Investigations on the complexation of metal ions with the model ligands can

be of great help to have a correct understanding of function of physiological systems.

Among these complexing ligands, Schiff bases are having special interest. Schiff

bases, named after its inventor Schiff [1], are formed by the condensation of primary

amine with an active carbonyl compound. They have an azomethine group —RCNR',

where R and R' are alkyl, cycloalkyl, aryl or heterocyclic group. The presence of a

lone pair of electron in the sp2 hybridised orbital on the imino nitrogen atom makes

the azomethinc group more significant chemically and biologically. Schiff bases with

an additional donor atom closer to the imino nitrogen form stable chelate with many

metal ions. The Schiff bases have been found to be involved in many biological

reactions. Moreover, Schiff base complexes find extensive application in the field of

analytical chemistry, medicine, industries, photonic devices and catalytic activities

The following points are noteworthy to demonstrate the importance of Schiff

base complex systems.

i. Schiff base derived from 2-hydroxy-5 -chi oroacetophenone and 4-amino-5-

mercapto-3 -methyl-I ,2,4-triazole and its coordination compounds with Ti(ll I),

VO(IV), Cr(III), Mn(lll), Fe(lII), Zr(IV), M00 2(VI) and UO2(VI) are having

antibacterial activity [5].

ii. Schiff base complexes of Cu(II), Ni(II), Pb(ll), Co(III) and La(III) with

2,6-diam inopyridine and 1, 3 -bis(2-carbo x yal dchydephenoxy)pro pane have

anti -ftrromagnctic interaction [6].

ill. Pd(II) Schiff base complexes of

(R)-2,2'-bis(3 ,5-dichloro-2-

hydroxybenzylideneamino)- 1,1 '-binaphthyl and (R)-2,2'-bis(3,5-dichloro-2-

hydroxylbenzylideneamino)-5,5',6,6',7,7',8,8'_octahydro .. 1,1 '-binaphthyl catalyse

the epoxidation of styrene [7].

iv. The Schiff base ligand, 5-phenylazo-2-phenyliminomethylphenols ha. nonlinear

optical property [8]. Copper(1I) Schiff base complex derived from (S)-2-arniño-

I , I -di(3,5-di-t-butylphenyl)propanol and 2-hydroxy-5-nitrobenzaldehyde were

used as catalyst for the cyclopropanation of styrene [9].

v. The cis-dioxomolybdenum(Vl) Schiff base complex derived from salicylaldehyde

and 3-alanine hydrazide can catalyst the peroxidic oxidation of sulfides [10].

Schiff base (N,NE',N,NE')-N,N'-(thiophcne-2,5-diylbis(methan- I -yl- l -

yl idcne))his(naphathalen-2-ylmcthanamine) is a chemosensor for Ni( Ii) and Pd(II)

[11).

vi. Schiff base complexes of Cd(Il), Cu(II), Co(II), Ni(II), Zn(II) and Sn(II) with

phthaldialdehyde and 2-(2-aminoethyliminomethyl)phenol have antimicrobial

activity [12]. The Copper(II) his(N-salicylidene-3-aminophenyl)sulfone form

double-helical structure and serves as a model for DNA [13]. Cobalt(111) Schiff

base complexes selectively inhibit zinc finger transcription factor [14]. The Cu(II)

complexes of o-vani Ilinsalicyl idcne-4-aminomethylcarbostyril and

chlorosalicylidene-4-aminomethylcarbostyril have antibacterial, antifungal and

antitumor activity [15].

vii. S-benzyl-I3-N-(2-pyridy1)-methy1cnedithiocarbaate is cytotox Ic against

T-lyrnphoblastic leukemic cells. Its Cu(11) and Cd(II) complexes are also effective

against colon cancer cells and show a higher antioxidant activity than the

a-tocopherol and comparable with butylated hydroxytoluene, a compound used as

synthetic antioxidant [16].

