Research Article(E)3-2-(1-(24-Dihydroxyphenyl)ethyldeneamino)phenyl)-2-methylquinazoline-4(3H)-one Schiff Base and Its MetalComplexes A New Drug of Choice against Methicillin-ResistantStaphylococcus aureus
K Siddappa1 Sunilkumar B Mane1 and Deene Manikprabhu2
1 Department of Post-Graduate Studies and Research in Chemistry Gulbarga University Gulbarga Karnataka 585106 India2Department of Microbiology Gulbarga University Gulbarga Karnataka 585106 India
Correspondence should be addressed to K Siddappa siddappa 65rediffmailcom
Received 31 October 2013 Revised 4 January 2014 Accepted 6 January 2014 Published 9 March 2014
Academic Editor Imre Sovago
Copyright copy 2014 K Siddappa et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited
The 3-(2-aminophenyl) quinazolin-2-methyl-4(3H)-one and 24-dihydroxyacetophenone undergo condensation to afford (E)3-2-(1-(24-dihydroxyphenyl)ethyldeneamino)phenyl)-2-methylquinazoline-4(3H)-one Schiff base (DHPEAPMQ) The newly syn-thesized Schiff base (DHPEAPMQ) and its metal complexes were evaluated for their antimicrobial activity against methicillin-resistant Staphylococcus aureus isolated from the Gulbarga region in India The Cu(II) Ni(II) and Zn(II) complexes of Schiff base(DHPEAPMQ) showed good antimicrobial activity So this could be a new drug of choice
1 Introduction
Bioinorganic chemistry is an emerging interdisciplinary fieldof science that utilizes Schiff bases and their transition metalcomplexes for various applications in biological medicaland environmental sciences [1] The Schiff base ligands areconsidered as ldquoprivileged ligandsrdquo because they are easilyprepared by the condensation between aldehydes and iminesand their use of analytical and biological processes ondifferent models has solved many serious problems [2 3]Over the past decade the synthesis of the privileged classesof heterocyclic molecules has become one of the main areasof interest in synthetic chemistry [1 2] These importantstructures have gained much attention owing to their poten-tial role as ligands which are capable of binding multiplebiological targets [3] Among nitrogen-containing hetero-cyclic molecules substituted quinazolinones and quinazo-lines are considered as important therapeutic scaffolds [4]Quinazoline-4(3H)-one and its derivatives gained extensiveimportance in medicinal chemistry because of their diversepharmacological activities such as antibacterial antifungal
anti-inflammatory anticancer anticonvulsant antioxidantantitubercular anti-HIV and analgesic [5]
Staphylococcus aureus (S aureus) resistant to methicillinis a major problem that the world is now facing Theantibiotic era barely 60 years old is also threatenedbecause of increase of resistance rhythm of this organismagainst different antibiotics [6] Todayrsquos challenging taskis to synthesize a new antimicrobial agent that does notgenerate microbial resistant so studies in finding outnew antimicrobial agents against methicillin-resistantStaphylococcus aureus (MRSA) are desperately required ifpublic health crisis is to be averted Substitutes for antibioticsare the Schiff base and its metal complexes owing highbiological activity Based on the biological importance ofquinazoline Schiff base and to find a new antimicrobialagent against MRSA an effort was made to synthesize a new(E)3-2-(1-(24-dihydroxyphenyl)ethyldeneamino)phenyl)-2-methylquinazoline-4(3H)-one (DHPEAPMQ) Schiff baseand its complexes The present investigation deals with thesynthesis of Schiff base (DHPEAPMQ) and its complexes forevaluation of antimicrobial activity against MRSA
Hindawi Publishing CorporationBioinorganic Chemistry and ApplicationsVolume 2014 Article ID 343540 8 pageshttpdxdoiorg1011552014343540
2 Bioinorganic Chemistry and Applications
2 Materials and Methods
All the reagents and chemicals were of AR grade Elementalanalyses (C H and N) were carried out on the Perkin Elmer240C model IR spectra of the Schiff base (DHPEAPMQ)and its complexes in KBr pellets were recorded using PerkinElmer Spectrum one FT-IR spectrometer in the spectralrange 4000ndash350 cmminus1 The electronic spectra of the Cu(II)and Ni(II) complexes were recorded on a ELICO SL-164double beam UV-Vis spectrophotometer in the range 200ndash1100 nm using dimethyl formaldehyde(DMF) as a solventThe 1H NMR spectra were recorded on AMX-400 NMRspectrometer using tetramethylsilane (TMS) as an internalstandard and DMSO-d
6
as a solvent Mass spectra wererecorded on JEOL GCMATE II GC-MS mass spectrometerMagnetic susceptibilities were measured using a Gouy bal-ance at room temperature using Hg[Co(NCS)
4
] as calibrantThe molar conductance data were recorded on the ELICO-CM-82T conductivity bridge in DMF solution at concentra-tion sim10minus3M and EPR spectra recorded on Bruker Biospin
21 Synthesis of 3-(2-Aminophenyl)-2-methylquinazolin-4(3H)-one In 100mL round bottom flask a homogeneousmixture of 2-methyl-aminobenzoate (001mol) and o-phenylenediamine (001mol) in ethanol (25mL) was mixedgently and heated to reflux on a water bath for 2-3 h Theresulting mixture obtained after reflux was separated asa solid product The solid product obtained was filteredwashed with hot ethanol and finally recrystallized fromtoluene
22 Synthesis of Schiff Base (DHPEAPMQ) The syntheticpathway involved in the synthesis of Schiff base(DHPEAPMQ) mentioned below a 30mL hot alcoholicsolution of 3-(2-aminophenyl)-2-methylquinazolin-4(3H)-one (001mol) and 20mL of 1-(24-dihydroxyphenyl)ethanone (001mol) was refluxed for about 4-5 h on waterbath On evaporating the solvent the solid product wasseparated out filtered followed by washing with ethanol andfinally recrystallized from hot ethanol to give (DHPEAPMQ)as shown in Scheme 1
23 Synthesis of Metal Complexes For the preparation of rep-resentative Cu(II) Ni(II) and Zn(II) complexes a solution(30mL) of the Schiff base (DHPEAPMQ) in hot methanolwas added to a stirred solution of metal(II) chloride in 20mLmethanol The mixture was refluxed for 3 h at a temperatureof sim78∘C The reaction mixture maintained to pH 60ndash70using sodium acetate and solid intense coloured complexesformed were precipitated out The precipitated complexeswere further refluxed for about an hour to check theirstability Later they were filtered off washed thoroughly withwater and little warm methanol for apparent dryness andfinally dried in a vacuum desiccator fused over CaCl
2
24 Isolation and Identification ofMRSA Samples like bloodpus and other exudates were obtained from different hospi-tals and health care centers of the Gulbarga region in India
All the samples were first inoculated onto blood agar (Hi-media) plates The plates were incubated at 37∘C for 24ndash48 h The colonies obtained on blood agar after incubationwere again inoculated onto mannitol salt agar the plateswere again incubated at 37∘C for 24ndash48 h The preliminaryidentification of S aureus isolates was detected by changein color of the medium from red to yellow due to mannitolfermentation Further the S aureus were identified basedon morphological microscopic and biochemical tests [6]among the identified S aureus the MRSA were detectedphenotypically using antibiotic susceptibility test as per theguidelines recommended by the Clinical and LaboratoryStandards Institute (CLSI-2012) [7]
25 Antimicrobial Activity of Schiff Base (DHPEAPMQ) andIts Complexes against MRSA The antibacterial activities ofthe newly synthesized Schiff base (DHPEAPMQ) and itsmetal complexs against MRSA were evaluated on MuellerHinton agar (MHA) by making a lawn of MRSA (05McFarland) with the help of sterile cotton swabs and wellsof 6mm diameter were punched carefully using a cork borerThe wells were loaded with 100120583L (1mgmL in DMSO as asolvent) of different investigated test compounds The plateswere incubated at 37∘C for 24 h Antibacterial activity wasdetermined by measuring the zone of inhibition
26 Determination of Minimum Inhibitory Concentration(MIC) TheMIC is that last tube in which no visible growthof microorganism was recorded To determine MIC differentvolumes of investigating test compounds (2 4 6 8 10 12 1416 18 20 22 24 26 28 30 32 34 36 38 and 40 120583gmL)and MRSA culture (05 McFarland) were added into MuellerHinton Broth (MHB) andwere incubated at 37∘C for 18 h Forcomparison purpose methicillin antibiotic was taken as thestandard
3 Results and Discussion
MRSA was isolated at low levels a decade ago but is currentlywidespread [8] due to the development of resistance tomethicillin antibiotic which exponentially increased highmorbidity and mortality [6 9] so there is an urgent need ofa new antimicrobial agent who does not generate resistanceagainst MRSA Alternate to antibiotics are Schiff base andtheirmetal complexes (especially quinazoline-4(3H)-one andtheir metal complexes) having a vast application in the fieldofmedicalmicrobiology Recently Prashanth andRevanasid-dappa showed antimicrobial activity of glutamine linked 23 disubstituted quinazolinone derivatives as potent antimi-crobial agent against both gram positive and gram negativebacteria [10] Similarly Kalagouda et al reported antibacterialactivity of Lanthanide(III) Complexes of 2-[2-hydroxy-3-methoxyphenyl]-3-[2-hydroxy-3 methoxybenzylamino]-12-dihydroquinazolin-4(3H)-one against bacteria like Pseu-domonas aeruginosa and Bacillus cirroflagellosus [11] Due tothe diverse antimicrobial activity of the Schiff base in the
Scheme 1 Synthetic route for the preparation of (DHPEAPMQ)
present investigation we report the synthesis and character-ization of new Schiff base (DHPEAPMQ) and its antimicro-bial activity against MRSA isolated from the Gulbarga regionin India
31 Structural Analysis of the Complexes The analytical andphysical parameters of the newly synthesized Schiff base(DHPEAPMQ) and its metal complexes reveal Schiff base(DHPEAPMQ) and its complexes were very stable and non-hygroscopic at room temperature and the complexes weresparingly soluble in commonorganic solvents and completelysoluble in DMF and DMSO The measured molar conduc-tance values were in the range of 12ndash16 Ohmminus1 cm2molminus1which indicates the nonelectrolytic nature ofmetal complexes[12] as shown in Table 1 The metals and chloride contentswere determined as per standard protocol [13]
The formations of prescribed geometries of metal com-plexes were achieved by various spectral studies such as UV-Visible IR 1H NMR and mass
The electronic spectra of a Schiff base (DHPEAPMQ)exhibit two bands between 33768 and 27397 cmminus1 dueto 120587 rarr 120587lowast and 119899 rarr 120587lowast transitions associated with -C=N andC=O respectivelyThe shift in frequencies to higherwavelength suggests the coordination of azomethine nitrogenand carboxylic oxygen with metal ions The electronic spec-trum of Cu(II) complex displayed a broad asymmetric bandin the region of 12540ndash17860 cmminus1 due to 2E
119892
rarr
2T2119892
transi-tion indicating the distorted octahedral geometry around theCu(II) ion [14]TheNi(II) complex shows three well-resolvedbands at 9382 18920 and 20860 cmminus1 assigned to 3A
2119892
(F)rarr3T2119892
(F) (]1
) 3A2119892
(F)rarr 3T1119892
(F) (]2
) and 3A2119892
(F)rarr 3T1119892
(P) (]3
) transitions respectively which show the octahedralgeometry around theNi(II) ion [15]The electronic parametervalues such as the Racah interelectronic repulsion parameter(1198611015840) ligand field splitting energy (10Dq) covalency factor (120573)and ligand field stabilization energy (LFSE) [16] have beencalculated by using band-fitting equation [17] The 1198611015840valuesfor the complexes were lower than the free ion values which
4 Bioinorganic Chemistry and Applications
Table 1 Elemental analysis of physical and magnetic data of Schiff base (DHPEAPMQ) and its complexes
Molecular formula ofligandcomplexes
Mol Wt(gmol)
m p∘C
Elemental analysis found (calculated) 120583eff (BM) Λ
119898
lowast
C H N M ClC23H19N3O3(DHPEAPMQ) 38542 270 7117
(7167)461(497)
1031(1090) mdash mdash mdash mdash
[Cu(C23H18N3O3)2] 83236 292 6638(6671)
401(436)
1010(1045)
736(790) mdash 181 1630
[Ni(C23H18N3O3)2] 82620 285 6610(6777)
403(438)
1001(1016)
694(709) mdash 439 1237
[Zn(C23H18N3O3)Cl)] 48527 291 5607(5693)
342(374)
852(866)
1328(1348)
722(731) Diam 1410
lowastMolar conductance values in Ohmminus1 cm2 molminus1
indicate orbital overlaps and delocalization of d-orbitalrsquosThecovalent factor 120573 equal to 1198611198611015840 for the complexes was lessthan one suggesting the considerable covalent character ofmetal-ligand bonds In the present study the 120573 (076) valuesobtained were less than unity which indicates the covalencyfor the metal-ligand bonds In addition the covalence factors(b12) Sinha parameter (120575) that is metal-ligand covalencypercent and the covalency angular overlap parameter (120578)have been calculated from the values of 120573 by using thefollowing expressions [18]
b12 = 12
[(1 minus 120573)
12
] 120575 () = [1 minus 120573
120573
] times 100
120578 =
[(1 minus 120573
12
)]
120573
12
(1)
The electronic spectral studies of the Cu(II) and Ni(II)complexes yield a positive value for (1-120573) b12 and 120575 as wellas 120578which suggest that the bonding betweenmetal and ligandwas covalent in the complexesThe values of the parameter ofbonding (12057312) and angular overlap parameter (120578) were foundto be positive which indicates a strong covalent bondingbetween the Schiff base (DHPEAPMQ) and its complexes asshown in Table 2
The IR spectrum of Schiff base (DHPEAPMQ) displays abroadband in the region of 3402ndash3380 cmminus1 due to ](2-OH)of 1-(24-dihydroxyphenyl) ethanone upon metal complexesformation the disappearance of one (-OH) groups indicatesthe involvement of phenolic oxygen bonding with metal ionvia deprotonation [19] However the peak in the region of3390ndash3395 cmminus1 that was retained in complexes shows thepresence of uncoordinated (-OH) group Furthermore theevidence for the coordination through only one or both ofthe phenolic oxygen was confirmed by 1H NMR spectralstudies The Schiff base (DHPEAPMQ) shows character-istic resonance signals at 120575 1143 ppm (s 1H OH) and 120575960 ppm (s 1H OH) upon metal complexes formationdisappearance of one -OH proton 120575 (960 ppm) on the otherhand the other proton remained unaltered at 120575 1143 ppm (s1H OH) (D
2
O exchangeable) indicates the participation ofonly one phenolic oxygen in coordination with metal ionvia deprotonation [20] as presented in (see supplementary
file 1(andashd) in Supplementary Material available online athttpdxdoiorg1011552014343540)
A characteristic high intense band due to azomethine](-C=N) in the IR spectrum of Schiff base (DHPEAPMQ)appeared in the region of 1598ndash1592 cmminus1 experiences anegative shift of 15ndash20 cmminus1 in their respective complexesand lower value of ](-C=N) stretching can be explained onthe basis of a drift of the lone-pair density of azomethinenitrogen towards the metal ions indicates coordination ofazomethine nitrogen with the metal ions [21] Further thiswas confirmed by NMR spectra owing to the downfield shiftof azomethine proton from 120575 835 ppm (s 1H -CH=N) ofSchiff base (DHPEAPMQ) to 120575 842 ppm (s 1H -CH=N) incomplexes which shows the involvement of -CH=N nitrogenin coordination
In the IR spectrum of Schiff base (DHPEAPMQ) ahigh intense strong band in the region of 1712ndash1702 cmminus1was assigned due to the carboxyl group of quinazoline ring(C=O) which shows a downfield shift of 20ndash30 cmminus1andindicates the participation of carboxylic oxygen upon com-plex formation [22]
All the complexes show medium intensity bands inthe region of 558ndash547 cmminus1 and 463ndash457 cmminus1 assigned to](M-O) and ](M-N) vibrations respectively which furthersupport the coordination of the Schiff base (DHPEAPMQ)through the nitrogen of azomethine and carboxylic and phe-nolic oxygen with various metal ions [23] Moreover a weakband was observed in the region of 355ndash350 cmminus1 assignedto ](M-Cl) this was a characteristic of the chloride atom inZn(II) complex and was further confirmed by quantitativechloride estimation The 1H NMR signal corresponds to therest of the protons such asmethyl protons 120575 252ndash264 ppm (s6H and CH
