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Title of The Major Research Project: Preparation Characterization and antibacterial screening of some organometallic compounds and metal complexes By Dr. Balgobind Thakur, Associate Profesor of Chemistry C. M. Sc. College Darbhanga (LNMU) Bihar UGC Reference No: 34-338/2008 (SR) UNITI

INTRODUCTION Bacteria 1 are microscopic, prokaryotic organisms often having characteristic shapes and sizes. Many bacteria are pathogenic to humans because they have large segments of DNA called pathogenicity islands that carry genes responsible for virulence. During the course of microbe and human evolution, these pathogens have evolved ways for escaping for host defenses. Their 2 body is membrane bound, which is a prerequisite for all living cells but they lack the ex tensive, complex internal membrane systems. The bacterial cell wall almost always has peptidoglycan and is chemically and morphologically complex. Most bacteria can be divided into gram positive and gram negative groups based on their cell wall structures and response to the gram strain. Bacterial cell wall 3 : Except for the mycoplasmas and some Archacabacteria, most bacteria have strong walls that give them shape and protect them from osmotic lysis. Wall shape and strength in primarily due to peptidoglycan. The cell walls of many pathogens have components that contribute to their pathogenicity. The cell wall can protect a cell from taking substances and is the site of action of several antibiotics. Gram-positive bacteria: They stain purple with gram stain. The cell wall consists of a sample 20 to 80 nm thick homogeneous peptidoglycan, or murin la yer.

Peptidoglycan or murin is an enormous polymer composed of two sugar derivatives N-acetylglucosamine and N -acetylmuramic acid and several defferent amino acid such as D -alanine, D-glutamic acid and meso di amino pimelic acid. The (+) isomer of D-amino acid protects against attack by most peptidases. The backbone of peptidoglycan is composed of alternating. N-acetylmuramic acid chain of linked peptidoglycan subunits are joined by cross links between peptides. Often the carboxyl group of the terminal D -alanine is connected directly to the amino group of diamino pimelic acid. Gram positive cell walls: They usually contain large amounts of teichoic acid polymers of glycerol an ribitol joined by phosphate groups which gives the cell wall its negative charge. Peptidoglycan layers often contains a peptide interbridge. Gram staining 4 : Thomas Christian gram devised gram staining method in 1882. It is a differential staining method of differentiating bacterial species based on chemical and physical propertiesof th eir cell walls. Gram staining is not used to classify acchaca bacteria since they give very variable response. Gram staining consists of four components. 1. 2. 3. 4. Primary stain (crystal violet, methyl violet or certain violet), Mordant (gram`s iodine) Decolourizer (ethyl alcohol, acetone or 1:1ethanol -acetone) Counterstain (dilute carbol fuchsine, safranine or menthol red)

Gram negative bacteria: The cell walls of gram negative bacteria are more complex than that of gram positive bacteria. The peptidog lycan layer of the cell wall is their (about 2 nm) contains one or two layers or sheets of peptidoglycan. The cell wall lack teichoic acid. There is an enter membrane that was outside the peptidoglycan layer. It is rich in Braun`s lipoprotein which is covalently joined to the underlying peptidoglycan layer. The outer membrane contains lipopolysaccharide (LPS).

They intend the host body through one of the body surface (skin , respiratory system, gastrointestinal system, urogenial system or the conjunctiva of the eye). The obligatory steps for the infectious process involving bacterial diseases are: the bacterium most be transmitted to a suitable host, grow and multiply within or on the host and interface with the normal peptidoglycan activities of the host. There is a plethora of diseases that are caused by bacteria. Tuberculosis is one of the bacterial diseases with highest disease burden. Today 1B remains a global health probe of numerous demonian. It is estimated that there are 1 billion (20% of the world`s population) infected worldwide with 10million new cases and over 3 million deaths per year. Recently, there has been a steady yearly increase in the number of TB cases as a resort of the AIDS epidemic. There has been an indicator of existence clone associations between AIDS and TB. Therefore, further spread of HIV infections among the population with a higher prevalence of TB in fections is resulting in dramatic increase in TB. Many diseases are treated with chemotherapeutic agents such as antibiotics that inhibit or kill the pathogens which having the host as little as possible. They disrupt microbial processes or structures that differ from those of the host. They many damage pathogen s by hampering cell wall synthesis, inhibiting microbial proteins and nucleic acid synthesis, disrupting the microbial membrane structure and function or blocking metabolic pathway through inhibition of key enzymes. Antibiotics can be either cidal (kills the target) or static (reversibly inhibit growth). Their activity is concentration dependent. It also varies with the target species. The effec tiveness of an antibiotic against the pathogens can be obtained from the minimal inhibitory concentration (MIC). MIC is the lowest drug concntration that kills the pathogens. A cidal antibiotic kills the pathogens at levels only 2 -4times the MIC, whereas a static antibiotic kills at much higher concentration (if at all). Antibiotics 5 have helped to extent to combat microbial diseases. But the excessive quantities of antibiotics being preparedand used have raised a new issue to be resolved. An increasing number of diseases are resisting treatment due to the spread of dry resistance. Re sistance of Neisseria gonorrhoeae from towards sulfonamides and later towards penicillin,

shigella spp. Towards chloramphenicol, tetracycline, streptomycine and sulfonamide, Haemophilus influenza type -b (responsible for children`s pneumonia, middle ear infections, respiratory infections and meningitis ) is now becoming increasingly resistant to tetracyclines, ampicilin and chloramphenicol. Staphylococcus species are resistant to penicillin -G, some to methicillin, gentamicein. There are few examples that mak e it clear that drug resistance is an extremely serious public health problem. One of the major reasons behind it is the drug misuse. It has been estimated that over 50% of the antibiotic prescriptions in hospitals are given without clear evidence of infections adequate medical indications. A recent study showed that over 50% of the patients diagnosed with cords and upper respiratory infections and 66% of those with chart cords (bronchitis) are given antibiotics, even through over 90% of these cases are caused by viruses. Frequently, antibiotics are prescribed without characterizing and identifying the pathogens. Toxic broad spectrum antibiotics are sometimes given in place of narrow spectrum drug as a substitute for culture and sensitivity testing, with the consequent rise of dangerous side effects, super infections and the situation of drug resistant mutants when the antibiotic treatment is ended too easily (without completion of the course of medications), drug resistance mutants may survive. Self adminis trations of antibiotic by people further increase the prevalence of drug resistance strains. Bacteria become drug resistance in several different ways. They may prevent the entrance of drug or pump out the drug after it has entered the cell or inactivate the drug through chemical modifications (e.g. hydrolysis of -lactam ring of penicillin by the enzyme penicillinase ) or they may use an alternate pathway to bypass the sequence inhibited by the agent or increase the productions of target metabolite. Several strategies can be employed to discourage the emergence of drug resistance. The drug can be given in high enough concentration to destroy susceptible bacteria and most spontaneous mutant that might arise during the treatment. Sometimes two different drugs can be given simultaneously so that each drug will prevent the resistance to the other . Broad spectrum antibiotics should be used only when definitely

necessary. If possible, the pathogens should be identified, drug sensitivity tests run and the prop er narrow spectrum drug employed. Another approach is to search for new antibiotics that microorganism have never encountered. To reduce the resistance of single antibiotic molecules attempts have been made to prepare their metal complexes as several meta ls reported in the literature are capable of inhibiting the growth of microorganisms. These coordination compounds have different physiological properties. On account of these properties it has been used in the different era of human life. It has been observed that chelating agent can be used therapeutically . A lot of research work has been done regarding the present research project. It shows the national and international status of the project under taken as well as it focuses on its significance also. Organometallic complexes with biological molecules: Triorganotin (IV) complexes with amoxicillin and ampicillin have been reported by R. Di Stefaano et. al 6 . Nobel triorganotin (IV) complexes of two -lactamic antibiotics 6 -[D-(-)-amino-p-hydroxymethyl-acetamido] penicillin (=Amoxicillin) and 6 [D-(-)--aminobenzyl] penicillin (=Ampicillin) have been synthesized and investigated both in solid and solution states. The complexes correspond to the general formula [R 3 Sn(IV)antibioH 2 O], (R= Me, nbutyl, phenyl; antibio = amoxicillinate or ampicillinate). Structural investigations about configuration in the solid state have been carried out by interpreting experimental IR an d 1 1 9 Sn Mssebauer data. In particular IR results suggested polymeric structures both for [R 3 Sn(IV)amoxH 2 O] and [R 3 Sn(IV)ampH 2 O]. Moreover both antibiotics appear to behave as monoanionic bidentate ligands coordinating the tin (IV) atom through ester type carboxylate as well as through -lactamic carbonyl. Evidence that in none of the se compounds, water molecules were involved in coordination was provided by thermogravimetric investigations. On the basis of 1 1 9 Sn Mssbauer spectroscopy it can be inferred that tin (IV) was pentacoordinated in all of the complexes in the

solid state, showing an equatorial R 3 Sn(IV) trigonalbipyramidal (TBP) configuration. The nature of the complexes in solution state was investigated by using 1 H and 1 3 C NMR spectroscopy while a 1 1 9 Sn spectrum was obtained for n -Bu 3 Sn(IV)ampH 2 O. Although 1 H and 1 3 C NMR measurements suggested that in dimethyl sulfoxide (DMSO) -d(6) solution the polymeric structure collapsed. Due to a solvolysis process of the -lactamic carbonyl bonding to the organometallic moiety, the complexes have been shown to maintain the same TBP config uration at tin (IV) atom by the coordination of a DMSO molecule. Cytotoxic activity of these novel semisynthetic antibiotic derivatives has tested towards spermatocyte chromosomes of the mussel Branchidonates pharaonis (Mollusca: Bivalvia) using two differ ent chromosome-staining techniques such as Giemsa and CMA (3). The occurrence of typical colchicinized-like (C-like) mitoses on slides obtained from animals exposed to organotin compounds directly confirmed the high mitotic spindle-inhibiting potency of th ese chemicals. In addition by comparative analysis of spermatocyte chromosomes from untreated specimens (negative controls) and specimens treated with the triorganotin (IV) complexes, structural damages such as achromatic lesions and chromosome breakages h ave been identified. Bacterials are those agents which can act as bacteriostatic or bactericidal, thereby preventing the multiplication and the growth of bacteria (microorganisms) in vitro or in vivo e.g.: sulpha compounds, antibiotics, fluoroquinolones et c. Few metals reported in the literature are capable of inhibiting the growth of microorganisms. Bismuth is included under this category, which can exhibit a good antibacterial activity. In the proposed plan of work attempts were made to prepare some complexes of various antibacterial drugs with bismuth citrate. These complexes were purified and confirmed by physical and spectral analysis. They were then screened for their antibacterial activit y 7 . The study of some transition metals (M) and amoxicillin trihydrate (ACT) ligand complexes (M -ACT) that formed in solution involved the spectrophotometric determination of stoichiometric ratios and their stability constants and these ratios were found to be M:A CT = 1:1, 1:2 and 2:1 in some instances. The calculated stability constants and these