2

viii. Mn(II), Cu(II), NI(II) and Co(II) complexes of Schiff-base ligand

bis(2-mercaptoanil)benzyl catalyse the oxidation of cyclohexene [17]. The Cu(1l)

and Ni(II) complexes with Schiff base ligands from the condensation of 3-formyl-

4-hydroxy-1,8-naphthyndin-2-one and diamines exhibit thermochromism [18].

ix. Retinal is the chromophore in several light sensitive proteins such as rhodopsin

and bacteriorhodopsin. In both proteins, the chromophore is covalently linked as a

protonated Schiff base [19]. A Schiff base compound 4-indolyl-2

guanidinothiazoles has anti-ulcer activity [20].

x. Salicylanilide and 2-(N-methyliminophenyl)phenol has double fluorescence

behaviour [21]. The transition metal complexes of Cu(II), Ni(ll) and Co(11) with

Schiff base ligand derived from 4-aminoantipyrine, 3-hydroxy-4-

nitrobenzaldehyde and o-phenylenediamine can cleave DNA [22].

Thus, by considering the importance of Schiff base metal complexes, in the

present investigation computational, equilibrium, synthesis and characterisation and

antibacterial studies on some Schiff base metal complex systems are carried out.

1.1 Computational studies

Plastic models and chemical drawing programmes are used for the

understanding of chemical phenomena. In a similar way, computational chemistry

simulates chemical structures and reactions in a numerical manner. It allows studying

chemical phenomena by performing calculation on computers rather than by

examining reactions and compounds experimentally. Using computational chemistry

not only stable molecules, but also intermediates and transition states can be studied

with equal ease. It is an independent research area and a vital adjunct to experimental

studies.

Molecular mechanics and electronic structural theory are the two broad areas

within computational chemistry. Molecular mechanical simulations are based on the

laws of classical physics to predict the structure and properties of molecules.

Molecular mechanical calculations do not explicitly treat the electrons in a molecular

system. Instead they perform computations based upon the interactions among the

nuclei. Electronic effects are implicitly included in force fields through

parameterisation.

The approximation makes molecular mechanical computations quite

inexpensive and allows them to be used for very large systems containing thousands

of atoms. However, it also carries several limitations such as i) no force field can be

generally useful for all molecular systems and ii) neglect of electrons means it can not

treat chemical problems where electronic effects predominate.

Electronic structural methods are based on laws of quantum mechanics rather

than classical physics. Quantum mechanics states that the energy and other related

properties of a molecule may be obtained by solving the Schrödinger equation.

Electronic structural methods are characterised by their various mathematical

approximations to the solutions. There are three major classes of electronic structural

methods viz. semiempirical methods, ab initio methods and density function methods

(DFT). Semiempirical methods such as AM I, PM3, MINDO/3, etc., solve an

approximate form of the Schrödinger equation. Ab initio method unlike either

molecular mechanics or semiempirical methods uses no experimental parameters in

this computation. Instead, their computations are based solely on the laws of quantum

mechanics. Ab initio methods compute solution to the Schrödinger equation using a

series of rigorous mathemaiical approximations.

4

Semiempirical calculations on molecular systems are relatively inexpensive as

compared to ab iniuio and DFT methods. Ab initio computations provide high quality

and quantitative prediction for a broad range of systems than semiempirical methods.

DFT methods are similar to ab inilio methods in many ways. They include the effects

of electron correlation. The fact that electrons in a molecular system interact to one

another's motion and attempt to keep out of one another's way. Ab initio calculations

consider this effect only in an average sense. Thus, DFT methods can provide better

results than ab initio methods [23].

1.2 Equilibrium studies

Solutions have many properties that change measurably as a result of complex

formation. In principle, all these measurements can give information on the existence

and stability of different species. Methods such as spectrophotometry, potentiometry,

polarography, solubility, optical rotatory power, NMR and distribution have been

available for the study of complex formation.

Solution studies provide information on in-vitro systems. The equilibria

attained and mechanism of complex formation in solution serves as model for the

metal complex in the biological systems. The extensive development in the field of

complex formation in the solution state was initiated by Bjerrum [24]. He elaborated a

general method for the determination and calculation of stability constants. The free

energy change of the reaction, stability constant, enthalpy and entropy change are

related by the Eqns. 1.1.1 and 1. 1.2

AG°= -RTInK 1.2.1

AG° = Al-I° - TAS° 1.2.2

I

where AG' is the standard Gibbs free energy change, K the stability constant and AH°

and AS' are the standard enthalpy change and the standard entropy change

respectively.

Stability constants can be calculated by numerical and graphical methods.