3
) and aromatic protons 120575 671ndash872 ppm (m 11Hand Ar-H) of Schiff base (DHPEAPMQ) and its complexeswere exhibited in their expected regions
Thus from the above it was inferred that the Schiffbase (DHPEAPMQ) acts as a tridentate ONO donor andforms octahedral geometry with Cu(II) Ni(II) complexesand tetrahedral geometry with Zn(II) complex via theinvolvement of phenolic oxygen azomethine nitrogen andcarboxylic oxygen as shown in Figures 1 and 2
The effective magnetic moments 120583eff expressed inmultiples of the Bohr Magneton calculated for Cu(II) andNi(II) complexes were in the range of 181ndash196 BM and
Bioinorganic Chemistry and Applications 5
Table 2 Ligand field Sinha metal-ligand covalency percent and covalency angular overlap parameters of Cu(II) and Ni(II) complexes
334ndash369 BM respectively due to mononuclear Cu(II) (d91 unpaired electron) and Ni(II) (d8 2 unpaired electrons)complexes which indicates their octahedral geometries [24]whereas the Zn(II) complex is diamagnetic in nature
The formation of a Schiff base (DHPEAPMQ) and itscomplexes was further confirmed by their mass spectralstudy All the spectra exhibit parent peaks due to molecularions (M+) and the isotopic peak owing to the chlorinesubstitution The proposed molecular formula of each com-pound was confirmed by its molecular formula weight withmz values The mass spectra of Schiff base (DHPEAPMQ)showed the formation of a molecular ion peak at mz 385[M]+ whereas Cu(II) Ni(II) and Zn(II) complexes showthe formation of molecular ion peaks along with isotopicpeaks atmz 832 [M]+ 826 [M]+ and 485 [M]+ 487 [M+2]+respectively corresponding to their molecular formula
311 ESR SpectrumofCu(II) Complex TheX-bandESR spec-tra of Cu(II) complex were recorded in the polycrystallinestate at room temperature at a frequency of 9387GHz witha field set of 3950G The information about the hyperfineand super hyperfine structure was obtained to explain thegeometry of the complex as well as the site of the metal-ligand bonding or chemical environment around the metalion In the present study the ESR spectral pattern of Cu(II)complex as depicted in supplementary file 1(e) gives the data119892
value was less than 23 and confirms thestrong covalent nature of themetal-ligand bondThe 119892
||
valueplays a significant role in elucidating the metal-ligand bondcharacter for ionic 119892
||
gt 23 and for covalent characters 119892||
lt
23 respectively [25] The ESR spectrum showed asymmetricbands with 119892
||
gt 119892
perp
gt 20023 representing that the unpairedelectrons lay predominantly in the119889
119909
2minus119910
2 orbital with possiblemixing of 119889
119911
2 because of low symmetry [26]TheG value wascalculated by using the formula 119866 = (119892
||
minus 20023)(119892
perp
minus
20023) which was greater than 4 as shown in Table 3 andindicates the negligible exchange interaction in solid complexas suggested by Hathaway and Billing [27]
32 Antimicrobial Activity of Schiff Base (DHPEAPMQ) andIts Complexes against MRSA The antimicrobial activity ofthe Schiff base (DHPEAPMQ) and its complexes was eval-uated against MRSA and isolated from different hospitalsand health care centers of the Gulbarga region in IndiaFigure 3 shows the good antimicrobial activity of the Schiffbase (DHPEAPMQ) against MRSA with a zone of inhibition(12mm) however upon complex formation the antimicro-bial activity increased with a zone of inhibition (18mm16mm and 14mm) for Cu(II) Ni(II) and Zn(III) complexesrespectively
The antimicrobial property of the Schiff base was ratio-nalized due to the presence of azomethine (C=N) groupthis imports in elucidating the mechanism of transamina-tion and resamination reactions in biological system [28]The formation of hydrogen bonds through the azomethinegroup with the active centers of various cellular constituentsresults in interference with normal cellular processes [29]Furthermore it has also been suggested that the Schiff baseligands with nitrogen and oxygen donor systems mightinhibit enzyme production causing cell death [30]
The enhanced activity of metal complexes than theSchiff base can be explained by Tweedyrsquos chelation theorywhich suggests that the chelation could allow for the delo-calization of 120587-electrons over the entire chelate ring andenhances the lipophilicity of the complexes This increasedlipophilicity facilitates the penetration of the complexes intolipid membranes further restricting the proliferation of themicroorganisms [31]
6 Bioinorganic Chemistry and Applications
Table 3 ESR data of the [Cu(C23H18N3O3)2] metal complex
Complex 119892
119892
perp
119892av 119892iso 119866
[Cu(C23H18N3O3)2] 228 207 211 217 410
N
N
N
N C
N
N
N
N
N
N
N
N
HO
HO
OH
OH OH
C
C
O
O
O OZnCl
O
MO
C OH3C
H3C
CH3
CH3
CH3
CH3
CH3
CH3
Antimicrobial activity ofDHPEAPMQ and its complexes
DHPEAPMQ
Dihydroxyphenyl)ethylideneamino)phenyl)-2-
100120583gmLat concentration
Zn(II)M = Cu(II) and Ni(II)
(E)-3-(2-(1-(24-
methylquinazolin-4(3H)-one
Figure 3 Antimicrobial activity of Schiff base (DHPEAPMQ) and its complexes against MRSA [a1 Schiff base (DHPEAPMQ) a2 Cu(II)a3 Ni(II) and a4 Zn(II) complex]
33 Determination of Minimum Inhibitory Concentration(MIC) Table 4 shows MIC values of Schiff base(DHPEAPMQ) and its complexes which indicates Cu(II)as an excellent antimicrobial agent followed by Ni(II) andZn(III) complexes The enhanced activity of Cu(II) complexmay be due to their particle size and also may be attributedto its higher stability constants [32] when compared to theSchiff base (DHPEAPMQ) and other metal complexes
4 Conclusion
In conclusion we report the synthesis and characterizationof new Schiff base (DHPEAPMQ) and its metal complexesand their antimicrobial activity against MRSA isolated fromclinical samples of the Gulbarga region in India The synthe-ses were confirmed by UV-visible IR NMR mass and ESRspectral data and their results reveal that Cu(II) and Ni(II)
Table 4MIC values of Schiff base (DHPEAPMQ) and its complexesagainst MRSA
complexes exhibit an octahedral geometry while Zn(II) com-plex shows tetrahedral geometry The MIC values of Cu(II)Ni(II) and Zn(II) were 14 18 and 24 120583gmL respectivelywhich show an excellent antimicrobial activity againstMRSASo the same can be used as a new drug of choice
Bioinorganic Chemistry and Applications 7
Conflict of Interests
The authors have no conflict of interests to declare
Acknowledgments
The authors are thankful to the Chairman of Departmentof Chemistry Gulbarga University Gulbarga for providinglaboratory facilities Sunilkumar B Mane is thankful toUGC-MRP (F no 37-1712009(SR)) New Delhi India forproviding financial assistance
References
[1] S Palanisamy K Paramasivam B R Rachel H C Alanand D Nallasamy ldquoSynthesis of novel heterobimetallic cop-per(I)hydrazone Schiff base complexes a comparative studyon the effect of heterocyclic hydrazides towards interactionwith DNAprotein free radical scavenging and cytotoxicityrdquoMetallomics vol 4 no 5 pp 498ndash511 2012
[2] S Nahid G Zeinab and H Saba ldquoBinding studies ofa newwater-soluble iron(III)schiff base complex to DNAusingmultispectroscopicmethodsrdquoBioinorganic Chemistry andApplications vol 2012 Article ID 126451 9 pages 2012
[3] N E A El-Gamel ldquoCoordination behaviour and biopotency ofmetal NN salen complexesrdquo RSC Advances vol 2 no 13 pp5870ndash5876 2012
[4] H D Revanasiddappa K S Prasad L S Kumar and BJayalakshmi ldquoSynthesis and biological activity of new Schiffbases containing 4(3H)-quinazolinone ring systemrdquo Interna-tional Journal of ChemTech Research vol 2 no 2 pp 1344ndash13492010
[5] G Naganagowda and A Petsom ldquoSynthesis and antimicrobialactivity of some new 2-(3-chloro-1- benzothiophen-2-yl)-3-(substituted-phenyl)-4-(3H)-quinazolinones derivativesrdquo Jour-nal of Sulfur Chemistry vol 32 no 3 pp 223ndash233 2011
[6] D Manikprabhu and K Lingappa ldquoAntibacterial activity ofsilver nanoparticles against methicillin-resistant Staphylococcusaureus synthesized using model Streptomyces sp pigment byphoto-irradiation methodrdquo Journal of Pharmacy Research vol6 no 2 pp 255ndash260 2013
[7] CLSI ldquoPerforming Standards for Antimicrobial SusceptibilityTesting Twenty-second Informational Supplement CLSI doc-ument M100-S22rdquo Clinical and Laboratory Standards InstituteWayne Pa USA 2012
[8] T P Tim Cushine and J L Andrew ldquoAntimicrobial activity offlavonoidsrdquo International Journal of Antimicrobial Agents vol26 no 5 pp 343ndash356 2005
[9] D Nelson D M Priscyla G I H de Souza L O Alves and EEsposito ldquoAntibacterial effect of silver nanoparticles producedby fungal process on textile fabrics and their effluent treatmentrdquoJournal of Biomedical Nanotechnology vol 3 no 2 pp 203ndash2082007
[10] M K Prashanth and H D Revanasiddappa ldquoSynthesis ofsome new glutamine linked 23 disubstituted quinazolinonederivatives as potent antimicrobial and antioxidant agentsrdquoMedicinal Chemistry Research vol 22 no 6 pp 2665ndash26762013
[11] B G Kalagouda C H Vidyadhar A P Siddappa and R PBasavaraj ldquoAntimicrobial study of newly synthesized lantha-nide(III) complexes of 2-[2-hydroxy-3-methoxyphenyl]-3-[2-hydroxy-3-methoxybenzylamino]-1 2-dihydroquinazolin-4(3H)-onerdquo Metal-Based Drugs vol 2007 Article ID 37348 7pages 2007
[12] W J Geary ldquoThe use of conductivity measurements in organicsolvents for the characterisation of coordination compoundsrdquoCoordination Chemistry Reviews vol 7 no 1 pp 81ndash122 1971
[13] A I Vogel A Text Book of Quantitative Inorganic AnalysisLongman ELBS London UK 3rd edition 1968
[14] S Biswas K Mitra C H Schwalbe C R Lucas S KChattopadhyay and B Adhikary ldquoSynthesis and characteriza-tion of some Mn(II) and Mn(III) complexes of NN1015840-o-phe-nylenebis(salicylideneimine)(LH
2
) and NN1015840-o-phenylene-bis(5-bromosalicylideneimine)(L1015840H
2
) Crystal structures of[Mn(L)(H
2
O)(ClO4
)] [Mn(L)(NCS)] and an infinite linearchain of [Mn(L)(OAc)]rdquo Inorganica Chimica Acta vol 358 no8 pp 2473ndash2481 2005
[15] N S Youssef E El-Zahany A M A El-Seidy A Caselli andS Cenini ldquoSynthesis and characterization of some transitionmetal complexes with a novel Schiff base ligand and their useas catalysts for olefin cyclopropanationrdquo Journal of MolecularCatalysis A vol 308 no 1-2 pp 159ndash168 2009
[16] D N Satyanarayana Electronic Absorption Spectroscopy andRelated Techniques University Press India Limited New DelhiIndia 2001
[17] K Abe K Matsufuji M Ohba and H Okawa ldquoSite specificityof metal ions in heterodinuclear complexes derived from anldquoend-offrdquo compartmental ligandrdquo Inorganic Chemistry vol 41no 17 pp 4461ndash4467 2002
[18] S P Tandon and P C Mehta ldquoSpectral intensities of somePr+3120573-diketonatesrdquoThe Journal of Chemical Physics vol 52 no1 pp 4313ndash4315 1970
[19] K N Kumar and R Ramesh ldquoSynthesis luminescent redoxand catalytic properties of Ru(II) carbonyl complexes contain-ing 2N2O donorsrdquo Polyhedron vol 24 no 14 pp 1885ndash18922005
[20] S Saydam ldquoSynthesis and characterisation of the new thiazoleSchiff base 2-(2-hydroxy)naphthylideneaminobenzothiazoleand its complexes withCo(II) Cu(II) andNi(II) ionsrdquo Synthesisand Reactivity in Inorganic and Metal-Organic Chemistry vol32 no 3 pp 437ndash447 2002
[21] C Jayabalakrishnan andKNatarajan ldquoRuthenium(II) carbonylcomplexes with tridentate Schiff bases and their antibacterialactivityrdquo Transition Metal Chemistry vol 27 no 1 pp 75ndash792002
[22] M Muthukumar and P Viswanathamurthi ldquoSynthesis spectralcharacterization and catalytic studies of new ruthenium(II)chalcone thiosemicarbazone complexesrdquo Central EuropeanJournal of Chemistry vol 8 no 1 pp 229ndash240 2010
[23] S Chandra and L K Gupta ldquoEPR mass IR electronic andmagnetic studies on copper(II) complexes of semicarbazonesand thiosemicarbazonesrdquo Spectrochimica Acta A vol 61 no 1-2pp 269ndash275 2005
[24] K B Gudasi M S Patil R S Vadavi R V Shenoy S A Patiland M Nethaji ldquoX-ray crystal structure of the N-(2-hydroxy-1-naphthalidene)phenylglycine Schiff base Synthesis and char-acterization of its transition metal complexesrdquo Transition MetalChemistry vol 31 no 5 pp 580ndash585 2006
[25] D Kilveson ldquoPublications of daniel kivelsonrdquo Journal of Physi-cal Chemistry B vol 101 no 43 pp 8631ndash8634 1997
8 Bioinorganic Chemistry and Applications
[26] H Liu H Wang F Gao D Niu and Z Lu ldquoSelf-assemblyof copper(II) complexes with substituted aroylhydrazones andmonodentate N-heterocycles Synthesis structure and proper-tiesrdquo Journal of Coordination Chemistry vol 60 no 24 pp2671ndash2678 2007
[27] B J Hathaway and D E Billing ldquoThe electronic properties andstereochemistry of mono-nuclear complexes of the copper(II)ionrdquo Coordination Chemistry Reviews vol 5 no 2 pp 143ndash2071970
[28] P P Dholakiya andM N Patel ldquoMetal complexes preparationmagnetic spectral and biocidal studies of some mixed-ligandcomplexes with Schiff bases containing NO and NN donoratomsrdquo Synthesis and Reactivity in Inorganic and Metal-OrganicChemistry vol 34 no 3 pp 553ndash563 2004
[29] 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
[30] Z H Chohan M Arif M A Akhtar and C T SupuranldquoMetal-based antibacterial and antifungal agents synthesischaracterization and in vitro biological evaluation of Co(II)Cu(II) Ni(II) and Zn(II) complexes with amino acid-derivedcompoundsrdquo Bioinorganic Chemistry and Applications vol2006 Article ID 83131 13 pages 2006
[31] N Raman R Jeyamurugan M Subbulakshmi R Boomi-nathan and C R Yuvarajan ldquoSynthesis DNA binding andantimicrobial studies of novel metal complexes containing apyrazolone derivative Schiff baserdquo Chemical Papers vol 64 no3 pp 318ndash328 2010
[32] S M Jadhav V A Shelke A S Munde S G Shankarwar V RPatharkar and T K Chondhekar ldquoSynthesis characterizationpotentiometry and antimicrobial studies of transition metalcomplexes of a tridentate ligandrdquo Journal of CoordinationChemistry vol 63 no 23 pp 4153ndash4164 2010
All the reagents and chemicals were of AR grade Elementalanalyses (C H and N) were carried out on the Perkin Elmer240C model IR spectra of the Schiff base (DHPEAPMQ)and its complexes in KBr pellets were recorded using PerkinElmer Spectrum one FT-IR spectrometer in the spectralrange 4000ndash350 cmminus1 The electronic spectra of the Cu(II)and Ni(II) complexes were recorded on a ELICO SL-164double beam UV-Vis spectrophotometer in the range 200ndash1100 nm using dimethyl formaldehyde(DMF) as a solventThe 1H NMR spectra were recorded on AMX-400 NMRspectrometer using tetramethylsilane (TMS) as an internalstandard and DMSO-d
6
as a solvent Mass spectra wererecorded on JEOL GCMATE II GC-MS mass spectrometerMagnetic susceptibilities were measured using a Gouy bal-ance at room temperature using Hg[Co(NCS)
4
] as calibrantThe molar conductance data were recorded on the ELICO-CM-82T conductivity bridge in DMF solution at concentra-tion sim10minus3M and EPR spectra recorded on Bruker Biospin
21 Synthesis of 3-(2-Aminophenyl)-2-methylquinazolin-4(3H)-one In 100mL round bottom flask a homogeneousmixture of 2-methyl-aminobenzoate (001mol) and o-phenylenediamine (001mol) in ethanol (25mL) was mixedgently and heated to reflux on a water bath for 2-3 h Theresulting mixture obtained after reflux was separated asa solid product The solid product obtained was filteredwashed with hot ethanol and finally recrystallized fromtoluene
22 Synthesis of Schiff Base (DHPEAPMQ) The syntheticpathway involved in the synthesis of Schiff base(DHPEAPMQ) mentioned below a 30mL hot alcoholicsolution of 3-(2-aminophenyl)-2-methylquinazolin-4(3H)-one (001mol) and 20mL of 1-(24-dihydroxyphenyl)ethanone (001mol) was refluxed for about 4-5 h on waterbath On evaporating the solvent the solid product wasseparated out filtered followed by washing with ethanol andfinally recrystallized from hot ethanol to give (DHPEAPMQ)as shown in Scheme 1
