 2001

[14] M C Mandewale B R Thorat D Shelke R Patil and RYamgar ldquoSynthesis characterization and fluorescence study ofN1015840-[(E)-(2-hydroxyquinolin-3-yl)methylidene]-1-benzofuran-2-carbohydrazide and its metal complexesrdquo Heterocyclic lettersvol 5 no 2 pp 251ndash259 2015

[15] N Dharmaraj P Viswanathamurthi and K Natarajan ldquoRuthe-nium(II) complexes containing bidentate Schiff bases and theirantifungal activityrdquo Transition Metal Chemistry vol 26 no 1-2pp 105ndash109 2001

[16] MCMandewale B RThorat andR S Yamgar ldquoSynthesis andanti-mycobacterium study of some fluorine containing Schiffbases of quinoline and their metal complexesrdquo Der PharmaChemica vol 7 no 5 pp 207ndash215 2015

[17] A Srivastava and R M Singh ldquoVilsmeier-Haack reagenta facile synthesis of 2-chloro-3-formylquinolines from N-arylacetamides and transformation into different functionali-tiesrdquo Indian Journal of Chemistry vol 44 no 9 pp 1868ndash18752005

[18] M Mustapha B R Thorat S Sawant R G Atram and RYamgar ldquoSynthesis of novel Schiff bases and its transition metalcomplexesrdquo Journal of Chemical and Pharmaceutical Researchvol 3 no 4 pp 5ndash9 2011

[19] G G Mohamed M M Omar and A M Hindy ldquoMetalcomplexes of Schiff bases preparation characterization andbiological activityrdquo Turkish Journal of Chemistry vol 30 pp361ndash382 2006

[20] DA SkoogDMWest F JHoller and S R CrouchAnalyticalChemistry An Introduction chapter 15 7th edition 2000

[21] M C S Lourenco M V N de Souza A C Pinheiro et alldquoEvaluation of anti-tubercular activity of nicotinic and isoniazidanaloguesrdquo ARKIVOC vol 2007 no 15 pp 181ndash191 2007

[22] B G Tweedy ldquoPossible mechanism for reduction of elementalsulfur byMonilinia fructicolardquo Phytopathology vol 55 pp 910ndash914 1964

[23] A K Kralova K Kissova O Svajlenova and J VancoldquoBiological activity of copper (II) N-salicylideneaminoacidatocomplexes Reduction of chlorophyll content in freshwater algaChlorella vulgaris and inhibition of photosynthetic electrontransport in spinach chloroplastsrdquo Chemical Papers vol 58 no5 pp 357ndash361 2004

[24] J Parekh P Inamdhar R Nair S Baluja and S Chanda ldquoSyn-thesis and antibacterial activity of some Schiff bases derivedfrom 4-aminobenzoic acidrdquo Journal of the Serbian ChemicalSociety vol 70 no 10 pp 1155ndash1161 2005

[25] Y K Vaghasiya R Nair M Soni S Baluja and S ChandaldquoSynthesis structural determination and antibacterial activityof compounds derived from vanillin and 4-aminoantipyrinerdquoJournal of the Serbian Chemical Society vol 69 no 12 pp 991ndash998 2004

[26] N Raman ldquoAntibacterial study of the mannich base N-(1-morpholino-benzyl) semicarbazide and its transition metal(II)complexesrdquo Research Journal of Chemistry and Environmentvol 4 p 9 2005

[27] U Galm S Heller S Shapiro M Page S-M Li and LHeide ldquoAntimicrobial and DNA gyrase-inhibitory activitiesof novel clorobiocin derivatives produced by mutasynthesisrdquoAntimicrobial Agents andChemotherapy vol 48 no 4 pp 1307ndash1312 2004

[28] E J Alvarez V H Vartanian and J S Brodbelt ldquoMetal com-plexation reactions of quinolone antibiotics in a quadrupole iontraprdquo Analytical Chemistry vol 69 no 6 pp 1147ndash1155 1997

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy


Carbohydrate Chemistry

International Journal of


Journal of

Chemistry


Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of


Chromatography Research International


Applied ChemistryJournal of



Theoretical ChemistryJournal of


Journal of

Spectroscopy

Analytical ChemistryInternational Journal of


Journal of


Quantum Chemistry


Organic Chemistry International

ElectrochemistryInternational Journal of



CatalystsJournal of


effective antitubercular drugs but recently because of theappearance ofMTB resistant strainsmany attempts have beenmade to explain the mechanism of interaction of this drugand the origin of drug resistance and research its novelnewdrugs for the treatment of tuberculosis Therefore it is stilla challenge for the researchers to develop drugs of moreefficiency more effective with less toxicity to treat signs andsymptoms of tuberculosis

