major research project in chemistry (c. m. sc. college, darbhanga)

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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

Bacteria1 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.

Their2 body is membrane bound, which is a prerequisite for all living cells but they lack the extensive, 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 wall3:

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 layer.

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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 staining4:

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 their cell walls. Gram staining is not used to classify acchaca bacteria since they give very variable response.

Gram staining consists of four components.

1. Primary stain (crystal violet, methyl violet or certain violet),2. Mordant (gram`s iodine)3. Decolourizer (ethyl alcohol, acetone or 1:1ethanol-acetone)4. 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 peptidoglycan 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).

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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 infections 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 pathogens 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 effectiveness 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).

Antibiotics5 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. Resistance of Neisseria gonorrhoeae from towards sulfonamides and later towards penicillin,

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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 make 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 administrations 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 β-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

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necessary. If possible, the pathogens should be identified, drug sensitivity tests run and the proper 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 metals 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. al6.

Nobel triorganotin (IV) complexes of two β-lactamic antibiotics 6-[D-(-)-β-amino-p-hydroxymethyl-acetamido] penicillin (=Amoxicillin) and 6-[D-(-)-α-aminobenzyl] penicillin (=Ampicillin) have been synthesized and investigated both in solid and solution states. The complexes correspond to the general formula [R 3Sn(IV)antibioH2O], (R= Me, n-butyl, phenyl; antibio = amoxicillinate or ampicillinate). Structural investigations about configuration in the solid state have been carried out by interpreting experimental IR and 119Sn Mössebauer data. In particular IR results suggested polymeric structures both for [R3Sn(IV)amoxH2O] and [R3Sn(IV)ampH2O]. Moreover both antibiotics appear to behave as monoanionic bidentate ligands coordinating the tin (IV) atom through ester type carboxylate as well as through β-lactamic carbonyl. Evidence that in none of these compounds, water molecules were involved in coordination was provided by thermogravimetric investigations. On the basis of 119Sn Mössbauer spectroscopy it can be inferred that tin (IV) was pentacoordinated in all of the complexes in the

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solid state, showing an equatorial R 3Sn(IV) trigonalbipyramidal (TBP) configuration. The nature of the complexes in solution state was investigated by using 1H and 13C NMR spectroscopy while a 119Sn spectrum was obtained for n-Bu 3Sn(IV)ampH2O. Although 1H and 13C NMR measurements suggested that in dimethyl sulfoxide (DMSO)-d(6) solution the polymeric structure collapsed. Due to a solvolysis process of the β-lactamic carbonyl bonding to the organometallic moiety, the complexes have been shown to maintain the same TBP configuration 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 different 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 these 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 have 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 etc. 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 activity 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:ACT = 1:1, 1:2 and 2:1 in some instances. The calculated stability constants and these

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chelates, under selected optimum conditions, using molar ratio method have values ranging from K f = 107 to 1014. These data were confirmed by calculations of their free energy of formation ΔG, 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 2O)w

(H2O)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 ν (NH) (2968 cm -1) to 2984-2999 cm -1

of imino group of the ligand ACT and the absence of ν (CO) (β-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 the 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

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present study was carried out 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 10.

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 transfer reaction. The reactivity of isoniazid metal complexes as prototypes for novel self activating metallodrugs against TB with the aim to overcome resistance has been studied11. Reactivity studies were conducted with hydrogen peroxide, hexacyanoferrate (III) and aquopentacyanoferrate (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 suggested that the pathway of a carbonyl centered radical might be favoured upon coordination to the Fe (II) owing to the Π-back bonding effect promoted by this metal center. Therefore, the isoniazid metal complex could serve as a potential metallodrug. Enzymatic inhibition assays 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 (NH3)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.

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A number of organomercury (II) complexes involving isoniazid (1) of the type RHgCl(L) (II) (R = phenyl, o-hydroxyphenyl, p-hydroxyphenyl, p-acetoxyphenyl, 2-furyl, L = isonizid) have been synthesized and characterized. Conductance measurements indicate that 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. 1H and 13C NMR support the stoichiometry of the complexes. From fluorescence 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 degradation have been enumerated. In addition the fragmentation pattern of the complexes has been analyzed 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.)12

Crystal structure of a new Cu (II) ofloxacin complex has been reported by B. MaCias et. al13,14.