chelates, under selected optimum conditions, using molar ratio method have values ranging from K f = 10 7 to 10 1 4 . These data were confirmed by calculations of their free e nergy of formation G, which corresponded to their stabilities. The separated solid complexes were studied using elemental analysis, IR, reflectance spectra, magnetic measurements, mass spectra and thermal analysis (TGA and DTA). The proposed general formulae of these complexes were found to be ML(H 2 O) w (H 2 O) x (OH) y (Cl) z , where M = Fe (II), Co (III), w = 0, x= 2, y = 1, z = 0; M = Co (II), w = 0, x = 1, y = 0, z = 1; M = Fe (III), w = 0, x = 1, y = 2, z = 0; M = Ni (II), Cu (II) and Zn (II), w = 2, x= 0, y = 1, z = 0; where w = water of crystallization, x = coordinated water, y = coordinated HO - and z = Cl - in the outer sphere of the complex. The IR spectra show a shift of ( N H ) (2968 cm - 1 ) to 2984-2999 cm - 1 of imino group of the ligand ACT and the absence o f ( C O ) (-lactam) band at 1774 cm - 1 and the appearance of the band at 1605 -1523 cm - 1 in all complexes suggest that 6, 7 -enolization takes place before coordination of the ligand to the metal ions. The bands of M -N (at 625-520 cm - 1 ) and of M-O (at 889-750 cm - 1 ) proved the bond of N (of amino and imino groups) and O of C-O group of the ligand to the metal ions. The reflectance spectra and room temperature magnetic measurement refer to octahedral complexes of Fe (II) and Fe (III); square planar form of Co (II), reduced Co(III), Ni (II) and Cu (II) -ACT complexes but tetrahedral from of Zn-ACT complex. The thermal degradation of these complexes is confirmed by their mass spectral fragmentation. These data confirmed the proposed structural and general formulae of these complexes 8 . Synthesis, characterization and in vitro screening of amoxicillin and its complexes with Ag (I), Co (II), Cu (II), Ni (II) and Zn (II) has been reported by Muhammad Imran et.al 9 . New complexes of amoxicillin with some transition metal ions such as Ag (I), Co (II), Cu (II), Ni (II) and Zn (II) has been synthesized and characterized on the basis of physical, spectral and analytical data. These complexes have also been screened for th e antibacterial activity against several bacterial strains such as Escheria coli, Staphylococcus aurous, Pseudonomous aerugionosa. The metal complexes showed enhanced antibacterial activity as compared to simple antibiotic. The

present study was carried ou t in the search of target antibiotic moiety instead of broad spectrum antibiotic. Some first row transition metal complexes of isoniazid have been reported by I. R. Allan et. al 1 0 . Complexes of the chlorides and bromides of manganese (II), iron (II), cobalt (II), nickel (II), copper (II) and zinc (II) with isoniazid (INH) have been prepared and studied by means of their magnetic susceptibilities, infrared and electronic spectra. All of the complexes have octahedral structures with the exception of the zinc complex and the chloro complexes of manganese and iron which are tetrahedral. The chloro complex of copper is square planar. Isoniazid metal complex reactivity and insights for a novel anti disruption which does not promote an electron transfe r reaction. The reactivity of isoniazid metal complexes as prototypes for novel self activating metallodrugs against TB wit h the aim to overcome resistance has been studied 1 1 . Reactivity studies were conducted with hydrogen peroxide, hexacyanoferrate (III) and aquope ntacyanoferrate (III). The species showed a preference for the inner -sphere electron transfer reaction pathway. Additionally, electron transfer reaction performed with either free isoniazid or isoniazid pentacyanoferrate (II) complex resulted in similar oxidized isoniazid derivatives as observed when the KatG enzyme was used, however upon metal coordination a significant enhancement in the formation of isonicotinic acid was observed compared with that of isonicotinamide. These results suggest ed that the pathway of a carbonyl centered radical might be favoured upon coordination to the Fe (II) owing to the -back bonding effect promoted by this metal center. Therefore, the isoniazid metal complex could serve as a potential metallodrug. Enzymatic inhibition ass ays conducted with INHA showed that the cyanoferrate moiety is not the major player involved in this inhibition but the presence of isoniazid is required in this process. Other isoniazid metal complexes [Ru (CN) 5 (Izd)] (3) and [Ru (NH 3 ) 5 (Izd)] (2), (where, Izd = isoniazid), were also unable to inhibit INHA, supporting self activating mechanism of action. Clearly Isoniazid reactivity can be rationally modulated by metal coordination chemistry, leading to the development of novel anti -TB metallodrugs.

A number of organomercury (II) complexes involving isoniazid (1) of the type RHgCl(L) (II) (R = phenyl, o -hydroxyphenyl, p-hydroxyphenyl, pacetoxyphenyl, 2-furyl, L = isonizid) have been synthesized and characterized. Conductance measurements indicate th at the complexes are non electrolytes. From IR and UV studies, it is concluded that isoniazid acts as a bidentate ligand, coordinating through hydrizinic nitrogen and carbonyl oxygen. 1 H and 1 3 C NMR support the stoichiometry of the complexes. From fluoresc ence studies a number of photochemical parameters have been elucidated. For the PhHgCl(L) , p HO-PhHgCl(L) and p-Aco- PhHgCl(L) complexes, thermo gravimetric studies have been carried out and relevant kinetic and thermodynamic parameters for thermal degrad ation have been enumerated. In addition the fragmentation pattern of the complexes has been analyz ed on the basis of mass spectra. The PhHgCl(L) and p-HO-PhHgCl(L) complexes have been screened for tuberculosis activity (S. Bhatia et. al.) 1 2 Crystal structure of a new Cu (II) ofloxacin complex has been reported by B. MaCias et. al 1 3 , 1 4 . The X-ray crystallographic, NMR and antimicrobial activity studies of magnesium complexes of fluoroquinolones -racemic ofloxacin and its Sform levofloxacin has been reported by P. Drevensek et. al 1 5 . The mechanism of differential activities of ofloxacin enantiomers has been reported by I. Morrissey et. al 1 6 . This paper well explains the mechanistic path of ofloxacin. Ofloxacin, a potent quinolone antibacterial agent has a tricyclic ring structure with methyl group attached to the asymmetric carbon at the C 3 position on the oxazine ring. The S -isomer of ofloxacin has antibacterial activity up to 2 orders of magnitude greater than that of the R-isomer. This differential antibacterial was not due to different drug transport mechanism of the two isomers but was found to be derived from the inhibitory activity against the target enzyme, DNA gyrase. Previous mechanistic studies have suggested that the bactericidal effect of the drug is mediated through the stabilization of a cleavable complex via a cooperative drug binding process to a partially denatured DNA

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pocket created by DNA gyrase. The drug binds to supercoild DNA in a manner similar to that to which it binds to the e nzyme-DNA complex. In the present studies, we first examined the binding of the two radiolabeled ofloxacin enantiomers to supercoiled PUC9 plasmid DNA. Surprisingly the two enantiomers possessed similar apparent binding affinities and binding cooperatives. The major difference in binding between the two stereoisomers was the molar binding ratio 1:4 for the more active S-isomer versus 2 for the less active R -isomer.The relative binding potencies of the stereoisomers to the DNA -DNA gyrase complex have been studied. The results of a competition assay showed that S ofloxacin binds 12-fold better to the complex than R -ofloxacin. The binding potencies of the two enantiomers and two other quinolones correlated well with their respective concentrations causing 50% inhibition against DNA gyrase. The results are interpreted by a stacking model by using the concept of the cooperative drug -DNA binding mechanism, indicating that the potencies of quinolones cannot be determined solely by the DNA binding affinity and cooper ativity but can also be determined by their capability in maximally saturating the binding site. The capability of the drug in saturating the binding pocket manifests itself in an increased efficacy at inhibiting the enzyme through a direct interaction between the drug and the enzyme. The result is similar to the argument of previous suggestion that the binding pocket in the enzyme-DNA complex involves multiple receptor groups including not only DNA bases but also a gyrase subunit. The higher level of potency of S-ofloxacin is proposed to derive from the fact that a greater number of molecules optimizes the interactions between the drug and the enzyme possibly through a contact between the C -7 substituent and the quinolone pocket on the B -subunit of DNA gyrase. The significance of the methyl group on the oxazine ring of ofloxacin derivatives in the inhibition of bacterial and mammalian type -II topoisomeraseshas been reported by K. Hoshino et. al 1 7 . A study was made of the correlation between the in vitro inh ibitory effects of several quinolones including four ofloxacin derivatives. On bacterial DNA gyrase from E.coli KL -16 and on topoisomerase-II from fetal calf thymus no correlation was observed between the inhibitors of

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DNA gyrase activity and topoisomerase -II activity. On the other hand, the inhibitory effects of these quinolones against topoisomerase -II were closely correlated with their inhibition of cell growth. Furthermore among the oxazine derivatives tested, the derivative with a methyl group at position 3 in an S-configuration showed the highest activity against DNA gyrase and derivatives without a methyl group on the oxazine ring were more potent against topoisomerase -II than those with a methyl group. Among these derivatives DR -3355, the S-isomer of ofloxacin showed the highest activity against DNA gyrase and low activity against topoisomerase-II. These results indicate that the ethyl group on the oxazine activity of ofloxacin derivatives for these enzymes. Again inhibitory effects of quinolones on D NA gyrase of E. coli and topoisomerase-II of the fetal calf thymus has also been reported by K. Hoshino et. al 1 8 . The in vitro inhibitor effects of quinolones on the bacterial DNA gyrase of E. coli KL-16 and topoisomerase II of fetal calf thymus were compared. All the quinolones tested required higher concentration existed among their inhibitory activities against both enzymes. However there was a large difference among the quinolones in their selectivities between the bacterial enzyme and its eukaryotic c ounterpart. The selectivity of ofloxacin was highest and the selectivities of CI -934 and nalidixic acid were lowest. The inhibitory effects of quinolones on pro and eukaryotic DNA topoisomerase-I and II has been reported by N. J. Moreau et. al 1 9 . The crystal structure, biological studies of water soluble rare earth metal complexes with an ofloxacin derivative has been reported by Min Xu et. al 2 0 . The synthesis and crystal structure of Zn (II) and Co (II) complexes with ofloxacin and enoxacin has been reported by Liang Cai Yu et. al 2 1 .

The antibacterial, SOD mimic and nuclease activities of Copper (II) complexes containing ofloxacin and neutral bidentate ligands has been reported by Mohan N. Patil et. al 2 2 .

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The ruthenium organometallic complexes of antibacterial agent ofloxacin, crystal structure and interactions with DNA have been reported 2 3 . Coordination numbers and geometry of the complexes: The shape of a coordination compound is the product of several interacting factors. One factor may be domi nant in one compound, with another factor dominant in another 2 4 . Some factors involved in determining the stru ctures of coordination complexes include following: Occupancy of d-orbitals. Cystal field stabilization energy. Strength of ligands and Steric interference by large ligands crowding each other around the central metal.