On the side the various pharmacological properties ofquinoline and their derivatives attracted great attention in thelast few decades because of their vast occurrence in naturalproducts and drugs [9] A large number of efforts have beenmade to develop quinoline-based compounds as importantantitubercular agent which is active on different clinicallyapproved therapeutic targets showing excellent therapeuticpotency in the past decade The literature survey showsthat 5 to 6 membered heterocyclic compounds containinga quinoline ring in a linear fashion were found to exhibitstrong anticancer and antimicrobial activities [10 11] Variousderivatives of quinoline have been employed in the synthe-sis of antifungal antihypertensive and antibacterial drugsRecently interest in the study of Schiff base hydrazones hasbeen increasing because of their antitumour antitubercularand antimicrobial activities Schiff base hydrazones play animportant role in inorganic chemistry as they easily form sta-ble coordination complexes with most transition series metalionsThe developments in the field of bioinorganic chemistryhave increased the interest in hydrazone complexes becauseit has been known that many of these complexes may act aslead for biologically important species [12ndash16]

2 Experimental

The chemicals and solvents used in this work were ofanalytical grade and purchased from Merck and Sigma-Aldrich Chemicals The zinc chloride copper chloride andDMF (NN-dimethylformamide) were purchased from SDFine Chemicals

21 Synthesis of Schiff Base Hydrazones from 6-Fluoro-2-hydroxyquinoline-3-carbaldehyde 6-Fluoro-2-hydroxyquin-oline-3-carbaldehyde was synthesized by Vilsmeier-Haackreaction starting with 4-fluoroacetanilide as per reportedmethod [17 18]

6-Fluoro-2-hydroxyquinoline-3-carbaldehyde (0200 g00015 moles) was dissolved in 5mL ethanol and compounds1andash1e (00015 moles) were added A drop of glacial acetic acidwas added as a catalyst for the reactionThe reaction mixturewas refluxed for half an hour The reaction mixture wascooled in ice bath and precipitated product was filtered Theproduct was then dried in oven Structures of synthesizedhydrazone derivatives have been shown in Figure 10 andTable 1

211 Preparation of N1015840-[(E)-(6-Fluoro-2-hydroxyquinoline-3-yl)methylidene]pyridine-3-carbohydrazide [2a] MP 293ndash295∘C UV 120582max 383 nm MS [M + H] 31159 FTIR (KBrcmminus1) 3208 (phenolic -OH) 3073 (-N-H amide) 1660(azomethine -CH=N-) 1625 (C=O amide) 1425 (phenolic

C-O) 1294 (C-F quinoline) 1H NMR (300MHz DMSO-d6) 120575 735ndash742 (m 2H) 755 (s 1H) 775ndash778 (d 1H) 825ndash

828 (d 1H) 849 (s 1H) 869ndash875 (m 2H) 908 (s 1H)1209 (s 1H) 1216 (s 1H) 13C NMR (75MHz DMSO-d

6)

120575 16301 (-C=O amide) 16163 (-C-O phenolic) 15002 (-C-Fquinoline) 14875 14824 14726 14623 (-C=N- azomethine)13328 13099 13066 13050 12790 12663 12499 119431105 elemental analysis observed (calculated) C 6197(6193) H 366 (357) N 1820 (1806)

212 Preparation of N1015840-[(E)-(6-Fluoro-2-hydroxyquinoline-3-yl)methylidene]pyridine-4-carbohydrazide[2b] MPgt300∘CUV 120582max 388 nm MS [M minus H] 30927 FTIR (KBr cmminus1)3488 (phenolic -OH) 3153 (N-H amide) 3025 (aromatic C-H) 1650 (imine -CH=N-) 1630 (C=O amide) 1427 (phenolicC-O) 1288 (C-F quinoline) 1H NMR (300MHz DMSO-d6) 120575 732ndash745 (m 2H) 777ndash785 (m 3H) 850 (s 1H)

871 (m 2H) 877 (s 1H) 1213 (s 1H) 1226 (s 1H) 13CNMR (75MHz DMSO-d

6) 120575 1648 (-C=O amide) 16252 (-

C-O phenolic) 15232 (C-F quinoline) 15001 14726 14097(-C=N- azomethine) 13457 13102 13152 12743 1257111946 11821 1105 elemental analysis observed (calculated)C 6198 (6193) H 372 (357) N 1817 (1806)

