CHAPTER - I

INTRODUCTION

Synthesis of new Schiff bases and their metal complexes played an important

role in the development of coordination chemistry as they readily form stable

complexes with most of the transition metals. Generally transition metals have been

used as templates[1]. Transition metal macrocyclic complexes have been received great

attention due to their biological activities including antiviral, anticarcinogenic[2], anti

bacterial and anti fungal[3]. Marco Cyclic metal complexes of Gd(III) are used as

MRI(Magnetic Resonance Imaging) contrast agents[4]. There is a continuing interest in

transition metal complexes of schiff base because of the presence of both nitrogen and

oxygen donor atoms in the back bone of these ligands. Some of these complexes exhibit

physical and chemical properties and potentially useful for biological activities[5].

1.1 Coordination Chemistry

In chemistry, a coordination metal complex is a structure consisting a central

atom or ion (usually metallic), bonded to surrounding array of molecules or anions

(ligands complexing agents. The atom within a ligand that is directly bonded to the

central atom or ion is called the donor atom. Polydentate (multiple bonded) ligands can

form a chelate complex. The key break through occurred when Alfred Werner proposed

in 1893 that Co(III) bears six ligands in an octahedral geometry.

In classical coordination chemistry ligands bind to metals almost via their „lone

pairs‟ of electrons residing on the main group atom of the ligands to give coordination .

(typical ligands are H2O, NH3, Cl-,CN

-,en

-). Hence a coordination complex is the

product of the Lewis acid-base reaction in the neutral molecules or anions (called

2

ligands) bond to a central metal atom (or ion) by coordinate covalent bonds.

Coordination compounds and complexes are distinct chemical Species- their properties

and behaviors are different from the metal atom or ion and ligands from which they are

composed .

1.1.1 History of Coordination Complexes

Compounds that contain a coordination complex are called Coordination

compounds. The Central atom or ion , together, with all ligands form the Coordiantion

sphere. In Coordination chemistry, a structure is first described by its coordination

number (the number of σ-type bonds between ligands and the central metal atom).

Coordination numbers are normally between two and nine, but large number of ligands

are not uncommon for the lanthanides and actinides. The number of bonds depends on

the size, charge and electron configuration of the metal ion and the ligands. The

chemistry of complexes is dominated by interactions between s and p molecular orbitals

of the ligands and the d orbitals of the metal ion. The maximum coordination number

for a certain metal is thus related to the electronic configuration of the metal ion (more

specifically the number of empty orbitals) and to the ratio of the size of ligands and the

metal ion. Large metals and small ligands lead to high coordination number

e.g.[Mo(CN)8]4-

small metals with large ligands lead to low coordination number e.g.

Pt [PC(me)3)]2. Different ligand structural arrangement result from the coordination

number. The orbital overlap between ligand and metal and ligand to ligand repulsion

tend to lead a certain regular geometries. E.g. Octahedral, Square planar, tetrahedral

etc.,

Many of properties of metal complexes are dictated by their electronic

structures. The electronic structure can be described by a relatively ionic model that

3

ascribes formal charges to the metals and ligands. This approach is the essence of

Crystal field theory (CFT) introduced by Hans Bethe in 1929 gives a quantum

mechanically based attempt at understanding complexes. But CFT treats all

interactions in a complex as ionic and assumes that ligands can be approximately by

negative point charges. More sophisticated models embrace covalency and this

approach is described by Ligand field theory (LFT) and molecular orbital theory. LFT

introduced in 1935 and built from Molecular orbital theory, can handle a broader range

of complexes and can explain complexes in which the interactions are covalent. The

chemical applications of group theory can aid in the understanding of crystal or ligand

field theory by allowing simple, symmetry based solution to the formal equations.

1.1.2 Applications of Coordination Compounds

The important applications of coordination compounds find use in qualitative

and quantitative chemical analyses. Many familiar colour reactions are given by metal

ions with number of ligands. Similarly purification of metal can be achieved through

formation and subsequence decomposition of the coordination compounds. The

importance of macrocyclic complexes in coordination chemistry is because of its

various application in biological process such as photosynthesis and dioxygen transport.

The pigment responsible for photosynthesis chlorophyll is a coordinated compound of

magnesium. Haemoglobin, the red pigment of blood which act as oxygen carrier is a

coordination compound of iron.

There is growing interest in the user of chelate therapy in medicinal chemistry.

An example is the treatment of problem caused by the presence of metal in toxic

proportion in plant and animal. Thus excess of copper and iron are removed by

chelating ligands D-penicillamine and desferrioxime B, via formation of the

4

coordination compounds. Some coordination compounds of platinum effectively inhibit

the growth of tumors.

The coordination compounds are used as dyes and pigments[6]. They are used

as catalysts for many industrial process[7] and other transformations of organic and

inorganic chemistry. The applications of coordination complexes are of great

importance because these are widely present in the mineral, plant and animals. Thus

coordination compounds finds its applications in the area of biological function system,

Industry and in medicine .It is also used as radiotherapeutic agents[8].

1.2 Schiff Base Ligand

Aromatic compounds containing different inter linking groups such as –CH2-,

-CH2-CH2- etc., could not be used for many applications. Since these linkages contain

no π electrons. In order to achieve this property –CH=N- group(azomethine) was

introduced between aromatic rings by P.Subramanian et al[9]. The incorporation of the

azomethine group will increase the stability, flexibility, and Photochemical properties

due to the extension of conjugation syn-anti isomerism exhibited by this group.

1.2.1 Chemistry of Azomethine Group

Schiff bases are condensation products of primary amine and aliphatic or

aromatic carbonyl compounds with the general formula(RCH=N-R), that makes the

schiff base a stable imine. The linkage azomethine group contains a pair of π electrons

bonded between carbon and nitrogen (-CH=N-). In addition, the nitrogen atom present

in the azomethine group has a lone pair of electron and this add distinct properties to

this group. An azomethine (-CH=N-) linkage finds position only in the inner part of the

backbone of a molecule among the three linkages –CH=CH-, -CH=N- and –C=O. The

5

azomethine –CH=N- linkage has intermediate properties, since nitrogen has an

electronegative value inbetween carbon and oxygen atom. The electronegative values

are C=2.5, N=3, O=3.5.

Layton[10] found a linear relationship between infra-red stretching frequency

and inter nuclear distance. From their relation, the following bond length were observed

C N 1.47Å, C=N 1.29-1.31Å.

Bond Energies

The numerical value of bond energy involving carbon atom depends on the

knowledge of heat of sublimation of carbon. The thermochemical bond energy term is a

quantity assigned to each of the bond in a molecule, so that the sum of over all bond

energy is equal to the heat of atomization of a molecule. Cottrell calculated the bond

energy values of C-C, C=C, C=N etc., From the data of coates[11] and the typical bond

energies are given as

EC-C 347kJmol-1

EC=C 611kJmol-1

EC=N 615kJmol-1

EC-N 305kJmol-1

EN-N

456kJmol-1

Formations of –C=N-Bond

The condensation of primary amines with carbonyl compounds was first

reported by Schiff[12], the reaction was later reviewed by sprung[13] and layer[14].

Depending on the reactivity of the amines and carbonyl compounds, the experimental

conditions varied. The by product formed during the reactions is removed by distillation

6

or by using suitable solvent forming azotropic mixture with water. Stable aromatic

azomethine compounds can be obtained by the condensation of aromatic aldehyde with

aromatic amine under mild condition in a suitable solvent.

C6H5-CHO+H2N-C6H5 C6H5-CH=N.C6H5. It was reported[15] that the

ultraviolet irradiation of aldehyde with aromatic amine results in the formation of

azomethine compounds.

Mechanism of –C=N Formation

The mechanism[16] of the formation of the azomethine linkage consists of two

steps. The first step is initial addition of the anion group to carbonyl group to form an

carbinol amine. In the second step –C=N bond is formed by dehydration process.

R

O

C

H

+ R-NH 2 R

O-

C

H

N+

R

H

H

B+

BH+

R

OH

C

H

N R

H

R C

H

N R

H

+R C

H

N R-BH

+B

1.2.2 Chemsitry of Naphthalene Ring System

A Naphthelene molecule is composed of two fused benzene rings (in organic

chemistry, rings are fused if they share two or more atoms). Accordingly naphthalene

classified as a benzanoid polycyclic aromatic hydrocarbon (PAH). Naphthalene has

three resonanace structures (fig1). Naphthalene has two sets of equivalent hydrogens.

The α positions are 1,4,5 and 8 The β-positions are positions 2,3,6 and 7. Naphthalene

is mainly used as a precursor to other chemicals

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1.2.3 Biological Importance of Schiff Base Ligand

Studies of a new kind of chemotherapeutic Schiff bases are now attracting the

attention of biochemists earlier work reported that some drugs showed increased

activity under administered as metal complexes rather than organic compounds.