However it is perhaps difficult to predict shapes and all predictions should be addressed skeptically unless backed by experimental evidences. Coordination number-four 2 5 : Tetrahedral and square-planar structures are two common structures with four ligands. Crowding around small ions of high positive charge and prevents high coordination number. Many d 0 and d 1 0 configuration of central metals or metal ions have tetrahedral structures su ch as MnO - 4 , CrO 2 - 4 and [Cu(py) 4 ] + with a few d 5 , such as [Mn(Cl) 4 ] 2 - . In such cases, the shape can be explained on the basis of VSEPR arguments, because the d-orbitals occupancy is spherically symmetrical with zero one or two electrons in each d -orbitals. Splitting in Td-point group: In order to form four coordinated tetrahedral geometry all four ligands approach the metal d -orbitals between the axes, consequently, the dxy, dxz and dyz (collectively called t 2 in Td-point group), which are almost directed at the surrounded ligands are now raised in energy. On the other hand, dz 2 and dx 2 -y 2 (collectively called e in Td -point group), which are directed between the surrounding ligands are relatively unaffected by the field. Again the degeneracy of the five d -orbitals dissolved but in

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opposite manner as degeneracy dissolved in the case of octahedral geometry. Thus the five d -orbitals split into two sets of orbitals with t 2 at higher energy and e at lower energy. The separation between t 2 and esets of orbitals is now denoted by t . the splitting of d -orbitals in tetrahedral geometry also obeys barycenter rule. The splitting may be diagrammatically shown as:

Factors favourable for tetrahedral geometry: The d 0 , d 5 (in presence of weak ligands) and d 1 0 systems have zero CFSE in octahedral and tetrahedral geometry and comparatively less in square planar geometry. Since, ligand -ligand repulsion is comparatively less in tetrahedral field so, these systems prefer to form tetrahedral complex. It favoured by steric requirements either simple electrostatic repulsion of charged ligands or Van der Waals repulsions of large ones. Smaller metal ions those with a noble gas configuration usually forms tetrahedral complexes. The metal ions with pseudo noble gas configuration such as Zn 2 + generally form tetrahedral complexes. Those transition metal ions which do not strongly favour other structures by CFSE such as Co 2 + ion form tetrahedral complexes. Pt (II)], although Ni (II) and Cu (II) can have tetrahedral, square pl anar or intermediate shapes depending on both the ligand and the counter ion in the crystal. The metal ion Zn 2 + , which has zero CFSE in octahedral as well as in square planar field, pseudo noble gas configuration (d 1 0 -system) and do

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not strongly favour oth er structures, hence tetrahedral complex of Zn 2 + ion are observed with taken ligand in our project work. Square-planar geometry is also possible for four -coordinate species. The only common square-planar complexes are formed by a planar ligand with metal containing d 8 ions [for example; Ni (II), Pd (II). Splitting in D 4 h -point group: A square planar complex may be considered as strongly distorted octahedral complex in which two of the ligands lie on the z -axis is completely removed, square plan ar complex is formed. As a result, orbitals having a z-component will experience a decrease in electrostatic repulsion from the ligands and will therefore be stabilized. At the same time orbitals having z and y -component will experience a greater electrostatic repulsion from ligand and will therefore be destabilized with maintaining constancy of barycenter. Since, both e g and t 2 g sets of orbitals contain z-axis as well as x and y -axis. So, the overall result is that the e g -set of orbitals splits into two se ts with the dx 2 -y 2 (b 1 g ) at higher energy and dz 2 (a 1 g ) at lower energy and t 2 g set splits into a dxy (b 2 g ) and a doubly degenerate e g (dxz and dyz) at lower energy. The energy separation between b 2 g and b 1 g levels is denoted by s q . The splitting pattern may be shown as:

Factors favourable for square planar geometry: Strong ligand,

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Metal ions having d 8 configuration such as Ni 2 + ions and The d 9 -systems (Cu 2 + ion), as it has CFSE value comparatively larger in square planar geometry. In present research work complexes of Ni (II) and Cu (II) ions with all ligands such as amoxicillin, ciprofloxacin, cloxacillin, isoniazid and ofloxacin have square planar geometry as suggested by the spectral and analytical evidences. The geomet ry for the complexes formed by the Zn (II) metal ion with the same ligands has been predicted tetrahedral on account of the spectral and analytical evidences, as discussed in the unit of Results and Discussion. Coordination number-six: Six is the most co mmon coordination number. The most common structure is octahedral 2 6 ; some trigonal prismatic. Structures are also known. If a metal ion is large enough to allow six ligands to fit around it and the d-electrons are ignored, an octahedral shape results from VSEPR arguments. Such compounds exist for most of the transition metals. Splitting in Oh-point group: When the d-orbitals of a metal ion are placed in an octahedral field of ligand electron pairs, any electrons in them are repelled by the field. As a result, the dx 2 -y 2 and dz 2 orbitals, which are directed at the surrounding ligands are raised in energy. The dxy, dxz and dyz orbitals, which are directed between the surrounding ligands are relatively unaffected by the field i.e. the degeneracy of the five d -orbitals dissolved and they split into two sets of d -orbitals with the dz 2 and dx 2 y 2 (collectively called e g ) at a higher energy and dxz, dyz and dxy (collectively called t 2 g ) at lower energy. The difference between e g and t 2 g set of orbitals is denoted by o or 10 D q . The splitting of d -orbitals does not alter the average energy of the five d -orbitals i.e. it maintains the constancy of barycenter. To maintain the constancy of barycenter, it is necessary for the doubly degenerat e e g -orbitals to be further repelled by 0.6 o while triply degenerate t 2 g -orbitals are stabilized to an extent of 0.4 o . It may be pictorially represented as:

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Factors favourable for octahedral geometry: It is the most common geometry, which formed by a lmost all metals or metal ions, even by lanthanide and actinide rare earth metal ions for which higher coordination number is most common. With certain metal ions octahedral complexes are predominant. For example, Cr (III) and Co (III) are almost octahedra l in their complexes. Complexes of Pr (III) and Nd (III) ion with ofloxacin are six coordinated suggested on account of the spectral and analytical evidences. Larger coordination numbers: Coordination numbers are known up to 16 but most over 8 are special cases 2 7 . For example [La(NH 3 ) 9 ] 3 + has a capped square-antiprismatic structure. In the present research work all complexes of Ln 3 + metal ions with all ligands such as amoxicillin, ciprofloxacin, cloxacillin, isoniazid and ofloxacin have the higher c oordination numbers. Complexes of Pr (III) ion with amoxicillin and isoniazid are eight coordinated. Complexes of Nd (III) ion with isoniazid is seven coordinated. Complexes of Pr (III) and Nd (III) ion with ofloxacin are six coordinated.

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18. K. Hoshino, K. Sato, T. Une and Y. Osada Antimicrob Agents Chemother, 33 (10), 1816 -1810, Oct. 1989. 19. N. J. Moreau, H. Robaux, L. Baron and X. Tabarg - Antimicrob Agents Chemother, 34 (10), 1955 -1960, Oct. 1990. 20. Min Xu, Yu Cui Zhang, Zhihong Xu and Zheng Zhi Zeng Inorganica Chimica Acta, Dec -2011 21. Liang Cai Yu, Lan Lai Rong Xia Sheng Li Liu Journal of Coordination Chemistry, vol-62, Issue8, 1313-1319, 2009. 22. Mohan N. Patel, Pradhuman A. Parmar and Deepan S. Gandhi Applied Organometalic Chemistry, vol -25 Issue-1, 2010. 23. Pu Xue Yu Guang and Pu Fen Xi Guang National Laboratory of rare earth Material Chemistry and Application, Ja n. 28 (6), 14201425, 2008. 24. K. Chordroudis, T. J. McCarthy and M. G. Kanatzidis - Inorg. Chem., 1996, 35, 3451. 25. M. C. Favas and D. L. Kepert, Pr og. Inorg. Chem., 1980, 27, 325. 26. A. F. Wells-Structural Inorganic Chemistry, 5 t h ed., Oxford University, Oxford, 1984, p-413. 27. M. C. Favas and D. L. Kepert, Prog. Inorg. Chem., 1981, 28, 309.

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UNIT-II.

2. PREPARATION OF COMPLEXES
1. Preparation of transition metal complexes amoxicillin a. Complexes of amoxicillin with Fe (III) ion: with ligand

All chemicals such as amoxicillin trihydrate, iron (III) chloride, methyl alcohol, ethyl alcohol, n -pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: The 0.21 g of ligand amoxicillin trihydrate, as required for making 0.01 M solution, was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously for three hours till it becomes clear soluti on. The solution was filtered to remove any insoluble residue left. A 0.01 M solution of Fe (II) chloride was prepared by dissolving 0.08 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue left. Preparation of complex: The complex was prepared by the addition of freshly prepared 50 ml of 0.01 M metal salt solution to freshly prepared 50 ml of 0.01 M of ligand amoxicillin solution with continuous stirring at ice cold t emperature and at pH values 8.2-8.8 adjusted by solution of 0.1 M Na 2 CO 3 using a pH meter. The solution was converted into syrupy liquid which when filtered in suction pump, washed with distilled water, ethanol and acetone several times and dried in a dess icator over anhydrous calcium chloride, then green solid complex was obtained.

20

A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble i n alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 491.75 % of Fe % of % of % of C H N Calculated 11.36 39.04 4.47 8.54 Found 11.12 38.74 4.39 8.38

b. Complexes of amoxicillin with Ni (II) ion: All chemicals such as amoxicillin trihydrate, Nickel (II) chloride hexahydrate, methyl alcohol, ethyl alcohol, n -pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: The 0.21 g of ligand amoxicillin trihydrate, as required for making 0.01 M solution, was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously for three hours till it becomes cle ar solution. The solution was filtered to remove any insoluble residue left.

21

A 0.01 M solution of Ni (II) chloride was prepared by dissolving 0.11 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered t o remove any insoluble residue left. Preparation of complex: The complex was prepared by the addition of freshly prepared 50 ml of 0.01 M metal salt solution to freshly prepared 50 ml of 0.01 M of ligand amoxicillin solution with continuous stirring at i ce cold temperature and at pH values 8.2 8.8 adjusted by solution of 0.1 M Na 2 CO 3 using a pH meter. The solution was converted into syrupy liquid which when filtered in suction pump, washed with distilled water, ethanol and acetone several times and dried in a dessicator over anhydrous calcium chloride, then green solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out a t Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 458.63 % of Ni % of % of % of C H N Calculated 12.80 41.86 3.92 9.16 Found 12.68 41.52 3.88 8.98

c.

Complexes of amoxicillin with Cu (II) ion:

22

All chemicals such as amoxicillin trihydrate, copper (II) chloride hexahydrate methyl alcohol, ethyl alcohol, n -pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: The 0.21 g of ligand amoxicillin trihydrate, as required for making 0.01 M solution, was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously for three hours till it becomes cle ar solution. The solution was filtered to remove any insoluble residue left. A 0.01 M solution of Cu (II) chlorid e was prepared by dissolving 0.07 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered t o remove any insoluble residue left. Preparation of complex: The complex was prepared by the addition of freshly prepared 50 ml of 0.01 M metal salt solution to freshly prepared 50 ml of 0.01 M of ligand amoxicillin solution with continuous stirring at i ce cold temperature and at pH values 8.2 8.8 adjusted by solution of 0.1 M Na 2 CO 3 using a pH meter. The solution was converted into syrupy liquid which when filtered in suction pump, washed with distilled water, ethanol and acetone several times and dried in a dessicator over anhydrous calcium chloride, then green solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out a t Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 463.46

23

% of % of % of % of Cu C H N Calculated 13.71 41.52 3.92 9.06 Found 13.53 41.28 3.88 8.91

d. Complexes of amoxicillin with Zn (II) ion: All chemicals such as amoxicillin trihydrate, zinc (II) chloride hexahydrate methyl alcohol, ethyl alcohol, n -pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: The 0.21 g of ligand amoxicillin trihydrate, as r equired for making 0.01 M solution, was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously for three hours till it becomes clear solution. The solution was filtered to remove any insoluble residue left. A 0.01 M solution of Zn (II) chloride was prepared by dissolving 0.07 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue left. Preparation of complex: The complex was prepared by the addition of freshly prepared 50 ml of 0.01 M metal salt solution to freshly prepared 50 ml of 0.01 M of ligand amoxicillin solution with continuous stirring at ice cold temperature and at pH values 8.2 8.8 adjusted by solution of 0.1 M Na 2 CO 3 using a pH meter. The solution was converted into syrupy liquid which when filtered in suction pump, washed with distilled water, ethanol and acetone several times and dried in a dessicator over anhydrous calcium chlori de, then green solid complex was obtained.

24

A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Luckn ow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 465.29 % of % of % of % of Zn C H N Calculated 14.05 41.22 3.87 9.03 Found 13.89 41.01 3.83 8.91

e. Complexes of amoxicillin with Pr (III) ion: All chemicals such as amoxicillin trihydrate, Pr (III) nitrate methyl alcohol, ethyl alcohol, n -pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: The 0.21 g of ligand amoxicillin trihydrate, as required for making 0.01 M solution, was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously for three hours till it becomes clear solution. The solution was filtered to remove any insoluble residue left. A 0.01 M solution of Pr (III) nitrat e was prepared by dissolving 0.16 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue left.