213 Preparation of N1015840-[(E)-(6-Fluoro-2-hydroxyquinoline-3-yl)methylidene]-6-methylpyridine-3-carbohydrazide[2c] MPgt300∘C UV 120582max 385 nm MS [M + H] 32516 FTIR(KBr cmminus1) 3444 (phenolic -OH) 3228 (N-H amide) 2933(aromatic C-H) 2886 (aliphatic C-H) 1662 (imine -CH=N-)1628 (C=O amide) 1438 (phenolic C-O) 1234 (C-F quino-line) 1H NMR (300MHz DMSO-d

6) 120575 254 (s 3H) 736ndash

743 (m 3H) 776ndash779 (m 1H) 817ndash819 (m 1H) 849 (s 1H)870 (s 1H) 897 (s 1H) 1216 (s 2H) 13C NMR (75MHzDMSO-d

6) 120575 16331 (-C=O amide) 16040 (-C-O- phenolic)

15547 (-C-F quinoline) 15848 14794 14566 14129 (-C=N-azomethine) 13129 13106 13001 12869 12672 1252312208 11793 1124 2397 (-CH

3pyridine) elemental analysis

observed (calculated) C 6287 (6296) H 413 (404)N 1734 (1728)

214 Preparation of 2-[(7-Bromo-23-dihydro-1H-inden-4-yl)oxy]-N1015840-[(E)-(6-fluoro-2-hydroxyquinoline-3-yl)methylid-ene]acetohydrazide [2d] MP gt300∘C UV 120582max 382 nmMS [M +H] 45800 FTIR (KBr cmminus1) 3538 (phenolic -OH)3432 (N-H amide) 3002 (aromatic C-H) 2848 (aliphatic C-H) 1656 (imine -CH=N-) 1627 (C=O amide) 1425 (phenolicC-O) 1263 (C-F quinoline) 1HNMR (300MHz DMSO-d

6)

120575 285ndash297 (m 6H) 448 (s 2H) 724ndash747 (m 2H) 759ndash762 (m 1H) 774ndash781 (m 1H) 823 (s 1H) 842 (s 1H)851 (s 1H) 1182 (s 1H) 1213 (s 1H) 13C NMR (75MHzDMSO-d

6) 120575 16850 (-C=O amide) 16275 (C-O- phenolic)

15914 (C-F quinoline) 15580 15455 14626 14372 (-C=N-azomethine) 13514 13359 13179 13006 12743 1259312220 (-C-Br) 12093 11197 10995 6783 (-CH

2-O-) 2983

(CH2aliphatic) 2977 (CH

2aliphatic) 2578 (CH

2aliphatic)

elemental analysis observed (calculated) C 5550 (5504)H 369 (374) N 920 (917)




a

N

O

NHNH2

N

NN

O

HF N

OH

84 Dark yellow

bN

O

NHNH2

N

NN

O

HF

N

OH

87 Yellow

c

N

O

NH2

H3C

NH

N

NN

O

HF N

OH

76 Faint yellow

d

O

Br

ONH2

NH

N

NN

O

HF

O

Br

OH

90 Pale yellow

e

OO

NH2

NH

N

N N

O

H

FO

OH

84 Pale yellow


6) 120575 199


6) 120575 16840 (-C=O amide) 16296 (-C-


2


2aliphatic) ele-



2 CuCl




2 Structures of







6





3a

NO

N NH

O

F

NO

O

F

Zn

N

N

H2O

NHN

OH2 92 Brightyellow

3b

NO

N

O

F

NO

O

F

Zn

N

N

H2O OH2

NH

NHN

90 Darkyellow

3c

NO

N

O

F

NO

O

F

Zn

N

N

NHN

H2O OH2

NH

93 Darkyellow

3d

NO

N NH

O

F

NO

O

F

Zn

O

O

Br

Br

H2O OH2

NHN

88 Shinyyellow


Table 2 Continued


3e

NO

N NH

O

F

NO

O

F

Zn

O

O

H2O OH2

NHN

92 Darkyellow

3f

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

90 Darkgreen

3g

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

87 Green

3h

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

89 Green


Table 2 Continued


3i

NO

N

O

F

NO

O

F

Cu

O

O

Br

Br

H2O OH2

NHN

NH

86 Green

3j

NO

N NH

O

F

NO

O

F

Cu

O

O

H2O OH2

NHN

91 Darkgreen














0

2

4

6

8

10

()


ZnCu














(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(C-F)Cmminus1

2a 3208 1660 1625 1425 12942b 3488 1650 1630 1427 12882c 3444 1662 1628 1438 12342d 3538 1656 1627 1425 12632e 3193 1668 1625 1428 1232