23 Synthesis of Metal Complexes For the preparation of rep-resentative Cu(II) Ni(II) and Zn(II) complexes a solution(30mL) of the Schiff base (DHPEAPMQ) in hot methanolwas added to a stirred solution of metal(II) chloride in 20mLmethanol The mixture was refluxed for 3 h at a temperatureof sim78∘C The reaction mixture maintained to pH 60ndash70using sodium acetate and solid intense coloured complexesformed were precipitated out The precipitated complexeswere further refluxed for about an hour to check theirstability Later they were filtered off washed thoroughly withwater and little warm methanol for apparent dryness andfinally dried in a vacuum desiccator fused over CaCl
2
24 Isolation and Identification ofMRSA Samples like bloodpus and other exudates were obtained from different hospi-tals and health care centers of the Gulbarga region in India
All the samples were first inoculated onto blood agar (Hi-media) plates The plates were incubated at 37∘C for 24ndash48 h The colonies obtained on blood agar after incubationwere again inoculated onto mannitol salt agar the plateswere again incubated at 37∘C for 24ndash48 h The preliminaryidentification of S aureus isolates was detected by changein color of the medium from red to yellow due to mannitolfermentation Further the S aureus were identified basedon morphological microscopic and biochemical tests [6]among the identified S aureus the MRSA were detectedphenotypically using antibiotic susceptibility test as per theguidelines recommended by the Clinical and LaboratoryStandards Institute (CLSI-2012) [7]
25 Antimicrobial Activity of Schiff Base (DHPEAPMQ) andIts Complexes against MRSA The antibacterial activities ofthe newly synthesized Schiff base (DHPEAPMQ) and itsmetal complexs against MRSA were evaluated on MuellerHinton agar (MHA) by making a lawn of MRSA (05McFarland) with the help of sterile cotton swabs and wellsof 6mm diameter were punched carefully using a cork borerThe wells were loaded with 100120583L (1mgmL in DMSO as asolvent) of different investigated test compounds The plateswere incubated at 37∘C for 24 h Antibacterial activity wasdetermined by measuring the zone of inhibition
26 Determination of Minimum Inhibitory Concentration(MIC) TheMIC is that last tube in which no visible growthof microorganism was recorded To determine MIC differentvolumes of investigating test compounds (2 4 6 8 10 12 1416 18 20 22 24 26 28 30 32 34 36 38 and 40 120583gmL)and MRSA culture (05 McFarland) were added into MuellerHinton Broth (MHB) andwere incubated at 37∘C for 18 h Forcomparison purpose methicillin antibiotic was taken as thestandard
3 Results and Discussion
MRSA was isolated at low levels a decade ago but is currentlywidespread [8] due to the development of resistance tomethicillin antibiotic which exponentially increased highmorbidity and mortality [6 9] so there is an urgent need ofa new antimicrobial agent who does not generate resistanceagainst MRSA Alternate to antibiotics are Schiff base andtheirmetal complexes (especially quinazoline-4(3H)-one andtheir metal complexes) having a vast application in the fieldofmedicalmicrobiology Recently Prashanth andRevanasid-dappa showed antimicrobial activity of glutamine linked 23 disubstituted quinazolinone derivatives as potent antimi-crobial agent against both gram positive and gram negativebacteria [10] Similarly Kalagouda et al reported antibacterialactivity of Lanthanide(III) Complexes of 2-[2-hydroxy-3-methoxyphenyl]-3-[2-hydroxy-3 methoxybenzylamino]-12-dihydroquinazolin-4(3H)-one against bacteria like Pseu-domonas aeruginosa and Bacillus cirroflagellosus [11] Due tothe diverse antimicrobial activity of the Schiff base in the
Scheme 1 Synthetic route for the preparation of (DHPEAPMQ)
present investigation we report the synthesis and character-ization of new Schiff base (DHPEAPMQ) and its antimicro-bial activity against MRSA isolated from the Gulbarga regionin India
31 Structural Analysis of the Complexes The analytical andphysical parameters of the newly synthesized Schiff base(DHPEAPMQ) and its metal complexes reveal Schiff base(DHPEAPMQ) and its complexes were very stable and non-hygroscopic at room temperature and the complexes weresparingly soluble in commonorganic solvents and completelysoluble in DMF and DMSO The measured molar conduc-tance values were in the range of 12ndash16 Ohmminus1 cm2molminus1which indicates the nonelectrolytic nature ofmetal complexes[12] as shown in Table 1 The metals and chloride contentswere determined as per standard protocol [13]
The formations of prescribed geometries of metal com-plexes were achieved by various spectral studies such as UV-Visible IR 1H NMR and mass
The electronic spectra of a Schiff base (DHPEAPMQ)exhibit two bands between 33768 and 27397 cmminus1 dueto 120587 rarr 120587lowast and 119899 rarr 120587lowast transitions associated with -C=N andC=O respectivelyThe shift in frequencies to higherwavelength suggests the coordination of azomethine nitrogenand carboxylic oxygen with metal ions The electronic spec-trum of Cu(II) complex displayed a broad asymmetric bandin the region of 12540ndash17860 cmminus1 due to 2E
119892
rarr
2T2119892
transi-tion indicating the distorted octahedral geometry around theCu(II) ion [14]TheNi(II) complex shows three well-resolvedbands at 9382 18920 and 20860 cmminus1 assigned to 3A
2119892
(F)rarr3T2119892
(F) (]1
) 3A2119892
(F)rarr 3T1119892
(F) (]2
) and 3A2119892
(F)rarr 3T1119892
(P) (]3
) transitions respectively which show the octahedralgeometry around theNi(II) ion [15]The electronic parametervalues such as the Racah interelectronic repulsion parameter(1198611015840) ligand field splitting energy (10Dq) covalency factor (120573)and ligand field stabilization energy (LFSE) [16] have beencalculated by using band-fitting equation [17] The 1198611015840valuesfor the complexes were lower than the free ion values which
4 Bioinorganic Chemistry and Applications
Table 1 Elemental analysis of physical and magnetic data of Schiff base (DHPEAPMQ) and its complexes
Molecular formula ofligandcomplexes
Mol Wt(gmol)
m p∘C
Elemental analysis found (calculated) 120583eff (BM) Λ
119898
lowast
C H N M ClC23H19N3O3(DHPEAPMQ) 38542 270 7117
(7167)461(497)
1031(1090) mdash mdash mdash mdash
[Cu(C23H18N3O3)2] 83236 292 6638(6671)
401(436)
1010(1045)
736(790) mdash 181 1630
[Ni(C23H18N3O3)2] 82620 285 6610(6777)
403(438)
1001(1016)
694(709) mdash 439 1237
[Zn(C23H18N3O3)Cl)] 48527 291 5607(5693)
342(374)
852(866)
1328(1348)
722(731) Diam 1410
lowastMolar conductance values in Ohmminus1 cm2 molminus1
indicate orbital overlaps and delocalization of d-orbitalrsquosThecovalent factor 120573 equal to 1198611198611015840 for the complexes was lessthan one suggesting the considerable covalent character ofmetal-ligand bonds In the present study the 120573 (076) valuesobtained were less than unity which indicates the covalencyfor the metal-ligand bonds In addition the covalence factors(b12) Sinha parameter (120575) that is metal-ligand covalencypercent and the covalency angular overlap parameter (120578)have been calculated from the values of 120573 by using thefollowing expressions [18]
b12 = 12
[(1 minus 120573)
12
] 120575 () = [1 minus 120573
120573
] times 100
120578 =
[(1 minus 120573
12
)]
120573
12
(1)
The electronic spectral studies of the Cu(II) and Ni(II)complexes yield a positive value for (1-120573) b12 and 120575 as wellas 120578which suggest that the bonding betweenmetal and ligandwas covalent in the complexesThe values of the parameter ofbonding (12057312) and angular overlap parameter (120578) were foundto be positive which indicates a strong covalent bondingbetween the Schiff base (DHPEAPMQ) and its complexes asshown in Table 2
The IR spectrum of Schiff base (DHPEAPMQ) displays abroadband in the region of 3402ndash3380 cmminus1 due to ](2-OH)of 1-(24-dihydroxyphenyl) ethanone upon metal complexesformation the disappearance of one (-OH) groups indicatesthe involvement of phenolic oxygen bonding with metal ionvia deprotonation [19] However the peak in the region of3390ndash3395 cmminus1 that was retained in complexes shows thepresence of uncoordinated (-OH) group Furthermore theevidence for the coordination through only one or both ofthe phenolic oxygen was confirmed by 1H NMR spectralstudies The Schiff base (DHPEAPMQ) shows character-istic resonance signals at 120575 1143 ppm (s 1H OH) and 120575960 ppm (s 1H OH) upon metal complexes formationdisappearance of one -OH proton 120575 (960 ppm) on the otherhand the other proton remained unaltered at 120575 1143 ppm (s1H OH) (D
2
O exchangeable) indicates the participation ofonly one phenolic oxygen in coordination with metal ionvia deprotonation [20] as presented in (see supplementary
file 1(andashd) in Supplementary Material available online athttpdxdoiorg1011552014343540)
A characteristic high intense band due to azomethine](-C=N) in the IR spectrum of Schiff base (DHPEAPMQ)appeared in the region of 1598ndash1592 cmminus1 experiences anegative shift of 15ndash20 cmminus1 in their respective complexesand lower value of ](-C=N) stretching can be explained onthe basis of a drift of the lone-pair density of azomethinenitrogen towards the metal ions indicates coordination ofazomethine nitrogen with the metal ions [21] Further thiswas confirmed by NMR spectra owing to the downfield shiftof azomethine proton from 120575 835 ppm (s 1H -CH=N) ofSchiff base (DHPEAPMQ) to 120575 842 ppm (s 1H -CH=N) incomplexes which shows the involvement of -CH=N nitrogenin coordination
In the IR spectrum of Schiff base (DHPEAPMQ) ahigh intense strong band in the region of 1712ndash1702 cmminus1was assigned due to the carboxyl group of quinazoline ring(C=O) which shows a downfield shift of 20ndash30 cmminus1andindicates the participation of carboxylic oxygen upon com-plex formation [22]
All the complexes show medium intensity bands inthe region of 558ndash547 cmminus1 and 463ndash457 cmminus1 assigned to](M-O) and ](M-N) vibrations respectively which furthersupport the coordination of the Schiff base (DHPEAPMQ)through the nitrogen of azomethine and carboxylic and phe-nolic oxygen with various metal ions [23] Moreover a weakband was observed in the region of 355ndash350 cmminus1 assignedto ](M-Cl) this was a characteristic of the chloride atom inZn(II) complex and was further confirmed by quantitativechloride estimation The 1H NMR signal corresponds to therest of the protons such asmethyl protons 120575 252ndash264 ppm (s6H and CH
3
) and aromatic protons 120575 671ndash872 ppm (m 11Hand Ar-H) of Schiff base (DHPEAPMQ) and its complexeswere exhibited in their expected regions
Thus from the above it was inferred that the Schiffbase (DHPEAPMQ) acts as a tridentate ONO donor andforms octahedral geometry with Cu(II) Ni(II) complexesand tetrahedral geometry with Zn(II) complex via theinvolvement of phenolic oxygen azomethine nitrogen andcarboxylic oxygen as shown in Figures 1 and 2
The effective magnetic moments 120583eff expressed inmultiples of the Bohr Magneton calculated for Cu(II) andNi(II) complexes were in the range of 181ndash196 BM and
Bioinorganic Chemistry and Applications 5
Table 2 Ligand field Sinha metal-ligand covalency percent and covalency angular overlap parameters of Cu(II) and Ni(II) complexes
334ndash369 BM respectively due to mononuclear Cu(II) (d91 unpaired electron) and Ni(II) (d8 2 unpaired electrons)complexes which indicates their octahedral geometries [24]whereas the Zn(II) complex is diamagnetic in nature
The formation of a Schiff base (DHPEAPMQ) and itscomplexes was further confirmed by their mass spectralstudy All the spectra exhibit parent peaks due to molecularions (M+) and the isotopic peak owing to the chlorinesubstitution The proposed molecular formula of each com-pound was confirmed by its molecular formula weight withmz values The mass spectra of Schiff base (DHPEAPMQ)showed the formation of a molecular ion peak at mz 385[M]+ whereas Cu(II) Ni(II) and Zn(II) complexes showthe formation of molecular ion peaks along with isotopicpeaks atmz 832 [M]+ 826 [M]+ and 485 [M]+ 487 [M+2]+respectively corresponding to their molecular formula
311 ESR SpectrumofCu(II) Complex TheX-bandESR spec-tra of Cu(II) complex were recorded in the polycrystallinestate at room temperature at a frequency of 9387GHz witha field set of 3950G The information about the hyperfineand super hyperfine structure was obtained to explain thegeometry of the complex as well as the site of the metal-ligand bonding or chemical environment around the metalion In the present study the ESR spectral pattern of Cu(II)complex as depicted in supplementary file 1(e) gives the data119892
value was less than 23 and confirms thestrong covalent nature of themetal-ligand bondThe 119892
||
valueplays a significant role in elucidating the metal-ligand bondcharacter for ionic 119892
||
gt 23 and for covalent characters 119892||
lt
23 respectively [25] The ESR spectrum showed asymmetricbands with 119892
||
gt 119892
perp
gt 20023 representing that the unpairedelectrons lay predominantly in the119889
119909
2minus119910
2 orbital with possiblemixing of 119889
119911
2 because of low symmetry [26]TheG value wascalculated by using the formula 119866 = (119892
||
minus 20023)(119892
perp
minus
20023) which was greater than 4 as shown in Table 3 andindicates the negligible exchange interaction in solid complexas suggested by Hathaway and Billing [27]
32 Antimicrobial Activity of Schiff Base (DHPEAPMQ) andIts Complexes against MRSA The antimicrobial activity ofthe Schiff base (DHPEAPMQ) and its complexes was eval-uated against MRSA and isolated from different hospitalsand health care centers of the Gulbarga region in IndiaFigure 3 shows the good antimicrobial activity of the Schiffbase (DHPEAPMQ) against MRSA with a zone of inhibition(12mm) however upon complex formation the antimicro-bial activity increased with a zone of inhibition (18mm16mm and 14mm) for Cu(II) Ni(II) and Zn(III) complexesrespectively
The antimicrobial property of the Schiff base was ratio-nalized due to the presence of azomethine (C=N) groupthis imports in elucidating the mechanism of transamina-tion and resamination reactions in biological system [28]The formation of hydrogen bonds through the azomethinegroup with the active centers of various cellular constituentsresults in interference with normal cellular processes [29]Furthermore it has also been suggested that the Schiff baseligands with nitrogen and oxygen donor systems mightinhibit enzyme production causing cell death [30]
The enhanced activity of metal complexes than theSchiff base can be explained by Tweedyrsquos chelation theorywhich suggests that the chelation could allow for the delo-calization of 120587-electrons over the entire chelate ring andenhances the lipophilicity of the complexes This increasedlipophilicity facilitates the penetration of the complexes intolipid membranes further restricting the proliferation of themicroorganisms [31]
6 Bioinorganic Chemistry and Applications
Table 3 ESR data of the [Cu(C23H18N3O3)2] metal complex
Complex 119892
119892
perp
119892av 119892iso 119866
[Cu(C23H18N3O3)2] 228 207 211 217 410
N
N
N
N C
N
N
N
N
N
N
N
N
HO
HO
OH
OH OH
C
C
O
O
O OZnCl
O
MO
C OH3C
H3C
CH3
CH3
CH3
CH3
CH3
CH3
Antimicrobial activity ofDHPEAPMQ and its complexes
DHPEAPMQ
Dihydroxyphenyl)ethylideneamino)phenyl)-2-
100120583gmLat concentration
Zn(II)M = Cu(II) and Ni(II)
(E)-3-(2-(1-(24-
methylquinazolin-4(3H)-one
Figure 3 Antimicrobial activity of Schiff base (DHPEAPMQ) and its complexes against MRSA [a1 Schiff base (DHPEAPMQ) a2 Cu(II)a3 Ni(II) and a4 Zn(II) complex]