25

Preparation of complex: The complex was prepared by the addition of freshly prepared 50 ml of 0.01 M metal salt solution to freshly prepared 50 ml of 0.01 M of ligand amoxicillin solution with continuous stirring at ice cold temperature and at pH values 8.2 8.8 adjusted by solution of 0.1 M Na 2 CO 3 using a pH meter. The solution was converted into syrupy liquid which when filtered in suction pump, washed with distilled water, ethanol and acetone several times and dried in a dessicator over anhydrous calcium chloride, then green solid complex was obtained. A solubility test of this complex was performed. It was f ound soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulph uric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 463.91 % of Pr % of C Calculated 30.37 Found 30.02 15.52 15.28 % of H 1.51 1.52 % of N 15.09 15.04

f. Complexes of amoxicillin with Nd (III) ion: All chemicals such as amoxicillin trihydrate, Nd (III) chloride methyl alcohol, ethyl alcohol, n -pentane, acetone, DMF and DMSO used in this

26

study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: The 0.21 g of ligand amoxicillin trihydrate, as required for making 0.01 M solution, was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously for three hours till it becomes clear solution. The solution was filtered to remove any insoluble residue left. A 0.01 M solution of Nd (III) chloride was prepared by dissolving 0.17 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue left. Preparation of complex: The complex was prepared by the addition of freshly prepared 50 ml of 0.01 M metal salt solution to freshly prepared 50 ml of 0.01 M of ligand amoxicillin solution with continuous stirring at ice cold temperature and at pH values 8.2 8.8 adjusted by solution of 0.1 M Na 2 CO 3 using a pH meter. The solution was converted into syrupy liquid which when filtered in suction pump, washed with distilled water, ethanol and acetone several times and dried in a dessicator over anhydrous calcium chloride, then green solid complex was obt ained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using op en capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 524.74 % of Nd % of C % of H % of N

27

Calculated Found

27.49 27.25

13.72 13.48

1.33 1.35

8.00 7.93

2. Preparation of transition metal complexes ciprofloxacin a. Complexes of Ciprofloxacin with Fe (III) ion:

with

ligand

All chemicals such as ciprofloxacin, iron (III) chloride, methyl alcohol, ethyl alcohol, n-pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: A 0.17 g of ligand ciprofloxacin, as required for making 0.01 M solution was taken in a dry and clean conical flask containing 50 ml of redistilled water with continuous stirring we get a clear solution. A 0.01 M solution of Fe (III) chloride was prepared by dissolving 0.08 g of metal salt in 10 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue. Preparation of complex: The complex was prepared by the slow addition of 10 ml of 0.01 M metal salt solution to the continuous electrically stirred 50 ml of 0.01 M aqueous solution of ligand ciprofloxacin at room temperature for 4 hrs. The solution was attained yellow syrupy state. The concentration of final solution gave rise to a yellow colour precipitate, which was filtered and washed with distilled water, ethanol and ether regularly and repeatedly three times. The precipitate was dried in a desiccator over dry calcium chloride, and then solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone.

28

Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 769.35 % of % of % of % of Fe C H N Calculated 7.26 53.03 4.68 10.92 Found 7.13 52.78 4.58 10.79

b. Complexes of Ciprofloxacin with Ni (II) ion: All chemicals such as ciprofloxacin, nickel (II) chloride hexahydrate, methyl alcohol, ethyl alcohol, n -pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: A 0.17 g of ligand ciprofloxacin, as required for making 0.01 M solution was taken in a dry and clean conical flask containing 50 ml of redistilled water with continuous stirring we get a clear solution. A 0.01 M solution of Ni (II) chloride was prepared by dis solving 0.11 g of metal salt in 10 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue. Preparation of complex: The complex was prepared by the slow addition of 10 ml of 0.01 M metal salt solution to the continuous electrically stirred 50 ml of 0.01 M aqueous solution of ligand ciprofloxacin at room temperature for 4 hrs. The solution was attained yellow syrupy state. The concentration of final solution gave rise to a yellow colour precipitate, which was filtered and

29

washed with distilled water, ethanol and ether regularly and repeatedly three times. The precipitate was dried in a desiccator over dry calcium chloride, and then solid complex was obtained. A solubility test of this complex was p erformed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 718.71 % of % of % of % of Ni C H N Calculated 8.17 56.77 4.73 11.69 Found 8.01 56.34 4.69 11.55

c. Complexes of Ciprofloxacin with Cu (II) ion: All chemicals such as ciprofloxacin, copper (II) chloride, methyl alcohol, ethyl alcohol, n-pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: A 0.17 g of ligand ciprofloxacin, as require d for making 0.01 M solution was taken in a dry and clean conical flask containing 50 ml of redistilled water with continuous stirring we get a clear solution.

30

A 0.01 M solution of Cu (II) chloride was prepared by dissolving 0.07 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue. Preparation of complex: The complex was prepared by the slow addition of 10 ml of 0.01 M metal salt solution to the continuous electrically st irred 50 ml of 0.01 M aqueous solution of ligand ciprofloxacin at room temperature for 4 hrs. The solution was attained yellow syrupy state. The concentration of final solution gave rise to a yellow colour precipitate, which was filtered and washed with distilled water, ethanol and ether regularly and repeatedly three times. The precipitate was dried in a desiccator over dry calcium chloride, and then solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melti ng point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table.

Elemental analysis: Mass = 723.54 % of % of % of % of Cu C H N Calculated 8.78 56.39 4.70 11.61 Found 8.34 56.18 4.69 11.48

31

d. Complexes of Ciprofloxacin with Zn (II) ion: All chemicals such as ciprofloxacin, zinc (II) chloride, methyl alcohol, ethyl alcohol, n-pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: A 0.17 g of ligand ciprofloxacin, as required for making 0.01 M solution was taken in a dry and clean conical flask containing 50 ml of redistilled water with continuous stirring we get a clear solution. A 0.01 M solution of Zn (II) chlorid e was prepared by dissolving 0.07 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue. Preparation of complex: The complex was prepared by the slow addition of 50 ml of 0.01 M metal salt solution to the continuous electrically stirred 50 ml of 0.01 M aqueous solution of ligand ciprofloxacin at room temperature for 4 hrs. The solution was attained yellow syrupy state. The concentration of final solution gave rise to a yellow colour precipitate, which was filtered and washed with distilled water, ethanol and ether regularly and repeatedly three times. The precipitate was dried in a desiccator over dry calcium chloride, and then solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis:Mass = 914.66

32

% of % of % of % of Zn C H N Calculated 16.44 20.99 1.97 4.59 Found 16.12 20.72 1.93 4.52

e. Complexes of Ciprofloxacin with Pr (III) ion: All chemicals such as ciprofloxacin, Pr (III) nitrate, methyl alcohol, ethyl alcohol, n-pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: A 0.17 g of ligand ciprofloxacin, as required for making 0.01 M solution was taken in a dry and clean conical flask containing 50 ml of redistilled water with continuous stirring we get a clear solution. A 0.01 M solution of Pr (III) nitrate was prepared by dis solving 0.16 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue. Preparation of complex: The complex was prepared by the slow addition of 10 ml of 0.01 M metal salt solution to the continuous electrically stirred 50 ml of 0.01 M aqueous solution of ligand ciprofloxacin at room temperature for 4 hrs. The solution was attained yellow syrupy state. The concentration of final solution gave rise to a yellow colour precipitate, which was filtered and washed with distilled water, ethanol and ether regularly and repeatedly three times. The precipitate was dried in a desiccator over dry calcium chloride, and then solid complex was obtained. A solubility test of this complex was p erformed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone.

33

Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 1130.91 % of % of % of % of Pr C H N Calculated 12.46 54.12 4.51 11.14 Found 12.38 53.87 4.49 11.03

f. Complexes of Ciprofloxacin with Nd (III) ion: All chemicals such as ciprofloxacin, Nd (III) chloride, methyl alcohol, ethyl alcohol, n-pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: A 0.17 g of ligand ciprofloxacin, as required for making 0. 01 M solution was taken in a dry and clean conical flask containing 50 ml of redistilled water with continuous stirring we get a clear solution. A 0.01 M solution of Nd (III) chloride was prepared by dissolving 0.17 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue. Preparation of complex:

34

The complex was prepared by the slow addition of 10 ml of 0.01 M metal salt solution to the continuous electrically stirred 50 ml of 0.01 M aqueous solution of ligand ciprofloxacin at room temperature for 4 hrs. The solution was attained yellow syrupy state. The concentration of final solution gave rise to a yellow colour precipitate, which was filtered and washed with distilled water, ethanol and ether regularly and repeatedly three times. The precipitate was dried in a desiccator over dry calcium chloride, and then solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis:Mass = 1134.24 % of % of % of % of Nd C H N Calculated 12.72 53.92 4.50 11.11 Found 12.56 53.68 4.47 11.02

3. Complexes of cloxacillin with transition metals a. Complexes of cloxacillin with Fe (III) ion: All chemicals such as cloxacillin, iron (III) chloride, methyl alcohol, ethyl alcohol, n-pentane, acetone, DMF and DMSO used in this study

35

were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: The 0.22 g of ligand cloxacillin, as required for making 0.01 M solution, was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously for three hours till it becomes clear solution. The solution was filtered to remove any insoluble residue left. A 0.01 M solution of Fe (III) chloride was prepared by dissolving 0.08 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue left. Preparation of complex: The complex was prepared by the addition of freshly prepared 50 ml of 0.01 M metal salt solution to freshly prepared 50 ml of 0.01 M of ligand cloxacillin solution with continuous stirring at ice cold temperature and at pH values 8.2 8.8 adjusted by solution of 0 .1 M Na 2 CO 3 using a pH meter. The solution was converted into syrupy liquid which when filtered in suction pump, washed with distilled water, ethanol and acetone several times and dried in a dessicator over anhydrous calcium chloride, then green solid comp lex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determin ed using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 579.85 % of Fe % C of % H of % N of

36

Calculated 9.63 Found 9.43

39.32 39.08

3.97 3.92

7.24 7.11

b. Complexes of cloxacillin with Ni (II) ion: All chemicals such as cloxacillin, Nickel (II) chloride hexahydrate, methyl alcohol, ethyl alcohol, n -pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck.

Preparation of solution: The 0.22 g of ligand cloxacillin, as required for making 0.01 M solution, was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously for three hours till it becomes clear solution. The solution was filtered to remove any insoluble residue left. A 0.01 M solution of Ni (II) chloride was prepared by dissolving 0.11 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any inso luble residue left. Preparation of complex: The complex was prepared by the addition of freshly prepared 50 ml of 0.01 M metal salt solution to freshly prepared 50 ml of 0.01 M of ligand cloxacillin solution with continuous stirring at ice cold temperatu re and at pH values 8.2 8.8 adjusted by solution of 0.1 M Na 2 CO 3 using a pH meter. The solution was converted into syrupy liquid which when filtered in suction pump, washed with distilled water, ethanol and acetone several times and dried in a dessicator over anhydrous calcium chloride, then green solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alco hol, ether and acetone.