1.2.4 Antimicrobial Activities

Schiff base[17] derived from furylglyoxal and p-toluidene show antibacterial

activity against Escherichia coli, staphylococcus aureus, Bacillus subtilis and proteus

vulgaris. Complexes of thallium I with benzothiazolines[18] show antibacterial activity

against pathogenic bacteria. Tridentate Schiff bases and their metal complexes show

antibacterial activities against E.Coli, S.aureus, B.Subtilis and B.pumpilis. Some

heterocyclic Schiff bases[19] can act as a antibacterial agent. Isatin derived Schiff

bases[20][21] posses anti-HIV activity and antibacterial activity. Schiff bases ligands

containing cyclobutane and thiazole rings show antimicrobial activity. Schiff bases of

pyrolidione, pyridine with o-phenylene diamine and their metal complexes[22] show

antibacterial activity. Schiff base conjugates of p-amino salicyclic acid[23] enhance

antimycobacterium activity. Lysine based Schiff bases and their complexes with La,

Co,Fe show antibacterial activity to B.subtilis, E.coli and S.aureus. Zn(II), Cd(II) and

Ni(II) and Cu(II) complexes with furfural and semicarbazide and with furfurylidene

diamine[24] schiff bases show antibacterial activities.

1.2.5 Antifungal Activities

Thiazole and benzothiazole Schiff bases[25] possess effective antifungal

activity. Presence of methoxy halogen and naphthyl groups enhance fungicidal activity

towards carvularia. Some schiff bases of quinazolinones show antifungal activity

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against candida albicans, Trichophyton rubrum, A.niger etc., Schiff bases and their

metal complexes[26] formed between furan and furyl glycoxal with various amines

show anti fungal activity against Helminthosporium, gramineum (causing stripe

disease in barely) syncephalosturum racemosus (causing fruit rot in tomato) and

C.capsic (causing die back disease in chillies). Molybdenum and manganese schiff

base complex control disease (caused by A.alternata) in brinjal crop. Copper(II)

Complexes[27] of benzoylpridine schiff base show antifungal activities. Schiff bases of

sali cylaldehyde and o,o–dimethyl thiophosphoramide and their complexes with

Cu(II) , Ni(II), and Zn(II) are efective chemicals to kill Tetranychus bimaculatus.

1.2.6 Anti Viral Activities

Schiff base of gossypol [28] show high antiviral activity. Silver complexes in

oxidation state I showed inhibition against Cucumber mosaic virus; glycine

salicylaldehyde schiff base AgI [29] gave effective results up to 74.7% towards

C.mosaic virus.

1.2.7 Synergistic Action on Insecticides

Schiff bases [30] derived from sulfane thiadizole and salicylaldehyde or

thiophene-2-aldehyde and their complexes show toxicities against insects.

Flourination[31] on aldehyde part of Schiff base enhance insectoacracicidal activity.

1.2.8 Other Therapeutic Activities

Several Schiff bases possess anti-inflammatory allergic inhibitors reducing

activity[32] radial scavenging, analgesic[33] and anti-oxidative action[34]. Thiazole

derived Schiff bases[35] show analgesic and anti-inflammatory activity. Schiff base of

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chitosan and carboxy methyl-chitosan shows an anti-oxidant activity such as superoxide

and hydroxyl scanvenging. Furan semi carbazone metal complexes exhibit significant

anthelmintic and analgesic activity[36].

1.2.9 Antitumor and Cytotoxic Activities

Salicylidiene anthranilic acid[37] possess antiulcer activity and complexation

behaviour with copper complexes which show increases in antiulcer activity. Some

Schiff bases[38] and their metal complexes containing Cu, Ni, Zn and Co were

synthesized from salicylaldehyde, 2,4-dihydroxy benzaldehyde, glycine and L-alanine

possess antitumor activity and their order of reactivity with metal complexes is

Ni>Cu>Zn>Co. Amino Schiff bases[39] derived with aromatic and heterocyclic amine

possess high activity against human tumor cell lines. Aryl azo Schiff bases exhibit anti

cancer activity.

1.2.10 Anti Fertility and Enzymatic Activity

Schiff bases[40] of hydrazine carboxamide and hydrazine and metal complexes

of dioxo Mo(IV) and Mn(II) might alter reproductive physiology. Schiff base linkage

with pyridoxal 5-phosphate from lysine to alanine or histidine abolishes enzyme

activity in protein.

Dyes

Chromium azomethine cobalt complex, Schiff base unsymmetrical complex 1:2

chromium dyes give fast colours to leathers, food packages, wools etc., Novel

tetradentate schiffbase acts as a chromogenic reagent for determination of Ni in some

natural food samples[41].

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Miscellaneous Applications

Tetradentate Schiff base and its metal complexes with Mn(II), Ni(II), Cu(II) and

Zn(II) show miscellaneous effect on membrane in amylase production. Zn(II) and

Mn(II) complexes stimulated amylose transportion through membrane while Ni(II) and

Cu(II), complexes inhibited it.

1.3 Transition Metal Complexes

Metals have an esteemed place in medicinal chemistry. Transition metals

represents the d block element which includes groups 3-12 on the periodic table. Their

d-shells are in process of filling. This property of transition metals resulted in the

foundation of coordination complexes. Sophus Jorgensen in Denmark synthesized metal

conjugates for the first time in the mid 1870‟s. In 1893 the major break through in this

field was occurred when Alfred Werner investigated a series of compounds, which

contained cobalt, chlorine and ammonia. He was awarded the Noble prize in 1913 for

his work. The earliest reports on the therapeutic use of transition metal complexes in

cancer and leukemia date from the sixteenth century. In 1960, the anti-tumor activity of

an inorganic complex cis-diammine-dichloroplatinum(II)(cisplatin) was discovered.

Cisplatin has developed into one of the most frequently used and most effective

cytostatic drug for treatment of solid carcinomas. Other metal like Gallium,

Germanium, tin, bismuth, titanium, ruthenium, rhodium, iridium, molybdenum, copper,

gold were shown effective against tumors in man and animals.

1.3.1 Anticancer Agents

1.3.1.1 Platinum Based Anticancer Drugs

Platinum(II) complexes has been used as anti cancer drugs since long among

them cisplatin has proven to be highly effective chemotherapeutic agent for treating

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various type of cancers[42]. Cisplatin moves into the cell through diffusion and active

transport. Inside the cell it causes platination of DNA, to form adducts causes distortion

and results in inhibition of DNA replication[43]. The binding of HMG-domain

protein[44] to cisplatin DNA adduct has been suggested to enhance anticancer effect of

the drug[45].

1.3.1.2 Non Platinum Anticancer Agency

Titanium complexes such as Titanocene dichloride had been recognized as

active anticancer drug against breast and gastrointestinal carcinomas used to treat

various forms of cancer. Gold complexes, Lanthanum complexes have also been used to

treat various forms of cancer[46]. Mn(II) complexes have been studied by Ansar et

al[47] induce tumour selective apoptosis of human cells. Ru(II), Ru(III) complexes

show antitumor activity against metastasis cancers. Ruthenocene complexes with

aromatic ligands represent a relatively new group of compounds with antitumor

activity.

Ru(III) imidazole and Ru(III) indazole exhibit anticancer properties complexes

of transition metal like iron have shown remarkable anti proliferative[48], properties.

Silica gold nanoshells technology used for thermal ablative therapy of cancer. It has

been reported that silver nanoparticles exhibit anti proliferative activity.

Mercaptopurines are well known antileukemic drugs but their use has been hampered

by their short half life. This has been overcome by the use of gold nano particles in

combination with mercaptopurines.

1.3.1.3 Anti Infective Agents

Transition metals like silver have been used as antimicrobial agents silver has

low toxicity as compared to other transition metals Silver(I) sulfazine used to treat

12

severe burns to prevent them from bacterial infections, organometallic complexes of Pt,

Rh, Ir, Pd and Os with active organic molecules have been reported to exhibit

trypanocidal activity.

An increasing amount of data showing the beneficial use of zinc(Zn) in treating

diarrhorea continues to emerge from epidemiological and clinical trials. Nitrogen

containing macrocyclic complexes of Manganese(II) have shown antimicrobial activity,

many manganese complexes have been screened against a number of pathogenic fungi

and bacteria to evaluate their growth and potential[49]. Metal complexes of Pt(II)and

Ru(II) with o-vanillin-(4-methyl thiosemicarbazone) and o-vallinine (4-phenyl

thiosemicarbozone ) have been proven more efficient anti-infective agents.

Transition metals have also been proved useful in the treatment of malaria. One

strain plasmodium falciparum has become resistant to major antimalarial drugs such as

quinolines. Metal complexes of Ga(III), Al(III) and Fe(III) were found to be active

against malaria.

1.3.1.4 Anti Inflammatory Agents And Free Radical Quenchers

Transition metals have also been used as anti-inflammatory and anti-arthritic

agents. Several inject able gold complexes like sodium aurothiomalate, aurothioglucose

and sodium aurothiopropanol are used clinically in the treatment of severe cases of

rheumatoid arthritis. Gold and silver nano particles conjugated with heparin derivative

possess anti angiogenesis properties[50]. Gold has been used in the treatment of

peripheral psoriatic arthropathy.

Among transition metals complexes of Cu and Fe are capable of catalyzing

dismutation of the superoxide anion. In addition, Mn complexes does not bind to NO

and react slowly with H2O2, demonstrating specificity towards superoxide anion. NO

13

are an excellent ligand for transition metal ions and these metal nitrosyls having

therapeutic values. sodium nitropruside is used clinically to treat cardiovascular

diseases by releasing NO but CN- toxicity limited its application.