33 Determination of Minimum Inhibitory Concentration(MIC) Table 4 shows MIC values of Schiff base(DHPEAPMQ) and its complexes which indicates Cu(II)as an excellent antimicrobial agent followed by Ni(II) andZn(III) complexes The enhanced activity of Cu(II) complexmay be due to their particle size and also may be attributedto its higher stability constants [32] when compared to theSchiff base (DHPEAPMQ) and other metal complexes
4 Conclusion
In conclusion we report the synthesis and characterizationof new Schiff base (DHPEAPMQ) and its metal complexesand their antimicrobial activity against MRSA isolated fromclinical samples of the Gulbarga region in India The synthe-ses were confirmed by UV-visible IR NMR mass and ESRspectral data and their results reveal that Cu(II) and Ni(II)
Table 4MIC values of Schiff base (DHPEAPMQ) and its complexesagainst MRSA
complexes exhibit an octahedral geometry while Zn(II) com-plex shows tetrahedral geometry The MIC values of Cu(II)Ni(II) and Zn(II) were 14 18 and 24 120583gmL respectivelywhich show an excellent antimicrobial activity againstMRSASo the same can be used as a new drug of choice
Bioinorganic Chemistry and Applications 7
Conflict of Interests
The authors have no conflict of interests to declare
Acknowledgments
The authors are thankful to the Chairman of Departmentof Chemistry Gulbarga University Gulbarga for providinglaboratory facilities Sunilkumar B Mane is thankful toUGC-MRP (F no 37-1712009(SR)) New Delhi India forproviding financial assistance
References
[1] S Palanisamy K Paramasivam B R Rachel H C Alanand D Nallasamy ldquoSynthesis of novel heterobimetallic cop-per(I)hydrazone Schiff base complexes a comparative studyon the effect of heterocyclic hydrazides towards interactionwith DNAprotein free radical scavenging and cytotoxicityrdquoMetallomics vol 4 no 5 pp 498ndash511 2012
[2] S Nahid G Zeinab and H Saba ldquoBinding studies ofa newwater-soluble iron(III)schiff base complex to DNAusingmultispectroscopicmethodsrdquoBioinorganic Chemistry andApplications vol 2012 Article ID 126451 9 pages 2012
[3] N E A El-Gamel ldquoCoordination behaviour and biopotency ofmetal NN salen complexesrdquo RSC Advances vol 2 no 13 pp5870ndash5876 2012
[4] H D Revanasiddappa K S Prasad L S Kumar and BJayalakshmi ldquoSynthesis and biological activity of new Schiffbases containing 4(3H)-quinazolinone ring systemrdquo Interna-tional Journal of ChemTech Research vol 2 no 2 pp 1344ndash13492010
[5] G Naganagowda and A Petsom ldquoSynthesis and antimicrobialactivity of some new 2-(3-chloro-1- benzothiophen-2-yl)-3-(substituted-phenyl)-4-(3H)-quinazolinones derivativesrdquo Jour-nal of Sulfur Chemistry vol 32 no 3 pp 223ndash233 2011
[6] D Manikprabhu and K Lingappa ldquoAntibacterial activity ofsilver nanoparticles against methicillin-resistant Staphylococcusaureus synthesized using model Streptomyces sp pigment byphoto-irradiation methodrdquo Journal of Pharmacy Research vol6 no 2 pp 255ndash260 2013
[7] CLSI ldquoPerforming Standards for Antimicrobial SusceptibilityTesting Twenty-second Informational Supplement CLSI doc-ument M100-S22rdquo Clinical and Laboratory Standards InstituteWayne Pa USA 2012
[8] T P Tim Cushine and J L Andrew ldquoAntimicrobial activity offlavonoidsrdquo International Journal of Antimicrobial Agents vol26 no 5 pp 343ndash356 2005
[9] D Nelson D M Priscyla G I H de Souza L O Alves and EEsposito ldquoAntibacterial effect of silver nanoparticles producedby fungal process on textile fabrics and their effluent treatmentrdquoJournal of Biomedical Nanotechnology vol 3 no 2 pp 203ndash2082007
[10] M K Prashanth and H D Revanasiddappa ldquoSynthesis ofsome new glutamine linked 23 disubstituted quinazolinonederivatives as potent antimicrobial and antioxidant agentsrdquoMedicinal Chemistry Research vol 22 no 6 pp 2665ndash26762013
[11] B G Kalagouda C H Vidyadhar A P Siddappa and R PBasavaraj ldquoAntimicrobial study of newly synthesized lantha-nide(III) complexes of 2-[2-hydroxy-3-methoxyphenyl]-3-[2-hydroxy-3-methoxybenzylamino]-1 2-dihydroquinazolin-4(3H)-onerdquo Metal-Based Drugs vol 2007 Article ID 37348 7pages 2007
[12] W J Geary ldquoThe use of conductivity measurements in organicsolvents for the characterisation of coordination compoundsrdquoCoordination Chemistry Reviews vol 7 no 1 pp 81ndash122 1971
[13] A I Vogel A Text Book of Quantitative Inorganic AnalysisLongman ELBS London UK 3rd edition 1968
[14] S Biswas K Mitra C H Schwalbe C R Lucas S KChattopadhyay and B Adhikary ldquoSynthesis and characteriza-tion of some Mn(II) and Mn(III) complexes of NN1015840-o-phe-nylenebis(salicylideneimine)(LH
2
) and NN1015840-o-phenylene-bis(5-bromosalicylideneimine)(L1015840H
2
) Crystal structures of[Mn(L)(H
2
O)(ClO4
)] [Mn(L)(NCS)] and an infinite linearchain of [Mn(L)(OAc)]rdquo Inorganica Chimica Acta vol 358 no8 pp 2473ndash2481 2005
[15] N S Youssef E El-Zahany A M A El-Seidy A Caselli andS Cenini ldquoSynthesis and characterization of some transitionmetal complexes with a novel Schiff base ligand and their useas catalysts for olefin cyclopropanationrdquo Journal of MolecularCatalysis A vol 308 no 1-2 pp 159ndash168 2009
[16] D N Satyanarayana Electronic Absorption Spectroscopy andRelated Techniques University Press India Limited New DelhiIndia 2001
[17] K Abe K Matsufuji M Ohba and H Okawa ldquoSite specificityof metal ions in heterodinuclear complexes derived from anldquoend-offrdquo compartmental ligandrdquo Inorganic Chemistry vol 41no 17 pp 4461ndash4467 2002
[18] S P Tandon and P C Mehta ldquoSpectral intensities of somePr+3120573-diketonatesrdquoThe Journal of Chemical Physics vol 52 no1 pp 4313ndash4315 1970
[19] K N Kumar and R Ramesh ldquoSynthesis luminescent redoxand catalytic properties of Ru(II) carbonyl complexes contain-ing 2N2O donorsrdquo Polyhedron vol 24 no 14 pp 1885ndash18922005
[20] S Saydam ldquoSynthesis and characterisation of the new thiazoleSchiff base 2-(2-hydroxy)naphthylideneaminobenzothiazoleand its complexes withCo(II) Cu(II) andNi(II) ionsrdquo Synthesisand Reactivity in Inorganic and Metal-Organic Chemistry vol32 no 3 pp 437ndash447 2002
[21] C Jayabalakrishnan andKNatarajan ldquoRuthenium(II) carbonylcomplexes with tridentate Schiff bases and their antibacterialactivityrdquo Transition Metal Chemistry vol 27 no 1 pp 75ndash792002
[22] M Muthukumar and P Viswanathamurthi ldquoSynthesis spectralcharacterization and catalytic studies of new ruthenium(II)chalcone thiosemicarbazone complexesrdquo Central EuropeanJournal of Chemistry vol 8 no 1 pp 229ndash240 2010
[23] S Chandra and L K Gupta ldquoEPR mass IR electronic andmagnetic studies on copper(II) complexes of semicarbazonesand thiosemicarbazonesrdquo Spectrochimica Acta A vol 61 no 1-2pp 269ndash275 2005
[24] K B Gudasi M S Patil R S Vadavi R V Shenoy S A Patiland M Nethaji ldquoX-ray crystal structure of the N-(2-hydroxy-1-naphthalidene)phenylglycine Schiff base Synthesis and char-acterization of its transition metal complexesrdquo Transition MetalChemistry vol 31 no 5 pp 580ndash585 2006
[25] D Kilveson ldquoPublications of daniel kivelsonrdquo Journal of Physi-cal Chemistry B vol 101 no 43 pp 8631ndash8634 1997
8 Bioinorganic Chemistry and Applications
[26] H Liu H Wang F Gao D Niu and Z Lu ldquoSelf-assemblyof copper(II) complexes with substituted aroylhydrazones andmonodentate N-heterocycles Synthesis structure and proper-tiesrdquo Journal of Coordination Chemistry vol 60 no 24 pp2671ndash2678 2007
[27] B J Hathaway and D E Billing ldquoThe electronic properties andstereochemistry of mono-nuclear complexes of the copper(II)ionrdquo Coordination Chemistry Reviews vol 5 no 2 pp 143ndash2071970
[28] P P Dholakiya andM N Patel ldquoMetal complexes preparationmagnetic spectral and biocidal studies of some mixed-ligandcomplexes with Schiff bases containing NO and NN donoratomsrdquo Synthesis and Reactivity in Inorganic and Metal-OrganicChemistry vol 34 no 3 pp 553ndash563 2004
[29] 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
[30] Z H Chohan M Arif M A Akhtar and C T SupuranldquoMetal-based antibacterial and antifungal agents synthesischaracterization and in vitro biological evaluation of Co(II)Cu(II) Ni(II) and Zn(II) complexes with amino acid-derivedcompoundsrdquo Bioinorganic Chemistry and Applications vol2006 Article ID 83131 13 pages 2006
[31] N Raman R Jeyamurugan M Subbulakshmi R Boomi-nathan and C R Yuvarajan ldquoSynthesis DNA binding andantimicrobial studies of novel metal complexes containing apyrazolone derivative Schiff baserdquo Chemical Papers vol 64 no3 pp 318ndash328 2010
[32] S M Jadhav V A Shelke A S Munde S G Shankarwar V RPatharkar and T K Chondhekar ldquoSynthesis characterizationpotentiometry and antimicrobial studies of transition metalcomplexes of a tridentate ligandrdquo Journal of CoordinationChemistry vol 63 no 23 pp 4153ndash4164 2010
Scheme 1 Synthetic route for the preparation of (DHPEAPMQ)
present investigation we report the synthesis and character-ization of new Schiff base (DHPEAPMQ) and its antimicro-bial activity against MRSA isolated from the Gulbarga regionin India
31 Structural Analysis of the Complexes The analytical andphysical parameters of the newly synthesized Schiff base(DHPEAPMQ) and its metal complexes reveal Schiff base(DHPEAPMQ) and its complexes were very stable and non-hygroscopic at room temperature and the complexes weresparingly soluble in commonorganic solvents and completelysoluble in DMF and DMSO The measured molar conduc-tance values were in the range of 12ndash16 Ohmminus1 cm2molminus1which indicates the nonelectrolytic nature ofmetal complexes[12] as shown in Table 1 The metals and chloride contentswere determined as per standard protocol [13]
The formations of prescribed geometries of metal com-plexes were achieved by various spectral studies such as UV-Visible IR 1H NMR and mass
The electronic spectra of a Schiff base (DHPEAPMQ)exhibit two bands between 33768 and 27397 cmminus1 dueto 120587 rarr 120587lowast and 119899 rarr 120587lowast transitions associated with -C=N andC=O respectivelyThe shift in frequencies to higherwavelength suggests the coordination of azomethine nitrogenand carboxylic oxygen with metal ions The electronic spec-trum of Cu(II) complex displayed a broad asymmetric bandin the region of 12540ndash17860 cmminus1 due to 2E
119892
rarr
2T2119892
transi-tion indicating the distorted octahedral geometry around theCu(II) ion [14]TheNi(II) complex shows three well-resolvedbands at 9382 18920 and 20860 cmminus1 assigned to 3A
2119892
(F)rarr3T2119892
(F) (]1
) 3A2119892
(F)rarr 3T1119892
(F) (]2
) and 3A2119892
(F)rarr 3T1119892
(P) (]3
) transitions respectively which show the octahedralgeometry around theNi(II) ion [15]The electronic parametervalues such as the Racah interelectronic repulsion parameter(1198611015840) ligand field splitting energy (10Dq) covalency factor (120573)and ligand field stabilization energy (LFSE) [16] have beencalculated by using band-fitting equation [17] The 1198611015840valuesfor the complexes were lower than the free ion values which
4 Bioinorganic Chemistry and Applications
Table 1 Elemental analysis of physical and magnetic data of Schiff base (DHPEAPMQ) and its complexes
Molecular formula ofligandcomplexes
Mol Wt(gmol)
m p∘C
Elemental analysis found (calculated) 120583eff (BM) Λ
119898
lowast
C H N M ClC23H19N3O3(DHPEAPMQ) 38542 270 7117
(7167)461(497)
1031(1090) mdash mdash mdash mdash
[Cu(C23H18N3O3)2] 83236 292 6638(6671)
401(436)
1010(1045)
736(790) mdash 181 1630
[Ni(C23H18N3O3)2] 82620 285 6610(6777)
403(438)
1001(1016)
694(709) mdash 439 1237
[Zn(C23H18N3O3)Cl)] 48527 291 5607(5693)
342(374)
852(866)
1328(1348)
722(731) Diam 1410
lowastMolar conductance values in Ohmminus1 cm2 molminus1
indicate orbital overlaps and delocalization of d-orbitalrsquosThecovalent factor 120573 equal to 1198611198611015840 for the complexes was lessthan one suggesting the considerable covalent character ofmetal-ligand bonds In the present study the 120573 (076) valuesobtained were less than unity which indicates the covalencyfor the metal-ligand bonds In addition the covalence factors(b12) Sinha parameter (120575) that is metal-ligand covalencypercent and the covalency angular overlap parameter (120578)have been calculated from the values of 120573 by using thefollowing expressions [18]
b12 = 12
[(1 minus 120573)
12
] 120575 () = [1 minus 120573
120573
] times 100
120578 =
[(1 minus 120573
12
)]
120573
12
(1)
The electronic spectral studies of the Cu(II) and Ni(II)complexes yield a positive value for (1-120573) b12 and 120575 as wellas 120578which suggest that the bonding betweenmetal and ligandwas covalent in the complexesThe values of the parameter ofbonding (12057312) and angular overlap parameter (120578) were foundto be positive which indicates a strong covalent bondingbetween the Schiff base (DHPEAPMQ) and its complexes asshown in Table 2
The IR spectrum of Schiff base (DHPEAPMQ) displays abroadband in the region of 3402ndash3380 cmminus1 due to ](2-OH)of 1-(24-dihydroxyphenyl) ethanone upon metal complexesformation the disappearance of one (-OH) groups indicatesthe involvement of phenolic oxygen bonding with metal ionvia deprotonation [19] However the peak in the region of3390ndash3395 cmminus1 that was retained in complexes shows thepresence of uncoordinated (-OH) group Furthermore theevidence for the coordination through only one or both ofthe phenolic oxygen was confirmed by 1H NMR spectralstudies The Schiff base (DHPEAPMQ) shows character-istic resonance signals at 120575 1143 ppm (s 1H OH) and 120575960 ppm (s 1H OH) upon metal complexes formationdisappearance of one -OH proton 120575 (960 ppm) on the otherhand the other proton remained unaltered at 120575 1143 ppm (s1H OH) (D
2
O exchangeable) indicates the participation ofonly one phenolic oxygen in coordination with metal ionvia deprotonation [20] as presented in (see supplementary
file 1(andashd) in Supplementary Material available online athttpdxdoiorg1011552014343540)
A characteristic high intense band due to azomethine](-C=N) in the IR spectrum of Schiff base (DHPEAPMQ)appeared in the region of 1598ndash1592 cmminus1 experiences anegative shift of 15ndash20 cmminus1 in their respective complexesand lower value of ](-C=N) stretching can be explained onthe basis of a drift of the lone-pair density of azomethinenitrogen towards the metal ions indicates coordination ofazomethine nitrogen with the metal ions [21] Further thiswas confirmed by NMR spectra owing to the downfield shiftof azomethine proton from 120575 835 ppm (s 1H -CH=N) ofSchiff base (DHPEAPMQ) to 120575 842 ppm (s 1H -CH=N) incomplexes which shows the involvement of -CH=N nitrogenin coordination
In the IR spectrum of Schiff base (DHPEAPMQ) ahigh intense strong band in the region of 1712ndash1702 cmminus1was assigned due to the carboxyl group of quinazoline ring(C=O) which shows a downfield shift of 20ndash30 cmminus1andindicates the participation of carboxylic oxygen upon com-plex formation [22]
All the complexes show medium intensity bands inthe region of 558ndash547 cmminus1 and 463ndash457 cmminus1 assigned to](M-O) and ](M-N) vibrations respectively which furthersupport the coordination of the Schiff base (DHPEAPMQ)through the nitrogen of azomethine and carboxylic and phe-nolic oxygen with various metal ions [23] Moreover a weakband was observed in the region of 355ndash350 cmminus1 assignedto ](M-Cl) this was a characteristic of the chloride atom inZn(II) complex and was further confirmed by quantitativechloride estimation The 1H NMR signal corresponds to therest of the protons such asmethyl protons 120575 252ndash264 ppm (s6H and CH
3
) and aromatic protons 120575 671ndash872 ppm (m 11Hand Ar-H) of Schiff base (DHPEAPMQ) and its complexeswere exhibited in their expected regions
Thus from the above it was inferred that the Schiffbase (DHPEAPMQ) acts as a tridentate ONO donor andforms octahedral geometry with Cu(II) Ni(II) complexesand tetrahedral geometry with Zn(II) complex via theinvolvement of phenolic oxygen azomethine nitrogen andcarboxylic oxygen as shown in Figures 1 and 2