Computers are used to calculate stability constants and calculation of concentrations

of different species. McMaster and Schaap [25] were the first to use electronic

computers for calculating stability constants. The basis of their approach was a least

square treatment of polarographic data. Rydherg and Sullivan [26] developed the

computer method of calculation suitable for solvent extraction and potentiometric

titration data. Computer programmes have been published for the rigorous analysis of

potentiometric complex formation and proton dissociation data [27].

Computer programmes like SCGOS [28], MINIQUAD [29] and BEST [30]

are helpful for the calculation of stability constants and species distribution of metal

complexes. Hopgood and Leussing [31] have developed a computer program SCHIFF

based on curve fitting method to calculate stability constant and species distribution

for Schiff base complex equilibria. The stability constant values of Schiff base

complexes have been found to be higher than the statistically calculated values of the

simple mixed ligand complexes.

1.3 Synthesis and characterisation studies

One of the most prominent and fascinating features of transition metal

complex is its large variability of molecular geometry, which can largely be attributed

to the electronic structure of the metal ions. The environment around metal centre

plays a vital role in the reactivity of metal complexes. The structure of the complex

provides infoniation on physical and chemical properties and biological activities.

Synthesis and charactensation of complexes provide a clear understanding about the

structure, nature of bonding and other properties. Solid state studies are considered to

be the primary evidence for any new venture.

Schiff bases are synthesised by two different techniques viz, direct synthesis

and metal template synthesis. In the direct synthesis solid Schiff base ligands are

synthesised and the complex is synthesised by the reaction of ligand and the metal

ions [32]. In metal ion template reaction, the metal ions function as a trap for Schiff

base internediates, thus facilitating the formation and isolation of metal complexes

[33]. A variety of experimental methods have been used for the characterisation of

complexes. TLC, CHN analysis, metal estimation, molecular weight determination,

conductivity, IR and UV-Visible are the main studies involved in the characterization.

NMR, ESR, MASS, X-ray, ORD, TG and CD studies have also been used.

1.4 Antibacterial studies

Bacteria are single-cell organisms with wide range of shapes, from spheres to

rods to spirals. They are one of the most ancient of living things on this planet.

Bacteria are present in every habitat on Earth, growing in soil, acidic hot springs,

radioactive waste, seawater and deep in the Earth's crust. Unlike cells of animals and

other eukaryotes, bacterial cells do not contain a nucleus and rarely harbour

membrane-bound organelles. Most of the bacteria were not characterised and only

about half of the phyla of bacteria have species that can be cultured in the laboratory.

Bacteria may be conveniently divided into two further groups, depending upon

their ability to retain a crystal violet-iodine dye. This reaction is referred to as the

Gram reaction. Bacteria which can retain a crystal violet-iodine complex are called

Gram-positive bacteria. Gram-negative bacteria cannot retain the crystal violet-iodine

complex. •..

7

Although the vast majority of the bacteria are harmless or beneficial, a few

pathogenic bacteria cause infectious diseases, including cholera, syphilis, anthrax,

leprosy, tuberculosis and plague. A wide variety of chemicals called antibacterial

agents are available for controlling the growth of bacteria. Chemotherapeutic agents,

including antibiotics are used internally. Disinfectants are chemical agents used on

inanimate objects to lower the level of microbes present on the object. Antiseptics are

chemicals used on living tissue to decrease the number of microbes present in that

tissue. The methods commonly used to measure its activity are paper disc technique

and dilution method.

No single antibacterial agent is most effective for use in all situations. The

variables to consider in the selection of an antibacterial agent include pH, solubility,

toxicity, organic material present and cost. Once an agent has been selected, it is

important to evaluate its effectiveness. In evaluating the effectiveness of antibacterial

agents, the concentration, length of contact and whether it is lethal or inhibiting at that

concentration and exposure are the important criteria [34].

1.5 Review

A brief review of literature related to Schiff base complexes of amino acids

are listed below.

The kinetics of formation of Schiff base of salicylaldehyde and glycine in

presence of metal ions have been studied by Hopgood and Leussing [31]. The

function of the metal ion is prominastic rather than template. Leussing and Anderson

[35] have reported the rate of reaction of pyruvate with glycinate in the presence of

Zn (11). In this reaction, Zn (II) ion brings the ligands into proximity by forming a

labile ternary complex but imposes a minimum geometric constrain upon them.