(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(M-N)Cmminus1

120592(M-O)Cmminus1

3a 3399 1650 1631 1376 574 4743b 3372 1646 1614 1369 590 4493c 3392 1652 1619 1380 599 4823d 3369 1650 1631 1376 599 4683e 3392 1621 1589 1425 592 4703f 3436 1665 1616 1380 597 4703g 3357 1610 1558 1375 501 4603h 3432 1658 1616 1386 566 4743i 3426 1658 1617 1382 530 4533j 3368 1663 1616 1380 599 472



Zn complexes

3a 363b 493c 323d 293e 53

Cu complexes

3f 7303g 4833h 6423i 4743j 332








Ciprofloxacin 2a 2b

2e2d2c


Ciprofloxacin 2a 2b

2c 2d 2e

12



38 Biological Assay




Ciprofloxacin

2d

2b

2e

2c

2a








Hydrazones

2a 502b 252c 502d 502e 25

Zn complexes

3a 253b 253c 1253d 253e 125

Cu complexes

3f 6253g 1253h 6253i 1253j 25





Arabinogalactan

Peptidoglycan











2a2b2c

2d2e

0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



3a3b3c3d3e

3f3g3h3i3j


0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



4 Conclusions


2a2b2c

2d2e


0

50

100

150

200

250

300

350

400

450

Fluo

resc

ence

inte

nsity

minus50


0

100

200

300

400

500

600

700

800

900Fl

uore

scen

ce in

tens

ity


3a3b3c3d3e

3f3g3h3i3j





Acknowledgments



N

FH

O

EtOH

N

NN R

O

H

FR

N

O

NH H

H


OHΔ

OH


+

Figure 10

N

NN R

O

H

F

+

RefluxEtOH

NO

NR

O

F

NO

OR

F

MOH

M = Cu(II) Zn(II)

MCl2 H2O OH2

NH

NHN

(2andash2e)

(3andash3j)

Figure 11






References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of




a

N

O

NHNH2

N

NN

O

HF N

OH

84 Dark yellow

bN

O

NHNH2

N

NN

O

HF

N

OH

87 Yellow

c

N

O

NH2

H3C

NH

N

NN

O

HF N

OH

76 Faint yellow

d

O

Br

ONH2

NH

N

NN

O

HF

O

Br

OH

90 Pale yellow

e

OO

NH2

NH

N

N N

O

H

FO

OH

84 Pale yellow


6) 120575 199


6) 120575 16840 (-C=O amide) 16296 (-C-


2


2aliphatic) ele-



2 CuCl




2 Structures of







6





3a

NO

N NH

O

F

NO

O

F

Zn

N

N

H2O

NHN

OH2 92 Brightyellow

3b

NO

N

O

F

NO

O

F

Zn

N

N

H2O OH2

NH

NHN

90 Darkyellow

3c

NO

N

O

F

NO

O

F

Zn

N

N

NHN

H2O OH2

NH

93 Darkyellow

3d

NO

N NH

O

F

NO

O

F

Zn

O

O

Br

Br

H2O OH2

NHN

88 Shinyyellow


Table 2 Continued


3e

NO

N NH

O

F

NO

O

F

Zn

O

O

H2O OH2

NHN

92 Darkyellow

3f

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

90 Darkgreen

3g

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

87 Green

3h

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

89 Green


Table 2 Continued


3i

NO

N

O

F

NO

O

F

Cu

O

O

Br

Br

H2O OH2

NHN

NH

86 Green

3j

NO

N NH

O

F

NO

O

F

Cu

O

O

H2O OH2

NHN

91 Darkgreen














0

2

4

6

8

10

()


ZnCu














(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(C-F)Cmminus1

2a 3208 1660 1625 1425 12942b 3488 1650 1630 1427 12882c 3444 1662 1628 1438 12342d 3538 1656 1627 1425 12632e 3193 1668 1625 1428 1232




(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(M-N)Cmminus1

120592(M-O)Cmminus1

3a 3399 1650 1631 1376 574 4743b 3372 1646 1614 1369 590 4493c 3392 1652 1619 1380 599 4823d 3369 1650 1631 1376 599 4683e 3392 1621 1589 1425 592 4703f 3436 1665 1616 1380 597 4703g 3357 1610 1558 1375 501 4603h 3432 1658 1616 1386 566 4743i 3426 1658 1617 1382 530 4533j 3368 1663 1616 1380 599 472