Many human diseases are associated with the over production of oxygen free

radicals that inflict cell damage. A manganese(II) complex with bis

(cyclohexylpyridine)- substituted macrocyclic ligand has designed as a functional

mimic of the superoxide dismutase(SOD) enzymes that normally remove these

radicals[51]. Manganese complexes have also been used to treat cell and tissue

oxidative injuries by acting as superoxide anion scanvenger. Magnesium is used for the

treatment of asthema in children. Some Cu complexes are also active against

inflammation[52]. Cu(II) complexes tend to dissociate and bind to natural ligands such

as albumins[53]. Zn has been proved to be involved in the inhibition of

proinflammatory cytokines[54].

1.3.1.5 Anti-Diabetic Agents

Vanadium and zinc in the form of inorganic salts has been used to control

glucose level in the blood plasma. It has been shown that elements are poorly absorbed

in their inorganic forms and required high doses. Vanadium complexes have proved to

be less toxic with improved solubility and lipophilicity. There are a number of

vanadium complexes that have been developed all of which have insulin-mimetic

properties. The molecular mechanism responsible for the insulin-like effects of

vanadium compounds have been shown to involve the activation of several key

components of insulin signaling pathways. Higher zinc intake has also been associated

with a slightly lower risk of the type 2 diabetes in women[55].

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1.3.1.6 Neurological Drugs

Transition metal complexes are also used in the treatment of neurological

disorders. Lithium has been used to cure many neurological disorders like Huntingtons

chorea, tardive dyskinesia, headache etc., Neuronal zinc(II) serves as an important,

highly regulated signaling component responsible for the initiation of a neuroprotective

pathway[56].

With the advancement in the field of inorganic chemistry the role of transition

metal complexes as therapeutic compounds its becoming increasingly important. Recent

advances in inorganic chemistry have made possible formation of number of transition

metal complexes with organic ligand of interest which can be used as therapeutic agent.

The use of transition metal complexes as therapeutic compounds has become more and

more pronounced. These complexes offer a great diversity in their action.

1.4 Biological Importance of Copper and Copper Complexes

It is an essential metal, daily dietary requirements have been recommended by a

number of agencies. The American medical Association has recommended 1.2-1.3

mg/day as the dietary requirements for copper. It is required for the normal functioning

in plants, animals and most micro organisms. The chemical nature of copper is very

important in determining its biological availability. Some of the uses of copper come

from its ability to control the growth of organism. This occurs when copper is

biologically available and at concentrations that are detrimental. As a result, copper is

used in range of bactericidal agents. Copper has been demonstrated to be an effect

antibacterial, anti plaque agent in mouthwashes and tooth pastes. Copper also continues

to be widely used for the control of unwanted organisms in fish farming. Evidence in

both fresh water and salt water indicates no hazardous effect to consumes of the fish.

15

Copper is the third most abundant essential trace mineral in the body, after iron

and zinc. Copper has been recognized as an essential nutrient since the 1920s[57]. In

the past seventy years, much has been learned about the important biological roles of

copper and the copper dependent enzymes[58]. In fact, copper is emerging as one of the

most important minerals in our diet. Copper has an entirely different role in the body

being a component of two of our most important antioxidant enzymes, copper-zinc

superoxide dismutase and ceruloplasmin[59].

Copper in our body is bond to either transport Proteins (ceruloplasmin and

copper –albumin), storage protein(Metallothioneins) or copper containing enzyme.

Copper essential for the proper function of these copper dependent enzymes, including

cyto chrome C-oxidase (energy production) super oxide dismutase (anti oxidant

protection) tyrosinase pigmentation dopamine hydroxylase (catecholamine production),

lysyl oxidase (collagen and elastin formation) clotting factor (blood clotting) and

ceruloplasmin (anti oxidant protection), iron metabolism ,and copper transport[60].

Severe copper deficiency can be explained by failure of one or more copper dependent

enzymes e.g the lysyl oxidase deficiency cause defect of collagen and elastin causing

abnormalities in the connective tissue and vascular system. The Copper deficiency

doesn‟t necessarily lower the level of copper dependent enzymes, it does significantly

lower their activity. As an example copper dependent their enzyme lysyl oxidase

ensures the proper cross linking of collagen and elastin, vital for the strength and

flexibility of our connective tissue. A reduction in lysyl oxidase activity affects the

integrity of numerous tissues, including our skin bones and blood vessels. In copper

deficiency the level of lysyl oxidase is not altered, but the activity of enzyme can be

reduced by more than 50%. Maintaining a steady level of copper (between 80 to 150

mg) stored in liver in the body depends upon a balance between intestinal absorption

16

and biliary excretion. Biliary excretion of copper is capable of substantially increasing

when excess copper is ingested, Otherwise due to lack of circulating cerulo plasmin,

Copper accumalation in the liver causing genetic disease called wilson‟s

disease(hepatolenticular degeneration) affecting approximately 1500 americans,

vitamin/mineral supplements containing vitamin C or zinc are strong antagonists of

copper status and absorption. In the case small increase in zinc significantly lower

copper absorption[61]. This antagonism has been utilized as a treatment of Wilson‟s

disease[62]. While the evidence for benefits from taking megadoses of zinc (>50mg

daily) and vitamin C(>1000mg daily) are tentative at best, the negative consequences of

poor copper status are well documented and certain. The long term effects of marginal

subclinical copper deficiency are not well defined it has been hypothesized that low

copper status and only common, but play a substantial role in numerous common,

degenerative diseases and conditions. Copper‟s role in cardiovascular disease, diabetes,

arthritis, osteoporosis, free radical damage, cancer, inflammatory disease, immune

function, blood lipids and thyroid function. The copper complexes have been

extensively studied for their anti-inflammatory and antioxidant activity, as well as their

ability to mimic the superoxide – radical scavenging activity of superoxide

dismutase[63].

1.4.1 Copper and Cardiovascular Disease

Copper is a contributing factor for the relationship between nutrition and

cardiovascular disease[64]. Copper has been known to be associated with lipid

metabolism its deficiency can significantly increase the plasmacholestrol concentration.

This increase in cholesterol results in an increase in LDL- cholesterol and a decrease in

HDL - cholesterol, resulting in an increase in cardio vascular disease risk people who

17

die with ischaemic heart disease are hypertrophied and fibrotic, with edema, loss of

cellular outline and heart rupture often being found[65], all of these pathological

changes are found is deficient in copper. Administration of addition copper resulted in

further increase in serum copper, a significant decrease in serum cholesterol and an

increase and normalization in aorta and liver copper levels. It has been shown that

excess dietary cholesterol causes cardiovascular disease by lowering the absorption of

copper, an effect that is prevented by increasing the copper level in the diet[66]. Taken

as a whole, the role of copper in maintaining cardiovascular health is well established

copper is essential both for its role in anti oxidant enzymes, like Cu-Zn superoxide

dismutase and ceruloplasmin as well as its role in lysyl oxidase essential for the strength

and integrity of the heart and blood vessels.

1.4.2 Copper and Free Radicals

Copper deficiency has been shown to result in a 2-fold increase in the level of

lipid hydro peroxides in liver mitochondria[67], the specific activity of Cu-Zn SOD

decreased significantly. The decrease in antioxidant protection caused by copper

deficiency goes beyond a decrease in the activity of copper-dependent antioxidant

enzymes by inducing a wide range of disturbances in other antioxidant enzyme system.

Additionally, copper deficiency depresses Cu-Zn SOD activity and prostacyclin

synthesis in the aorta as well as increases the susceptibility of lipoproteins and heart

tissue to peroxidation providing strong evidence that copper plays a vital role in the

production of the cardio vascular system from free radical mediated damage and

disease[68].

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1.4.3 Copper and Osteo Porosis

Almost two hundred years ago, the German physician Rademacher empirically

established that broken bones healed faster when the patient was given copper

supplements[69], compelling evidence has established a vital role for copper in the

biosynthesis of bone and connective tissues and their maintenance. Skeletal

abnormalities have often been found concurrently with low copper status and these have

usually been associated with osteoporitic changes and increased susceptibility to

fractures. Insufficient copper intake has also been show to lower bone calcium levels

during long term deficiency.

1.4.4 Copper and Immune Function

Immune function was significantly impaired at dietary copper levels that didn‟t

seems to decrease tissue copper or the activity of red blood cell Cu, Zn- super oxide

dismutase(SOD)[70]. However, neutrophil SOD- activity and neutrophil function was

significantly diminished, suggesting that immune function may be more sensitive to

diets low in copper than standard measures of copper status. The adverse effects of

inadequate copper intake on neutrophil activity occur rapidly and are readily reversed

by dietary copper repletion. Additionally it has been demonstrated that copper

deficiency reversibly impairs DNA synthesis in activated T-cells by limiting interleukin

2 activity up to 50 % and this was reversible with copper supplementation[71].

1.4.5 Copper, Cancer and Carcinogenesis

Numerous studies examining varied types of tumors have demonstrated that

with remission usually comes a decrease in serum copper levels to normal[72] .Patients

who responded to therapy or surgery usually had a return to normal serum copper

19

levels, while non responders had a persistently elevated serum copper level.

Interestingly, most tumor cells have decreased Cu-Zn SOD activity compared to normal

cells[73], and it has been suggested that the elevation in serum copper is a physiological

response designed to activate SOD or other copper enzymes in cancer cells to inhibit

their growth. Indeed numerous copper complexes that demonstrate SOD-mimetic

properties, including copper salicyclate, have been shown to possess anticancer,

anticarcinogenic and antimutagenic effects both in vitro and in vivo. In fact there is

some experimental evidence that copper complexes can cause established tumor cells to

redifferentiate into normal cells[74]. And because of this, it has been suggested that,

“the future use of copper complexes to threat neo plastic diseases has some exciting

possibilities”.