37

Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 546.69 % of Ni % of % of % of C H N Calculated 10.73 41.70 3.47 7.68 Found 10.51 41.52 3.43 7.48

c. Complexes of cloxacillin with Cu (II) ion: All chemicals such as cloxacillin, copper (II) chloride hexahydrate methyl alcohol, ethyl alcohol, n -pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: The 0.22 g of ligand cloxacillin, as required for making 0.01 M solution, was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously for three hours till it becomes clear solution. The solution was filtered to remove any insoluble residue left. A 0.01 M solution of Cu (II) chlorid e was prepared by dissolving 0.07 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue left. Preparation of complex: The complex was prepared by the addition of freshly prepared 50 ml of 0.01 M metal salt solution to freshly prepared 50 ml of 0.01 M of ligand

38

cloxacillin solution with continuous stirring at ice cold temperature and at pH values 8.2 8.8 adjusted by solution of 0.1 M Na 2 CO 3 using a pH meter. The solution was converted into syrupy liquid which when filtered in suction pump, washed with distilled water, ethanol and aceto ne several times and dried in a dessicator over anhydrous calcium chloride, then green solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 551.54 % of % of % of % of Cu C H N Calculated 11.52 41.34 3.44 7.61 Found 11.39 41.18 3.41 7.48

d. Complexes of cloxacillin with Zn (II) ion: All chemicals such as cloxacillin, Zinc (II) chloride hexa hydrate methyl alcohol, ethyl alcohol, n -pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution:

39

The 0.22 g of ligand cloxacillin, as required for making 0.01 M solution, was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously for three hours till it becomes clear solution. The so lution was filtered to remove any insoluble residue left. A 0.01 M solution of Zn (II) chloride was prepared b y dissolving 0.07 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insolu ble residue left. Preparation of complex: The complex was prepared by the addition of freshly prepared 50 ml of 0.01 M metal salt solution to freshly prepared 50 ml of 0.01 M of ligand cloxacillin solution with continuous stirring at ice cold temperature and at pH values 8.2 8.8 adjusted by solution of 0.1 M Na 2 CO 3 using a pH meter. The solution was converted into syrupy liquid which when filtered in suction pump, washed with distilled water, ethanol and acetone several times and dried in a dessicator o ver anhydrous calcium chloride, then green solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcoho l, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 553.39 % of % of % of % of Zn C H N Calculated 11.81 41.20 3.43 7.58 Found 11.68 41.01 3.41 7.37

40

e. Complexes of cloxacillin with Pr (III) ion: All chemicals such as cloxacillin, Pr (III) nitrate methyl alcohol, ethyl alcohol, n-pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: The 0.22 g of ligand cloxacillin, as required for making 0.01 M solution, was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously for three hours till it becomes clear s olution. The solution was filtered to remove any insoluble residue left. A 0.01 M solution of Pr (III) nitrate was prepare d by dissolving 0.16 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered to re move any insoluble residue left. Preparation of complex: The complex was prepared by the addition of freshly prepared 50 ml of 0.01 M metal salt solution to freshly prepared 50 ml of 0.01 M of ligand cloxacillin solution with continuous stirring at ice c old temperature and at pH values 8.2-8.8 adjusted by solution of 0.1 M Na 2 CO 3 using a pH meter. The solution was converted into syrupy liquid which when filtered in suction pump, washed with distilled water, ethanol and acetone several times and dried in a dessicator over anhydrous calcium chloride, then green solid complex was obt ained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using op en capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table.

41

Elemental analysis: Mass = 1490.40 % of % of % of % of Pr C H N Calculated 9.45 45.89 3.42 8.45 Found 9.21 45.63 3.39 8.32

f. Complexes of cloxacillin with Nd (III) ion: All chemicals such as cloxacillin, Nd (III) chloride hexa hydrate methyl alcohol, ethyl alcohol, n -pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: The 0.22 g of ligand cloxacillin, as required f or making 0.01 M solution, was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously for three hours till it becomes clear solution. The solution was filtered to remove any insoluble residue left. A 0.01 M solution of Nd (III) chloride was prepared by dissolving 0.17 g of metal salt in 50 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue left.

Preparation of complex: The complex was prepared by the addition of freshly prepared 50 ml of 0.01 M metal salt solution to freshly prepared 50 ml of 0.01 M of ligand cloxacillin solution with continuous stirring at ice cold temperature and at pH values 8.2 8.8 adjusted by solution of 0.1 M Na 2 CO 3 using a pH

42

meter. The solution was converted into syrupy liquid which when filtered in suction pump, washed with distilled water, ethanol and acetone several times and dried in a dessicator over anhydrous calcium chloride, then green solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 1048.74 % of % of % of % of Nd C H N Calculated 13.75 43.48 3.24 8.01 Found 13.52 43.24 3.19 7.89

4. Preparation ofloxacin

of

transition

metal

complexes

with

ligand

a. Complexes of Ofloxacin with Fe (III) ion: All chemicals such as Ofloxacin, iron (III) chloride, methyl alcohol, ethyl alcohol, n-pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution:

43

A 0.18 g of ligand ofloxacin, as required for making 0.01 M so lution was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously with glass rod for two hours. To make it clear solution it was vigorously stirred with an electrical stirrer for three hours. But we failed to get its clear solution. So its suspension was used as such for complexation. A 0.01 M solution of Fe (III) chloride hexa hydrate was prepared by dissolving0.08 g of metal salt in 10 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue. Preparation of complex: The complex was prepared by the slow addition of 10 ml of 0.01 M metal salt solution to the magnetically stirred 50 ml of 0.01 M of ligand ofloxacin suspension at room temperature. As the amount of metal Fe (II) cation was increased ofloxacin dissolved. Th e solution was attained yellow syrupy state. The concentration of final solution gave rise to a yellow colour precipitate, which was filtered and washed with distilled water, ethanol and ether regularly and repeatedly three times. The precipitate was dried in a desiccator over calcium chloride, and then solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Dr ug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table.

44

Elemental analysis:Mass = 914.66 % of % of % of % of Fe C H N Calculated 16.44 20.99 1.97 4.59 Found 16.12 20.72 1.93 4.52

b. Complexes of Ofloxacin with Ni (II) ion: All chemicals such as Ofloxacin, nickel (II) chloride hexahydrate, methyl alcohol, ethyl alcohol, n -pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: A 0.18 g of ligand ofloxacin, as required for making 0.01 M solution was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously with glass rod for two hours. To make it clear solution it was vigorously stirred with an electrical stirrer for three hours. But I failed to get its clear solution. So its suspension was used as such for complexation. A 0.01 M solution of Ni (II) chloride hexa hydrate was prepared by dissolving 0.11 g of metal salt in 10 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue. Preparation of complex: The complex was prepared by the slow addition of 10 ml of 0.01 M metal salt solution to the magnetically stirred 50 ml of 0.01 M of ligand ofloxacin suspension at room temperature. As the amount of metal Ni (II) cation was increased ofloxacin dissolved. Th e solution was attained yellow syrupy state. The concentration of final solution gave rise to a yellow colour precipitate, which was filtered and washed with distilled water, ethanol and ether regularly and repeatedly three times. The

45

precipitate was dried in a desiccator over calcium chloride, and then solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Dr ug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 778.71 % of % of % of % of Ni C H N Calculated 8.15 55.48 4.11 10.79 Found 7.89 55.21 4.08 10.65

c. Complexes of Ofloxacin with Cu (II) ion: All chemicals such as Ofloxacin, copper (II) chloride, methyl alcohol, ethyl alcohol, n-pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: A 0.18 g of ligand ofloxacin, as required for making 0.01 M solution was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously with glass rod for two hours. To make it clear solution it was vigorously stirred

46

with an electrical stirrer for three hours. But I failed to get its clear solution. So its suspension was used as such for complexation. A 0.01 M solution of Cu (II) chlorid e was prepared by dissolving 0.07 g of metal salt in 10 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue. Preparation of complex: The complex was prepared by the slow addition of 10 ml of 0.01 M metal salt solution to the magnetic ally stirred 50 ml of 0.01 M of ligand ofloxacin suspension at room temperature. As the amount of metal Cu (II) cation was increased ofloxacin dissolved. The solution was attained yellow syrupy state. The concentration of final solution gave rise to a yellow colour precipitate, which was filtered and washed with distilled water, ethanol and ether regularly and repeatedly three times. The precipitate was dried in a desiccator over calcium chloride, and then solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 783.54 % of % of % of % of Cu C H N Calculated 8.82 55.13 4.08 10.72 Found 8.58 54.78 4.01 10.57

47

d. Complexes of Ofloxacin with Zn (II) ion: All chemicals such as Ofloxacin, zinc (II) chloride, methyl alcohol, ethyl alcohol, n-pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: A 0.18 g of ligand oflo xacin, as required for making 0.01 M solution was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously with glass rod for two hours. To make it clear solution it was vigorously stirred with an electrical stirrer for three hours. But I failed to get its clear solution. So its suspension was used as such for complexation. A 0.01 M solution of Zn (II) chlorid e was prepared by dissolving 0.07 g of metal salt in 10 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue.

Preparation of complex: The complex was prepared by the slow addition of 10 ml of 0.01 M metal salt solution to the magnetically stirred 50 ml of 0.01 M of ligand ofloxacin suspension at room temperature. As the amount of metal Zn (II) cation was increased ofloxacin dissolved. The solution was attained yellow syrupy state. The concentration of final solution gave rise to a yellow colour precipitate, which was filtered and washed with distilled water, ethanol and ether regularly and repeatedly three times. The precipitate was dried in a desiccator over calcium chloride, and then solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c.

48

The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 785.37 % of % of % of % of Zn C H N Calculated 8.32 54.80 4.07 10.69 Found 8.17 54.41 4.01 10.51

e. Complexes of Ofloxacin with Pr (III) ion: All chemicals such as Ofloxacin, praseodimum (III) nitrate, methyl alcohol, ethyl alcohol, n -pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: A 0.18 g of ligand ofloxacin, as required for making 0.01 M solution was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously with glass rod for two hours. To make it clear solution it was vigo rously stirred with an electrical stirrer for three hours. But I failed to get its clear solution. So its suspension was used as such for complexation. A 0.01 M solution of Pr (III) nitrat e was prepared by dissolving 0.16 g of metal salt in 10 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue. Preparation of complex: The complex was prepared by the slow addition of 10 ml of 0.01 M metal salt solution to the magnetically stirred 50 ml of 0.01 M of ligand ofloxacin suspension at room temperature. As the amount of metal Pr

49

(III) cation was increased ofloxacin dissolved. The solution was attained yellow syrupy state. The concentration of final solution gave rise to a yellow colour precipitate, which was filtered and washed with distilled water, ethanol and ether regularly and repeatedly three times. The precipitate was dried in a desiccator over calcium chloride, and then solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 914.66 % of % of % of % of Pr C H N Calculated 16.44 20.99 1.97 4.59 Found 16.12 20.72 1.93 4.52

f. Complexes of Ofloxacin with Nd (III) ion: All chemicals such as Ofloxacin, neodimium (III) chloride, methyl alcohol, ethyl alcohol, n -pentane, acetone, DMF and DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck. Preparation of solution: A 0.18 g of ligand ofloxacin, as required for making 0.01 M solution was taken in a dry and clean conical flask containing 50 ml of redistilled water. The flask was fitted with cork and stirred vigorously with glass

50

rod for two hours. To make it clear solution it was vigor ously stirred with an electrical stirrer for three hours. But I failed to get its clear solution. So its suspension was used as such for complexation. A 0.01 M solution of Nd (III) chloride was prepared by dissolvi ng 0.17 g of metal salt in 10 ml of redistilled water in a dry and clean conical flask. The solution was filtered to remove any insoluble residue. Preparation of complex: The complex was prepared by the slow addition of 10 ml of 0.01 M metal salt solution to the magnetically stirred 50 ml of 0.01 M of ligand ofloxacin suspension at room temperature. As the amount of metal Nd (III) cation was increased ofloxacin dissolved. The solution was attained yellow syrupy state. The concentration of final solution gave rise to a yellow colour precipitate, which was filtered and washed with distilled water, ethanol and ether regularly and repeatedly three times. The precipitate was dried in a desiccator over calcium chloride, and then solid complex was obtained. A solubility test of this complex was performed. It was found soluble in dimethyl sulphoxide (DMSO), dimethyl formamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone. Its melting point was determined using open capillary tube in kjeldal flask filled with concentrated sulphuric acid. Its melting point was greater than 300 0 c. The elemental analysis of the complex was carried out at Central Drug Research Institute (CDRI), Lucknow. The elemental analysis of the complex is as given in following table. Elemental analysis: Mass = 914.66 % of % of % of % of Nd C H N Calculated 16.44 20.99 1.97 4.59 Found 16.12 20.72 1.93 4.52