The effective magnetic moments 120583eff expressed inmultiples of the Bohr Magneton calculated for Cu(II) andNi(II) complexes were in the range of 181ndash196 BM and
Bioinorganic Chemistry and Applications 5
Table 2 Ligand field Sinha metal-ligand covalency percent and covalency angular overlap parameters of Cu(II) and Ni(II) complexes
334ndash369 BM respectively due to mononuclear Cu(II) (d91 unpaired electron) and Ni(II) (d8 2 unpaired electrons)complexes which indicates their octahedral geometries [24]whereas the Zn(II) complex is diamagnetic in nature
The formation of a Schiff base (DHPEAPMQ) and itscomplexes was further confirmed by their mass spectralstudy All the spectra exhibit parent peaks due to molecularions (M+) and the isotopic peak owing to the chlorinesubstitution The proposed molecular formula of each com-pound was confirmed by its molecular formula weight withmz values The mass spectra of Schiff base (DHPEAPMQ)showed the formation of a molecular ion peak at mz 385[M]+ whereas Cu(II) Ni(II) and Zn(II) complexes showthe formation of molecular ion peaks along with isotopicpeaks atmz 832 [M]+ 826 [M]+ and 485 [M]+ 487 [M+2]+respectively corresponding to their molecular formula
311 ESR SpectrumofCu(II) Complex TheX-bandESR spec-tra of Cu(II) complex were recorded in the polycrystallinestate at room temperature at a frequency of 9387GHz witha field set of 3950G The information about the hyperfineand super hyperfine structure was obtained to explain thegeometry of the complex as well as the site of the metal-ligand bonding or chemical environment around the metalion In the present study the ESR spectral pattern of Cu(II)complex as depicted in supplementary file 1(e) gives the data119892
value was less than 23 and confirms thestrong covalent nature of themetal-ligand bondThe 119892
||
valueplays a significant role in elucidating the metal-ligand bondcharacter for ionic 119892
||
gt 23 and for covalent characters 119892||
lt
23 respectively [25] The ESR spectrum showed asymmetricbands with 119892
||
gt 119892
perp
gt 20023 representing that the unpairedelectrons lay predominantly in the119889
119909
2minus119910
2 orbital with possiblemixing of 119889
119911
2 because of low symmetry [26]TheG value wascalculated by using the formula 119866 = (119892
||
minus 20023)(119892
perp
minus
20023) which was greater than 4 as shown in Table 3 andindicates the negligible exchange interaction in solid complexas suggested by Hathaway and Billing [27]
32 Antimicrobial Activity of Schiff Base (DHPEAPMQ) andIts Complexes against MRSA The antimicrobial activity ofthe Schiff base (DHPEAPMQ) and its complexes was eval-uated against MRSA and isolated from different hospitalsand health care centers of the Gulbarga region in IndiaFigure 3 shows the good antimicrobial activity of the Schiffbase (DHPEAPMQ) against MRSA with a zone of inhibition(12mm) however upon complex formation the antimicro-bial activity increased with a zone of inhibition (18mm16mm and 14mm) for Cu(II) Ni(II) and Zn(III) complexesrespectively
The antimicrobial property of the Schiff base was ratio-nalized due to the presence of azomethine (C=N) groupthis imports in elucidating the mechanism of transamina-tion and resamination reactions in biological system [28]The formation of hydrogen bonds through the azomethinegroup with the active centers of various cellular constituentsresults in interference with normal cellular processes [29]Furthermore it has also been suggested that the Schiff baseligands with nitrogen and oxygen donor systems mightinhibit enzyme production causing cell death [30]
The enhanced activity of metal complexes than theSchiff base can be explained by Tweedyrsquos chelation theorywhich suggests that the chelation could allow for the delo-calization of 120587-electrons over the entire chelate ring andenhances the lipophilicity of the complexes This increasedlipophilicity facilitates the penetration of the complexes intolipid membranes further restricting the proliferation of themicroorganisms [31]
6 Bioinorganic Chemistry and Applications
Table 3 ESR data of the [Cu(C23H18N3O3)2] metal complex
Complex 119892
119892
perp
119892av 119892iso 119866
[Cu(C23H18N3O3)2] 228 207 211 217 410
N
N
N
N C
N
N
N
N
N
N
N
N
HO
HO
OH
OH OH
C
C
O
O
O OZnCl
O
MO
C OH3C
H3C
CH3
CH3
CH3
CH3
CH3
CH3
Antimicrobial activity ofDHPEAPMQ and its complexes
DHPEAPMQ
Dihydroxyphenyl)ethylideneamino)phenyl)-2-
100120583gmLat concentration
Zn(II)M = Cu(II) and Ni(II)
(E)-3-(2-(1-(24-
methylquinazolin-4(3H)-one
Figure 3 Antimicrobial activity of Schiff base (DHPEAPMQ) and its complexes against MRSA [a1 Schiff base (DHPEAPMQ) a2 Cu(II)a3 Ni(II) and a4 Zn(II) complex]
33 Determination of Minimum Inhibitory Concentration(MIC) Table 4 shows MIC values of Schiff base(DHPEAPMQ) and its complexes which indicates Cu(II)as an excellent antimicrobial agent followed by Ni(II) andZn(III) complexes The enhanced activity of Cu(II) complexmay be due to their particle size and also may be attributedto its higher stability constants [32] when compared to theSchiff base (DHPEAPMQ) and other metal complexes
4 Conclusion
In conclusion we report the synthesis and characterizationof new Schiff base (DHPEAPMQ) and its metal complexesand their antimicrobial activity against MRSA isolated fromclinical samples of the Gulbarga region in India The synthe-ses were confirmed by UV-visible IR NMR mass and ESRspectral data and their results reveal that Cu(II) and Ni(II)
Table 4MIC values of Schiff base (DHPEAPMQ) and its complexesagainst MRSA
complexes exhibit an octahedral geometry while Zn(II) com-plex shows tetrahedral geometry The MIC values of Cu(II)Ni(II) and Zn(II) were 14 18 and 24 120583gmL respectivelywhich show an excellent antimicrobial activity againstMRSASo the same can be used as a new drug of choice
Bioinorganic Chemistry and Applications 7
Conflict of Interests
The authors have no conflict of interests to declare
Acknowledgments
The authors are thankful to the Chairman of Departmentof Chemistry Gulbarga University Gulbarga for providinglaboratory facilities Sunilkumar B Mane is thankful toUGC-MRP (F no 37-1712009(SR)) New Delhi India forproviding financial assistance
References
[1] S Palanisamy K Paramasivam B R Rachel H C Alanand D Nallasamy ldquoSynthesis of novel heterobimetallic cop-per(I)hydrazone Schiff base complexes a comparative studyon the effect of heterocyclic hydrazides towards interactionwith DNAprotein free radical scavenging and cytotoxicityrdquoMetallomics vol 4 no 5 pp 498ndash511 2012
[2] S Nahid G Zeinab and H Saba ldquoBinding studies ofa newwater-soluble iron(III)schiff base complex to DNAusingmultispectroscopicmethodsrdquoBioinorganic Chemistry andApplications vol 2012 Article ID 126451 9 pages 2012
[3] N E A El-Gamel ldquoCoordination behaviour and biopotency ofmetal NN salen complexesrdquo RSC Advances vol 2 no 13 pp5870ndash5876 2012
[4] H D Revanasiddappa K S Prasad L S Kumar and BJayalakshmi ldquoSynthesis and biological activity of new Schiffbases containing 4(3H)-quinazolinone ring systemrdquo Interna-tional Journal of ChemTech Research vol 2 no 2 pp 1344ndash13492010
[5] G Naganagowda and A Petsom ldquoSynthesis and antimicrobialactivity of some new 2-(3-chloro-1- benzothiophen-2-yl)-3-(substituted-phenyl)-4-(3H)-quinazolinones derivativesrdquo Jour-nal of Sulfur Chemistry vol 32 no 3 pp 223ndash233 2011
[6] D Manikprabhu and K Lingappa ldquoAntibacterial activity ofsilver nanoparticles against methicillin-resistant Staphylococcusaureus synthesized using model Streptomyces sp pigment byphoto-irradiation methodrdquo Journal of Pharmacy Research vol6 no 2 pp 255ndash260 2013
[7] CLSI ldquoPerforming Standards for Antimicrobial SusceptibilityTesting Twenty-second Informational Supplement CLSI doc-ument M100-S22rdquo Clinical and Laboratory Standards InstituteWayne Pa USA 2012
[8] T P Tim Cushine and J L Andrew ldquoAntimicrobial activity offlavonoidsrdquo International Journal of Antimicrobial Agents vol26 no 5 pp 343ndash356 2005
[9] D Nelson D M Priscyla G I H de Souza L O Alves and EEsposito ldquoAntibacterial effect of silver nanoparticles producedby fungal process on textile fabrics and their effluent treatmentrdquoJournal of Biomedical Nanotechnology vol 3 no 2 pp 203ndash2082007
[10] M K Prashanth and H D Revanasiddappa ldquoSynthesis ofsome new glutamine linked 23 disubstituted quinazolinonederivatives as potent antimicrobial and antioxidant agentsrdquoMedicinal Chemistry Research vol 22 no 6 pp 2665ndash26762013
[11] B G Kalagouda C H Vidyadhar A P Siddappa and R PBasavaraj ldquoAntimicrobial study of newly synthesized lantha-nide(III) complexes of 2-[2-hydroxy-3-methoxyphenyl]-3-[2-hydroxy-3-methoxybenzylamino]-1 2-dihydroquinazolin-4(3H)-onerdquo Metal-Based Drugs vol 2007 Article ID 37348 7pages 2007
[12] W J Geary ldquoThe use of conductivity measurements in organicsolvents for the characterisation of coordination compoundsrdquoCoordination Chemistry Reviews vol 7 no 1 pp 81ndash122 1971
[13] A I Vogel A Text Book of Quantitative Inorganic AnalysisLongman ELBS London UK 3rd edition 1968
[14] S Biswas K Mitra C H Schwalbe C R Lucas S KChattopadhyay and B Adhikary ldquoSynthesis and characteriza-tion of some Mn(II) and Mn(III) complexes of NN1015840-o-phe-nylenebis(salicylideneimine)(LH
2
) and NN1015840-o-phenylene-bis(5-bromosalicylideneimine)(L1015840H
2
) Crystal structures of[Mn(L)(H
2
O)(ClO4
)] [Mn(L)(NCS)] and an infinite linearchain of [Mn(L)(OAc)]rdquo Inorganica Chimica Acta vol 358 no8 pp 2473ndash2481 2005
[15] N S Youssef E El-Zahany A M A El-Seidy A Caselli andS Cenini ldquoSynthesis and characterization of some transitionmetal complexes with a novel Schiff base ligand and their useas catalysts for olefin cyclopropanationrdquo Journal of MolecularCatalysis A vol 308 no 1-2 pp 159ndash168 2009
[16] D N Satyanarayana Electronic Absorption Spectroscopy andRelated Techniques University Press India Limited New DelhiIndia 2001
[17] K Abe K Matsufuji M Ohba and H Okawa ldquoSite specificityof metal ions in heterodinuclear complexes derived from anldquoend-offrdquo compartmental ligandrdquo Inorganic Chemistry vol 41no 17 pp 4461ndash4467 2002
[18] S P Tandon and P C Mehta ldquoSpectral intensities of somePr+3120573-diketonatesrdquoThe Journal of Chemical Physics vol 52 no1 pp 4313ndash4315 1970
[19] K N Kumar and R Ramesh ldquoSynthesis luminescent redoxand catalytic properties of Ru(II) carbonyl complexes contain-ing 2N2O donorsrdquo Polyhedron vol 24 no 14 pp 1885ndash18922005
[20] S Saydam ldquoSynthesis and characterisation of the new thiazoleSchiff base 2-(2-hydroxy)naphthylideneaminobenzothiazoleand its complexes withCo(II) Cu(II) andNi(II) ionsrdquo Synthesisand Reactivity in Inorganic and Metal-Organic Chemistry vol32 no 3 pp 437ndash447 2002
[21] C Jayabalakrishnan andKNatarajan ldquoRuthenium(II) carbonylcomplexes with tridentate Schiff bases and their antibacterialactivityrdquo Transition Metal Chemistry vol 27 no 1 pp 75ndash792002
[22] M Muthukumar and P Viswanathamurthi ldquoSynthesis spectralcharacterization and catalytic studies of new ruthenium(II)chalcone thiosemicarbazone complexesrdquo Central EuropeanJournal of Chemistry vol 8 no 1 pp 229ndash240 2010
[23] S Chandra and L K Gupta ldquoEPR mass IR electronic andmagnetic studies on copper(II) complexes of semicarbazonesand thiosemicarbazonesrdquo Spectrochimica Acta A vol 61 no 1-2pp 269ndash275 2005
[24] K B Gudasi M S Patil R S Vadavi R V Shenoy S A Patiland M Nethaji ldquoX-ray crystal structure of the N-(2-hydroxy-1-naphthalidene)phenylglycine Schiff base Synthesis and char-acterization of its transition metal complexesrdquo Transition MetalChemistry vol 31 no 5 pp 580ndash585 2006
[25] D Kilveson ldquoPublications of daniel kivelsonrdquo Journal of Physi-cal Chemistry B vol 101 no 43 pp 8631ndash8634 1997
8 Bioinorganic Chemistry and Applications
[26] H Liu H Wang F Gao D Niu and Z Lu ldquoSelf-assemblyof copper(II) complexes with substituted aroylhydrazones andmonodentate N-heterocycles Synthesis structure and proper-tiesrdquo Journal of Coordination Chemistry vol 60 no 24 pp2671ndash2678 2007
[27] B J Hathaway and D E Billing ldquoThe electronic properties andstereochemistry of mono-nuclear complexes of the copper(II)ionrdquo Coordination Chemistry Reviews vol 5 no 2 pp 143ndash2071970
[28] P P Dholakiya andM N Patel ldquoMetal complexes preparationmagnetic spectral and biocidal studies of some mixed-ligandcomplexes with Schiff bases containing NO and NN donoratomsrdquo Synthesis and Reactivity in Inorganic and Metal-OrganicChemistry vol 34 no 3 pp 553ndash563 2004
[29] 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
[30] Z H Chohan M Arif M A Akhtar and C T SupuranldquoMetal-based antibacterial and antifungal agents synthesischaracterization and in vitro biological evaluation of Co(II)Cu(II) Ni(II) and Zn(II) complexes with amino acid-derivedcompoundsrdquo Bioinorganic Chemistry and Applications vol2006 Article ID 83131 13 pages 2006
[31] N Raman R Jeyamurugan M Subbulakshmi R Boomi-nathan and C R Yuvarajan ldquoSynthesis DNA binding andantimicrobial studies of novel metal complexes containing apyrazolone derivative Schiff baserdquo Chemical Papers vol 64 no3 pp 318ndash328 2010
[32] S M Jadhav V A Shelke A S Munde S G Shankarwar V RPatharkar and T K Chondhekar ldquoSynthesis characterizationpotentiometry and antimicrobial studies of transition metalcomplexes of a tridentate ligandrdquo Journal of CoordinationChemistry vol 63 no 23 pp 4153ndash4164 2010
Table 1 Elemental analysis of physical and magnetic data of Schiff base (DHPEAPMQ) and its complexes
Molecular formula ofligandcomplexes
Mol Wt(gmol)
m p∘C
Elemental analysis found (calculated) 120583eff (BM) Λ
119898
lowast
C H N M ClC23H19N3O3(DHPEAPMQ) 38542 270 7117
(7167)461(497)
1031(1090) mdash mdash mdash mdash
[Cu(C23H18N3O3)2] 83236 292 6638(6671)
401(436)
1010(1045)
736(790) mdash 181 1630
[Ni(C23H18N3O3)2] 82620 285 6610(6777)
403(438)
1001(1016)
694(709) mdash 439 1237
[Zn(C23H18N3O3)Cl)] 48527 291 5607(5693)
342(374)
852(866)
1328(1348)
722(731) Diam 1410
lowastMolar conductance values in Ohmminus1 cm2 molminus1
indicate orbital overlaps and delocalization of d-orbitalrsquosThecovalent factor 120573 equal to 1198611198611015840 for the complexes was lessthan one suggesting the considerable covalent character ofmetal-ligand bonds In the present study the 120573 (076) valuesobtained were less than unity which indicates the covalencyfor the metal-ligand bonds In addition the covalence factors(b12) Sinha parameter (120575) that is metal-ligand covalencypercent and the covalency angular overlap parameter (120578)have been calculated from the values of 120573 by using thefollowing expressions [18]
b12 = 12
[(1 minus 120573)
12
] 120575 () = [1 minus 120573
120573
] times 100
120578 =
[(1 minus 120573
12
)]
120573
12
(1)
The electronic spectral studies of the Cu(II) and Ni(II)complexes yield a positive value for (1-120573) b12 and 120575 as wellas 120578which suggest that the bonding betweenmetal and ligandwas covalent in the complexesThe values of the parameter ofbonding (12057312) and angular overlap parameter (120578) were foundto be positive which indicates a strong covalent bondingbetween the Schiff base (DHPEAPMQ) and its complexes asshown in Table 2
The IR spectrum of Schiff base (DHPEAPMQ) displays abroadband in the region of 3402ndash3380 cmminus1 due to ](2-OH)of 1-(24-dihydroxyphenyl) ethanone upon metal complexesformation the disappearance of one (-OH) groups indicatesthe involvement of phenolic oxygen bonding with metal ionvia deprotonation [19] However the peak in the region of3390ndash3395 cmminus1 that was retained in complexes shows thepresence of uncoordinated (-OH) group Furthermore theevidence for the coordination through only one or both ofthe phenolic oxygen was confirmed by 1H NMR spectralstudies The Schiff base (DHPEAPMQ) shows character-istic resonance signals at 120575 1143 ppm (s 1H OH) and 120575960 ppm (s 1H OH) upon metal complexes formationdisappearance of one -OH proton 120575 (960 ppm) on the otherhand the other proton remained unaltered at 120575 1143 ppm (s1H OH) (D