The X-ray crystallographic, NMR and antimicrobial activity studies of magnesium complexes of fluoroquinolones-racemic ofloxacin and its S-form levofloxacin has been reported by P. Drevensek et. al 15.

The mechanism of differential activities of ofloxacin enantiomers has been reported by I. Morrissey et. al 16. 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 pocket

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created by DNA gyrase. The drug binds to supercoild DNA in a manner similar to that to which it binds to the enzyme-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 cooperativity 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 17.

A study was made of the correlation between the in vitro inhibitory 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 DNA gyrase of E. coli and topoisomerase-II of the fetal calf thymus has also been reported by K. Hoshino et. al18.

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 counterpart. 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 19.

The crystal structure, biological studies of water soluble rare earth metal complexes with an ofloxacin derivative has been reported by Min Xu et. al20.

The synthesis and crystal structure of Zn (II) and Co (II) complexes with ofloxacin and enoxacin has been reported by Liang Cai Yu et. al21.

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 22.

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The ruthenium organometallic complexes of antibacterial agent ofloxacin, crystal structure and interactions with DNA have been reported23.

Coordination numbers and geometry of the complexes:

The shape of a coordination compound is the product of several interacting factors. One factor may be dominant in one compound, with another factor dominant in another 24. Some factors involved in determining the structures 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 25:

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 d10 configuration of central metals or metal ions have tetrahedral structures such as MnO -

4, CrO2-

4 and [Cu(py)4]+ with a few d5, 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, dz2 and dx2-y2 (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 e-sets of orbitals is now denoted by Δ 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 d0, d5 (in presence of weak ligands) and d 10 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 planar or intermediate shapes depending on both the ligand and the counter ion in the crystal.

The metal ion Zn2+, which has zero CFSE in octahedral as well as in square planar field, pseudo noble gas configuration (d 10-system) and do

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not strongly favour other 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 d8 ions [for example; Ni (II), Pd (II).

Splitting in D4h-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 planar 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 t2g sets of orbitals contain z-axis as well as x and y-axis. So, the overall result is that the eg-set of orbitals splits into two sets with the dx 2-y2 (b1g) at higher energy and dz 2 (a1g) at lower energy and t 2g set splits into a dxy (b2g) and a doubly degenerate e g (dxz and dyz) at lower energy. The energy separation between b2g and b1g levels is denoted by Δ sq. The splitting pattern may be shown as:

Factors favourable for square planar geometry:

Strong ligand,

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Metal ions having d8 configuration such as Ni2+ ions and The d9-systems (Cu2+ 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 geometry 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 common coordination number. The most common structure is octahedral26; 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 dx2-y2 and dz2 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 dx2-y2 (collectively called eg) at a higher energy and dxz, dyz and dxy (collectively called t 2g) at lower energy. The difference between e g and t2g set of orbitals is denoted by Δ o

or 10Dq. 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 degenerate eg-orbitals to be further repelled by 0.6 Δ o while triply degenerate t2g-orbitals are stabilized to an extent of 0.4 Δ 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 almost 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 octahedral 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 cases27. 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 coordination 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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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, Jan. 28 (6), 1420-1425, 2008.

24. K. Chordroudis, T. J. McCarthy and M. G. Kanatzidis- Inorg. Chem., 1996, 35, 3451.

25. M. C. Favas and D. L. Kepert, Prog. Inorg. Chem., 1980, 27, 325.

26. A. F. Wells-Structural Inorganic Chemistry, 5 th ed., Oxford University, Oxford, 1984, p-413.

27. M. C. Favas and D. L. Kepert, Prog. Inorg. Chem., 1981, 28, 309.

19

UNIT-II.

2. PREPARATION OF COMPLEXES

1. Preparation of transition metal complexes with ligand amoxicillina. Complexes of amoxicillin with Fe (III) ion:

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 solution. 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 temperature and at pH values 8.2-8.8 adjusted by solution of 0.1 M Na 2CO3 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.

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 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 3000c.

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 C

% of H

% of 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.



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 to remove any insoluble residue left.


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 2CO3 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.





% of Ni % of C

% of H

% of 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:

All chemicals such as amoxicillin trihydrate, copper (II) chloride hexahydrate methyl alcohol, ethyl alcohol, n-pentane, acetone, DMF and

22

DMSO used in this study were of analytical grade. These chemicals purchased from CDH or Merck.



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 left.







% of Cu

% of C

% of H

% of N

23

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.