51

Antibacterial Screening: The antibacterial screening of the newly synthesized complexes was performed in Kumar Clinical and Prasad Bio -Laboratory Subhash Chowk, Darbhanga846004. The antibacterial test of the complexes is as given in following table: Table: I.a
Amox Concn
E.coli S.typhi P.pneu moniae 10-2 ++ ++ ++ 10-1 +++ +++ +++

Amox1
10-2 ++ ++ +++ 10-1 +++ +++ +++ + + -

Amox2
10-2 10-1 + ++ +

Amox3
10-2 ++ ++ ++ 10-1 ++ + ++ + ++

Amox4
10-2 ++ ++ +++ 10-1 ++ + ++ + ++ ++

Amox5
10-2 ++ + ++ + ++ + 10-1 ++ + ++ ++ ++ ++

Amox6
10-2 ++ ++ ++ 10-1 ++ + ++ + ++ +

++

Table: I.b
Amox Concn
E.coli S.typhi P.pneu moniae 10 18 17 16
-2

Amox1
-1

Amox2
10 13 17
-2

Amox3
-1

Amox4
10 20 18 23
-2

Amox5
-1

Amox6
10-2 19 18 19 10-1 24 25 24

10 22 21 21

10 20 19 22

-2

10 23 24 27

-1

10 15 21

10 19 20 17

-2

10 21 24 19

-1

10 25 24 26

10 21 22 22

-2

10 27 26 26

-1

The complexs of Fe (II), Zn (II), Pr (III) and Nd (III) complexes with amoxicillin are more effective towards bacterium Escherichia coli. The complex of Cu (II) with amoxicillin is approxinately similar efective while complex of Ni (II) is less effective towards bacterium Escherichia coli with respect to the standard drug amoxicillin. The complexs of Fe (II), Cu (II) Zn (II), Pr (III) and Nd (III) complexes with amoxicillin are more effective towards bacterium Salmonella typhi. The complex of Ni (II) has no effect on towards bacterium Salmonella typhi with respect to the standard drug amoxicillin. The complexs of Fe (II), Zn (II), Pr (III) and Nd (III) complexes with amoxicillin are more effective towards bacterium P. pneumoniae. The complex of Cu (II) and Ni (II) with amoxicillin is approxinately similar efective towards bacterium P. pneumoniae with respect to the standard drug amoxicillin. Table: II.a

52

Cipro Concn
E.coli 10-2 10-1

Cipro1
10-2 10-1

Cipro2
10-2 10-1

Cipro3
10
-2

Cipro4
10-2 10-1

Cipro5
10-2 10
-1

Cipro6
10-2 10-1

10-1

++

+++

++ + ++ + ++ +

+++ + +++

+++

++ ++ -

S.typhi

++

+++

+ + + + + + +

++ ++ ++ + ++ +

+++

++ ++ ++ ++ ++ ++

++

+ + + + + + + +

++

++

+++

++

++

++

P.pneu moniae

++

+++

+++ +

++

++ +

++

++

++

++

Table: II.b
Cipro Concn
E.coli S.typhi P.pneu moniae 10-2 10-1

Cipro1
10-2 10-1

Cipro2
10-2 10-1

Cipro3
10
-2

Cipro4
10-2 10-1

Cipro5
10-2 10
-1

Cipro6
10-2 10-1

10-1

20 18 17

24 23 22

23 21 21

27 25 27

21 19

26 24

22 19 18

26 24 25

21 22 20

26 27 26

18 19 18

20 22 21

17 16 17

20 19 19

The complexs of Fe (II), Ni (II), Cu (II) and Zn (II), complexes with ciprofloxacin are more effective towards bacterium Escherichia coli. The complexs of Fe (II), Cu (II) and Zn (II), complexes with ciprofloxacin are more effective towards bacterium Escherichia coli and P. pneumoniae. the complex of Ni (II) is no effective towards Salmonella typhi while it is similar effective as the standard drug towards P. pneumoniae. The complexes of Pr (III) and Nd (III) with ciprofloxacin is approxinately moderately efective bacterium Escherichia coli, Salmonella typhi and P. pneumoniae with respect to the standard drug ciprofloxacin.

Table: III.a
Clox Concn
E.coli S.typhi P.pneu moniae 10-2 ++ ++ ++ 10-1 +++ +++ +++

Clox1
10-2 +++ ++ +++ 10-1 +++ +++ +++ + + +

Clox2
10-2 10-1 + ++ ++ +

Clox3
10-2 ++ ++ ++ 10-1 ++ + ++ + ++

Clox4
10-2 ++ ++ +++ 10-1 ++ + ++ + ++ ++

Clox5
10-2 ++ + ++ + ++ + 10-1 ++ + ++ ++ ++ ++

Clox6
10-2 ++ ++ ++ 10-1 ++ + ++ + ++ +

++

53

Table: III.b
Clox Concn
E.coli S.typhi P.pneu moniae 10-2 19 16 16 10-1 21 22 21

Clox1
10-2 21 20 22 10-1 24 23 27 14 15 17

Clox2
10-2 10-1 15 17 21

Clox3
10-2 20 18 17 10-1 23 22 19 21 19 23

Clox4
10-2 10-1 25 24 26

Clox5
10-2 21 22 22 10-1 27 26 26

Clox6
10-2 19 18 19 10-1 24 25 24

The complexs of Fe (II), Zn (II), Pr (III) and Nd (III) complexes with cloxacillin are more effective towards bacterium Escherichia coli. The complex of Cu (II) with cloxacillin is approxinately similar efective while complex of Ni (II) is less effective towards bacterium Escherichia coli with respect to the standard drug cloxacillin. The complexs of Fe (II), Zn (II), Pr (III) and Nd (III) complexes with cloxacillin are more effective towards bacterium Salmonella typhi and P. pneumoniae. The complex of Ni (II) and Cu (II) has similar effect on towards bacterium Salmonella typhi and P. pneumoniae with respect to the standard drug cloxacillin.

Table: IV.a
Inz Concn
M.tube rculosis
10-2 10-1

Inz1
10-2 10-1 10
-2

Inz2
10-1

Inz3
10-2 10-1

Inz4
10-2 10-1

Inz5
10-2 10
-1

Inz6
10-2 10-1

++

+++

++

+++

+ +

+++

++

++ +

++

++ ++

++

+ + +

++

++ +

Table: IV.b
Inz Concn
M.tuber culosis 10-2 10-1

Inz1
10-2 10-1 10
-2

Inz2
10-1

Inz3
10-2 10-1

Inz4
10-2 10-1

Inz5
10-2 10
-1

Inz6
10-2 10-1

20

25

19

23

18

24

17

25

19

26

17

22

16

21

54

The all complexs of Fe (II), Ni (II), Cu (II), Zn (II), Pr (III) and Nd (III) with isoniazid are almost similar effective towards bacterium Mycobacterium tuberculosis. Table: V.a
Oflo Concn
E.coli 10-2 10-1

Oflo1
10-2 10-1

Oflo2
10-2 10-1
-2

Oflo3
10 10-1

Oflo4
10-2 10-1

Oflo5
10-2 10
-1

Oflo6
10-2 10-1

++

+++

++ + ++ + ++ +

+++ + +++

+++

++ ++ -

S.typhi

++

+++

+ + + + + + +

++ ++ ++ + ++ +

+++

++ ++ ++ ++ ++ ++

++

+ + + + + + + +

++

++

+++

++

++

++

P.pneu moniae

++

+++

+++ +

++

++ +

++

++

++

++ +

Table: V.b
Oflo Concn
E.coli S.typhi P.pneu moniae 10-2 10-1

Oflo1
10-2 10-1

Oflo2
10-2 10-1
-2

Oflo3
10 10-1

Oflo4
10-2 10-1

Oflo5
10-2 10
-1

Oflo6
10-2 10-1

18 16 19

22 23 24

21 19 20

24 25 24

21 18 19

26 22 24

22 19 18

26 24 25

21 22 20

26 27 26

16 18 20

20 22 24

17 16 17

20 19 23

The complexs of Fe (II), Ni (II), Cu (II) and Zn (II), complexes with ciprofloxacin are more effective towards bacterium Escherichia coli. The complexs of Fe (II), Cu (II) and Zn (II), complexes with ciprofloxacin are more effective towards bacterium Escherichia coli and P. pneumoniae. the complex of Ni (II) is almost similar effective towards Salmonella typhi and P. pneumoniae. The complexes of Pr (III) and Nd (III) with ciprofloxacin is approxinately moderately efective bacterium Escherichia coli, Salmonella typhi and P. pneumoniae with respect to the standard drug ciprofloxacin.

55

UNIT. III.

3. RESULTS, DISCUSSION AND CONCLUSION

Complexes of amoxicillin The complexes of amoxicillin with lanthanide metal (III) ions (Pr 3 + and Nd 3 + ) and transition metal (II) ions (Ni 2 + , Cu 2 + and Zn 2 + ) anhydrous as evident from analytical, spectral studies. All these complexes are quite stable at room temperature. The complexes are generally soluble in common organic solvents such as alcohol, benzene, DMF, DMSO but partially soluble in diethyl ether, and in water. The non-electrolytic nature of the complexes has exhibited by the too low value of molar conductance for any dissociation. The molar

56

conductance of these complexes are record ed in nitrobenzene and given in following table.
Complexes
[Fe(am ox)] [Ni (am ox)Cl ] [C u(am ox)Cl ] [Zn(am ox)C l ] [Pr(am ox) 2 NO 2 ]

Colour
Brown Green Li ght green Cream yel low Greeni s h

M.Pt.
>300 0 c >300 0 c >300 0 c >300 0 c >300 0 c

Solublity
DM SO and DM F DM SO and DM F DM SO and DM F DM SO and DM F DM SO and DM F

Conductance ( - 1 )
13.20 11.23 10.30 12.60 15.21

eff
Di am agnet i c Di am agnet i c 1.73 Di am agnet i c 3.48

Spectra l Studies M 2 + and M3+ Comple xes with amoxici llin:

Infrared and 1 H [Nd(amox) 2 Cl ] Dirt y >300 0 c DM SO 14.19 3.60 yel low and DM F NMR and electronic spectra of these complexes were obtained from external agency C.D.R.I., Lucknow. The infrared spectra of the solid M 2 + and M 3 + complexes with ligand amoxicillin are given below.

Fig. IR spectrum of ligand Amoxicillin

57

Fig. IR Spectrum of complex Pr 3 + with ligand Amoxicillin

Fig. IR spectrum of complex Nd 3 + with ligand Amoxicillin

The IR spectral data, assignment of the bands and its Ln 3 + metal complexes are given in following table.
Com po und (CN) cycli c 137 9 137 5 (NH2) (CO) lacta me 177 4 . (NH) am id e 296 8 293 4 (COO-) (MO) (NO2) (MN) (enol)

Amo x [Pr(L) 3 NO 2 ]

320 0 325 0

158 2 158 0

. 445

. 208

. 610

. 158 0

58 [ Nd(L) 2 Cl] [ Ni(am o x)Cl] 137 8 137 7 326 0 324 0 . . 292 7 293 5 159 5 159 0 435 415 .. . 555 580 160 0 157 5

The infr [Cu(amo x)C] 138 2 324 5 . 294 5 157 7 425 . 585 154 5 ared Z n(am o x)Cl] 138 0 327 0 . 295 0 156 0 430 . 595 156 0 spe ctra 3+ of complexes of amoxicillin with Ln ions, Transition metal (II) ions and the ligand amoxicillin were recorded in the range of 400 4000 cm - 1 . The highest frequency of the bands of the ligand at ~3200 cm - 1 can be assigned to the asymmetric NH vibration of the amino group 1 . The other band at 3000 cm - 1 may be due to the vibration of the imino group. These two bands are shifted from 3200cm - 1 to ~3130 cm - 1 and from 3000 cm - 1 to ~2924 cm - 1 on complexations indicating the involvement of both NH 2 and NH groups in complex formation 2 . The shift of N H to lower frequency on complexation suggests coordination through the NH 2 and NH of the amide group. The absence of a C=O ( -lactam) ligand band 3 at 1774 cm - 1 and the appearance of the b and at 16001545 cm - 1 in all complexes, suggest that 6, 7 -enolization takes place before coordination with metal ions. The occurance of bands at 610 555 cm - 1 (MN) and 415445 cm - 1 (MO) prove the bonding of nitrogen and oxygen to the metal ions 1 . The spectra of the complexes exhibited a lack of broad band about 36003440 cm - 1 indicating the absence of water molecules in the complexes. The spectral data for the solution of metal Ln 3 + ion complexes with ligand amoxicillin investigated in acetonitrile as recorded in CDRI, Lucknow and presented in the following table. TABLE: Electronic spectral data of amox with Ln 3 + ions in cm - 1
Ln 3 + compl exes [Fe(am ox)(H 2 O) 2 Cl ] Spect ral bands
18500, 22700, 24875, 24900, 25000, 27900, 29500, and 32400.