8

99mTc2...hydroxybenzaldehyde..am mo (glyci ne, alani ne, aspartic acid and

histidine) Schiff base complexes were synthesised and their biodistributions in mice

were investigated. It was found that bone uptake of the complexes is high [36].

Li et a! [37] synthesised and characterised Cu(Il), Ni(lI) and Mn(III) complexes of

salicylaldehyde with gI ycine, N-(2-aminoethyl)morphol in 4-(2-aminoethyl)phenylic

acid and 4-(2-aminoethyl)benzsulfamide. The complexes are having antimicrobial

activities. Offiong et a! [38] reported the Pd(II) and Pt(II) complexes of substituted o-

hydroxyacetophenone-glycine. The ligands coordinate through imino nitrogen and the

carboxylate group. The complexes have square planar geometry. The ligands, as well

as their complexes exhibit toxicity against Ehrlich ascites tumor cells.

[LnL(HL).nH 2 0] (Ln = La, Cc, Pr, Nd, Sm and Eu; H 2 L = salicylideneglycine; n = 3,

3.5) were synthesised and characterised by Zhang et a! [39]. Hermann and Erxleben

[40] have prepared and structurally characterised the Zn(lI) Schiff base complex

[Mg(H 20)6 1[ {Zn2 L 1 (CH 3CO2 )} 2(m3-OH)2 ].6H70 ( H 3 L 1 = Schiff base derived from

2,6-diformyl-4- met hylphenol and glycine). The complex anion consists of two

identical dinuclear Zn2/L 1 subunits connected through m3-OH bridges. Two

N-pyridoxylideneamino acidato complexes of oxovanadium(IV), [VO(pyr-D,L-

met)(bipy)] and [VO(pyr-D,L-thr)(bipy)].H 20 with Schiff bases involving

DL-methionine or DL-threonine and pyridoxal were prepared by an amine-diffusion

reaction and characterised by single crystal X-ray diffraction. 'Both the complexes are

triclinic in nature [41].

Binuclear Schiff base complexes derived from glycine and 3-acetylpyridine

with M(OAc)2 [M = Co(II), Ni(lI), Cu(lI), Zn(lI) and Cd(lI)] were synthesised and

characterised by Nawar et a! [42). Shanbhag and Martell [43] have investigated

potentiometrically the Schiff base Mn(lI), Co(ll), Ni(II), Cu(II) and Zn(lI) complex

equilibria of pyridoxal-5'-phosphate and 5'-deoxypyridoxal with phenyiglycine,

(4-methoxyphenyl)glycine, and (4-sulfophenyl)glycine at 25 °C and ionic strength

0. I M (KNO3). The monoprotonated form of the Schiff base is the most stable species

in each of these systems. Protonated 1:1 Cu(II)-Schiff base complexes and 1:1 and 2:1

Schiff base complexes of Mn(lI), Co(11), Ni(11) and Zn(1l) are formed.

A relationship between antimicrobial activities and the formation constants of amino

acid Schiff bases prepared from DL-amino acids (DL-glycine, DL-alanine) and halo

aldehydes (5-chloro-2-hydroxybenzaldehyde, 5-bromo-2-hydroxybenzaldehyde) and

their Cu(11) and NI(II) complexes were studied by Sari and Sakiyan [44]. Dinuclear

Zn( 11) complex [Zn 2 L 1 (CH 3 CO2 )2 ]Cl04 (L-aminopeptidase) promotes hydrolysis of

glycineethyl ester, the hydrolysis product of glycine with the complex leads to the

conversion of the ligand into corresponding Schiff base [45]. The reactions of the

tripodal I igand bpaAc-Gly-OEt (bpaAc-Gly-OEt = (N,N-bispicolylamino)acylglycine

ethyl ester) with three different transition metal dihalides MCI? (M = Ni(lI), Cu(Ll),

Zn(ll)) were studied by Niklas and coworkers [46].

Schiff bases derived from salicylaldehyde, glycine, alanine, serine, tyrosine,

and phenylalanine and their Ni(1I), Cu(1l) and Zn(1I) complex formation equilibria

were investigated by potentiometric method in aqueous solution. The order of the

formation constant values of the Schiff bases was sal-ala> sal-gly> sal-ser> sal-phe

> sal-tyr [47].