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.



24





% of Zn

% of C

% of H

% of 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.



A 0.01 M solution of Pr (III) nitrate 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







% of Pr % of C % of H % of N

Calculated 30.37 15.52 1.51 15.09

Found 30.02 15.28 1.52 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.



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.







% of Nd % of C % of H % of N

27

Calculated 27.49 13.72 1.33 8.00

Found 27.25 13.48 1.35 7.93

2. Preparation of transition metal complexes with ligand ciprofloxacin

a. Complexes of Ciprofloxacin with Fe (III) ion:

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.


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.


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), dimethylformamide (DMF). It was sparingly soluble in water and insoluble in alcohol, ether and acetone.

28




% of Fe

% of C

% of H

% of 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.



A 0.01 M solution of Ni (II) chloride 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.


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.





% of Ni

% of C

% of H

% of 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.



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.







% of Cu

% of C

% of H

% of 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.



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.






Elemental analysis:Mass = 914.66

32

% of Zn

% of C

% of H

% of 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.



A 0.01 M solution of Pr (III) nitrate 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.




33




% of Pr

% of C

% of H

% of 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.



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.


34






% of Nd

% of C

% of H

% of 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.


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.


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 2CO3 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.





% of Fe % of C

% of H

% of N

36

Calculated 9.63 39.32 3.97 7.24

Found 9.43 39.08 3.92 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.



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 insoluble residue left.




37




% of Ni % of C

% of H

% of 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.



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 left.


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 2CO3 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.





% of Cu

% of C

% of H

% of 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.


39


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.







% of Zn

% of C

% of H

% of 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.



A 0.01 M solution of Pr (III) nitrate 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.


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 2CO3 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.




41


% of Pr

% of C

% of H

% of 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.



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.


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 2CO3 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.





% of Nd

% of C

% of H

% of N

Calculated 13.75 43.48 3.24 8.01

Found 13.52 43.24 3.19 7.89

4. Preparation of transition metal complexes with ligand ofloxacin

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.


43

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 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.


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. 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.




44


% of Fe

% of C

% of H

% of 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.


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.


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. 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

45

precipitate was dried in a desiccator over calcium chloride, and then solid complex was obtained.





% of Ni

% of C

% of H

% of 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.


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) chloride 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.


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 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.





% of Cu

% of C

% of H

% of 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.



A 0.01 M solution of Zn (II) chloride 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.


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.



48



% of Zn

% of C

% of H

% of 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.



A 0.01 M solution of Pr (III) nitrate 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.


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.





% of Pr

% of C

% of H

% of 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.


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 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 Nd (III) chloride was prepared by dissolving 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.


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.





% of Nd

% of C

% of H

% of 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, Darbhanga–846004. The antibacterial test of the complexes is as given in following table:

Table: I.a

Amox Amox1 Amox2 Amox3 Amox4 Amox5 Amox6

Concn 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1

E.coli ++ +++ ++ +++ + + ++ +++

++ +++

+++

+++

++ +++

S.typhi ++ +++ ++ +++ - - ++ +++

++ +++

+++

++++

++ +++

P.pneumoniae

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

++ +++

++ ++ +++ ++++

+++

++++

++ +++

Table: I.b

Amox Amox1 Amox2 Amox3 Amox4 Amox5 Amox6

Concn 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1

E.coli 18 22 20 23 13 15 19 21 20 25 21 27 19 24S.typhi 17 21 19 24 - - 20 24 18 24 22 26 18 25

P.pneumoniae

16 21 22 27 17 21 17 19 23 26 22 26 19 24

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 Cipro1 Cipro2 Cipro3 Cipro4 Cipro5 Cipro6

Concn 10-2 10-1 10-2 10-1 10-2 10-1 10-2

10-1 10-2 10-1 10-2 10-1

10-2 10-1

E.coli ++ +++ +++

++++

+++ ++++

+++

++++

+++ ++++

++ ++

++ ++

S.typhi ++ +++ +++

+++ - - ++

+++

+++ ++++

++ +++

++ ++

P.pneumoniae

++ +++ +++

++++

++ +++

++

+++

++ ++++

++ +++

++ ++

Table: II.b

Cipro Cipro1 Cipro2 Cipro3 Cipro4 Cipro5 Cipro6

Concn 10-2 10-1 10-2 10-1 10-2 10-1 10-2

10-1 10-2 10-1 10-2 10-1

10-2 10-1

E.coli 20 24 23 27 21 26 22 26 21 26 18 20 17 20S.typhi 18 23 21 25 - - 19 24 22 27 19 22 16 19P.pneumoniae