Trans iti ons

6 4 A1g T 1 g , 4 T 2 g (G), 4 E g , 4 A 1 g , 4 T 2 g (D)

[Ni (amo x)Cl] [C u (amo x)Cl] [Zn(amo x)Cl]

548, 515, 475. 12000.

3 2

B1g Eg
2

Eg, 3B2g, 3A2g.

T2g

59 [Pr(L) 3 NO 2 ] [Nd(L) 2 Cl ] 2225, 21220, 20640 and 16875 19476, 17250, 136015 and12420
3 3 H4 P2, 3P1, 3P0 1 and D 2 . 4 2 I9/2 G9/2, 4G5/2 or 2 2 G 7 / 2 , S 3 / 2 or 4 F 7 / 2 and 4 F 5 / 2 or 4 H 9 / 2

Spectral Studies Ln 3 + Complexes with Ciprofloxacin: The infrared, 1 H NMR and electronic spectra of the complexes were obtained from external agency C.D.R.I., Lucknow. The infrared spectra of the solid Ln 3 + and transition metal (II) complexes with ligand ciprofloxacin are given below.
Complexes Colour M.Pt .
>300 >300 >300 >300 >300 >300 0 c

Solublit y
DM SO and DM F DM SO and DM F DM SO and DM F DM SO and DM F DM SO and DM F DM SO and DM F

Conductance ( - 1 cm - 1 mol 1 )
13.52 12.59 11.30 10.94 12.41 11.51

eff

[Fe(cipro)2(H2O)Cl] [Ni(cipro)2] [Cu(cipro)2] [Zn(cipro)2] [Pr(cipro)2(H2O)2]

Deep grey Grey Greeni s h ash Yell owi s h whi t e Greeni s h Deep brown

Di am agnet i c Di am agnet i c 1.73 Di am agnet i c 3.48 3.60

[Nd(amox) 2 Cl ]

60

Fig. IR Spectrum of Ligand ciprofloxacin

61

62

The IR spectral data and the assignment of the ligand and its Ln 3 + metal complexes are given in following table.

Com pound

OH St r.

NH st r.

C O of C arbox yl

(CO) qui nol one

NH bendi ng

(C) of oxo group

63
Ciprofloxacin [Pr(cipro)2(H2O)2] [Nd(cipro)2(H2O)2] [Fe(cipro)2(H2O)Cl] [Ni(cipro)2] [Cu(cipro)2] [Zn(cipro)2] 3450 .. .. .. .. .. 2975 2970 2974 2970 2968 2973 2975 1720 1705 1700 1690 1680 1695 1675 1650 1590 1625 1610 1600 1620 1585 1400 . . . .. .. .. 1175 1225 1245 1240 1190 1225 1180

The infrared spectra of complexes of ciprofloxacin with Ln 3 + ions and the ligand ofloxacin were recorded in the range of 400 4000 cm - 1 . The highest frequency o f the bands of the ligand at ~3450 cm - 1 can be assigned 4 to the stretching O H vibration of the OH group of carboxyl group in the ligand ciprofloxacin. This band is disappear in the all complexes of Ln 3 + metal ions indicates that the complexation of the hydroxyl group through metal ions. The infrared spectra of the ligand ciprofloxacin shows a peat at 17 20 cm - 1 due to stretching frequency of the C=O of carbyxyl group 5 . This peak is reduced to the range of 1675 1705 cm - 1 . It also indicates the participation of the carboxyl group in the complexation with metal ions. The frequency at 16 50 cm - 1 in IR spectra of the ligand due to the carbonyl group present in the qu inolone ring 6 reduced to 1585-1625 cm - 1 in the metal complexes. It also indicates the participation of the carbonyl group in the complexation. The highest frequency o f the bands of the ligand at ~ 2975 cm - 1 can be assigned to the stretching N H vibration of the piperazine ring of the ligand ciprofloxacin. This band appears at almost same frequency in all complexes of transition metal and Ln 3 + metal ions indicates that the non participation of the group in the complexation. Thus, on account of infrared spectral properties one can say that ciprofloxacin acts as bidentate ligand.

64

Spectral Studies Ln 3 + Complexes with cloxacillin Infrared and 1 H NMR and electronic spectra of these complexes were obtained from external agency C.D.R.I., Lucknow. The infrared spectra of the solid Ln 3 + complexes with ligand cloxacillin are given below.
Complexes
[Fe(Clox)(H2O)3Cl] [Ni(Clox)(H2O)Cl] [Cu(Clox)(H2O)Cl] [Zn(Clox)(H2O)Cl] [Pr(Clox)3] [Nd(Clox)3]

M.Pt. Solublity ( 0 c)
>300 >300 >300 >300 >300 >300 DM SO and DM F DM SO and DM F DM SO and DM F DM SO and DM F DM SO and DM F DM SO and DM F

Conductance e f f ( - 1 )
13.21 12.73 11.26 10.40 12.28 12.57 Di am agnet i c Di am agnet i c 1.73 Di am agnet i c 3.48 3.60

Colour
Dark Brown Green Li ght green whi t e Greeni s h Dirt y yel low

65

66

The IR spectral data, assignment of the bands and its Ln 3 + metal complexes are given in following table.
Com po und (CN) cycli c 132 5 137 5 137 8 138 0 137 7 138 2 138 0 (NH2) (CO) lacta me 177 0 . . . . . (NH) am id e 296 8 293 4 292 7 295 0 293 5 291 0 292 5 (COO-) (MO) (NO2) (MN) (enol)

Amo x [Pr(L) 3 NO 2 ] [ Nd(L) 2 Cl]

[Fe(Clox)(H2 O)3Cl] [Ni(Clox)(H2 O)Cl] [Cu(Clox)(H2 O)Cl] [Zn(Clox)(H2 O)Cl]

329 0 328 5 328 8 3295 329 0 328 3 328 7

160 0 158 5 159 5 1570 159 0 159 2 158 8

. 445 435 410 415 425 430

. 208 .. . . .

. 610 555 545 580 585 595

. 158 0 160 0 1585 157 5 154 5 156 0

67

The infrared spectra of complexes of cloxacillin with Ln 3 + ions, Transition metal (II) ions and the ligand cloxacillin were recorded in the range of 4004000 cm - 1 . The highest frequency of the bands of the ligand at ~3290 cm - 1 can be assigned to the asymmetric N H vibration of the amino group. This band appears at almost same frequency in all complexes of transition metal and Ln 3 + metal ions, which indicates non participation of the group in complexation. The other band at 2968 cm - 1 may be due to the vibration of the imino group. This band is shifted from ~2910 cm - 1 to ~2934 cm - 1 on complexation indicating the involvement of NH groups in complex formation 7 . The absence of a C= O (-lactam) ligand band at 1770 cm - 1 and the appearance of the band at 1600 1545 cm - 1 in all complexes, suggest that 6, 7-enolization 3 takes place before coordination with metal ions. The occurance of bands at 610 555 cm - 1 (MN) and 415445 cm - 1 (MO) prove the bonding of nitrogen and oxygen to the metal ions 1 . The spectra of the complexes exhibited a lack of broad band about 3600 3440 cm - 1 indicating the absence of water molecules in the complexes. The absorption spectral data for the solution of metal Ln 3 + ion complexes with ligand cloxacillin investigated in acetonitrile as recorded in CDRI, Lucknow and presented in the following table. TABLE: Electronic spectral data of cloxacillin with transition metal (II) and Ln 3 + ions in cm - 1
Ln 3 + compl exes [Fe(Cl ox)(H 2 O) 3 C l]
[Ni(Clox)(H2O)Cl] [Cu(Clox)(H2O)Cl] [Zn(Clox)(H2O)Cl]

Spect ral bands

18575, 22750, 24900, 25000, 29540, and 32550. 24845, 27900,

Trans iti ons

6A1g 4T1g, 4T2g (G), 4Eg,

4A1g, 4T2g 3 2

(D)
3 2

8750, 14525, 25375 610 . 2225, 21220, 20640 and 16875 19476, 17250, 136015 and12420

A2g Tg

Tg, 3T1g (F), 3T1g (P).

Eg

[Pr(L) 3 NO 2 ] [Nd(L) 2 Cl ]

The comp lexes of isonicotinic acid hydrazid (isoniazid, INH), with lanthanide metal ions

3 H4 P2, 3P1, 3P0 1 and D 2 . 4 2 I9/2 G9/2, 4G5/2 or 2 2 G 7 / 2 , S 3 / 2 or 4 F 7 / 2 and 4 F 5 / 2 or 4 H 9 / 2

Com plexe s of isoni azid

68

(Pr 3 + , Nd 3 + and Sm 3 + ) are anhydrous as evident from analytical, spectral studies. All these complexes are quite stable at room temperature. The complexes are generally soluble in common organic solvents such as alcohol, benzene, DMF, DMSO but partially soluble in diethyl ether, and in water. The molar conductance values are too low to account for any dissociation. Thus complexes are non electrolytes. The molar conductance of these complexes in nitrobenzene is given in following table.

Complexes
[Fe(Inh)Cl3(H2O)] [Ni(Inh)Cl2] [Cu(Inh)Cl2] [Zn(Inh)Cl2] [Pr(Inh)NO3] [Nd(Inh)2Cl3]

M.Pt. ( 0 c)
135 140 160 185 215 235

Solublity
Wat er and al cohol Wat er and al cohol Wat er and al cohol Wat er and al cohol Wat er and al cohol Wat er and al cohol

Conductance ( - 1 )
11.30 12.61 13.82 10.76 11.06 13.17

eff
5.92 Di am agnet i c 1.7 4 Di am agnet i c 3.6 0 3.55

Colour
Dark Brown Green Li ght green whi t e Green Li ght pi nk

Spectral Studies Transition metal (II) and Ln 3 + Complexes with Isoniazid: The infrared, 1 H NMR and electronic spectra of these complexes were obtained from external agency C.D.R.I., Lucknow. The infrared spectra of the solid Ln 3 + and Transition metal (II) complexes with ligand isoniazid are given below.

69

The IR spectral data and the assignment of the ligand isoniazid and its Ln 3 + metal complexes are given in following table. The isoniazid expected to act as tridentate one, the possible coordination sites being pyridine-nitrogen, carbonyl of amide and NH 2 groups. The infrared frequencies in the present ligand associated with amide group (carbonyl-oxygen), NH 2 group and heterocyclic nitrogen are expected to lie influenced on complex formation with metal ions have been discussed.