Wang [48] studied the Schiff base complexes of the type ML, obtained from

2, 4-dihydroxyben7aldehyde and glycyl-DL-phenylalanine with Cu(l I), Zn(1I), NI(II)

and Co(Il). In these complexes the ligand is coordinated to the metal through its

phenolic oxygen, carboxyl oxygen, imino nitrogen and amide nitrogen. All the

complexes are nonelectrolytes. [N-[(2-hydroxyphenyl)methylene]-L-

10

phenyl alaninato]manganesemonohydrate was prepared and characterised. In the

presence of the complex, cyclohexene was effectively oxidised by molecular oxygen

[49]. Synthesis, properties, and antimicrobial activities of copper(Il) complexes

Cu(sal-L-glu)X, ( sal-L-glu = Schiff base derived from salicylaldehyde and

L-glutamic acid and X l-methylimidazole, 2-methylimidazole, 4-methylimidazole,

2-ethylimidazole, 2-methylpyridine, 3-methylpyridine and 4-methylpyridine) were

reported by Kohutova ci a! [50]. The complexes adopted square pyramidal geometry

with the basal plane sites being occupied by the donor atoms of tridentate Schiff base

and N-donor atom of the corresponding N-molecular ligand. The apical position is

occupied by carboxylato oxygen of adjacent complex unit. The complexes exhibit

significant activity against the bacteria Staphylococcus aureus.

Schiff base formed between pyridoxal-5-phosphate and poly-L-lysine of low

polymerisation degree has been studied in aqueous solution. Formation of a Schiff

base was observed. The stability maximum is found to be at around pH 7-9 [51].

Six-coordinated chiral Ru(Il) Schiff base complexes of the type [RuLX(Y)2]

[ L = Schiff base derived from L-tyrosine, L-phenylalanine with 3,5-RRC6H3CHO

(R = CMe3, R, = H; R = R 1 = H, CMe3 , Cl, NO), X = PPh 3 , Y = H20J have been

investigated as catalysts for enantioselective epoxidation of 4-R2C6H4CH:CH2

[R 2 = H, Cl, N07, Me]. In general, the catalysts based on L-tyrosine were found to

have better effects than those derived from L-phenylalanine. The best results were

obtained with catalysts containing 3,5-(Me 3 C)2C61-I 3CHO and 4-nitrostyrene [52].

Basak ci a! [53] synthesised and characterised Schiff base complexes of

general formula [Re(lII)(L)Cl(PPh 3 )2 ] by reacting H 2 L and [ReOCI 3(PPh3)2] in

ethanol. H 2 L represents imines of a-amino acids (glycine, 1-alanine, 1-valine,

11

1-phenylalanine) derived from salicylaldehyde and naphthaldehyde. The complexes

are mononuclear and paramagnetic in nature.

Raso el al [54] have synthesised and characterised [(N-salicylidene-L-

alaninato)(aqua)zinc(lI)].0.25H 20 and [(N-saucy! idene-L-valinato)(aqua)zinc(II)].

The coordination geometry of the zinc atom in both structures is between distorted

trigonal bipyramidal and distorted square pyramidal. The crystals are constituted by

polymeric [(N-sal icylidene-L-ami noacidato)zinc(Il)] moieties forming helical arrays

-3-fold screw axes. The NMR studies in DMSO agree with a general endo disposition

between the side chain of the amino acid and the aromatic ring of the salicylidene

moiety.

Stability constants and structures of the complexes formed in the reaction of

copper( 11), nickel( II) and zinc(l1) ions and N-glycylbis(pyridine-2-yl)methylamine

and N-histidylbis(pyridin-2-yl)methylamine ligands have been determined by

potentiometric, UV-Visible and EPR spectroscopic methods by Osz and co-workers

[55]. The formation of four-coordinate 1:1 copper(II) complexes and octahedral

mono and bis(ligand) nickel(II) and zinc(II) complexes were detected. The

bis(pyridin-2-yl)methyl moiety is the main binding site in acidic media, while

deprotonation and coordination of the amide nitrogen take place in the physiological

pH range. The stability of the complexes of the bis(pyridin-2-yl)methyl ligands is

lower than that of analogous bis(imidazol-2-yl)mcthyl compounds.