1.4.6 Copper, Inflammation and Arthiritis

As long ago as 1000BC, foods high in copper and copper bracelets were thought

to be beneficial in treating arthiritic conditions[75] copper complexes were successfully

used from the 1940‟s to 1970‟s in the treatment of numerous conditions characterized

by arthiritic changes and inflammation[76]. Copper complexes possess anti

inflammatory activity, many popular anti-inflammatory drugs are their copper chelates.

Interest in copper complexes as anti-inflammatory drugs and anti arthritics is evidenced

by the large number of reviews and symposia proceedings published in recent

years[77]. Most human supplements of copper contain either copper sulphate or copper

glucotate two well utilized forms of copper.

1.5 Biological Importance of Manganese

Manganese is an essential trace nutrient in all forms of life. The classes of

enzymes that have manganese cofactors are very broad and include oxidoreductases,

20

transferases, hydrolases, lyases, isomerases, ligases, lectins and integrins. The reverse

transcriptases of many retroviruses contain manganese. The best known manganese

containing polypeptides may be arginase, the diphtheria toxin, and Mn- containing

superoxide dismutase(Mn-SOD)[78]. The human body contains about 10mg of

manganese, which is stored mainly in the liver and kidney. In the human brain the

manganese is bound to manganese metalloproteins most notably glutamine synthetase

in astrocytes[79]. Mn-SOD is the type of SOD present in eukaryotic mitochondria, and

also in most bacteria (this fact is in keeping with the bacterial origin theory of

mitochondria). The Mn-SOD enzyme is probably one of the most ancient for nearly all

organisms living in the presence of oxygen use it to deal with the toxic effects of

superoxide, formed from the 1-electron reduction of dioxygen. Exceptions include a

few kind of bacteria such as Lactobacillus plantarum and related lactobacilli, which use

a different non-enzymatic mechanism, involving manganese (Mn+2

) ions complexed

with polyphosphate directly for this task indicating how this function possibly evolved

in aerobic life. Manganese is also important in photosynthetic oxygen evolution in

chloroplasts in plants. The oxygen evolving complex (OEC) is a part of Photosystem II

contained in the thylakoid membranes of chloroplast, it is responsible for the terminal

photooxidation of water during the light reactions of photosynthesis and has a

metalloenzyme core containing four atoms of manganese[80]. For this reason, most

broad spectrum plant fertilizers contain manganese. Manganese is a chemical that can

be considered both an heavy metal pollutant and essential trace mineral for all known

living being[81].

Mn(II)ions function as cofactors or a number of enzymes in higher organisms,

where they are essential detoxification of superoxide free radicals, it aids in the

21

formation of connective tissue, it enables the body to utilize vitamin C, B1, biotin as

well as chlorine.

Severe deficiencies are rare and can cause growth retardation changes in

circulation HDL chloestrol and glucose levels, reproductive failure. Serious deficiency

in children can result paralysis, deafness and blindness, sub-clinical deficiencies can be

linked to depression, weakness tumors, irrational behaviour, leg cramps.

1.5.1 Antiaging Activity and Skin Health

Needed to build collagen

It helps to have a high bone density

Necessary for energy production

Active in DNA repair – related to cofactor activity in the MnSOD.

Antioxidants scavenge damaging particles in the body known as free radicals.

These particles occur naturally in the body but can damage cell membranes, interact

with genetic material and possibly contribute to the aging process as well as the

development of a number of health conditions. Antioxidants such as MnSOD can

neutralize free radicals and may reduce or even help prevent some of the damage they

cause.

Recent studies have shown that antioxidant enzyme expression and activity are

drastically reduced in most human skin diseases leading to propagation of oxidative

stress and continuous disease progression. Numerous studies have shown that MnSOD

can be induced to protect against prooxidant insults resulting from cylokine treatment,

uv light, irradiation, certain tumors, amyotropic lateral sclerosis, and ischemia/

reperfusion. In addition, over expression of MnSOD has been shown to protect against

22

pro-apoptotic stumili as well as ischemic damage. Regulation of antioxidant activity is a

new target for dermatologists.

Probably the role of MnSOD beyond its essential role for survival and suggest a

novel strategy for an antioxidant approach to cancer intervention several form of

supplementary Mn including manganese gluconate, Mn sulfate, Mn ascorbate and Mn

amino acid chelates. Typical supplemental intake of Mn ranges from 2-5 mg daily.

European states that Mn is requested for production of enzymes involved in

proleic and lipidic metabolism. Mn contributes to the normal main fracture of collagen.

Redox-active metals are paramount importance for biological functions. Their impact

and cellular activities participate in the physiological and pathophysiological processes

of the central nervous system(CNS) including inflammatory responses. Mn is an

essential trace element and it is required for normal biological activities and abiquitious

enzymatic reactions[82]. Mn is a vital nutritional element, especially for the activation

of enzymes. This essential micromineral is necessary throughout the body, from protein

metabolism to brain function. High levels of Mn are found in the pancreas, pituitary

gland and kidneys. In the body, Manganese promotes proper utilization of glucose helps

to improve memory and to reduce nervous irritability, as well as normal pancreas

function. and development. Minerals are poorly absorbed from the small intestine

unless they are properly chelated with amino acids. Mn chelates provides better

absorption (60% to 70%) bio availability and tolerance than Mn salt. Trophics patented

Albion Mn chelated with natural amino acid provides superior biological activity of or

bioavailability and absorption effect of manganese on the activity of Antibiotic against

microorganism. Mn is essential for enzymatic activity. Maintaining three dimensional

stress of protein, for the synthesis of nucleic acid and protein. Deficiency of Mn causes

different life threatening disease. Because of this, the optimum level of Mn must be

23

maintained in all biological system. This experiment, therefore was designed to

evaluate the effect of Mn on the activity of different antibiotics(ciprofloxacin,

cephradine, amoxicillin, gentamycin, tetra cycline, cloxacillin, nalidixic acid,

ceftriaxone, metronidazole and carbenicillin) against different microorganisms. It has

been observed that antimicrobial activity of an antibiotic increased significantly with

concomitant use of Mn salt ranging from 600-6000ng/antibiotic disc(p<0.05). It is

revealed from the experiment that Mn increase the activity of antibiotic against bacterial

strains[83].

The study focuses on the catalytic behaviour of a series of Mn oxide molecular

sieves with different structures. The fuel alloy catalyst used for the biological activity

was a commercial alloy catalyst. The effect of the growth of psychotrophic bacteria,

pseudomonas oleovorans and Rhodococcus in fuels was studied in the presence of fuel

alloy catalyst. The growth was monitor over a maximum of 8 week period. The fuel

alloy, catalyst has been capable of arresting the bacterial growth and preventing

bacterial spoilage of fuels.

1.6 Biological Importance of Nickel

Nickel plays important roles in the biology of micro organisms and plants[84].

An enzyme urease which assist in the hydrolysis of urea contains Nickel. The NiFe-

hydrogenase contain nickel in addition to iron-sulphur clusters such [Ni Fe]-

hydrogenase characteristically oxidizes H2. A Nickel-tetrapyrrole co enzyme, F430, is

present in the methyl coenzyme m reductase which powers methanogenic archaea. One

of the carbon monooxide dehydrogenase enzymase consist of an Fe-Ni-S cluster[84].

Other Nickel containing enzymes include a class of superoxide dismutase[85] and a

glyoxalase[86].

24

In 1975, the National Academy of sciences published a monograph on nickel in

which numerous enzyme systems were studied. The Nickel ion(II) under various

condtions, could either activate or inhibit several enzymatic reaction which are

considered to be of crucial importance in humans and other animals and that

interference with these reactions could have severe deleterious effects. The deficient of

nickel included abnormalities of the sub-cellular organelles such as rough endoplasmic

reticulum and mitochondria, decrease in phospholipids, depressed hematoerity and

generally thinner more unhealthy appearing animals[87]. Many of these changes are

considered to be indicative function essential role for nickel in protein sythesis in

animals. Calcium also appears to have a physiological relationship with nickel that may

be mediated by specific genes. Cap43, in a transformed human lung cell[88] line

describes the specific induction by Ni compounds of a novel gene other studies have

suggested that Nickel has a function that is related to changes cause by deprivation of

folic acid pyridoxine or vitamin B12. These vitamins are involved in sulfur amino acid

metabolism of coenzyme m reduetase including synthesis of homocysteine. Together,

these results suggest a possible interaction between Nickel and homocysteine regarding

intracellular calcium levels and neuro muscular signal pathways, calcium is one of the

element whose concentrations have been consistently found to be altered by Nickel

deprivation in muscle and bone test animals.

In plants and microorganism, the importance of Nickel has been well

documented. Nickel is needed for the proper functioning of various plant enzymes such

as urease and hydrogenase. In the decreased presence of urease, due to the lack of

adequate Nickel, urea accumulation leads to necrosis of the plant[89]. In soyabeans,

where hydrogenase activity was depressed due to Nickel-depletion only low levels of

nitrogen fixation occurred, which resulted in slow plant growth and decreased crop

25

yield. Nickel depletion has also been linked to necrosis of the leaves and stems of a

variety of plants. The specific role of Nickel in microorganisms is not just an anecdotal

one or one that occurs in rare and exotic enzyme system. Nickel was discovered as a

key component of the enzyme methyl-coenzyme M reductase, which is the key enzyme

in biological methane formation in certain bacteria . Hence Nickel is essential for higher

plant in that a plant grown in a medium adequately purged of that element fails to grow

normally or complete its life cycle[90].