70

Generally, all amides show two absorption bands 1 at 1640 cm - 1 related to C=O, group known as amide -I band and 16001500 cm - 1 known as amide-II band. The amide-I band in INH appear at 1660 1640 cm - 1 . The complexes show a considerable negative shift in C = O indicating a decrease in the stretching frequency due to the decrease in force constant of C=O as a consequence of coordination through the carbonyl oxygen atom of the ligand isoniazid. The amide -II band appears at the normal position in the NH-deformation rather than CN link. In the isoniazid, the absorption in 1565 -1560 cm - 1 reason has been assigned to amide -II absorption. The NH stretching absorption in free ligand occurs 8 at 3290 and 3220 cm - 1 which remains unaffected after complexation. This excludes the possibility of coordination through imine nitrogen. In spectra of all these complexes, the band occurs in the range of 3200 cm 1 attributed to NH 2 group ( N H 2 ), shifted to lower wave number and appears in 32753150 cm - 1 region indicating the involvement of nitrogen atom of NH 2 group in coordination 9 , 1 0 . The strong bands observed at 1575-1520 and 1080-1000 cm - 1 are tentatively assigned 8 to asymmetric and symmetric C = C + C = N of pyridine ring and pyridine ring stretching and deformations remain practically unchanged in frequency and band intensities revealing non -involvement of pyridine-nitrogen and complexation through metal ions. Thus, on account of infrared spectral propert ies one can say that isoniazid acts as bidentate ligand. Another band appears at 290 305 cm - 1 region in the complexes Nd 3 + and Sm 3 + with isoniazid indicating complexation of chloride ion through metal (Ln 3 + ) ions supporting the previous band 1 2 . In Pr 3 + complex, a new band 1 3 appears at 491 cm - 1 . it may be due to Ln O stretching vibration. Five absorption peaks 1 1 at 1505 cm - 1 ( 1 ), 1025 cm - 1 ( 2 ), 817 cm - 1 ( 3 ), 1295 cm - 1 ( 4 ) and 740 cm - 1 ( 5 ), = 1 4 i.e. 205 cm - 1 in the spectra of complex are due to coordinated nitrates which behaves as bidentate ligand 1 4 . An nmr triplet peak at = 5.90 ppm indicating -CO-NH- proton and a doublet peak at = 6.20 ppm indicating NH 2 proton shift to downfield in the range of = 6.3 ppm to 7.80 ppm respectively. It indicates that NH 2 group involves in complexation they decreases the electron density

71

around the NH 2 group which shift the value to downfield. Further, with the involvement of carbonyl group in complexation the v alue of NH 2 group also shift downfield from 5.9 to 6.3 ppm. The spectral data for the solution of Ln 3 + complexes with ligand isoniazid investigated in acetonitrile as recorded in CDRI, Lucknow are as below; TABLE: Electronic spectral data of isoniazid w ith Ln 3 + ions in cm - 1
Ln 3 + compl exes
[Fe(Inh)Cl3(H2O)]

Spect ral bands

18590, 22800, 24910, 25250, 29550, and 32550. 24850, 27850,

Trans iti ons 6A 4T , 4T (G), 4E , 1g 1g 2g g 4A1g, 4T2g (D)

3 2

[Ni(Inh)Cl2]

880 0, 145 5 0, 253 50 625

A2g Tg
2

Tg, 3T1g (F), 3T1g (P).

[C u ( I n h ) C l 2 ] [Zn ( I n h ) C l 2 ] [Pr(INH) 2 (NO 3 ) 3 ] [Nd(INH) 2 Cl 3 ]

Eg

20620, 21230, 2230, and 16880 19480, 17260, 13630 and12430

3 1

3 H4 P 0 , 3 P 1 , 3 P 2 , and D2. 4 2 I9/2 G 9 / 2 , 4 G 5 / 2 or 2 G 7 / 2 , 2 S 3 / 2 or 4 F 7 / 2 and 4 F 5 / 2 or 4 H 9 / 2

Complexes of Ofloxacin: The complexes of ofloxacin (Oflo), with lanthanide metal and transition metal ions (Ni 2 + , Cu 2 + , Zn 2 + , Pr 3 + and Nd 3 + ,) are anhydrous as evident from analytical, spectral studies. All these complexes are quite stable at room temperature. The complexes are generally soluble in common organic solvents such as alcohol, benzene, DMF, DMSO but partially soluble in diethyl ether, and in water. The molar conductance values are too low to account for any dissociation. Thus complexes are non electrolytes. The molar conductance of these complexes in nitrobenzene is given in following table.
Complexes M.Pt. Insoluble ( 0 c) Conductance ( - 1 cm 2 mol 1 ) eff Colour

72
[Fe(Inh)Cl3(H2O)] [Ni(Inh)Cl2] [Cu(Inh)Cl2] [Zn(Inh)Cl2] [Pr(Oflo)3] [Nd(Oflo)3]

165 19 2 210 230 290 >300

Wat er and al cohol Wat er and al cohol Wat er and al cohol Wat er and al cohol Wat er and al cohol Wat er and al cohol

12.04 11.28 13.34 13.01 14.07 12.58

5.92 Di am agnet i c 1.7 4 Di am agnet i c 3.5 7 3.5 2

Dark red Em eral d g reen Li ght green whi t e Greeni s h Pi nkis h whi t e

Spectral Studies Ln 3 + Complexes with Ofloxacin: The infrared, 1 H NMR and electronic spectra of the complexes were obtained from external agency C.D.R.I., Lucknow. The infrared spectra of the solid Ln 3 + and transition metal (II) complexes with ligand ofloxacin are given below.

Fig. IR Spectrum of Ligand ofloxacin

73

74

75

The IR spectral data and the assignment of the ligand and its Ln 3 + metal complexes are given in following table.
Com pound OH St r. C O of C arbox yl 1713 1670 1675 1650 1625 1640 1660 (CO) qui nol one 1622 1590 1580 1540 1570 1585 1605 OH bendi ng 1400 . . .. .. .. .. (C) of oxo group 1150 1225 1245 1140 1190 1225 1180

Ofl oxaci n [Pr(Oflo) 3 ] [Nd(Ofl o) 3 ] [Fe(ofl o) 3 ] [Ni (ofl o) 2 ] [C u(ofl o) 2 ] [Zn(ofl o) 2 ]

3050 .. .. . .. .. ..

The infrared spectra of complexes of amoxicillin with Ln 3 + ions and the ligand ofloxacin were recorded in the range of 400 4000 cm - 1 . The highest frequency of the bands of the ligand at ~3050 cm - 1 can be assigned 1 4 to the stretching N H vibration of the OH group of carboxyl group in the ligand ofloxacin. This band is disappear in the all complexes of Ln 3 + metal ions indicates that the complexation 1 5 of the hydroxyl group in through metal ions. The infrared spectra of the ligand ofloxacin shows a peat at 1713 cm - 1 due to stretching frequency of the C=O of carboxyl group. This peak is reduced to the range of 1625 -1670 cm - 1 . It also indicates the participation of the carboxyl group in the

76

complexation 8 , 1 6 with metal ions. The frequency at 1622 cm - 1 in IR spectra of the ligand due to the carbonyl group present in the quinolo ne ring reduced to 1585 -1605 cm - 1 in the metal complexes. It also indicates the participation of the carbonyl group in the complexation. Thus, on account of infrared spectral properties one can say that ofloxacin acts as bidentate ligand.

Conclusion:
On the basis of IR analysis it is clea r that the ligand amoxicillin acts a tridentate ligand coordinating through -lactam C=O group, NH group at C-7 and C=O group at 8 -position, while cloxacillin acts as bidentate ligand coordinating through -lactam C=O group, NH group. On the other hand, isoniazid acts as a bidentate ligand coordinating through NH 2 and C=O group. The both quinolone ligands ciprofloxacin and ofloxacin also acts as bidentate ligand coordinating through carboxylic acid group and quinol one C=O group. Elemental analysis shows that the complex of Fe (III) with amoxicillin has one chloride, one amoxicillin and two water molecule. So, structures of complexes are six coordinated as below:

The complexes of Ni (II), Cu (II) and Zn (II) ion with amoxicillin have one chloride and one amoxicillin. So, structures of the complexes are four coordinated. The Ni (II) and Cu (II) complexes are square planar while complex of Zn (II) is tetrahedral as below:

77

The complex of Pr (III) ion with ligand amoxicillin has one nitrate in addition to two amoxicillin ligand. Hence the structure of complex is eight coordinated as:

On the other hand, complexes of Nd (III) with amox icillin have one chloride and two amoxicillin. So, structures of complexes are seven coordinated as below:

78

The complex of Fe (III) with ciprofloxacin has one chloride, one ciprofloxacin and one water molecule. So, structures of complexes are six coordinated as below:

The complexes of Ni (II), Cu (II) and Zn (II) ion with ciprofloxacin have only two ciprofloxacin molecule . So, structures of the complexes are four coordinated. The Ni (II) and Cu (II) complexes are square planar while complex of Zn (II) is tetrahedral as below:

79

The complex of Pr (III) and Nd (III) ion with ligand ciprofolxacin has three ciprofolxacin ligands. Hence the structure of complex is eight coordinated as:

80

The complex of Fe (III) with cloxacillin has one chloride, one cloxacillin and three water molecule. So, structures of complexes are six coordinated as below:

The complexes of Ni (II), Cu (II) and Zn (II) ion with cloxacillin have one chloride, one water and one cloxacillin. So, structures of the complexes are four coordinated. But the Ni (II) and Cu (II) complexes are square planar while comple x of Zn (II) is tetrahedral as below:

The complex of Fe (III) with isoniazid has three chlorides, one isoniazid and a water molecule. So, structures of complexes are six coordinated as below:

81

The complexes of Ni (II), Cu (II) and Zn (II) ion with isoniazid have only an isoniazid and two chloride ions. So, structures of the complexes are four coordinated. The Ni (II) and Cu (II) complexes are square planar while complex of Zn (II) is tetrahedral as below:

The complex of Pr (III) ion with ligand isoniazid has an isoniazid and three nitro groups as bidentate ligands while complex of Nd (III) ion with isoniazid has two isoniazid and three chloride ligands . Hence the structure of complex is eight and seven coordinated respectively as:

The complex of Fe (III), Pr (III) and Nd (III) ions with ofloxacin has only three ofloxacin as ligand. So, structures of complexes are six coordinated as below:

82

The complexes of Ni (II), Cu (II) and Zn (II) ion with ofloxacin have only two ofloxacin molecules. So, structures of the complexes are four coordinated. The Ni (II) and Cu (II) complexes are square planar while complex of Zn (II) is tetrahedral as below:

83

References: 1. K. Nakamoto Infrared Spectra of Inorganic and Coordination Compounds, Wiley, New York, 1970. 2. B. N. Figgis 3. Clayden, Greewis, Warren and Wother Organic Chemistry, 1 s t ed., p-366, 2001. 4. J. R. Dyer Applications of Spectrospy, p -36, 2002. 5. P. Y. Bruice Organic Chemistry, p -332, 4 t h ed., 2003. 6. Clayden, Greewis, Warren and Wother Organic Chemistry, 1 s t ed., p-412, 2001. 7. A. Thomas, J. Tocher, A.D.I. Edwadrs J. Antimicrob. Chemother., 25, 5, 733-744, 1990. 8. L. J. Bellamy Infrared Spectra of Complex Molecules, 3 r d ed. Chapman and Hall, London, 1975. 9. R. K. Agarwal, P. Dutt and J. Prakash Polish J. Chem., 66, 899, 1992. 10. R. K. Agarwal and J. Praksh, Polyhedron, 10, 2399, 1991. 11. A. P. Mishra 12. J. M. nelson, T. M. chiller, J. H. Power and F. J. Angulo ClinInfects. Dis., 44, 7, 977 -980, 2007. 13. G. F. Liu, Y. N. Zhao and X. X. Liu Acta Chim. Sinica, 50, 473, 1992. 14. R. W. Jhonson and A. Blum Southern Medical Journal, 84, 9, 458, 1991.

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15. S. F. Jones ans Smith B. M. J. Clinical Research, 314, 7084, 869, 1997. 16. Liang Cai Yu, Lan Lai, Rong Xia, Sheng Liu J. Coordination Chemistry, Vol.62, 8, 1313 -1319, 2009.