Zn complexes

3a 363b 493c 323d 293e 53

Cu complexes

3f 7303g 4833h 6423i 4743j 332








Ciprofloxacin 2a 2b

2e2d2c


Ciprofloxacin 2a 2b

2c 2d 2e

12



38 Biological Assay




Ciprofloxacin

2d

2b

2e

2c

2a








Hydrazones

2a 502b 252c 502d 502e 25

Zn complexes

3a 253b 253c 1253d 253e 125

Cu complexes

3f 6253g 1253h 6253i 1253j 25





Arabinogalactan

Peptidoglycan











2a2b2c

2d2e

0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



3a3b3c3d3e

3f3g3h3i3j


0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



4 Conclusions


2a2b2c

2d2e


0

50

100

150

200

250

300

350

400

450

Fluo

resc

ence

inte

nsity

minus50


0

100

200

300

400

500

600

700

800

900Fl

uore

scen

ce in

tens

ity


3a3b3c3d3e

3f3g3h3i3j





Acknowledgments



N

FH

O

EtOH

N

NN R

O

H

FR

N

O

NH H

H


OHΔ

OH


+

Figure 10

N

NN R

O

H

F

+

RefluxEtOH

NO

NR

O

F

NO

OR

F

MOH

M = Cu(II) Zn(II)

MCl2 H2O OH2

NH

NHN

(2andash2e)

(3andash3j)

Figure 11






References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of




3a

NO

N NH

O

F

NO

O

F

Zn

N

N

H2O

NHN

OH2 92 Brightyellow

3b

NO

N

O

F

NO

O

F

Zn

N

N

H2O OH2

NH

NHN

90 Darkyellow

3c

NO

N

O

F

NO

O

F

Zn

N

N

NHN

H2O OH2

NH

93 Darkyellow

3d

NO

N NH

O

F

NO

O

F

Zn

O

O

Br

Br

H2O OH2

NHN

88 Shinyyellow


Table 2 Continued


3e

NO

N NH

O

F

NO

O

F

Zn

O

O

H2O OH2

NHN

92 Darkyellow

3f

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

90 Darkgreen

3g

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

87 Green

3h

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

89 Green


Table 2 Continued


3i

NO

N

O

F

NO

O

F

Cu

O

O

Br

Br

H2O OH2

NHN

NH

86 Green

3j

NO

N NH

O

F

NO

O

F

Cu

O

O

H2O OH2

NHN

91 Darkgreen














0

2

4

6

8

10

()


ZnCu














(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(C-F)Cmminus1

2a 3208 1660 1625 1425 12942b 3488 1650 1630 1427 12882c 3444 1662 1628 1438 12342d 3538 1656 1627 1425 12632e 3193 1668 1625 1428 1232




(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(M-N)Cmminus1

120592(M-O)Cmminus1

3a 3399 1650 1631 1376 574 4743b 3372 1646 1614 1369 590 4493c 3392 1652 1619 1380 599 4823d 3369 1650 1631 1376 599 4683e 3392 1621 1589 1425 592 4703f 3436 1665 1616 1380 597 4703g 3357 1610 1558 1375 501 4603h 3432 1658 1616 1386 566 4743i 3426 1658 1617 1382 530 4533j 3368 1663 1616 1380 599 472



Zn complexes

3a 363b 493c 323d 293e 53

Cu complexes

3f 7303g 4833h 6423i 4743j 332








Ciprofloxacin 2a 2b

2e2d2c


Ciprofloxacin 2a 2b

2c 2d 2e

12



38 Biological Assay




Ciprofloxacin

2d

2b

2e

2c

2a








Hydrazones

2a 502b 252c 502d 502e 25

Zn complexes

3a 253b 253c 1253d 253e 125

Cu complexes

3f 6253g 1253h 6253i 1253j 25





Arabinogalactan

Peptidoglycan











2a2b2c

2d2e

0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



3a3b3c3d3e

3f3g3h3i3j


0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



4 Conclusions


2a2b2c

2d2e


0

50

100

150

200

250

300

350

400

450

Fluo

resc

ence

inte

nsity

minus50


0

100

200

300

400

500

600

700

800

900Fl

uore

scen

ce in

tens

ity


3a3b3c3d3e

3f3g3h3i3j





Acknowledgments



N

FH

O

EtOH

N

NN R

O

H

FR

N

O

NH H

H


OHΔ

OH


+

Figure 10

N

NN R

O

H

F

+

RefluxEtOH

NO

NR

O

F

NO

OR

F

MOH

M = Cu(II) Zn(II)

MCl2 H2O OH2

NH

NHN

(2andash2e)

(3andash3j)

Figure 11






References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Table 2 Continued


3e

NO

N NH

O

F

NO

O

F

Zn

O

O

H2O OH2

NHN

92 Darkyellow

3f

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

90 Darkgreen

3g

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

87 Green

3h

NO

N

O

F

NO

O

F

Cu

N

N

H2O OH2

NHN

NH

89 Green


Table 2 Continued


3i

NO

N

O

F

NO

O

F

Cu

O

O

Br

Br

H2O OH2

NHN

NH

86 Green

3j

NO

N NH

O

F

NO

O

F

Cu

O

O

H2O OH2

NHN

91 Darkgreen














0

2

4

6

8

10

()