The chemistry of thiosemicarbazones has revealed considerable attention in

view of their variable bonding modes, promising biological implications, structural

diversity, and ion- sensing ability. They have been used as drugs and reported to

possess a wide variety of biological activities against bacteria, fungi and certain type of

tumors and they are also useful model for bioinorganic process thiosemicarbazone

complexes have been intensively investigated for antiviral, anti cancer, antitumoural,

antimicrobial, antiamoebic and anti-inflammatory activities. The inhibitory action is

attributed due to their chelating properties.

1.7 Biological Activity of Zinc

Zinc is known to play a central role in the immune system and zinc deficient

person experience increased susceptibility to a variety of pathogenes. The immunologic

mechanics whereby zinc modulates increased susceptibility to infection have been

studied for several decades. Zinc is crucial for normal development and function of

cells, mediating non specific immunity such as neutrophills and natural kill cells. Zinc

deficiency also affects development of acquired immunity by preventing both the

outgrowth and ceratin function of T.lympocytes such as activation. This effects of zinc

on these key immunologic mediators is rooted in the myriad role for zinc in basic

26

cellular function such as DNA replication , RNA transcription cell division and cell

activation. Apoptosis is potentiated by zinc deficiency. Zn also function, as an

antioxidant and can stabilize membrane[91].

Recently a second motif for DNA binding protein “The Zinc Finger” emerged

from sequence analysis of TA11A4 a factor involved in the control transcription of the

Xenopus 5S RNA gene. The finger structure is based on pairs of cys and His resides

which are arranged around a tetrahedrally coordinate zinc ion[92]. Zinc fingers have

been observed in the DNA binding protein domains of transcriptional activators in

yeast[93] and man and in several regulatory proteins of Drosophila[94].

Zinc finds immune function in the biological basis of altered resistance to

infection. A comparison of zinc metabolism, inflammation and disease severity in

critically ill infected and noninfected adults early after intensive care unit admission.

Zinc supplementation for the prevention of acute lower respiratory infection in children

in developing countries, meta-analysis and meta-regression of randomized trials. Zinc

decreases C-reactive protein, lipid, peroxidation and inflammatory cyclokines in elderly

subjects, a potential implication of zinc as an arthero protective agent. Zinc modifies the

association between Nasopharyngeal streplococcus pneumoniae carriage and Risk of

Acute lower respiration infection among young children. Zinc supplements for severe

cholera,” Zinc oxide protects cultured enterocytes from the damage inclured by

Escherichia coli. Zinc is a protective nutrients and functional foods for the

gastrointestinal track. Zinc protects against apoptosis of endothelial cells include by

linoleic acid and tumor necrosis factor(Alpha). Zinc rivals platinum in the fight against

cancer. New zinc complexes that show promising anticancer activity could be used as

an alternative to platinum base drugs such as cisplatin. Zinc ion has a variety of

27

physiological roles and Zn(II) complexes are used in many biological field including as

radio protective agents and antidiabetic insulin-mimetics.

Zinc is low cost bio compatible metal with a large coordinative chemistry

interesting photophysical properties and is very promising for inorganic medicinal

chemistry. Zn(II) and Cu(II) complexes of cephalexin drug have shown improved

antimicrobial activity than cephalexin significantly. These results suggest that metallic

element should be seriously considered during drug design[95]. Zinc complexes are of

great interest in organic synthesis and bioinorganic synthesis. It is well known that zinc

plays an important role in many biological process.

1.8 Antimicrobial Activity

An anti-microbial is a substance that kills or inhibits the growth of

microorganisms such as bacteria, fungi or protozoans. Antimicrobial drugs either kill

microbes or prevent the growth of microbes. Most of the transition metal complexes

exhibit antimicrobial activity. It has been suggested that chelation/coordination reduces

the polarity of the metal ion mainly because of partial sharing of its positive charge with

donor group with in the whole chelate ring system[96][97]. This process of chelation

thus increases the lipophilic nature of the central metal atom, which in turn, favours its

permeation through the lipid layer of the membrane thus causing the metal complex to

cross the bacterial membrane more effectively thus increasing the activity of the

complexes. Besides this many other factors such as solubility, dipole moments,

conductivity influenced by metal ion may be possible reason for remarkable anti

microbial activity of transition metal complexes[98]. It has also been observed that

some moieties such as azomethine or heteroaromatic nucleus introduced into such

compounds exhibit extensive biological activity, that may be responsible for the

28

increase in hydrophobic character and liposolubility of the molecules in crossing the

cell membrane of the microorganism and enhance biological utilization ratio and

activity of complexes[99]. The metal complexes disturb the respiration process of cell

and thus block the synthesis of protein, which restricts further growth of the

organism[100].

Metal complexes are toxic to most microorganism at specific concentrations and

often cause serious upsets in biological process. Some of the metal complexes are

essential for the growth of micro organisms at very low concentrations and certain

metal ions inhibit the growth of many microorganisms at higher concentrations. The

toxicity of the metal complexes depends mainly upon the nature of metal ion, ligands

and their concentrations.

Schiff bases and their metal complexes have been found to possess important

biological activities. Azomethines bind to the metal ions through nitrogen, oxygen or

sulphur atoms so form an important class of biologically active ligand and provide

models for metal ligand binding sites in several enzymes[101]. These ligands and their

metal complexes are known to function as antimicrobial[102][103], anti malarial[104],

antitumor[105] and antileukemic agents[106].

1.9 DNA Cleavage

DNA repair refers to a collection of processes by which a cell identifies and

corrects damage to the DNA molecules that encode its genome. In human cells, both

normal metabolic activities and environmental factors such as UV light and radiation

can cause DNA damage, resulting in as many as one million individual molecular

lesions per cell per day. Many of these lesions cause structural damage to the DNA

molecule and can alter or eliminate the cell's ability to transcribe the gene that the

29

affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's

genome, which affect the survival of its daughter cells after it undergoes mitosis. As a

consequence, the DNA repair process is constantly active as it responds to damage in

the DNA structure shown in Figure 1.1. When normal repair processes fail, and when

cellular apoptosis does not occur, irreparable DNA damage may occur, including

double-strand breaks and DNA cross linkages.

Fig. 1.1 DNA damage resulting in multiple broken chromosomes

The rate of DNA repair is dependent on many factors, including the cell type, the age of

the cell, and the extracellular environment. A cell that has accumulated a large amount

of DNA damage, or one that no longer effectively repairs damage incurred to its DNA,

can enter one of three possible states:

1. An irreversible state of dormancy, known as senescence

2. Cell suicide, also known as apoptosis or programmed cell death

3. Unregulated cell division, which can lead to the formation of a tumour that is

cancerous.

30

The DNA repair ability of a cell is vital to the integrity of its genome and thus to

its normal functioning and that of the organism. Many genes that were initially shown

to influence life span have turned out to be involved in DNA damage repair and

protection. Failure to correct molecular lesions in cells that form gametes can introduce

mutations into the genomes of the offspring and thus influence the rate of evolution.

DNA Damage

DNA damage, due to environmental factors and normal metabolic processes

inside the cell, occurs at a rate of 1,000 to 1,000,000 molecular lesions per cell per day.

While this constitutes only 0.000165% of the human genome's approximately 6 billion

bases (3 billion base pairs), unrepaired lesions in critical genes (such as tumour

suppressor genes) can impede a cell's ability to carry out its function and appreciably

increase the likelihood of tumour formation. The vast majority of DNA damage affects

the primary structure of the double helix; that is, the bases themselves are chemically

modified. These modifications can in turn disrupt the molecules' regular helical

structure by introducing non-native chemical bonds or bulky adducts that do not fit in

the standard double helix. Unlike proteins and RNA, DNA usually lacks tertiary

structure and therefore damage or disturbance does not occur at that level. DNA is,

however, supercoiled and wound around "packaging" proteins called histones (in

eukaryotes), and both superstructures are vulnerable to the effects of DNA damage.

Sources of damage

DNA damage can be subdivided into two main types:

31

1. Endogenous damage such as attack by reactive oxygen species produced from

normal metabolic by products (spontaneous mutation), especially the process of

oxidative deamination

1. Also includes replication errors

2. Exogenous damage caused by external agents such as

1. Ultraviolet [UV 200-300 nm] radiation from the sun

2. Other radiation frequencies, including x-rays and gamma rays

3. Hydrolysis or thermal disruption

4. Certain plant toxins

5. Human-made mutagenic chemicals, especially aromatic compounds that act

as DNA intercalating agents

6. Cancer chemotherapy and radiotherapy

7. Viruses

The replication of damaged DNA before cell division can lead to the

incorporation of wrong bases opposite damaged ones. Daughter cells that inherit these

wrong bases carry mutations from which the original DNA sequence is unrecoverable

(except in the rare case of a back mutation, for example, through gene conversion).

Types of damage

There are five main types of damage to DNA due to endogenous cellular processes:

1. Oxidation of bases and generation of DNA strand interruptions from reactive

oxygen species.