17 22 21 27 19 24 18 25 20 26 18 21 17 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 Clox1 Clox2 Clox3 Clox4 Clox5 Clox6

Concn 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1

E.coli ++ +++ +++ +++ + + ++ +++

++ +++

+++

+++

++ +++

S.typhi ++ +++ ++ +++ + ++ ++ +++

++ +++

+++

++++

++ +++

P.pneumoniae

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

++ +++

++ ++ +++ ++++

+++

++++

++ +++

53

Table: III.b

Clox Clox1 Clox2 Clox3 Clox4 Clox5 Clox6

Concn 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1 10-2 10-1

E.coli 19 21 21 24 14 15 20 23 21 25 21 27 19 24S.typhi 16 22 20 23 15 17 18 22 19 24 22 26 18 25

P.pneumoniae

16 21 22 27 17 21 17 19 23 26 22 26 19 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 Inz1 Inz2 Inz3 Inz4 Inz5 Inz6

Concn 10-2 10-1 10-2 10-1 10-2

10-1 10-2 10-1 10-2 10-1 10-2 10-1

10-2 10-1

M.tuberculosis

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

+++ ++ +++

++ ++++

++ +++

++ +++

Table: IV.b

Inz Inz1 Inz2 Inz3 Inz4 Inz5 Inz6

Concn 10-2 10-1 10-2 10-1 10-2

10-1 10-2 10-1 10-2 10-1 10-2 10-1

10-2 10-1

M.tuberculosis

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 Oflo1 Oflo2 Oflo3 Oflo4 Oflo5 Oflo6

Concn 10-2 10-1 10-2 10-1 10-2 10-1 10-2

10-1 10-2 10-1 10-2 10-1

10-2 10-1

E.coli ++ +++ +++

++++

+++ ++++

+++

++++

+++ ++++

++ ++

++ ++

S.typhi ++ +++ +++

+++ - - ++

+++

+++ ++++

++ +++

++ ++

P.pneumoniae

++ +++ +++

++++

++ +++

++

+++

++ ++++

++ +++

++ +++

Table: V.b

Oflo Oflo1 Oflo2 Oflo3 Oflo4 Oflo5 Oflo6

Concn 10-2 10-1 10-2 10-1 10-2 10-1 10-2

10-1 10-2 10-1 10-2 10-1

10-2 10-1

E.coli 18 22 21 24 21 26 22 26 21 26 16 20 17 20S.typhi 16 23 19 25 18 22 19 24 22 27 18 22 16 19P.pneumoniae

19 24 20 24 19 24 18 25 20 26 20 24 17 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 Nd3+) and transition metal (II) ions (Ni 2+, Cu2+ and Zn2+) 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 recorded in nitrobenzene and given in following table.

Spectral Studies M2+ and M3+

Complexes with amoxicillin:

Infrared and 1H NMR and electronic spectra of these complexes were obtained from external agency C.D.R.I., Lucknow. The infrared spectra of the solid M2+ and M3+ complexes with ligand amoxicillin are given below.

Fig. IR spectrum of ligand Amoxicillin

Complexes Colour M.Pt. Solublity Conductance(Ω - 1)

µe f f

[Fe(amox)] Brown >300 0c DMSO and DMF

13.20 Diamagnetic

[Ni(amox)Cl] Green >300 0c DMSO and DMF

11.23 Diamagnetic

[Cu(amox)Cl] Light green

>300 0c DMSO and DMF

10.30 1.73

[Zn(amox)Cl] Cream yellow


12.60 Diamagnetic

[Pr(amox) 2NO2] Greenish >300 0c DMSO and DMF

15.21 3.48

[Nd(amox) 2Cl] Dirty yellow


14.19 3.60

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.

58

The

infrared spectra of complexes of amoxicillin with Ln 3+ 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 ν NH vibration of the amino group1. 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 νNH to lower frequency on complexation suggests coordination through the NH2 and NH of the amide group. The absence of a C=O (β-lactam) ligand band3 at 1774 cm -1 and the appearance of the band at 1600–1545 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 (M–N) and 415–445 cm -1 (M–O) 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 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

Compound ν ( C N )

cyclic

ν ( N H 2 ) ν ( C O )

β- lactame

ν ( N H )

amide

ν ( C O O - ) ν ( M O ) ν ( N O 2 )

Δνν ( M N ) ν ( e n o l )

Amox 1379 3200 1774 2968 1582 ……. ……. ……. …….