ZnCu














(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(C-F)Cmminus1

2a 3208 1660 1625 1425 12942b 3488 1650 1630 1427 12882c 3444 1662 1628 1438 12342d 3538 1656 1627 1425 12632e 3193 1668 1625 1428 1232




(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(M-N)Cmminus1

120592(M-O)Cmminus1

3a 3399 1650 1631 1376 574 4743b 3372 1646 1614 1369 590 4493c 3392 1652 1619 1380 599 4823d 3369 1650 1631 1376 599 4683e 3392 1621 1589 1425 592 4703f 3436 1665 1616 1380 597 4703g 3357 1610 1558 1375 501 4603h 3432 1658 1616 1386 566 4743i 3426 1658 1617 1382 530 4533j 3368 1663 1616 1380 599 472



Zn complexes

3a 363b 493c 323d 293e 53

Cu complexes

3f 7303g 4833h 6423i 4743j 332








Ciprofloxacin 2a 2b

2e2d2c


Ciprofloxacin 2a 2b

2c 2d 2e

12



38 Biological Assay




Ciprofloxacin

2d

2b

2e

2c

2a








Hydrazones

2a 502b 252c 502d 502e 25

Zn complexes

3a 253b 253c 1253d 253e 125

Cu complexes

3f 6253g 1253h 6253i 1253j 25





Arabinogalactan

Peptidoglycan











2a2b2c

2d2e

0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



3a3b3c3d3e

3f3g3h3i3j


0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



4 Conclusions


2a2b2c

2d2e


0

50

100

150

200

250

300

350

400

450

Fluo

resc

ence

inte

nsity

minus50


0

100

200

300

400

500

600

700

800

900Fl

uore

scen

ce in

tens

ity


3a3b3c3d3e

3f3g3h3i3j





Acknowledgments



N

FH

O

EtOH

N

NN R

O

H

FR

N

O

NH H

H


OHΔ

OH


+

Figure 10

N

NN R

O

H

F

+

RefluxEtOH

NO

NR

O

F

NO

OR

F

MOH

M = Cu(II) Zn(II)

MCl2 H2O OH2

NH

NHN

(2andash2e)

(3andash3j)

Figure 11






References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Table 2 Continued


3i

NO

N

O

F

NO

O

F

Cu

O

O

Br

Br

H2O OH2

NHN

NH

86 Green

3j

NO

N NH

O

F

NO

O

F

Cu

O

O

H2O OH2

NHN

91 Darkgreen














0

2

4

6

8

10

()


ZnCu














(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(C-F)Cmminus1

2a 3208 1660 1625 1425 12942b 3488 1650 1630 1427 12882c 3444 1662 1628 1438 12342d 3538 1656 1627 1425 12632e 3193 1668 1625 1428 1232




(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(M-N)Cmminus1

120592(M-O)Cmminus1

3a 3399 1650 1631 1376 574 4743b 3372 1646 1614 1369 590 4493c 3392 1652 1619 1380 599 4823d 3369 1650 1631 1376 599 4683e 3392 1621 1589 1425 592 4703f 3436 1665 1616 1380 597 4703g 3357 1610 1558 1375 501 4603h 3432 1658 1616 1386 566 4743i 3426 1658 1617 1382 530 4533j 3368 1663 1616 1380 599 472



Zn complexes

3a 363b 493c 323d 293e 53

Cu complexes

3f 7303g 4833h 6423i 4743j 332








Ciprofloxacin 2a 2b

2e2d2c


Ciprofloxacin 2a 2b

2c 2d 2e

12



38 Biological Assay




Ciprofloxacin

2d

2b

2e

2c

2a








Hydrazones

2a 502b 252c 502d 502e 25

Zn complexes

3a 253b 253c 1253d 253e 125

Cu complexes

3f 6253g 1253h 6253i 1253j 25





Arabinogalactan

Peptidoglycan











2a2b2c

2d2e

0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



3a3b3c3d3e

3f3g3h3i3j


0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



4 Conclusions


2a2b2c

2d2e


0

50

100

150

200

250

300

350

400

450

Fluo

resc

ence

inte

nsity

minus50


0

100

200

300

400

500

600

700

800

900Fl

uore

scen

ce in

tens

ity


3a3b3c3d3e

3f3g3h3i3j





Acknowledgments



N

FH

O

EtOH

N

NN R

O

H

FR

N

O

NH H

H


OHΔ

OH


+

Figure 10

N

NN R

O

H

F

+

RefluxEtOH

NO

NR

O

F

NO

OR

F

MOH

M = Cu(II) Zn(II)