Palanichamy and Anbu [56] determined potentiometrically the equilibrium

constants and species distribution of Schiff base complexes in aqueous solution

involving salicylaldehyde and some tridentate a-amino acids with metal ions Cu(l1),

NI(11) and Zn(II). The studies indicate that there is preference for the formation of

Schiff base complexes rather than the ligands binding as such to the metal ions.

12

Complexes of Ce(IlI) and La(III) with Schiff bases derived from the

condensation reaction of salicylaldehyde with glycine, DL-alanine and DL-valine

were reported by Gurkan and Sari [57]. The protonation constants of the Schiff bases

and stability constants of their ML-type complexes were determined

potentiometrically at 25 + 0.1 °C and 0.1 M (KCI) in aqueous solution. Pessoa et al

[58] have prepared and characterised oxovanadium(IV) Schiff base complexes

derived from amino acids (glycine, alanine, valine, leucine, isoleucine, methionine,

phenylalanine, threonine, aspartic acid and histidine) and salicylaldehyde or such

derivatives as 3-, 4-, or 5-methoxy-salicylaldehyde. Reaction of Sn(1I) methoxide

with Schiff bases derived by the condensation of 2-hydroxy-1-naphthaldehyde or

salicylaldehyde with glycine, -alanine, a-valine, cc-iso-Ieucine and a-tryptophan in

1:1 molar ratio gives Sn(1l) complexes. Schiff bases and their Sri have

antifungal and antibacterial activities [59]. The ' 3C, 5N NMR of Schiff bases and

their lithium salts, derivatives of amino acids (glycine, alanine, phenylalanine, valine

and leucine) and 2-hydroxynaphthylaldehyde in solid state and in DMSO have been

measured by Rozwadowski et a! [60] The results have shown that the Schiff bases

and their lithium salts exist mainly as the proton transferred NH form in solid state

and DMSO. The nitrogen atom is protonated by hydrogen originating from the

phenolic group.

Schiff base ligands derived from the condensation of

2-imidazolecarboxaldehyde with f3-alanine and 2-aminobenzoic acid and the

condensation of 2-pyridinecarboxaldehyde with 3- alanine, D,L-3-aminobutyric acid

and 4-aminobutyric acid with Cu(I1) and Schiff base Ni(II) complexes of

2-hydroxy-1-napthaldehyde with glycine, L-alanine, L-valine, L-Jeucine, DL-

isoleucine, DL-norleucine, L-serine and L-aspartic acid were synthesised and

13

characterised [61]. Schiff base N-(2-hydroxy-1-naphthalidene)phenylglycine and its

complexes with copper(II), nickel(Il), cobalt(II), manganese(II) and zinc(II)

complexes were synthesised and characterised by Gudasi et a! [62]. The ligand

coordinates through the carbonyl oxygen, azomethine nitrogen and deprotonated

hydroxyl oxygen. Schiff base N-2,4-dihydroxybenzal-D-glucosamine and its Fe(lII),

Co(II1), Cu(II) and Zn(l1) complexes were synthesised and characterised. Stabilities

of the complexes are agreeable to the Irving-Williams order of stability [63].

Nair and coworkers [64-68] have carried out extensive work on the mixed

ligand complex systems involving imida.zolcs, dipeptides and amino acids and

reported interesting results. Nair and David [69] have studied in detail the formation

of transition metal Schiff base complexes and reported the structure of these

complexes from the potentiometric and electronic spectral studies.

Recently, Nair eta! [70, 71] have reported the solution chemistry of some transition

metal Schiff base complexes involving o-vanillin and amino acids. Based on the

spectral studies, the probable structure of these complexes was reported.

Antimicrobial activities of these complexes have also been studied. The recent studies

on the Schiff base complexes in the solid state using elemental analysis, conductivity

measurements, magnetic behavior, infrared, electronic spectral measurements, X-ray

powder diffraction and biological studies are interesting [72, 73 }.

1.6 Scope of the present investigation

Life on the earth is bilingual. One of them is in the genes of organism, written

in the instruction language. This language is strung up together in the DNA molecule

in codes made up of three letter words, each made up using but four letters of the

alphabet. These letters are the heterocyclic bases A, G, C, T.