2
O exchangeable) indicates the participation ofonly one phenolic oxygen in coordination with metal ionvia deprotonation [20] as presented in (see supplementary
file 1(andashd) in Supplementary Material available online athttpdxdoiorg1011552014343540)
A characteristic high intense band due to azomethine](-C=N) in the IR spectrum of Schiff base (DHPEAPMQ)appeared in the region of 1598ndash1592 cmminus1 experiences anegative shift of 15ndash20 cmminus1 in their respective complexesand lower value of ](-C=N) stretching can be explained onthe basis of a drift of the lone-pair density of azomethinenitrogen towards the metal ions indicates coordination ofazomethine nitrogen with the metal ions [21] Further thiswas confirmed by NMR spectra owing to the downfield shiftof azomethine proton from 120575 835 ppm (s 1H -CH=N) ofSchiff base (DHPEAPMQ) to 120575 842 ppm (s 1H -CH=N) incomplexes which shows the involvement of -CH=N nitrogenin coordination
In the IR spectrum of Schiff base (DHPEAPMQ) ahigh intense strong band in the region of 1712ndash1702 cmminus1was assigned due to the carboxyl group of quinazoline ring(C=O) which shows a downfield shift of 20ndash30 cmminus1andindicates the participation of carboxylic oxygen upon com-plex formation [22]
All the complexes show medium intensity bands inthe region of 558ndash547 cmminus1 and 463ndash457 cmminus1 assigned to](M-O) and ](M-N) vibrations respectively which furthersupport the coordination of the Schiff base (DHPEAPMQ)through the nitrogen of azomethine and carboxylic and phe-nolic oxygen with various metal ions [23] Moreover a weakband was observed in the region of 355ndash350 cmminus1 assignedto ](M-Cl) this was a characteristic of the chloride atom inZn(II) complex and was further confirmed by quantitativechloride estimation The 1H NMR signal corresponds to therest of the protons such asmethyl protons 120575 252ndash264 ppm (s6H and CH
3
) and aromatic protons 120575 671ndash872 ppm (m 11Hand Ar-H) of Schiff base (DHPEAPMQ) and its complexeswere exhibited in their expected regions
Thus from the above it was inferred that the Schiffbase (DHPEAPMQ) acts as a tridentate ONO donor andforms octahedral geometry with Cu(II) Ni(II) complexesand tetrahedral geometry with Zn(II) complex via theinvolvement of phenolic oxygen azomethine nitrogen andcarboxylic oxygen as shown in Figures 1 and 2
The effective magnetic moments 120583eff expressed inmultiples of the Bohr Magneton calculated for Cu(II) andNi(II) complexes were in the range of 181ndash196 BM and
Bioinorganic Chemistry and Applications 5
Table 2 Ligand field Sinha metal-ligand covalency percent and covalency angular overlap parameters of Cu(II) and Ni(II) complexes
334ndash369 BM respectively due to mononuclear Cu(II) (d91 unpaired electron) and Ni(II) (d8 2 unpaired electrons)complexes which indicates their octahedral geometries [24]whereas the Zn(II) complex is diamagnetic in nature
The formation of a Schiff base (DHPEAPMQ) and itscomplexes was further confirmed by their mass spectralstudy All the spectra exhibit parent peaks due to molecularions (M+) and the isotopic peak owing to the chlorinesubstitution The proposed molecular formula of each com-pound was confirmed by its molecular formula weight withmz values The mass spectra of Schiff base (DHPEAPMQ)showed the formation of a molecular ion peak at mz 385[M]+ whereas Cu(II) Ni(II) and Zn(II) complexes showthe formation of molecular ion peaks along with isotopicpeaks atmz 832 [M]+ 826 [M]+ and 485 [M]+ 487 [M+2]+respectively corresponding to their molecular formula
311 ESR SpectrumofCu(II) Complex TheX-bandESR spec-tra of Cu(II) complex were recorded in the polycrystallinestate at room temperature at a frequency of 9387GHz witha field set of 3950G The information about the hyperfineand super hyperfine structure was obtained to explain thegeometry of the complex as well as the site of the metal-ligand bonding or chemical environment around the metalion In the present study the ESR spectral pattern of Cu(II)complex as depicted in supplementary file 1(e) gives the data119892
value was less than 23 and confirms thestrong covalent nature of themetal-ligand bondThe 119892
||
valueplays a significant role in elucidating the metal-ligand bondcharacter for ionic 119892
||
gt 23 and for covalent characters 119892||
lt
23 respectively [25] The ESR spectrum showed asymmetricbands with 119892
||
gt 119892
perp
gt 20023 representing that the unpairedelectrons lay predominantly in the119889
119909
2minus119910
2 orbital with possiblemixing of 119889
119911
2 because of low symmetry [26]TheG value wascalculated by using the formula 119866 = (119892
||
minus 20023)(119892
perp
minus
20023) which was greater than 4 as shown in Table 3 andindicates the negligible exchange interaction in solid complexas suggested by Hathaway and Billing [27]
32 Antimicrobial Activity of Schiff Base (DHPEAPMQ) andIts Complexes against MRSA The antimicrobial activity ofthe Schiff base (DHPEAPMQ) and its complexes was eval-uated against MRSA and isolated from different hospitalsand health care centers of the Gulbarga region in IndiaFigure 3 shows the good antimicrobial activity of the Schiffbase (DHPEAPMQ) against MRSA with a zone of inhibition(12mm) however upon complex formation the antimicro-bial activity increased with a zone of inhibition (18mm16mm and 14mm) for Cu(II) Ni(II) and Zn(III) complexesrespectively
The antimicrobial property of the Schiff base was ratio-nalized due to the presence of azomethine (C=N) groupthis imports in elucidating the mechanism of transamina-tion and resamination reactions in biological system [28]The formation of hydrogen bonds through the azomethinegroup with the active centers of various cellular constituentsresults in interference with normal cellular processes [29]Furthermore it has also been suggested that the Schiff baseligands with nitrogen and oxygen donor systems mightinhibit enzyme production causing cell death [30]
The enhanced activity of metal complexes than theSchiff base can be explained by Tweedyrsquos chelation theorywhich suggests that the chelation could allow for the delo-calization of 120587-electrons over the entire chelate ring andenhances the lipophilicity of the complexes This increasedlipophilicity facilitates the penetration of the complexes intolipid membranes further restricting the proliferation of themicroorganisms [31]
6 Bioinorganic Chemistry and Applications
Table 3 ESR data of the [Cu(C23H18N3O3)2] metal complex
Complex 119892
119892
perp
119892av 119892iso 119866
[Cu(C23H18N3O3)2] 228 207 211 217 410
N
N
N
N C
N
N
N
N
N
N
N
N
HO
HO
OH
OH OH
C
C
O
O
O OZnCl
O
MO
C OH3C
H3C
CH3
CH3
CH3
CH3
CH3
CH3
Antimicrobial activity ofDHPEAPMQ and its complexes
DHPEAPMQ
Dihydroxyphenyl)ethylideneamino)phenyl)-2-
100120583gmLat concentration
Zn(II)M = Cu(II) and Ni(II)
(E)-3-(2-(1-(24-
methylquinazolin-4(3H)-one
Figure 3 Antimicrobial activity of Schiff base (DHPEAPMQ) and its complexes against MRSA [a1 Schiff base (DHPEAPMQ) a2 Cu(II)a3 Ni(II) and a4 Zn(II) complex]
33 Determination of Minimum Inhibitory Concentration(MIC) Table 4 shows MIC values of Schiff base(DHPEAPMQ) and its complexes which indicates Cu(II)as an excellent antimicrobial agent followed by Ni(II) andZn(III) complexes The enhanced activity of Cu(II) complexmay be due to their particle size and also may be attributedto its higher stability constants [32] when compared to theSchiff base (DHPEAPMQ) and other metal complexes
4 Conclusion
In conclusion we report the synthesis and characterizationof new Schiff base (DHPEAPMQ) and its metal complexesand their antimicrobial activity against MRSA isolated fromclinical samples of the Gulbarga region in India The synthe-ses were confirmed by UV-visible IR NMR mass and ESRspectral data and their results reveal that Cu(II) and Ni(II)
Table 4MIC values of Schiff base (DHPEAPMQ) and its complexesagainst MRSA
complexes exhibit an octahedral geometry while Zn(II) com-plex shows tetrahedral geometry The MIC values of Cu(II)Ni(II) and Zn(II) were 14 18 and 24 120583gmL respectivelywhich show an excellent antimicrobial activity againstMRSASo the same can be used as a new drug of choice
Bioinorganic Chemistry and Applications 7
Conflict of Interests
The authors have no conflict of interests to declare
Acknowledgments
The authors are thankful to the Chairman of Departmentof Chemistry Gulbarga University Gulbarga for providinglaboratory facilities Sunilkumar B Mane is thankful toUGC-MRP (F no 37-1712009(SR)) New Delhi India forproviding financial assistance
References
[1] S Palanisamy K Paramasivam B R Rachel H C Alanand D Nallasamy ldquoSynthesis of novel heterobimetallic cop-per(I)hydrazone Schiff base complexes a comparative studyon the effect of heterocyclic hydrazides towards interactionwith DNAprotein free radical scavenging and cytotoxicityrdquoMetallomics vol 4 no 5 pp 498ndash511 2012
[2] S Nahid G Zeinab and H Saba ldquoBinding studies ofa newwater-soluble iron(III)schiff base complex to DNAusingmultispectroscopicmethodsrdquoBioinorganic Chemistry andApplications vol 2012 Article ID 126451 9 pages 2012
[3] N E A El-Gamel ldquoCoordination behaviour and biopotency ofmetal NN salen complexesrdquo RSC Advances vol 2 no 13 pp5870ndash5876 2012
[4] H D Revanasiddappa K S Prasad L S Kumar and BJayalakshmi ldquoSynthesis and biological activity of new Schiffbases containing 4(3H)-quinazolinone ring systemrdquo Interna-tional Journal of ChemTech Research vol 2 no 2 pp 1344ndash13492010
[5] G Naganagowda and A Petsom ldquoSynthesis and antimicrobialactivity of some new 2-(3-chloro-1- benzothiophen-2-yl)-3-(substituted-phenyl)-4-(3H)-quinazolinones derivativesrdquo Jour-nal of Sulfur Chemistry vol 32 no 3 pp 223ndash233 2011
[6] D Manikprabhu and K Lingappa ldquoAntibacterial activity ofsilver nanoparticles against methicillin-resistant Staphylococcusaureus synthesized using model Streptomyces sp pigment byphoto-irradiation methodrdquo Journal of Pharmacy Research vol6 no 2 pp 255ndash260 2013
[7] CLSI ldquoPerforming Standards for Antimicrobial SusceptibilityTesting Twenty-second Informational Supplement CLSI doc-ument M100-S22rdquo Clinical and Laboratory Standards InstituteWayne Pa USA 2012
[8] T P Tim Cushine and J L Andrew ldquoAntimicrobial activity offlavonoidsrdquo International Journal of Antimicrobial Agents vol26 no 5 pp 343ndash356 2005
[9] D Nelson D M Priscyla G I H de Souza L O Alves and EEsposito ldquoAntibacterial effect of silver nanoparticles producedby fungal process on textile fabrics and their effluent treatmentrdquoJournal of Biomedical Nanotechnology vol 3 no 2 pp 203ndash2082007
[10] M K Prashanth and H D Revanasiddappa ldquoSynthesis ofsome new glutamine linked 23 disubstituted quinazolinonederivatives as potent antimicrobial and antioxidant agentsrdquoMedicinal Chemistry Research vol 22 no 6 pp 2665ndash26762013
[11] B G Kalagouda C H Vidyadhar A P Siddappa and R PBasavaraj ldquoAntimicrobial study of newly synthesized lantha-nide(III) complexes of 2-[2-hydroxy-3-methoxyphenyl]-3-[2-hydroxy-3-methoxybenzylamino]-1 2-dihydroquinazolin-4(3H)-onerdquo Metal-Based Drugs vol 2007 Article ID 37348 7pages 2007
[12] W J Geary ldquoThe use of conductivity measurements in organicsolvents for the characterisation of coordination compoundsrdquoCoordination Chemistry Reviews vol 7 no 1 pp 81ndash122 1971
[13] A I Vogel A Text Book of Quantitative Inorganic AnalysisLongman ELBS London UK 3rd edition 1968
[14] S Biswas K Mitra C H Schwalbe C R Lucas S KChattopadhyay and B Adhikary ldquoSynthesis and characteriza-tion of some Mn(II) and Mn(III) complexes of NN1015840-o-phe-nylenebis(salicylideneimine)(LH
2
) and NN1015840-o-phenylene-bis(5-bromosalicylideneimine)(L1015840H
2
) Crystal structures of[Mn(L)(H
2
O)(ClO4
)] [Mn(L)(NCS)] and an infinite linearchain of [Mn(L)(OAc)]rdquo Inorganica Chimica Acta vol 358 no8 pp 2473ndash2481 2005
[15] N S Youssef E El-Zahany A M A El-Seidy A Caselli andS Cenini ldquoSynthesis and characterization of some transitionmetal complexes with a novel Schiff base ligand and their useas catalysts for olefin cyclopropanationrdquo Journal of MolecularCatalysis A vol 308 no 1-2 pp 159ndash168 2009
[16] D N Satyanarayana Electronic Absorption Spectroscopy andRelated Techniques University Press India Limited New DelhiIndia 2001
[17] K Abe K Matsufuji M Ohba and H Okawa ldquoSite specificityof metal ions in heterodinuclear complexes derived from anldquoend-offrdquo compartmental ligandrdquo Inorganic Chemistry vol 41no 17 pp 4461ndash4467 2002
[18] S P Tandon and P C Mehta ldquoSpectral intensities of somePr+3120573-diketonatesrdquoThe Journal of Chemical Physics vol 52 no1 pp 4313ndash4315 1970
[19] K N Kumar and R Ramesh ldquoSynthesis luminescent redoxand catalytic properties of Ru(II) carbonyl complexes contain-ing 2N2O donorsrdquo Polyhedron vol 24 no 14 pp 1885ndash18922005
[20] S Saydam ldquoSynthesis and characterisation of the new thiazoleSchiff base 2-(2-hydroxy)naphthylideneaminobenzothiazoleand its complexes withCo(II) Cu(II) andNi(II) ionsrdquo Synthesisand Reactivity in Inorganic and Metal-Organic Chemistry vol32 no 3 pp 437ndash447 2002
[21] C Jayabalakrishnan andKNatarajan ldquoRuthenium(II) carbonylcomplexes with tridentate Schiff bases and their antibacterialactivityrdquo Transition Metal Chemistry vol 27 no 1 pp 75ndash792002
[22] M Muthukumar and P Viswanathamurthi ldquoSynthesis spectralcharacterization and catalytic studies of new ruthenium(II)chalcone thiosemicarbazone complexesrdquo Central EuropeanJournal of Chemistry vol 8 no 1 pp 229ndash240 2010
[23] S Chandra and L K Gupta ldquoEPR mass IR electronic andmagnetic studies on copper(II) complexes of semicarbazonesand thiosemicarbazonesrdquo Spectrochimica Acta A vol 61 no 1-2pp 269ndash275 2005
[24] K B Gudasi M S Patil R S Vadavi R V Shenoy S A Patiland M Nethaji ldquoX-ray crystal structure of the N-(2-hydroxy-1-naphthalidene)phenylglycine Schiff base Synthesis and char-acterization of its transition metal complexesrdquo Transition MetalChemistry vol 31 no 5 pp 580ndash585 2006
[25] D Kilveson ldquoPublications of daniel kivelsonrdquo Journal of Physi-cal Chemistry B vol 101 no 43 pp 8631ndash8634 1997
8 Bioinorganic Chemistry and Applications
[26] H Liu H Wang F Gao D Niu and Z Lu ldquoSelf-assemblyof copper(II) complexes with substituted aroylhydrazones andmonodentate N-heterocycles Synthesis structure and proper-tiesrdquo Journal of Coordination Chemistry vol 60 no 24 pp2671ndash2678 2007
[27] B J Hathaway and D E Billing ldquoThe electronic properties andstereochemistry of mono-nuclear complexes of the copper(II)ionrdquo Coordination Chemistry Reviews vol 5 no 2 pp 143ndash2071970
[28] P P Dholakiya andM N Patel ldquoMetal complexes preparationmagnetic spectral and biocidal studies of some mixed-ligandcomplexes with Schiff bases containing NO and NN donoratomsrdquo Synthesis and Reactivity in Inorganic and Metal-OrganicChemistry vol 34 no 3 pp 553ndash563 2004
[29] 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
[30] Z H Chohan M Arif M A Akhtar and C T SupuranldquoMetal-based antibacterial and antifungal agents synthesischaracterization and in vitro biological evaluation of Co(II)Cu(II) Ni(II) and Zn(II) complexes with amino acid-derivedcompoundsrdquo Bioinorganic Chemistry and Applications vol2006 Article ID 83131 13 pages 2006
[31] N Raman R Jeyamurugan M Subbulakshmi R Boomi-nathan and C R Yuvarajan ldquoSynthesis DNA binding andantimicrobial studies of novel metal complexes containing apyrazolone derivative Schiff baserdquo Chemical Papers vol 64 no3 pp 318ndash328 2010
[32] S M Jadhav V A Shelke A S Munde S G Shankarwar V RPatharkar and T K Chondhekar ldquoSynthesis characterizationpotentiometry and antimicrobial studies of transition metalcomplexes of a tridentate ligandrdquo Journal of CoordinationChemistry vol 63 no 23 pp 4153ndash4164 2010