MCl2 H2O OH2

NH

NHN

(2andash2e)

(3andash3j)

Figure 11






References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of






0

2

4

6

8

10

()


ZnCu














(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(C-F)Cmminus1

2a 3208 1660 1625 1425 12942b 3488 1650 1630 1427 12882c 3444 1662 1628 1438 12342d 3538 1656 1627 1425 12632e 3193 1668 1625 1428 1232




(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(M-N)Cmminus1

120592(M-O)Cmminus1

3a 3399 1650 1631 1376 574 4743b 3372 1646 1614 1369 590 4493c 3392 1652 1619 1380 599 4823d 3369 1650 1631 1376 599 4683e 3392 1621 1589 1425 592 4703f 3436 1665 1616 1380 597 4703g 3357 1610 1558 1375 501 4603h 3432 1658 1616 1386 566 4743i 3426 1658 1617 1382 530 4533j 3368 1663 1616 1380 599 472



Zn complexes

3a 363b 493c 323d 293e 53

Cu complexes

3f 7303g 4833h 6423i 4743j 332








Ciprofloxacin 2a 2b

2e2d2c


Ciprofloxacin 2a 2b

2c 2d 2e

12



38 Biological Assay




Ciprofloxacin

2d

2b

2e

2c

2a








Hydrazones

2a 502b 252c 502d 502e 25

Zn complexes

3a 253b 253c 1253d 253e 125

Cu complexes

3f 6253g 1253h 6253i 1253j 25





Arabinogalactan

Peptidoglycan











2a2b2c

2d2e

0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



3a3b3c3d3e

3f3g3h3i3j


0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



4 Conclusions


2a2b2c

2d2e


0

50

100

150

200

250

300

350

400

450

Fluo

resc

ence

inte

nsity

minus50


0

100

200

300

400

500

600

700

800

900Fl

uore

scen

ce in

tens

ity


3a3b3c3d3e

3f3g3h3i3j





Acknowledgments



N

FH

O

EtOH

N

NN R

O

H

FR

N

O

NH H

H


OHΔ

OH


+

Figure 10

N

NN R

O

H

F

+

RefluxEtOH

NO

NR

O

F

NO

OR

F

MOH

M = Cu(II) Zn(II)

MCl2 H2O OH2

NH

NHN

(2andash2e)

(3andash3j)

Figure 11






References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of





(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(C-F)Cmminus1

2a 3208 1660 1625 1425 12942b 3488 1650 1630 1427 12882c 3444 1662 1628 1438 12342d 3538 1656 1627 1425 12632e 3193 1668 1625 1428 1232




(C=O)Cmminus1

Imine 120592(C=N)


(C-O)Cmminus1

120592(M-N)Cmminus1

120592(M-O)Cmminus1

3a 3399 1650 1631 1376 574 4743b 3372 1646 1614 1369 590 4493c 3392 1652 1619 1380 599 4823d 3369 1650 1631 1376 599 4683e 3392 1621 1589 1425 592 4703f 3436 1665 1616 1380 597 4703g 3357 1610 1558 1375 501 4603h 3432 1658 1616 1386 566 4743i 3426 1658 1617 1382 530 4533j 3368 1663 1616 1380 599 472



Zn complexes

3a 363b 493c 323d 293e 53

Cu complexes

3f 7303g 4833h 6423i 4743j 332








Ciprofloxacin 2a 2b

2e2d2c


Ciprofloxacin 2a 2b

2c 2d 2e

12



38 Biological Assay




Ciprofloxacin

2d

2b

2e

2c

2a








Hydrazones

2a 502b 252c 502d 502e 25

Zn complexes

3a 253b 253c 1253d 253e 125

Cu complexes

3f 6253g 1253h 6253i 1253j 25





Arabinogalactan

Peptidoglycan











2a2b2c

2d2e

0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



3a3b3c3d3e

3f3g3h3i3j


0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



4 Conclusions


2a2b2c

2d2e


0

50

100

150

200

250

300

350

400

450

Fluo

resc

ence

inte

nsity

minus50


0

100

200

300

400

500

600

700

800

900Fl

uore

scen

ce in

tens

ity


3a3b3c3d3e

3f3g3h3i3j





Acknowledgments



N

FH

O

EtOH

N

NN R

O

H

FR

N

O

NH H

H


OHΔ

OH


+

Figure 10

N

NN R

O

H

F

+

RefluxEtOH

NO

NR

O

F

NO

OR

F

MOH

M = Cu(II) Zn(II)

MCl2 H2O OH2

NH

NHN

(2andash2e)