14

The second language is the operating language or the action tongue used by

the workhorse molecules of life, the proteins. This language has, over the years,

managed with but twenty letters as its alphabet. Each of these letters is an amino acid.

Another class of biologically important elements which are present in trace

amounts in the body and regulate multitude of chemical reactions needed for life are

metal ions. Among the metal ions d-block elements play important role in many

biological reactions [74, 75].

Cobalt, a 3d-element is essential for many organisms including mammals.

It activates a number of enzymes. Co(II) complexes of Schiff base ligands give the

first real clue to the probable nature of the metal-dioxygen interaction [76].

Nickel is an essential trace element. Chick and rats having deficient diet of

nickel show impaired liver functions and morphology. It stabilizes polysomes and

involves as active metal in several hydrogenases [77].

Copper is essential to all organisms. It constitutes redox enzymes and

hemocyanin [78]. The importance of zinc to biochemistry, biology, pathology, clinical

and veterinary medicine is now generally recognised. It involves in nearly all aspects

of normal metabolism and provides the structural frame work for the zinc fingers that

regulate the function of genes. Moreover, it is a natural component in insulin and is

crucial for the synthesis of nucleic acids and consequently for cell division. It plays a

role in sexual maturation and reproduction [79].

Heterocyclic compounds are of great importance because; many of the

biochemical materials, essential to life belong to this class. Nucleic acids, pigments,

vitamins and antibiotics are some of the classes of compounds having heterocyclic

molecules. As a result, modern society becomes dependent on heterocyclic molecules

for use as pharmaceuticals, pesticides and herbicides as well as dyes and plastics [80].

15

Among the heterocyclic compounds oxy-heterocyclic compounds are found in many

plants and animals. Naturally occurring oxy-heterocyclic compounds are mainly

derived from two fundamental units, a-pyrone and y-pyrone [81].

2-furancarboxaldehyde is a well known natural compound used extensively in

vegetable oil, petroleum, plastic and rubber industries [81]- A synthetic compound

derived from 2-flirancarboxaldehydc and sorbitol has been exploited in the cosmetic

industry as a skin lotion. This activity is in connection with its antioxidant properties

towards free radicals naturally present in the atmosphere [82]. Chelating resins

synthesised by condensing the Schiff base of

o-hydroxyacetophcnone-4,4'-diami nod iphenylether with 2-furancarboxaldehyde

exhibits affinity for alkali, alkaline earth and transition metal ions [83]

Complexes of Co(1l), Ni(Il) and Cu(l1) with the Schiff bases formed by

condensation of 2-aminopyridine, ethyl enediamine, diethylenetriamine and

2-furancarboxaldehyde have antibacterial and antifungal activities [84]. Schiff base of

2-furancarboxaldehyde and anthranilic acid can act as antitumor agent [85]. Schiff

base of aminopropyl modified mesoporous molecular sieve MCM-41 with

2-furancarboxaldehyde used as catalyst for epoxidation of cyclooctene, cyclohexene,

1-hexene and 1-octene [86]. N-furfuryl-N,N-dimethyl chitosan was found to have

antibacterial activity against E. co/i [87]. Aging of insulation oil can be measured by

analysing 2-furancarboxaldehyde present in it [88]. Schiff base complexes derived

from Co(Il), Ni(II), Cu(11) and Zn(II) and glutamic acid—salicylaldehyde are having

antioxidant activity [89]. Cu (11) and NI(11) Schiff base complexes derived from 6-

hydroxy-3-carbaldehyde chromone and glycine have DNA binding ability [90].

By considering the above points, in the present investigation Schiff base

complexes of physiologically important 3d transition metal ions Co(lI), Ni(II), Cu(II)

16

and Zn(lL) with naturally occurring 2-furancarboxaldehye (fural) and some

biologically important amino acids were chosen. The amino acids chosen are

L-vaiine (vat), DL-tryptophane (trp), L-threoninc (thr), L-glutamine (gin), L-glutamic

acid (glu), L-aspartic acid (asp) and L-histidine (his). vat is potentially bidentate with

nonpolar side chain. This helps us to study the sterric effect of the side chain structure

on the stability of the ternary complexes. Trp, thr and gin are potentially tndentate and

have polar, but uncharged side chains. The possible additional donor sites are

respectively indoie, hydroxyl and amide group for trp, thr and gin. Glu and asp are

potentially tridentate amino acids with carboxylate group as an additional donor site.

his is a potentially tridentate basic amino acid with imidazole side chain.