2. Alkylation of bases (usually methylation).

3. Hydrolysis of bases, such as deamination, depurination, and depyrimidination.

4. "Bulky adduct formation".

32

5. Mismatch of bases, due to errors in DNA replication, in which the wrong

DNA base is stitched into place in a newly forming DNA strand, or a DNA base

is skipped over or mistakenly inserted.

Damage caused by exogenous agents comes in many forms. Some examples are:

1. UV-B light causes crosslinking between adjacent cytosine and thymine bases

creating pyrimidine dimers. This is called direct DNA damage.

2. UV-A light creates mostly free radicals. The damage caused by free radicals is

called indirect DNA damage.

3. Ionizing radiation such as that created by radioactive decay or in cosmic rays

causes breaks in DNA strands. Low-level ionizing radiation may induce

irreparable DNA damage (leading to replicational and transcriptional errors

needed for neoplasia or may trigger viral interactions) leading to pre-mature

aging and cancer.

4. Thermal disruption at elevated temperature increases the rate of depurination

(loss of purine bases from the DNA backbone) and single-strand breaks. For

example, hydrolytic depurination is seen in the thermophilic bacteria, which

grow in hot springs at 40-80°C. The rate of depurination (300 purine residues

per genome per generation) is too high in these species to be repaired by normal

repair machinery, hence a possibility of an adaptive response cannot be ruled

out.

5. Industrial chemicals such as vinyl chloride and hydrogen peroxide, and

environmental chemicals such as polycyclic hydrocarbons found in smoke, soot

and tar create a huge diversity of DNA adducts- ethenobases, oxidized bases,

alkylated phosphotriesters and Crosslinking of DNA just to name a few. UV

damage, alkylation/methylation, X-ray damage and oxidative damage are

33

examples of induced damage. Spontaneous damage can include the loss of a

base, deamination, sugar ring puckering and tautomeric shift.

DNA is a molecule that acts as a form of memory storage for genetic

information. DNA is usually the target of some anti-tumor reagents, these reagents react

with DNA thereby stopping the replication of DNA and inhibiting growth of tumor cell.

DNA offers the analytical chemist a powerful tool in recognition and monitoring of

many important molecules. Genetic engineering has brought new challenges and

opportunities for medicine and biomedical research. DNA strands would be damaged in

a cellular environment. The damage of DNA would cause mutations and genomic

instabilities that could contribute to a variety of human genetic diseases. One of the

most important achievements in our understanding of biochemistry of DNA is our

awareness that DNA double helix has considerable conformational flexibility. The

discovery of left handed DNA and other DNA conformations illustrate the concept of

structural flexibility.

Transition metal complexes capable of cleaving DNA and RNA under

physiological conditions via oxidative and hydrolytic mechanisms are of importance for

their potential use as new structural probes in nucleic acid chemistry and as therapeutic

agents. Among the active transition metal species, binuclear and polynuclear complexes

generally give higher cleavage rates provided that the ligand holds metal centers in an

appropriate geometry. Compared with mononuclear complexes, binuclear complexes

have higher activity as a result of cooperative interaction of metal ions in stabilizing the

transition state of phosphodiester cleavage. Such metal complexes would permit

targeting of specific DNA sites by matching the shape, symmetry and functionality of

the complexes to those of the DNA target. The increasing interest in using macrocycles

34

and their coordination compounds as artificial restriction enzymes for cleaving DNA

has prompted us to investigate the application of macrocyclic transition metal

complexes in this area. The DNA endonucleolytic cleavage, activated by metal ions has

been of interest to researchers. Transition metal mediated radical production may result

in an efficient DNA cleavage.

The general oxidative mechanisms proposed account of DNA cleavage by

hydroxyl radicals via abstraction of a hydrogen atom from sugar units predicts the

release of specific residues arising from transformed sugars, depending on the position

from which the hydrogen atoms is removed. It has been shown earlier that the cleavage

is inhibited by free radical scavengers, implying that or hydroxyl radical or peroxy

derivatives mediate the cleavage reaction. The reaction is modulated by a

metallocomplexes bound hydroxyl radical or a peroxo species generated from the co

reactant H2O2.

35

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41

1.10. LITERATURE SURVEY

Shouvik Chattopadhyay[1] et al have been reported that the 1:1 condensation of

2,4-pentanedione and 1,2 - diaminopropane gives a mixture two positional isomers of

tridentate mono-condensed product 7-amino-4-methyl-5-aza-3-octene-2-one (HAMAO)

and 7-amino-4,6-dimethyl-5-aza-3-heptene-2-one (HADAH) that reacted readily with

Ni(II) thiocyanate to yield exclusively a single product, [Ni(AMAO)NCS] (1) in which

the methyl substituent of diamine is „remote‟ from the imino nitrogen. The mixture of

tetra dentate ligands has been used for further condensation with pyridine-2-

carboxaldehyde or 2-acetylpyridine to obtain the unsymmetrical tetradentate Schiff base

ligands. The tetra dentate ligands formed by the condensation of it and pyridine-2-

carboxaldehyde readily yielded complexes with Cu(II) and Ni(II) (2 and 3,

respectively). Crystalstructure analysis shows that in 2 the condensation site of the

diamine with 2,4-pentanedione is the same as in 1 but that in 3 is different(the methyl

group of the diamine is located in the vicinity of 2,4-pentanedione), i.e., the tetra

dentate ligand is in two different isomeric forms in complexes 2 and 3. Another tetra

dentate ligand, obtained by the condensation of the tridentate ligands and 2-

acetylpyridineyielded a Ni(II) complex (4) where the methyl group is in the vicinity of

2,4-pentanedione as in 3. The isomerization in the Ni(II) complexes has been studied by

NMR spectroscopy.

42

Mau Sinha Ray[2] et al have been proved that the mononuclear copper(II)

complexes, [CuL1](ClO4) (1), and [CuL2](ClO4) (2) with unsymmetrical quadridentate

Schiff base ligands derived from the 1:1:1 condensation of 2,4-pentanedione, pyridine-

2-carboxaldehyde and 1,2-ethanediamine (HL1) or 1,3-propanediamine (HL2) have been

prepared and characterized. Complex 2 undergoes Cu(II)/H-catalyzed rearrangement

to[CuL3][ClO4]2 (3) where L3 is a symmetrical tetra dentate Schiff base involving 1,3-

propanediamine and pyridine-2-carboxaldehyde.Structures of all the three compounds

have been verified by single crystal X-ray analysis. The geometry around Cu(II) is

square planar in 1 and 2 whereas that in 3 is distorted octahedral with two axially

coordinated per chlorate ions.

Masaaki Kojima[3] et al have been proved that this article describes the crystal

structures of several vanadium complexes containing tetra dentate Schiff base ligands,

and their properties and relativities in the solid state. [VO{sal-(R,R)-stein}] (H2sal-

(R,R)-stein_/N,N-disalicylidene-(R,R)-1,2-diphenyl-1,2-ethanediamine) crystallized in

two different forms, green (from dichloromethane and chloroform) and orange (from

acetonitrile). X-ray structure analysis revealed that the green form contains

mononuclear square-pyramidal molecules of thecomplex, whereas the orange form has

43

a poly nuclear linear chain structure. The green crystals turn orange when heated at 120

8Cfor a few minutes (thermochromism). Both forms are vapochromic, the orange

crystals turning green on exposure to chloroformvapor, and the green crystals turning

orange on exposure to acetonitrile vapor. The color of the orange complex changes to

green on grinding (mechanochromism). [VO{3-EtOsal-(R,R)-2,4-ptn}] (H23-EtOsal-

(R,R)-2,4-ptn /N,N-di-3-ethoxysalicylidene-(R,R)-2,4-pentanediamine)also crystallizes

in two different forms, green and orange. The polymeric orange crystals turn into the

monomeric green form upon heating at 170 8C for 10 min. The mechanism of this

conversion was studied using X-ray structure analysis and thermal analysis. Thermal

isomerization in the solid state between a pair of diastereomers, I and II, of the

oxovanadium(IV) complex with an unsymmetrical tetradentate Schiff base

ligand, [VO{3-EtOsal,sal-(R,R)-chxn}] (H23-EtOsal,sal-(R,R)-chxn N-salicylidene-N-

3-ethoxysalicylidene-(R,R)-1,2-cyclohexanediamine), was studied at 195 8C. The two

diastereomerswere separated using column chromatography, and each crystallized in

two different colors: green (monomeric) and orange(polymeric). The orange complexes,

I (orange) and II (orange), turned green on heating at 195 8C for a few minutes. All

fourcomplexes, I (green), II (green), I (orange), and II (orange), undergo isomerization

at 195 8C to yield an equilibrium mixture, I:II:/1:1. On heating [VO(3-EtOsal-meso-

stien)](H23-EtOsal-meso-stien-/N,N-di-3-ethoxysalicylidene-(R,S)(S,R)-1,2-diphenyl-

1,2-ethanediamine) at 190 8C for 8 h, dehydrogenation took place at the two benzylic

carbon atom sites to form a C C double bond.