334ndash369 BM respectively due to mononuclear Cu(II) (d91 unpaired electron) and Ni(II) (d8 2 unpaired electrons)complexes which indicates their octahedral geometries [24]whereas the Zn(II) complex is diamagnetic in nature
The formation of a Schiff base (DHPEAPMQ) and itscomplexes was further confirmed by their mass spectralstudy All the spectra exhibit parent peaks due to molecularions (M+) and the isotopic peak owing to the chlorinesubstitution The proposed molecular formula of each com-pound was confirmed by its molecular formula weight withmz values The mass spectra of Schiff base (DHPEAPMQ)showed the formation of a molecular ion peak at mz 385[M]+ whereas Cu(II) Ni(II) and Zn(II) complexes showthe formation of molecular ion peaks along with isotopicpeaks atmz 832 [M]+ 826 [M]+ and 485 [M]+ 487 [M+2]+respectively corresponding to their molecular formula
311 ESR SpectrumofCu(II) Complex TheX-bandESR spec-tra of Cu(II) complex were recorded in the polycrystallinestate at room temperature at a frequency of 9387GHz witha field set of 3950G The information about the hyperfineand super hyperfine structure was obtained to explain thegeometry of the complex as well as the site of the metal-ligand bonding or chemical environment around the metalion In the present study the ESR spectral pattern of Cu(II)complex as depicted in supplementary file 1(e) gives the data119892
value was less than 23 and confirms thestrong covalent nature of themetal-ligand bondThe 119892
||
valueplays a significant role in elucidating the metal-ligand bondcharacter for ionic 119892
||
gt 23 and for covalent characters 119892||
lt
23 respectively [25] The ESR spectrum showed asymmetricbands with 119892
||
gt 119892
perp
gt 20023 representing that the unpairedelectrons lay predominantly in the119889
119909
2minus119910
2 orbital with possiblemixing of 119889
119911
2 because of low symmetry [26]TheG value wascalculated by using the formula 119866 = (119892
||
minus 20023)(119892
perp
minus
20023) which was greater than 4 as shown in Table 3 andindicates the negligible exchange interaction in solid complexas suggested by Hathaway and Billing [27]
32 Antimicrobial Activity of Schiff Base (DHPEAPMQ) andIts Complexes against MRSA The antimicrobial activity ofthe Schiff base (DHPEAPMQ) and its complexes was eval-uated against MRSA and isolated from different hospitalsand health care centers of the Gulbarga region in IndiaFigure 3 shows the good antimicrobial activity of the Schiffbase (DHPEAPMQ) against MRSA with a zone of inhibition(12mm) however upon complex formation the antimicro-bial activity increased with a zone of inhibition (18mm16mm and 14mm) for Cu(II) Ni(II) and Zn(III) complexesrespectively
The antimicrobial property of the Schiff base was ratio-nalized due to the presence of azomethine (C=N) groupthis imports in elucidating the mechanism of transamina-tion and resamination reactions in biological system [28]The formation of hydrogen bonds through the azomethinegroup with the active centers of various cellular constituentsresults in interference with normal cellular processes [29]Furthermore it has also been suggested that the Schiff baseligands with nitrogen and oxygen donor systems mightinhibit enzyme production causing cell death [30]
The enhanced activity of metal complexes than theSchiff base can be explained by Tweedyrsquos chelation theorywhich suggests that the chelation could allow for the delo-calization of 120587-electrons over the entire chelate ring andenhances the lipophilicity of the complexes This increasedlipophilicity facilitates the penetration of the complexes intolipid membranes further restricting the proliferation of themicroorganisms [31]
6 Bioinorganic Chemistry and Applications
Table 3 ESR data of the [Cu(C23H18N3O3)2] metal complex
Complex 119892
119892
perp
119892av 119892iso 119866
[Cu(C23H18N3O3)2] 228 207 211 217 410
N
N
N
N C
N
N
N
N
N
N
N
N
HO
HO
OH
OH OH
C
C
O
O
O OZnCl
O
MO
C OH3C
H3C
CH3
CH3
CH3
CH3
CH3
CH3
Antimicrobial activity ofDHPEAPMQ and its complexes
DHPEAPMQ
Dihydroxyphenyl)ethylideneamino)phenyl)-2-
100120583gmLat concentration
Zn(II)M = Cu(II) and Ni(II)
(E)-3-(2-(1-(24-
methylquinazolin-4(3H)-one
Figure 3 Antimicrobial activity of Schiff base (DHPEAPMQ) and its complexes against MRSA [a1 Schiff base (DHPEAPMQ) a2 Cu(II)a3 Ni(II) and a4 Zn(II) complex]
33 Determination of Minimum Inhibitory Concentration(MIC) Table 4 shows MIC values of Schiff base(DHPEAPMQ) and its complexes which indicates Cu(II)as an excellent antimicrobial agent followed by Ni(II) andZn(III) complexes The enhanced activity of Cu(II) complexmay be due to their particle size and also may be attributedto its higher stability constants [32] when compared to theSchiff base (DHPEAPMQ) and other metal complexes
4 Conclusion
In conclusion we report the synthesis and characterizationof new Schiff base (DHPEAPMQ) and its metal complexesand their antimicrobial activity against MRSA isolated fromclinical samples of the Gulbarga region in India The synthe-ses were confirmed by UV-visible IR NMR mass and ESRspectral data and their results reveal that Cu(II) and Ni(II)
Table 4MIC values of Schiff base (DHPEAPMQ) and its complexesagainst MRSA
complexes exhibit an octahedral geometry while Zn(II) com-plex shows tetrahedral geometry The MIC values of Cu(II)Ni(II) and Zn(II) were 14 18 and 24 120583gmL respectivelywhich show an excellent antimicrobial activity againstMRSASo the same can be used as a new drug of choice
Bioinorganic Chemistry and Applications 7
Conflict of Interests
The authors have no conflict of interests to declare
Acknowledgments
The authors are thankful to the Chairman of Departmentof Chemistry Gulbarga University Gulbarga for providinglaboratory facilities Sunilkumar B Mane is thankful toUGC-MRP (F no 37-1712009(SR)) New Delhi India forproviding financial assistance
References
[1] S Palanisamy K Paramasivam B R Rachel H C Alanand D Nallasamy ldquoSynthesis of novel heterobimetallic cop-per(I)hydrazone Schiff base complexes a comparative studyon the effect of heterocyclic hydrazides towards interactionwith DNAprotein free radical scavenging and cytotoxicityrdquoMetallomics vol 4 no 5 pp 498ndash511 2012
[2] S Nahid G Zeinab and H Saba ldquoBinding studies ofa newwater-soluble iron(III)schiff base complex to DNAusingmultispectroscopicmethodsrdquoBioinorganic Chemistry andApplications vol 2012 Article ID 126451 9 pages 2012
[3] N E A El-Gamel ldquoCoordination behaviour and biopotency ofmetal NN salen complexesrdquo RSC Advances vol 2 no 13 pp5870ndash5876 2012
[4] H D Revanasiddappa K S Prasad L S Kumar and BJayalakshmi ldquoSynthesis and biological activity of new Schiffbases containing 4(3H)-quinazolinone ring systemrdquo Interna-tional Journal of ChemTech Research vol 2 no 2 pp 1344ndash13492010
[5] G Naganagowda and A Petsom ldquoSynthesis and antimicrobialactivity of some new 2-(3-chloro-1- benzothiophen-2-yl)-3-(substituted-phenyl)-4-(3H)-quinazolinones derivativesrdquo Jour-nal of Sulfur Chemistry vol 32 no 3 pp 223ndash233 2011
[6] D Manikprabhu and K Lingappa ldquoAntibacterial activity ofsilver nanoparticles against methicillin-resistant Staphylococcusaureus synthesized using model Streptomyces sp pigment byphoto-irradiation methodrdquo Journal of Pharmacy Research vol6 no 2 pp 255ndash260 2013
[7] CLSI ldquoPerforming Standards for Antimicrobial SusceptibilityTesting Twenty-second Informational Supplement CLSI doc-ument M100-S22rdquo Clinical and Laboratory Standards InstituteWayne Pa USA 2012
[8] T P Tim Cushine and J L Andrew ldquoAntimicrobial activity offlavonoidsrdquo International Journal of Antimicrobial Agents vol26 no 5 pp 343ndash356 2005
[9] D Nelson D M Priscyla G I H de Souza L O Alves and EEsposito ldquoAntibacterial effect of silver nanoparticles producedby fungal process on textile fabrics and their effluent treatmentrdquoJournal of Biomedical Nanotechnology vol 3 no 2 pp 203ndash2082007
[10] M K Prashanth and H D Revanasiddappa ldquoSynthesis ofsome new glutamine linked 23 disubstituted quinazolinonederivatives as potent antimicrobial and antioxidant agentsrdquoMedicinal Chemistry Research vol 22 no 6 pp 2665ndash26762013
[11] B G Kalagouda C H Vidyadhar A P Siddappa and R PBasavaraj ldquoAntimicrobial study of newly synthesized lantha-nide(III) complexes of 2-[2-hydroxy-3-methoxyphenyl]-3-[2-hydroxy-3-methoxybenzylamino]-1 2-dihydroquinazolin-4(3H)-onerdquo Metal-Based Drugs vol 2007 Article ID 37348 7pages 2007
[12] W J Geary ldquoThe use of conductivity measurements in organicsolvents for the characterisation of coordination compoundsrdquoCoordination Chemistry Reviews vol 7 no 1 pp 81ndash122 1971
[13] A I Vogel A Text Book of Quantitative Inorganic AnalysisLongman ELBS London UK 3rd edition 1968
[14] S Biswas K Mitra C H Schwalbe C R Lucas S KChattopadhyay and B Adhikary ldquoSynthesis and characteriza-tion of some Mn(II) and Mn(III) complexes of NN1015840-o-phe-nylenebis(salicylideneimine)(LH
2
) and NN1015840-o-phenylene-bis(5-bromosalicylideneimine)(L1015840H
2
) Crystal structures of[Mn(L)(H
2
O)(ClO4
)] [Mn(L)(NCS)] and an infinite linearchain of [Mn(L)(OAc)]rdquo Inorganica Chimica Acta vol 358 no8 pp 2473ndash2481 2005
[15] N S Youssef E El-Zahany A M A El-Seidy A Caselli andS Cenini ldquoSynthesis and characterization of some transitionmetal complexes with a novel Schiff base ligand and their useas catalysts for olefin cyclopropanationrdquo Journal of MolecularCatalysis A vol 308 no 1-2 pp 159ndash168 2009
[16] D N Satyanarayana Electronic Absorption Spectroscopy andRelated Techniques University Press India Limited New DelhiIndia 2001
[17] K Abe K Matsufuji M Ohba and H Okawa ldquoSite specificityof metal ions in heterodinuclear complexes derived from anldquoend-offrdquo compartmental ligandrdquo Inorganic Chemistry vol 41no 17 pp 4461ndash4467 2002
[18] S P Tandon and P C Mehta ldquoSpectral intensities of somePr+3120573-diketonatesrdquoThe Journal of Chemical Physics vol 52 no1 pp 4313ndash4315 1970
[19] K N Kumar and R Ramesh ldquoSynthesis luminescent redoxand catalytic properties of Ru(II) carbonyl complexes contain-ing 2N2O donorsrdquo Polyhedron vol 24 no 14 pp 1885ndash18922005
[20] S Saydam ldquoSynthesis and characterisation of the new thiazoleSchiff base 2-(2-hydroxy)naphthylideneaminobenzothiazoleand its complexes withCo(II) Cu(II) andNi(II) ionsrdquo Synthesisand Reactivity in Inorganic and Metal-Organic Chemistry vol32 no 3 pp 437ndash447 2002
[21] C Jayabalakrishnan andKNatarajan ldquoRuthenium(II) carbonylcomplexes with tridentate Schiff bases and their antibacterialactivityrdquo Transition Metal Chemistry vol 27 no 1 pp 75ndash792002
[22] M Muthukumar and P Viswanathamurthi ldquoSynthesis spectralcharacterization and catalytic studies of new ruthenium(II)chalcone thiosemicarbazone complexesrdquo Central EuropeanJournal of Chemistry vol 8 no 1 pp 229ndash240 2010
[23] S Chandra and L K Gupta ldquoEPR mass IR electronic andmagnetic studies on copper(II) complexes of semicarbazonesand thiosemicarbazonesrdquo Spectrochimica Acta A vol 61 no 1-2pp 269ndash275 2005
[24] K B Gudasi M S Patil R S Vadavi R V Shenoy S A Patiland M Nethaji ldquoX-ray crystal structure of the N-(2-hydroxy-1-naphthalidene)phenylglycine Schiff base Synthesis and char-acterization of its transition metal complexesrdquo Transition MetalChemistry vol 31 no 5 pp 580ndash585 2006
[25] D Kilveson ldquoPublications of daniel kivelsonrdquo Journal of Physi-cal Chemistry B vol 101 no 43 pp 8631ndash8634 1997
8 Bioinorganic Chemistry and Applications
[26] H Liu H Wang F Gao D Niu and Z Lu ldquoSelf-assemblyof copper(II) complexes with substituted aroylhydrazones andmonodentate N-heterocycles Synthesis structure and proper-tiesrdquo Journal of Coordination Chemistry vol 60 no 24 pp2671ndash2678 2007
[27] B J Hathaway and D E Billing ldquoThe electronic properties andstereochemistry of mono-nuclear complexes of the copper(II)ionrdquo Coordination Chemistry Reviews vol 5 no 2 pp 143ndash2071970
[28] P P Dholakiya andM N Patel ldquoMetal complexes preparationmagnetic spectral and biocidal studies of some mixed-ligandcomplexes with Schiff bases containing NO and NN donoratomsrdquo Synthesis and Reactivity in Inorganic and Metal-OrganicChemistry vol 34 no 3 pp 553ndash563 2004
[29] 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
[30] Z H Chohan M Arif M A Akhtar and C T SupuranldquoMetal-based antibacterial and antifungal agents synthesischaracterization and in vitro biological evaluation of Co(II)Cu(II) Ni(II) and Zn(II) complexes with amino acid-derivedcompoundsrdquo Bioinorganic Chemistry and Applications vol2006 Article ID 83131 13 pages 2006
[31] N Raman R Jeyamurugan M Subbulakshmi R Boomi-nathan and C R Yuvarajan ldquoSynthesis DNA binding andantimicrobial studies of novel metal complexes containing apyrazolone derivative Schiff baserdquo Chemical Papers vol 64 no3 pp 318ndash328 2010
[32] S M Jadhav V A Shelke A S Munde S G Shankarwar V RPatharkar and T K Chondhekar ldquoSynthesis characterizationpotentiometry and antimicrobial studies of transition metalcomplexes of a tridentate ligandrdquo Journal of CoordinationChemistry vol 63 no 23 pp 4153ndash4164 2010
Table 3 ESR data of the [Cu(C23H18N3O3)2] metal complex
Complex 119892
119892
perp
119892av 119892iso 119866
[Cu(C23H18N3O3)2] 228 207 211 217 410
N
N
N
N C
N
N
N
N
N
N
N
N
HO
HO
OH
OH OH
C
C
O
O
O OZnCl
O
MO
C OH3C
H3C
CH3
CH3
CH3
CH3
CH3
CH3
Antimicrobial activity ofDHPEAPMQ and its complexes
DHPEAPMQ
Dihydroxyphenyl)ethylideneamino)phenyl)-2-
100120583gmLat concentration
Zn(II)M = Cu(II) and Ni(II)
(E)-3-(2-(1-(24-
methylquinazolin-4(3H)-one
Figure 3 Antimicrobial activity of Schiff base (DHPEAPMQ) and its complexes against MRSA [a1 Schiff base (DHPEAPMQ) a2 Cu(II)a3 Ni(II) and a4 Zn(II) complex]
33 Determination of Minimum Inhibitory Concentration(MIC) Table 4 shows MIC values of Schiff base(DHPEAPMQ) and its complexes which indicates Cu(II)as an excellent antimicrobial agent followed by Ni(II) andZn(III) complexes The enhanced activity of Cu(II) complexmay be due to their particle size and also may be attributedto its higher stability constants [32] when compared to theSchiff base (DHPEAPMQ) and other metal complexes
4 Conclusion
In conclusion we report the synthesis and characterizationof new Schiff base (DHPEAPMQ) and its metal complexesand their antimicrobial activity against MRSA isolated fromclinical samples of the Gulbarga region in India The synthe-ses were confirmed by UV-visible IR NMR mass and ESRspectral data and their results reveal that Cu(II) and Ni(II)
Table 4MIC values of Schiff base (DHPEAPMQ) and its complexesagainst MRSA
complexes exhibit an octahedral geometry while Zn(II) com-plex shows tetrahedral geometry The MIC values of Cu(II)Ni(II) and Zn(II) were 14 18 and 24 120583gmL respectivelywhich show an excellent antimicrobial activity againstMRSASo the same can be used as a new drug of choice
Bioinorganic Chemistry and Applications 7
Conflict of Interests
The authors have no conflict of interests to declare
Acknowledgments
The authors are thankful to the Chairman of Departmentof Chemistry Gulbarga University Gulbarga for providinglaboratory facilities Sunilkumar B Mane is thankful toUGC-MRP (F no 37-1712009(SR)) New Delhi India forproviding financial assistance
References
[1] S Palanisamy K Paramasivam B R Rachel H C Alanand D Nallasamy ldquoSynthesis of novel heterobimetallic cop-per(I)hydrazone Schiff base complexes a comparative studyon the effect of heterocyclic hydrazides towards interactionwith DNAprotein free radical scavenging and cytotoxicityrdquoMetallomics vol 4 no 5 pp 498ndash511 2012
[2] S Nahid G Zeinab and H Saba ldquoBinding studies ofa newwater-soluble iron(III)schiff base complex to DNAusingmultispectroscopicmethodsrdquoBioinorganic Chemistry andApplications vol 2012 Article ID 126451 9 pages 2012
[3] N E A El-Gamel ldquoCoordination behaviour and biopotency ofmetal NN salen complexesrdquo RSC Advances vol 2 no 13 pp5870ndash5876 2012