(3andash3j)

Figure 11






References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Ciprofloxacin 2a 2b

2e2d2c


Ciprofloxacin 2a 2b

2c 2d 2e

12



38 Biological Assay




Ciprofloxacin

2d

2b

2e

2c

2a








Hydrazones

2a 502b 252c 502d 502e 25

Zn complexes

3a 253b 253c 1253d 253e 125

Cu complexes

3f 6253g 1253h 6253i 1253j 25





Arabinogalactan

Peptidoglycan











2a2b2c

2d2e

0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



3a3b3c3d3e

3f3g3h3i3j


0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



4 Conclusions


2a2b2c

2d2e


0

50

100

150

200

250

300

350

400

450

Fluo

resc

ence

inte

nsity

minus50


0

100

200

300

400

500

600

700

800

900Fl

uore

scen

ce in

tens

ity


3a3b3c3d3e

3f3g3h3i3j





Acknowledgments



N

FH

O

EtOH

N

NN R

O

H

FR

N

O

NH H

H


OHΔ

OH


+

Figure 10

N

NN R

O

H

F

+

RefluxEtOH

NO

NR

O

F

NO

OR

F

MOH

M = Cu(II) Zn(II)

MCl2 H2O OH2

NH

NHN

(2andash2e)

(3andash3j)

Figure 11






References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Ciprofloxacin

2d

2b

2e

2c

2a








Hydrazones

2a 502b 252c 502d 502e 25

Zn complexes

3a 253b 253c 1253d 253e 125

Cu complexes

3f 6253g 1253h 6253i 1253j 25





Arabinogalactan

Peptidoglycan











2a2b2c

2d2e

0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



3a3b3c3d3e

3f3g3h3i3j


0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



4 Conclusions


2a2b2c

2d2e


0

50

100

150

200

250

300

350

400

450

Fluo

resc

ence

inte

nsity

minus50


0

100

200

300

400

500

600

700

800

900Fl

uore

scen

ce in

tens

ity


3a3b3c3d3e

3f3g3h3i3j





Acknowledgments



N

FH

O

EtOH

N

NN R

O

H

FR

N

O

NH H

H


OHΔ

OH


+

Figure 10

N

NN R

O

H

F

+

RefluxEtOH

NO

NR

O

F

NO

OR

F

MOH

M = Cu(II) Zn(II)

MCl2 H2O OH2

NH

NHN

(2andash2e)

(3andash3j)

Figure 11






References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of




Arabinogalactan

Peptidoglycan











2a2b2c

2d2e

0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



3a3b3c3d3e

3f3g3h3i3j


0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



4 Conclusions


2a2b2c

2d2e


0

50

100

150

200

250

300

350

400

450

Fluo

resc

ence

inte

nsity

minus50


0

100

200

300

400

500

600

700

800

900Fl

uore

scen

ce in

tens

ity


3a3b3c3d3e

3f3g3h3i3j





Acknowledgments



N

FH

O

EtOH

N

NN R

O

H

FR

N

O

NH H

H


OHΔ

OH


+

Figure 10

N

NN R

O

H

F

+

RefluxEtOH

NO

NR

O

F

NO

OR

F

MOH

M = Cu(II) Zn(II)

MCl2 H2O OH2

NH

NHN

(2andash2e)

(3andash3j)

Figure 11






References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


2a2b2c

2d2e

0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



3a3b3c3d3e

3f3g3h3i3j


0

05

1

15

2

25

3

Abso

rptio

n in

tens

ity



4 Conclusions


2a2b2c

2d2e


0

50

100

150

200

250

300

350

400

450

Fluo

resc

ence

inte

nsity

minus50


0

100

200

300

400

500

600

700

800

900Fl

uore

scen

ce in

tens

ity


3a3b3c3d3e

3f3g3h3i3j





Acknowledgments



N

FH

O

EtOH

N

NN R

O

H

FR

N

O

NH H

H


OHΔ

OH


+

Figure 10

N

NN R

O

H

F

+

RefluxEtOH

NO

NR

O

F

NO

OR

F

MOH

M = Cu(II) Zn(II)

MCl2 H2O OH2

NH

NHN

(2andash2e)

(3andash3j)

Figure 11






References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N

FH

O

EtOH

N

NN R

O

H

FR

N

O

NH H

H


OHΔ

OH


+

Figure 10

N

NN R

O

H

F

+

RefluxEtOH

NO

NR

O

F

NO

OR

F

MOH

M = Cu(II) Zn(II)

MCl2 H2O OH2

NH

NHN

(2andash2e)

(3andash3j)

Figure 11






References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

research article synthesis and biological evaluation of...

Documents