44

Xiu R. Bu[4] et al have been proved that five new tetra dentate unsymmetrical

ligands, ethylene-lli-(acetylacetoneimine) N‟orthohydroxylarylaldimine) (aryl=3,5-

dibromophenyl,3 methylphenyl, 3,6-dimethylphenyl, 3,5-dichlorophenyl, 3,5-

dibromoacetophenone),have been prepared and characterized for studies of the general

structure of their copper(I1)complexes and assessment of the substituent effects on

central metal ions. Upon reaction with copper(I1) ions, the ligands derived from aryls,

where aryls are 3,5-dibromophenyl, 3-methylphenyl, 3,6-dimethylphenyl and3,5-

dibromoacetophenone, give the corresponding copper(I1) complexes while the ligand

derived from 3,5-dichlorophenyl undergoes partial hydrolysis leading to the cleavage of

an acetylacetone moiety. The general coordination configuration has been revealed by

an X-ray crystallographic study of one of the complexes, ethylene-N-

(acetylacetoneiminato)-N‟-(o-hydroxy-3,5-dibromoacetophenoneiminato)copper(II),

which exhibits an approximately square-planar geometry with a slight tetrahedron

distortion. An ESR study of the copper(I1) complexes in solution indicates electronic

effects from substituents influence the reactivity of central metal ions. In addition, a key

step in preparation of the unsymmetrical ligands has been dramatically improvedto

ensure synthetic reproducibility and eliminate the decomposition of an intermediate, 7-

amino-4-methyl-5-azo-3-heptene-2-one, AMAHO. Thermal stability of the complexes

has been also evaluated to assess the compatibility of the two donating moieties.

45

Gangadhar B. Bagihalli[5] et al have been proved that a series of metal

complexes of cobalt(II), nickel(II) and copper(II) have been synthesized with newly

synthesized biologically active 1,2, 4-triazole Schiff bases derived from the

condensation of 3-substituted-4-amino-5-mercapto-1,2,4-triazole and 8-formyl-7-

hydroxy-4-methylcoumarin,which have been characterized by elemental analyses,

spectroscopic measurements (IR, UVevis, fluorescence, ESR), magnetic measurements

and thermal studies. Electrochemical study of the complexes is also reported. All the

complexes are soluble to limited extent in common organic solvents but soluble to

larger extent in DMF and DMSO and are non-electrolytes in DMF and DMSO. All

these Schiff bases and theircomplexes have also been screened for their antibacterial

(Escherichia coli, Staphylococcus aureus, Streptococcus pyogenes, Pseudo

monasaeruginosa and Salmonella typhi) and antifungal activities (Aspergillus niger,

Aspergillus flavus and Cladosporium) by MIC method. The brine shrimp bioassay was

also carried out to study their in vitro cytotoxic properties.

46

Esref Tas[6] et al have been proved that the synthesis, structure, spectroscopic

and electro-spectrochemical properties of sterically constrained Schiff-base ligands

(LnH) (n = 1,2, and 3) (L = (methylmercapto)aniline]-3,5-di-t-butylsalicylaldimine, m =

4, 3, and 2 positions, respectively) and theircopper(II)complexes [Cu(Ln)2] are

described. Three new dissymmetric bidentate salicylaldimine ligands containing a

donor set of ONNO were preparedby reaction of different primary amine with 3,5-di-t-

butyl-2-hydroxybenzaldehyde (3,5-DTB). The copper(II) metal complexes ofthese

ligands were synthesized by treating an methanolic solution of the appropriate ligand

with an equimolar amount of Cu(Ac)2-H2O.The ligands and their copper complexes

were characterized by FT-IR, UV–Vis, 1H and 13C NMR and elemental analysis

methods in additionto magnetic susceptibility, molar conductivity, and

spectroelectrochemical techniques. Analytical data reveal that copper(II)

metalcomplexes possess 1:2 metal–ligand ratios. On the basis of molar conductance, the

copper(II) metal complexes could be formulated as[Cu(Ln)2] due to their non-

electrolytic nature in dimethylforamide (DMF). The room temperature magnetic

moments of [Cu(Ln)2] complexesare in the range of 1.82–1.90 B.M which are typical

for mononuclear of Cu(II) compounds with a S = 1/2 spin state. The complexesdid not

47

indicate antiferromagnetic coupling of spin at this temperature. Electrochemical and

thin-layer spectroelectrochemical studies ofthe ligands and complexes were

comparatively studied in the same experimental conditions. The results revealed that all

ligands displayedirreversible reduction processes and the cathodic peak potential values

of (L3H) are shifted towards negative potential values compared tothose of (L1H) and

(L2H). It is attributed to the weak-electron-donating methyl sulfanyl group substituted

on the ortho (m = 2) position ofbenzene ring. Additionally, all copper complexes

showed one quasi-reversible one-electron reduction process in the scan rates of 0.025–

0.50 V s_1, which are assigned to simple metal-based one-electron processes;

[Cu(2+)(Ln)2] + e- ? [Cu(1+)(Ln)2]. The spectral changescorresponding to the ligands

and complexes during the applied potential in a thin-layer cell confirmed the ligand and

metal-based reduction processes, respectively.

Michelle K. Taylor[7] et al have been proved that a series of bis-salicylidene

based N2S2 copper macrocycles were prepared, structurally characterised and subjected

to electrochemical analysis. The aim was to investigate the effects of length of

polymethylene chains between either the imine donors or the sulfur donors on redox

state and potential of the metal. The complexes structurally characterised had either

distorted square planar or tetrahedral geometries depending on their oxidation state

(Cu2+ or Cu+, respectively), and the N–(CH2)n–N bridge was found to be most critical

48

moiety in determining the redox potential and oxidation state of the copper macro

cycles, with relatively little change in these properties caused by lengthening the S–

(CH2)n–S bridge from two to three carbons. In fact, a weakness was observed in the

complexes at the sulfur donor, as further lengthening of the S–(CH2)n–S methylene

bridge to four carbons caused fission of the carbon–sulfur bond to give dimeric rings

and supramolecular assemblies. Cu+ complexes could be oxidised to Cu2+ by tert-

butylhydroperoxide, with a corresponding change inthe spectrophotometric properties,

and likewise Cu2+ complexes could be reduced to Cu+ by treatment with b-

mercaptoethylamine.However, repeated redox cycles appeared to compromise the

stability of the macrocycles, most probably by a competing oxidation ofthe ligand. Thus

the copper N2S2 macrocycles show potential as redox sensors, but further development

is required to improve theirperformance in a biochemical environment.

Rongqing Li[8] et al have been proved that The synthesis and characterisation

of two dicopper(II) and two dinickel(II) macrocyclic complexes, [CuII2 LPr] (10),

[CuII2 LBu] (11),[NiII2 LPr] (12) and [NiII2 LBu] (13), are reported. The two new

Schiff-base macrocycles (LPr)4- and (LBu)4- are isolated as dimetalliccomplexes 10–

13 by the [2+2] condensation of 5,5-dimethyl-1,9-diformyldipyrromethane (9) and 1,3-

diaminopropane or 1,4-diaminobutane,respectively, using Cu2þ or Ni2þ template ions.

Single crystal X-ray structure determinations carried out on 10–13show that each metal

49

atom is in a square planar N4 geometry, being bound to twodeprotonated pyrrole

nitrogen atoms of onedipyrromethane unit and to the two adjacent imine nitrogen

atoms. NMR spectra obtained for the two dinickel(II) complexes 12and 13 show that in

CDCl3 solution they are highly symmetrical and diamagnetic.

Makoto Itagaki[9] et al have been proved that a remarkable increase in catalytic

activity is found for the asymmetric cyclopropanation of 2,5-dimethyl-2,4-hexadiene

withdiazoacetate by use of the chiral copper Schiff-base complexes, which are derived

from substituted salicylaldehydes, chiral aminoalcohols,and copper acetate

monohydrate. Furthermore, a combination of a chiral copper Schiff-base with a Lewis

acid showed an increase in yield(up to 90%) and enantioselectivity (up to 90% ee) for

the asymmetric cyclopropanation of the diene with t-butyl diazoacetate at 200C.

50

Ahmed A. Soliman[10] et al have been proved that the ternary complexes of

copper (II) with salicylidene-2-aminothiophenol (L) and glycine, alanine, valine and

histidene amino acids have been studied in solution and in solid state. The mixed ligand

complexes have been isolated and characterized based on elemental analyses, IR,UV-

Vis, mass spectra, magnetic moment and thermal analysis (TGA). The isolated

complexes were found to have the formula [M (L)(AA)] and the copper has the five

coordinated square bi pyramidal distorted trigonal bipyramidal (SBPTBP) geometry.

The thermal stability of the complexes was studied and the weight losses were

correlated with the mass fragmentation pattern. In all cases the amino acid moiety is

removed first followed by the Schiff base moiety leaving CuO as the metallic residue.

The metallic residue was also confirmed by powder XRD powder diffraction. The

kinetics of the thermal decompositions of the complexes was studied and the

thermodynamic parameters were reported.

Martin Breza[11] et al have been proved that [CuL$B]q model systems, where

L2K is the tridentate Schiff base ligand formed by the condensation of salicylaldehyde

with alanine, B is imidazole, qZK1, 0 and C1, are optimized at B3LYP/6-31G* level of

theory. Their electronic structure is described in terms of Mullikenpopulation analysis

and reactivity indices of Fukui. The total energy of [CuL$B]q species increases with the

51

electron removal. The reactivityindices suitable for the alcohol (sugar) adducts

formation (Cu/Osugar and Ophenoxyl/Hsugar interactions) are in the neutral molecule

as well as inthe singlet cation. Despite the similar trends in Cu–Ophenoxyl bonding and

significant Ophenoxyl spin density in triplet cation, the catalytic mechanism of sugars

oxidation proposed for the galactose oxidase cannot be used in our system because the

[CuL$B]C formation is energeticallyunfavorable. The imidazole nitrogen deprotonation

is more probable than of the alanine ternary carbon atom.