[Pr(L)3NO2] 1375 3250 ……. 2934 1580 445 208 610 1580

[Nd(L) 2Cl] 1378 3260 ……. 2927 1595 435 …….. 555 1600

[Ni(amox)Cl] 1377 3240 ……. 2935 1590 415 ……. 580 1575

[Cu(amox)C] 1382 3245 ……. 2945 1577 425 ……. 585 1545

Zn(amox)Cl] 1380 3270 ……. 2950 1560 430 ……. 595 1560

59

Spectral Studies Ln3+ Complexes with Ciprofloxacin:

The infrared, 1H NMR and electronic spectra of the complexes were obtained from external agency C.D.R.I., Lucknow. The infrared spectra of the solid Ln3+ and transition metal (II) complexes with ligand ciprofloxacin are given below.

Complexes Colour M.Pt.

Solublity Conductance(Ω - 1cm - 1mol -

1)

µe f f

[Fe(cipro) 2(H 2O)Cl] Deep grey >300 DMSO and DMF

13.52 Diamagnetic

[Ni(cipro) 2] Grey >300 DMSO and DMF

12.59 Diamagnetic

[Cu(cipro) 2] Greenish ash

>300 DMSO and DMF

11.30 1.73

[Zn(cipro) 2] Yellowish white

>300 DMSO and DMF

10.94 Diamagnetic

[Pr(cipro) 2(H 2O) 2] Greenish >300 DMSO and DMF

12.41 3.48

[Nd(amox) 2Cl] Deep brown

>3000c

DMSO and DMF

11.51 3.60

Ln3 + complexes Spectral bands Transitions

[Fe(amox)(H 2O)2Cl] 18500, 22700, 24875, 24900, 25000, 27900, 29500, and 32400.

6A1 g 4T1 g , 4T2 g (G), 4Eg , 4A1 g , 4T2 g (D)

[Ni(amox)Cl] 548, 515, 475. 3B1g 3Eg, 3B2g, 3A2g.

[Cu(amox)Cl] 12000. 2Eg 2T2g

[Zn(amox)Cl][Pr(L) 3NO2] 2225, 21220,

20640 and 16875

3H4 3P2 , 3P1 ,

3P0 and 1D2 .

[Nd(L) 2Cl] 19476, 17250, 136015 and12420

4I9 / 2 2G9 / 2 , 4G5 / 2 or 2G7 / 2 , 2S3 / 2 or 4F7 / 2 and 4F5 / 2 or 4H9 / 2

60

Fig. IR Spectrum of Ligand ciprofloxacin

62

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

Compound νO H

Str.νN H

str.νC O of Carboxyl

ν ( C O )

quinolone

νN H

bending

ν ( C )

of oxo group

63

Ciprofloxacin 3450 2975 1720 1650 1400 1175

[Pr(cipro) 2(H 2O) 2] . .… 2970 1705 1590 …. 1225

[Nd(cipro) 2(H 2O) 2] . .… 2974 1700 1625 …. 1245

[Fe(cipro) 2(H 2O)Cl] …… 2970 1690 1610 …. 1240

[Ni(cipro) 2] . .… 2968 1680 1600 ..… 1190

[Cu(cipro) 2] . .… 2973 1695 1620 ..… 1225

[Zn(cipro) 2] . .… 2975 1675 1585 ..… 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 of the bands of the ligand at ~3450 cm -1 can be assigned4 to the stretching νOH vibration of the –OH group of carboxyl group in the ligand ciprofloxacin. This band is disappear in the all complexes of Ln3+ metal ions indicates that the complexation of the hydroxyl group through metal ions. The infrared spectra of the ligand ciprofloxacin shows a peat at 1720 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 1650 cm -1 in IR spectra of the ligand due to the carbonyl group present in the quinolone 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 of the bands of the ligand at ~2975 cm -1 can be assigned to the stretching νNH 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 Ln3+ Complexes with cloxacillin

Infrared and 1H NMR and electronic spectra of these complexes were obtained from external agency C.D.R.I., Lucknow. The infrared spectra of the solid Ln3+ complexes with ligand cloxacillin are given below.