In order to have an in-depth understanding about the complex systems under

investigation, studies on molecular modeling, solution equilibrium and synthesis and

characterisation were carried out. An attempt was also made to study their

antibacterial activities.

Computational studies

Molecular modeling serves as a theoretical method to solve chemistry

problems using computers. Modeling of structures gives geometrical parameters like

bond length, bond angle and dihedral angle. Computations also provide a means of

calculating bond order, charge density on the atoms, thermodynamic parameters and

spectral data of molecules. These parameters are very useful in the study of chemistry

as a whole. In the present study, DFT, ab initio and semiempirical methods are

adopted for the computational studies.

Molecular modeling studies were performed for fural and its complexes with

Co(ll), Ni(II), Cu(II) and Zn(Il). The Schiff base ligands derived from fural and seven

17

amino acids viz. valine (Val), tryptophan (trp), threonine (thr), glutamine (gin),

glutamic acid (glu), aspartic acid (asp) and histidine (his) have also been studied.

The theoretical studies were performed with the scope of getting information

of ligands regarding their stable conformation, potential energy diagram, equilibrium

geometry, basicity and charge distribution. Also, these studies are aimed at obtaining

information on the Co(H), Ni(H). Cu(II) and Zn(II) complexes with fural, mode of

metal binding with fural, amino acids and Schiff bases and also to study the

correlation between charge density on atoms and geometrical parameters, pK a and

stability constants.

Equilibrium studies

Most of the biological reactions are carried out in liquid phase using water as

solvent. As the present study is related to biologically important molecules and to be

served as a model for biological reactions, equilibrium studies were carried out in

aqueous medium. The equilibrium studies were carried out in aqueous medium for

Co(Il), Ni(ll), Cu(1l) and Zn(II) complex systems with naturally occurring

heterocyclic aldehyde fural and seven amino acids.

The following are the twenty eight ternary complex systems reported in this

thesis.

I. Co(lI)-fural-val

2. Co(II)-fural-trp

3. Co(II)-fiiral-thr

4. Co(lI)-fural-gln

5. Co(1I)-fural-glu

6.Co(I I)-fural-asp

7. Co(ll)-fural-his

18

The above seven ternary complex systems were also studied by replacing

Co(II) with Ni(1I), Cu(11) and Zn(11). All the studies have been carried out at

25±0.1 °C and l=O.1 mol.dm3.

The present investigation is aimed at throwing more light on the following

points:

1. To find out the nature of the ternary species formed.

2. To study the factors affecting the formation of the complexes.

3. To study the sterric effect on the stability of the complexes.

4. To study the effect of additional coordination site present in trp, thr, gin, glu,

asp and his on the stability of complexes.

5. To study the factors affecting the distribution of binary and ternary complex

species concentrations.

6. To study the stereo chemistry of the complexes.

7. To study the possible molecular recognition in the complexes.

Synthesis and characterisation

The Schiff base fural-val and the following eight complex systems were

synthesised and characterised.

i. Co(lI)/Ni(11)ICu(ll)/Zn(lI)-fiiral-vaf

ii. Co(II)/Ni(11)ICu(lI)IZn(IJ)-fiii-al-hjs

The complexes were charactensed by micro analysis, molecular weight

determination, spectral, conductivity, cyclic voltammetry and X-ray diffraction

studies to fulfill the following objectives,

1. To study the stoichiometry of the complexes.

2. To study the mode of binding of the ligands.

3. To study the structure of the complexes.

Antibacterial studies

It becomes clear from the review (section 1.5) that Schiff base complexes of

fural and amino acids have antibacterial activities. Eight complexes

Co(II)/Ni(1I)/Cu(fl)/Zn(I1)-fuz-aI-val/fural-his and Schiff base ligand fural-val were

tested for antibacterial activities against Escherichia coli (E.coi[) and Staphylococcus

aureus (S.aureus). Among them, E.coil is Gram negative and other is Gram positive

bacteria.

20

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