[4] H D Revanasiddappa K S Prasad L S Kumar and BJayalakshmi ldquoSynthesis and biological activity of new Schiffbases containing 4(3H)-quinazolinone ring systemrdquo Interna-tional Journal of ChemTech Research vol 2 no 2 pp 1344ndash13492010
[5] G Naganagowda and A Petsom ldquoSynthesis and antimicrobialactivity of some new 2-(3-chloro-1- benzothiophen-2-yl)-3-(substituted-phenyl)-4-(3H)-quinazolinones derivativesrdquo Jour-nal of Sulfur Chemistry vol 32 no 3 pp 223ndash233 2011
[6] D Manikprabhu and K Lingappa ldquoAntibacterial activity ofsilver nanoparticles against methicillin-resistant Staphylococcusaureus synthesized using model Streptomyces sp pigment byphoto-irradiation methodrdquo Journal of Pharmacy Research vol6 no 2 pp 255ndash260 2013
[7] CLSI ldquoPerforming Standards for Antimicrobial SusceptibilityTesting Twenty-second Informational Supplement CLSI doc-ument M100-S22rdquo Clinical and Laboratory Standards InstituteWayne Pa USA 2012
[8] T P Tim Cushine and J L Andrew ldquoAntimicrobial activity offlavonoidsrdquo International Journal of Antimicrobial Agents vol26 no 5 pp 343ndash356 2005
[9] D Nelson D M Priscyla G I H de Souza L O Alves and EEsposito ldquoAntibacterial effect of silver nanoparticles producedby fungal process on textile fabrics and their effluent treatmentrdquoJournal of Biomedical Nanotechnology vol 3 no 2 pp 203ndash2082007
[10] M K Prashanth and H D Revanasiddappa ldquoSynthesis ofsome new glutamine linked 23 disubstituted quinazolinonederivatives as potent antimicrobial and antioxidant agentsrdquoMedicinal Chemistry Research vol 22 no 6 pp 2665ndash26762013
[11] B G Kalagouda C H Vidyadhar A P Siddappa and R PBasavaraj ldquoAntimicrobial study of newly synthesized lantha-nide(III) complexes of 2-[2-hydroxy-3-methoxyphenyl]-3-[2-hydroxy-3-methoxybenzylamino]-1 2-dihydroquinazolin-4(3H)-onerdquo Metal-Based Drugs vol 2007 Article ID 37348 7pages 2007
[12] W J Geary ldquoThe use of conductivity measurements in organicsolvents for the characterisation of coordination compoundsrdquoCoordination Chemistry Reviews vol 7 no 1 pp 81ndash122 1971
[13] A I Vogel A Text Book of Quantitative Inorganic AnalysisLongman ELBS London UK 3rd edition 1968
[14] S Biswas K Mitra C H Schwalbe C R Lucas S KChattopadhyay and B Adhikary ldquoSynthesis and characteriza-tion of some Mn(II) and Mn(III) complexes of NN1015840-o-phe-nylenebis(salicylideneimine)(LH
2
) and NN1015840-o-phenylene-bis(5-bromosalicylideneimine)(L1015840H
2
) Crystal structures of[Mn(L)(H
2
O)(ClO4
)] [Mn(L)(NCS)] and an infinite linearchain of [Mn(L)(OAc)]rdquo Inorganica Chimica Acta vol 358 no8 pp 2473ndash2481 2005
[15] N S Youssef E El-Zahany A M A El-Seidy A Caselli andS Cenini ldquoSynthesis and characterization of some transitionmetal complexes with a novel Schiff base ligand and their useas catalysts for olefin cyclopropanationrdquo Journal of MolecularCatalysis A vol 308 no 1-2 pp 159ndash168 2009
[16] D N Satyanarayana Electronic Absorption Spectroscopy andRelated Techniques University Press India Limited New DelhiIndia 2001
[17] K Abe K Matsufuji M Ohba and H Okawa ldquoSite specificityof metal ions in heterodinuclear complexes derived from anldquoend-offrdquo compartmental ligandrdquo Inorganic Chemistry vol 41no 17 pp 4461ndash4467 2002
[18] S P Tandon and P C Mehta ldquoSpectral intensities of somePr+3120573-diketonatesrdquoThe Journal of Chemical Physics vol 52 no1 pp 4313ndash4315 1970
[19] K N Kumar and R Ramesh ldquoSynthesis luminescent redoxand catalytic properties of Ru(II) carbonyl complexes contain-ing 2N2O donorsrdquo Polyhedron vol 24 no 14 pp 1885ndash18922005
[20] S Saydam ldquoSynthesis and characterisation of the new thiazoleSchiff base 2-(2-hydroxy)naphthylideneaminobenzothiazoleand its complexes withCo(II) Cu(II) andNi(II) ionsrdquo Synthesisand Reactivity in Inorganic and Metal-Organic Chemistry vol32 no 3 pp 437ndash447 2002
[21] C Jayabalakrishnan andKNatarajan ldquoRuthenium(II) carbonylcomplexes with tridentate Schiff bases and their antibacterialactivityrdquo Transition Metal Chemistry vol 27 no 1 pp 75ndash792002
[22] M Muthukumar and P Viswanathamurthi ldquoSynthesis spectralcharacterization and catalytic studies of new ruthenium(II)chalcone thiosemicarbazone complexesrdquo Central EuropeanJournal of Chemistry vol 8 no 1 pp 229ndash240 2010
[23] S Chandra and L K Gupta ldquoEPR mass IR electronic andmagnetic studies on copper(II) complexes of semicarbazonesand thiosemicarbazonesrdquo Spectrochimica Acta A vol 61 no 1-2pp 269ndash275 2005
[24] K B Gudasi M S Patil R S Vadavi R V Shenoy S A Patiland M Nethaji ldquoX-ray crystal structure of the N-(2-hydroxy-1-naphthalidene)phenylglycine Schiff base Synthesis and char-acterization of its transition metal complexesrdquo Transition MetalChemistry vol 31 no 5 pp 580ndash585 2006
[25] D Kilveson ldquoPublications of daniel kivelsonrdquo Journal of Physi-cal Chemistry B vol 101 no 43 pp 8631ndash8634 1997
8 Bioinorganic Chemistry and Applications
[26] H Liu H Wang F Gao D Niu and Z Lu ldquoSelf-assemblyof copper(II) complexes with substituted aroylhydrazones andmonodentate N-heterocycles Synthesis structure and proper-tiesrdquo Journal of Coordination Chemistry vol 60 no 24 pp2671ndash2678 2007
[27] B J Hathaway and D E Billing ldquoThe electronic properties andstereochemistry of mono-nuclear complexes of the copper(II)ionrdquo Coordination Chemistry Reviews vol 5 no 2 pp 143ndash2071970
[28] P P Dholakiya andM N Patel ldquoMetal complexes preparationmagnetic spectral and biocidal studies of some mixed-ligandcomplexes with Schiff bases containing NO and NN donoratomsrdquo Synthesis and Reactivity in Inorganic and Metal-OrganicChemistry vol 34 no 3 pp 553ndash563 2004
[29] 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
[30] Z H Chohan M Arif M A Akhtar and C T SupuranldquoMetal-based antibacterial and antifungal agents synthesischaracterization and in vitro biological evaluation of Co(II)Cu(II) Ni(II) and Zn(II) complexes with amino acid-derivedcompoundsrdquo Bioinorganic Chemistry and Applications vol2006 Article ID 83131 13 pages 2006
[31] N Raman R Jeyamurugan M Subbulakshmi R Boomi-nathan and C R Yuvarajan ldquoSynthesis DNA binding andantimicrobial studies of novel metal complexes containing apyrazolone derivative Schiff baserdquo Chemical Papers vol 64 no3 pp 318ndash328 2010
[32] S M Jadhav V A Shelke A S Munde S G Shankarwar V RPatharkar and T K Chondhekar ldquoSynthesis characterizationpotentiometry and antimicrobial studies of transition metalcomplexes of a tridentate ligandrdquo Journal of CoordinationChemistry vol 63 no 23 pp 4153ndash4164 2010
The authors have no conflict of interests to declare
Acknowledgments
The authors are thankful to the Chairman of Departmentof Chemistry Gulbarga University Gulbarga for providinglaboratory facilities Sunilkumar B Mane is thankful toUGC-MRP (F no 37-1712009(SR)) New Delhi India forproviding financial assistance
References
[1] S Palanisamy K Paramasivam B R Rachel H C Alanand D Nallasamy ldquoSynthesis of novel heterobimetallic cop-per(I)hydrazone Schiff base complexes a comparative studyon the effect of heterocyclic hydrazides towards interactionwith DNAprotein free radical scavenging and cytotoxicityrdquoMetallomics vol 4 no 5 pp 498ndash511 2012
[2] S Nahid G Zeinab and H Saba ldquoBinding studies ofa newwater-soluble iron(III)schiff base complex to DNAusingmultispectroscopicmethodsrdquoBioinorganic Chemistry andApplications vol 2012 Article ID 126451 9 pages 2012
[3] N E A El-Gamel ldquoCoordination behaviour and biopotency ofmetal NN salen complexesrdquo RSC Advances vol 2 no 13 pp5870ndash5876 2012
[4] H D Revanasiddappa K S Prasad L S Kumar and BJayalakshmi ldquoSynthesis and biological activity of new Schiffbases containing 4(3H)-quinazolinone ring systemrdquo Interna-tional Journal of ChemTech Research vol 2 no 2 pp 1344ndash13492010
[5] G Naganagowda and A Petsom ldquoSynthesis and antimicrobialactivity of some new 2-(3-chloro-1- benzothiophen-2-yl)-3-(substituted-phenyl)-4-(3H)-quinazolinones derivativesrdquo Jour-nal of Sulfur Chemistry vol 32 no 3 pp 223ndash233 2011
[6] D Manikprabhu and K Lingappa ldquoAntibacterial activity ofsilver nanoparticles against methicillin-resistant Staphylococcusaureus synthesized using model Streptomyces sp pigment byphoto-irradiation methodrdquo Journal of Pharmacy Research vol6 no 2 pp 255ndash260 2013
[7] CLSI ldquoPerforming Standards for Antimicrobial SusceptibilityTesting Twenty-second Informational Supplement CLSI doc-ument M100-S22rdquo Clinical and Laboratory Standards InstituteWayne Pa USA 2012
[8] T P Tim Cushine and J L Andrew ldquoAntimicrobial activity offlavonoidsrdquo International Journal of Antimicrobial Agents vol26 no 5 pp 343ndash356 2005
[9] D Nelson D M Priscyla G I H de Souza L O Alves and EEsposito ldquoAntibacterial effect of silver nanoparticles producedby fungal process on textile fabrics and their effluent treatmentrdquoJournal of Biomedical Nanotechnology vol 3 no 2 pp 203ndash2082007
[10] M K Prashanth and H D Revanasiddappa ldquoSynthesis ofsome new glutamine linked 23 disubstituted quinazolinonederivatives as potent antimicrobial and antioxidant agentsrdquoMedicinal Chemistry Research vol 22 no 6 pp 2665ndash26762013
[11] B G Kalagouda C H Vidyadhar A P Siddappa and R PBasavaraj ldquoAntimicrobial study of newly synthesized lantha-nide(III) complexes of 2-[2-hydroxy-3-methoxyphenyl]-3-[2-hydroxy-3-methoxybenzylamino]-1 2-dihydroquinazolin-4(3H)-onerdquo Metal-Based Drugs vol 2007 Article ID 37348 7pages 2007
[12] W J Geary ldquoThe use of conductivity measurements in organicsolvents for the characterisation of coordination compoundsrdquoCoordination Chemistry Reviews vol 7 no 1 pp 81ndash122 1971
[13] A I Vogel A Text Book of Quantitative Inorganic AnalysisLongman ELBS London UK 3rd edition 1968
[14] S Biswas K Mitra C H Schwalbe C R Lucas S KChattopadhyay and B Adhikary ldquoSynthesis and characteriza-tion of some Mn(II) and Mn(III) complexes of NN1015840-o-phe-nylenebis(salicylideneimine)(LH
2
) and NN1015840-o-phenylene-bis(5-bromosalicylideneimine)(L1015840H
2
) Crystal structures of[Mn(L)(H
2
O)(ClO4
)] [Mn(L)(NCS)] and an infinite linearchain of [Mn(L)(OAc)]rdquo Inorganica Chimica Acta vol 358 no8 pp 2473ndash2481 2005
[15] N S Youssef E El-Zahany A M A El-Seidy A Caselli andS Cenini ldquoSynthesis and characterization of some transitionmetal complexes with a novel Schiff base ligand and their useas catalysts for olefin cyclopropanationrdquo Journal of MolecularCatalysis A vol 308 no 1-2 pp 159ndash168 2009
[16] D N Satyanarayana Electronic Absorption Spectroscopy andRelated Techniques University Press India Limited New DelhiIndia 2001
[17] K Abe K Matsufuji M Ohba and H Okawa ldquoSite specificityof metal ions in heterodinuclear complexes derived from anldquoend-offrdquo compartmental ligandrdquo Inorganic Chemistry vol 41no 17 pp 4461ndash4467 2002
[18] S P Tandon and P C Mehta ldquoSpectral intensities of somePr+3120573-diketonatesrdquoThe Journal of Chemical Physics vol 52 no1 pp 4313ndash4315 1970
[19] K N Kumar and R Ramesh ldquoSynthesis luminescent redoxand catalytic properties of Ru(II) carbonyl complexes contain-ing 2N2O donorsrdquo Polyhedron vol 24 no 14 pp 1885ndash18922005
[20] S Saydam ldquoSynthesis and characterisation of the new thiazoleSchiff base 2-(2-hydroxy)naphthylideneaminobenzothiazoleand its complexes withCo(II) Cu(II) andNi(II) ionsrdquo Synthesisand Reactivity in Inorganic and Metal-Organic Chemistry vol32 no 3 pp 437ndash447 2002
[21] C Jayabalakrishnan andKNatarajan ldquoRuthenium(II) carbonylcomplexes with tridentate Schiff bases and their antibacterialactivityrdquo Transition Metal Chemistry vol 27 no 1 pp 75ndash792002
[22] M Muthukumar and P Viswanathamurthi ldquoSynthesis spectralcharacterization and catalytic studies of new ruthenium(II)chalcone thiosemicarbazone complexesrdquo Central EuropeanJournal of Chemistry vol 8 no 1 pp 229ndash240 2010
[23] S Chandra and L K Gupta ldquoEPR mass IR electronic andmagnetic studies on copper(II) complexes of semicarbazonesand thiosemicarbazonesrdquo Spectrochimica Acta A vol 61 no 1-2pp 269ndash275 2005
[24] K B Gudasi M S Patil R S Vadavi R V Shenoy S A Patiland M Nethaji ldquoX-ray crystal structure of the N-(2-hydroxy-1-naphthalidene)phenylglycine Schiff base Synthesis and char-acterization of its transition metal complexesrdquo Transition MetalChemistry vol 31 no 5 pp 580ndash585 2006
[25] D Kilveson ldquoPublications of daniel kivelsonrdquo Journal of Physi-cal Chemistry B vol 101 no 43 pp 8631ndash8634 1997
8 Bioinorganic Chemistry and Applications
[26] H Liu H Wang F Gao D Niu and Z Lu ldquoSelf-assemblyof copper(II) complexes with substituted aroylhydrazones andmonodentate N-heterocycles Synthesis structure and proper-tiesrdquo Journal of Coordination Chemistry vol 60 no 24 pp2671ndash2678 2007
[27] B J Hathaway and D E Billing ldquoThe electronic properties andstereochemistry of mono-nuclear complexes of the copper(II)ionrdquo Coordination Chemistry Reviews vol 5 no 2 pp 143ndash2071970
[28] P P Dholakiya andM N Patel ldquoMetal complexes preparationmagnetic spectral and biocidal studies of some mixed-ligandcomplexes with Schiff bases containing NO and NN donoratomsrdquo Synthesis and Reactivity in Inorganic and Metal-OrganicChemistry vol 34 no 3 pp 553ndash563 2004
[29] 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
[30] Z H Chohan M Arif M A Akhtar and C T SupuranldquoMetal-based antibacterial and antifungal agents synthesischaracterization and in vitro biological evaluation of Co(II)Cu(II) Ni(II) and Zn(II) complexes with amino acid-derivedcompoundsrdquo Bioinorganic Chemistry and Applications vol2006 Article ID 83131 13 pages 2006
[31] N Raman R Jeyamurugan M Subbulakshmi R Boomi-nathan and C R Yuvarajan ldquoSynthesis DNA binding andantimicrobial studies of novel metal complexes containing apyrazolone derivative Schiff baserdquo Chemical Papers vol 64 no3 pp 318ndash328 2010
[32] S M Jadhav V A Shelke A S Munde S G Shankarwar V RPatharkar and T K Chondhekar ldquoSynthesis characterizationpotentiometry and antimicrobial studies of transition metalcomplexes of a tridentate ligandrdquo Journal of CoordinationChemistry vol 63 no 23 pp 4153ndash4164 2010
[26] H Liu H Wang F Gao D Niu and Z Lu ldquoSelf-assemblyof copper(II) complexes with substituted aroylhydrazones andmonodentate N-heterocycles Synthesis structure and proper-tiesrdquo Journal of Coordination Chemistry vol 60 no 24 pp2671ndash2678 2007
[27] B J Hathaway and D E Billing ldquoThe electronic properties andstereochemistry of mono-nuclear complexes of the copper(II)ionrdquo Coordination Chemistry Reviews vol 5 no 2 pp 143ndash2071970
[28] P P Dholakiya andM N Patel ldquoMetal complexes preparationmagnetic spectral and biocidal studies of some mixed-ligandcomplexes with Schiff bases containing NO and NN donoratomsrdquo Synthesis and Reactivity in Inorganic and Metal-OrganicChemistry vol 34 no 3 pp 553ndash563 2004
[29] 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
[30] Z H Chohan M Arif M A Akhtar and C T SupuranldquoMetal-based antibacterial and antifungal agents synthesischaracterization and in vitro biological evaluation of Co(II)Cu(II) Ni(II) and Zn(II) complexes with amino acid-derivedcompoundsrdquo Bioinorganic Chemistry and Applications vol2006 Article ID 83131 13 pages 2006
[31] N Raman R Jeyamurugan M Subbulakshmi R Boomi-nathan and C R Yuvarajan ldquoSynthesis DNA binding andantimicrobial studies of novel metal complexes containing apyrazolone derivative Schiff baserdquo Chemical Papers vol 64 no3 pp 318ndash328 2010
[32] S M Jadhav V A Shelke A S Munde S G Shankarwar V RPatharkar and T K Chondhekar ldquoSynthesis characterizationpotentiometry and antimicrobial studies of transition metalcomplexes of a tridentate ligandrdquo Journal of CoordinationChemistry vol 63 no 23 pp 4153ndash4164 2010