Complexes M.Pt.(0c)

Solublity Conductance(Ω - 1)

µe f f Colour

[Fe(Clox)(H 2O) 3Cl] >300 DMSO and DMF

13.21 Diamagnetic Dark Brown

[Ni(Clox)(H 2O)Cl] >300 DMSO and DMF

12.73 Diamagnetic Green

[Cu(Clox)(H 2O)Cl] >300 DMSO and DMF

11.26 1.73 Light green

[Zn(Clox)(H 2O)Cl] >300 DMSO and DMF

10.40 Diamagnetic white

[Pr(Clox) 3] >300 DMSO and DMF

12.28 3.48 Greenish

[Nd(Clox) 3] >300 DMSO and DMF

12.57 3.60 Dirty yellow

66

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

Compound ν ( C N )

cyclic

ν ( N H 2 ) ν ( C O )

β- lactame

ν ( N H )

amide

ν ( C O O - ) ν ( M O ) ν ( N O 2 )

Δνν ( M N ) ν ( e n o l )

Amox 1325 3290 1770 2968 1600 ……. ……. ……. …….

[Pr(L)3NO2] 1375 3285 ……. 2934 1585 445 208 610 1580

[Nd(L) 2Cl] 1378 3288 ……. 2927 1595 435 …….. 555 1600

[Fe(Clox)(H 2O) 3Cl]

1380

3295 …… 2950

1570 410 …… 545 1585

[Ni(Clox)(H 2O)Cl]

1377 3290 ……. 2935 1590 415 ……. 580 1575

[Cu(Clox)(H 2O)Cl]

1382 3283 ……. 2910 1592 425 ……. 585 1545

[Zn(Clox)(H 2O)Cl]

1380 3287 ……. 2925 1588 430 ……. 595 1560

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 400–4000 cm -1. The highest frequency of the bands of the ligand at ~3290 cm -1 can be assigned to the asymmetric νNH 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 formation7. The absence of a C=O (β-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 (M–N) and 415–445 cm -1

(M–O) 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 Ln3+ ions in cm -1

Complexes of isoniazid

Ln3 + complexes Spectral bands Transitions

[Fe(Clox)(H 2O)3Cl] 18575, 22750, 24845, 24900, 25000, 27900, 29540, and 32550.

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

[Ni(Clox)(H 2O)Cl] 8750, 14525, 25375 3A2g 3Tg, 3T1g (F), 3T1g (P).

[Cu(Clox)(H 2O)Cl] 610 2Tg 2Eg

[Zn(Clox)(H 2O)Cl] …….

[Pr(L) 3NO2] 2225, 21220, 20640 and 16875

3H4 3P2 , 3P1 ,

3P0 and 1D2 .

[Nd(L) 2Cl] 19476, 17250, 136015 and12420


68

The complexes of isonicotinic acid hydrazid (isoniazid, INH), with lanthanide metal ions (Pr 3+, Nd3+ and Sm3+) 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.(0c)

Solublity Conductance(Ω - 1)

µe f f Colour

[Fe(Inh)Cl 3(H 2O)] 135 Water and alcohol

11.30 5.92 Dark Brown

[Ni(Inh)Cl 2] 140 Water and alcohol

12.61 Diamagnetic Green

[Cu(Inh)Cl 2] 160 Water and alcohol


[Zn(Inh)Cl 2] 185 Water and alcohol


[Pr(Inh)NO 3] 215 Water and alcohol

11.06 3.60 Green

[Nd(Inh) 2Cl 3] 235 Water and alcohol

13.17 3.55 Light pink

Spectral Studies Transition metal (II) and Ln 3+ Complexes with Isoniazid:

The infrared, 1H 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 Ln3+ 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), NH2 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 1600–1500 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 ν 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 C–N 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 NH2 group (νNH2), shifted to lower wave number and appears in 3275–3150 cm -1 region indicating the involvement of nitrogen atom of NH2

group in coordination9,10. The strong bands observed at 1575-1520 and 1080-1000 cm -1 are tentatively assigned8 to asymmetric and symmetric νC=C + νC=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 properties one can say that isoniazid acts as bidentate ligand.

Another band appears at 290–305 cm -1 region in the complexes Nd 3+ and Sm3+ with isoniazid indicating complexation of chloride ion through metal (Ln3+) ions supporting the previous band 12.

In Pr3+ complex, a new band13 appears at 491 cm -1. it may be due to Ln–O stretching vibration. Five absorption peaks 11 at 1505 cm -1 (ν1), 1025 cm -1

(ν2), 817 cm -1 (ν3), 1295 cm -1 (ν4) and 740 cm -1(ν5), Δν = ν1– ν4 i.e. 205 cm -1 in the spectra of complex are due to coordinated nitrates which behaves as bidentate ligand 14.

An nmr triplet peak at δ = 5.90 ppm indicating -CO-NH- proton and a doublet peak at δ = 6.20 ppm indicating –NH 2 proton shift to downfield in the range of δ = 6.3 ppm to 7.80 ppm respectively. It indicates that –NH2 group involves in complexation they decreases the electron density

71

around the NH2 group which shift the δ value to downfield. Further, with the involvement of carbonyl group in complexation the δ value 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 with Ln 3+ ions in cm -1

Ln3 + complexes Spectral bands Transitions [Fe(Inh)Cl 3(H 2O)] 18590, 22800, 24850,

24910, 25250, 27850, 29550, and 32550.

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

[Ni(Inh)Cl 2] 8800, 14550, 25350 3A2g 3Tg, 3T1g (F), 3T1g (P).

[Cu(Inh)Cl 2] 625 2Tg 2Eg

[Zn(Inh)Cl 2]

[Pr(INH) 2(NO3)3] 20620, 21230, 2230, and 16880

3H4 3P0 , 3P1 ,

3P2 , and 1D2 .

[Nd(INH) 2Cl 3] 19480, 17260, 13630 and12430


Complexes of Ofloxacin:

The complexes of ofloxacin (Oflo), with lanthanide metal and transition metal ions (Ni2+, Cu2+, Zn2+, Pr3+ and Nd3+,) 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.(0c)

Insoluble Conductance(Ω - 1cm2mol -

1)

µe f f Colour

[Fe(Inh)Cl 3(H 2O)] 165 Water andalcohol

12.04 5.92 Dark red

72

[Ni(Inh)Cl 2] 192 Water and alcohol

11.28 Diamagnetic Emerald green

[Cu(Inh)Cl 2] 210 Water and alcohol


[Zn(Inh)Cl 2] 230 Water and alcohol


[Pr(Oflo) 3] 290 Water and alcohol

14.07 3.57 Greenish

[Nd(Oflo) 3] >300 Water and alcohol

12.58 3.52 Pinkish white

Spectral Studies Ln3+ Complexes with Ofloxacin:

The infrared, 1H NMR and electronic spectra of the complexes were obtained from external agency C.D.R.I., Lucknow. The infrared spectra of the solid Ln3+ and transition metal (II) complexes with ligand ofloxacin are given below.

Fig. IR Spectrum of Ligand ofloxacin

75

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

Compound νO H Str. νC O of Carboxyl

ν ( C O )

quinolone

νO H

bending

ν ( C )

of oxo group

Ofloxacin 3050 1713 1622 1400 1150

[Pr(Oflo) 3] . .… 1670 1590 …. 1225

[Nd(Oflo) 3] . .… 1675 1580 …. 1245

[Fe(oflo) 3] ……. 1650 1540 ….. 1140

[Ni(oflo) 2] . .… 1625 1570 ..… 1190

[Cu(oflo) 2] . .… 1640 1585 ..… 1225

[Zn(oflo) 2] . .… 1660 1605 ..… 1180

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 assigned14 to the stretching νNH vibration of the –OH group of carboxyl group in the ligand ofloxacin. This band is disappear in the all complexes of Ln3+ metal ions indicates that the complexation 15 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

complexation8,16 with metal ions. The frequency at 1622 cm -1 in IR spectra of the ligand due to the carbonyl group present in the quinolone 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 clear that the ligand amoxicillin acts a tridentate ligand coordinating through β-lactam C=O group, –NH group at C-7 and C=O group at 8-position, while cloxacillin acts as bidentate ligand coordinating through β-lactam C=O group, –NH group.

On the other hand, isoniazid acts as a bidentate ligand coordinating through –NH2 and C=O group. The both quinolone ligands ciprofloxacin and ofloxacin also acts as bidentate ligand coordinating through carboxylic acid group and quinolone 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 amoxicillin 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 complex 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.,

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major research project in chemistry (c. m. sc. college, darbhanga)

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