Jian Lv[12] et al have been proved that We have synthesized two cobalt(II) 2

and copper(II) 3 complexes of valine-derived Schiff bases. The obtained complexes

were characterized by elemental analysis, FT-IR and X-ray diffraction. Biological

studies of complexes 2 and 3 had been carried out in vitro for antimicrobial activity

against Gram-positive, Gram-negative bacteria and human pathogenic fungi.

Compound 3 was proven to be abroad spectrum agent, showed a significant inhibition

of the growth of Gram-positive bacteria (Staphylococcus aureus, methicillin-resistantS.

aureus, Bacillus subtilis, Micrococcus luteus), and pathogenic fungi (Candida spp.,

Cryptococcus neoformans, Rhodothece glutinis,Saccharomyces cerevisia, Aspergillus

spp., Rhizopus nigricans) tested and a moderate activity against Gram-negative bacteria

(Escherichiacoli, Pseudomonas aeruginosa, Proteus vulgaris and Enterobacter

aerogenes) tested. The in vitro cytotoxicity of compound 3 was evaluatedusing

52

hemolytic assay, in which the compound 3 was found to be non-toxic to human

erythrocytes even at a concentration of 500 lg/mL.

Mannar R. Maurya[13] et al have been proved that N,N-

Bis(salicylidene)cyclohexane-1,2-diamine (H2sal-dach) reacts with oxovanadium(IV)

and copper(II) exchanged zeolite-Y in refluxing methanol to yield the corresponding

zeolite-Y encapsulated metal complexes, abbreviated herein as [VO(sal-dach)]-Y and

[Cu(sal-dach)]-Y.Spectroscopic studies (IR, electronic and 1H NMR), thermal analysis,

scanning electron micrographs (SEM) and X-ray diffraction patterns have been used to

characterise these complexes. These encapsulated complexes catalyse the oxidation,

byH2O2, of styrene, cyclohexene and cyclohexaneefficiently in good yield. Under the

optimized conditions, the oxidation of styrene catalysed by [VO(sal-dach)]-Y and

[Cu(sal-dach)]-Y gave 94.6and 21.7% conversion, respectively, where styreneoxide,

benzaldehyde, benzoic acid, 1-phenylethane-1,2-diol and phenylacetaldehyde being

themajor products. Oxidation of cyclohexene catalysed by these complexes gave

cyclohexeneoxide, 2-cyclohexene-1-ol, cyclohexane-1,2-diol and2-cyclohexene-1-one

as major products. Conversion of cyclohexene achieved was 86.6% with [VO(sal-

dach)]-Y and 18.1% with [Cu(sal-dach)]-Y.A maximum of 78.1% conversion of

cyclohexane catalysed by [Cu(sal-dach)]-Y and only 21.0% conversion by [VO(sal-

53

dach)]-Y with majorreaction products of cyclohexanone, cyclohexanol and

cyclohexane-1,2-diol have been obtained.

M. Tuncel[14] et al have been proved that In this study, the Schiff base

monomers [(M1; N,No-p-phenylenebis(salicylideneimine)] and ethylenediamine (M2;

N,N0-p-ethylenebis(salicylideneimine)] were synthesized by the condensation reaction

between p-phenylenediamine andaromatic aldehydes. The Schiff base polymers (SBPs)

having double azomethine groups were prepared by oxidative polycondensation(OP)

react ion of monomers in aqueous a lkal ine medium with NaOCl [P1;

poly-(N,No-p-phenylenebis (salicylideneimine)) and P2; poly-(N,No-p-ethylenebis

(salicylideneimine))] as the oxidant at 90oC. Average molecular weights of SBP were

determined by gel permeation chromatography (GPC). Metal complexes of the SBP

were synthesizedby the reaction of polymers and metal salts. The monomers and SBP

were characterized by elemental analyses, GPC, thermogravimetricanalyses, UV–Vis,

FT-IR, 1H and 13C NMR spectroscopic studies. Also the new Cu(II), Ni(II) and

Co(II)complexes of SBP were prepared and characterized by elemental analyses,

UV–Vis, FT-IR, atomic absorption spectroscopy(AAS), thermogravimetric analyses

and magnetic susceptibility measurements. The results suggested that the SBPand metal

ions in 1:1 molar ratio produced binuclear complexes with oxygen and nitrogen donor

atoms. All synthesizedcomplexes have dimeric structures by the polymeric ligand units.

The weight losses of P1–Cu, P2–Ni and P1–Co complexeswere found as 57%, 60% and

61%, at 900 _C, respectively. Thermal stability of P1 complexes is higher than that of

54

P2 complexes.Magnetic moment studies showed that all complexes have various

configurations. The metal ion uptake studieswere done by batch technique. The

polymer P1 was determined to be more effective in removing Cu(II) ions than theP2

polymer in batch technique.

Davar M. Boghaei[15] et al have been proved that A series of new ternary

zinc(II) complexes [Zn(L1–10)(phen)], where phen is 1,10-phenanthroline and H2L1–

10 = tridentate Schiff base ligandsderived from the condensation of amino acids

(glycine, l-phenylalanine, l-valine, l-alanine, and l-leucine) and salicylaldehyde-5-

sulfonates(sodium salicylaldehyde-5-sulfonate and sodium 3-methoxy-salicylaldehyde-

5-sulfonate), have been synthesized. The complexes were characterizedby elemental

analysis, IR, UV–vis, 1H NMR, and 13C NMR spectra. The IR spectra of the

complexes showed large differences betweenνas(COO) and νs(COO), _ν

55

(νas(COO)−νs(COO)) of 191–225 cm−1

, indicating a monodentate coordination of the

carboxylate group. Spectraldata showed that in these ternary complexes the zinc atom is

coordinated with the Schiff base ligand acts as a tridentate ONO moiety, coordinating to

the metal through its phenolic oxygen, imine nitrogen, and carboxyl oxygen, and also

with the neutral planar chelating ligand, 1,10-phenanthroline,coordinating through

nitrogens.

X.-H. Lua[16] et al have been proved that A series of Schiff-base complexes has

been synthesized by the condensation of 1,2-diaminocyclohexane with salicylaldehyde,

2-pyridinecarboxaldehyde, and 2-hydroxy-1-naphthaldehyde, followed by the

metallation with manganese (1, 2, 3a), cobalt (3b), copper (3c) andiron (3d) salts. These

Schiff-base ligands L1–L3 and complexes 1, 2, 3a–d were then characterized by IR, 1H

NMR, 13C NMR, UV–vis spectra,and DSC measurement. Schiff-base Mn

complex(3a)resulting fromN,N-bis(2-hydroxy-1-naphthalidene) cyclohexane diamine

(L3) ligand wasconsiderably active for the catalytic epoxidation of styrene under mild

conditions, in which the highest yield of styrene oxide reached 91.2 mol%,notably

higher than those achieved from simple salt catalysts Mn(Ac)2·4H2O and

MnSO4·H2O. However, another two salen–Mn complexes 1 and2 derived from ligands

N,N-bis(salicylidene)cyclohexanediamine(L1) and N,N-bis(2pyridinecarboxalidene)

56

cyclohexanediamine (L2) exhibitedrelatively poor activity under identical experimental

conditions.

Nuanphun Chantarasiri[17] et al have been proved that Two hexadentate Schiff

base zinc complexes, ZnSal2trien and ZnVan2trien, where Sal ¼ salicylaldehyde, Van

¼ o-vanillin, and trien ¼ triethylenetetramine, have been synthesized by the reaction

between salicylaldehydes, triethylenetetramine and zinc acetate. The structure of

ZnSal2trien and ZnVan2trien were determined by single crystal X-ray crystallography.

It was found that both ZnSal2trien andZnVan2trien have a bent-shaped structure.

Properties of the complexes were examined using differential scanning calorimetry,

polarized optical microscopy and small angle X-ray scattering. Protonation constants of

the ligands Sal2trien and Van2trien and stability constants oftheir zinc complexes were

determined by potentiometric titration. Binding energies of ZnSal2trien and

ZnVan2trien complexes were obtainedby quantum chemical calculations.

57

J. Costa Pessoa[18] et al have been proved that A range of mostly new

oxovanadium(IV) complexes is described. They contain coordinated Schiff bases, made

from simple dipeptides (glycylglycine, glycylsarcosine, L-alanylglycine, L-alanyl-L-

alanine, D,L-alanyl-D,L-alanine and L-serylglycine), andsalicylaldehyde. The

compounds are characterised and the nature of their coordination spheres shown by

analysis, TLC, byappropriate spectroscopy (EPR, IR, electronic and circular dichroism

of solution and solids) and by magnetic susceptibility measurements. Serylglycine and

threonylglycine are formed by reaction of VO(salGlyGly) with formaldehyde and

acetaldehyde, respectively.

Abdou Saad El-Tabl[19] et al have been proved that phenylaminodi-

benzoylhydrazone have been synthesized and characterized by elementals analyses, IR

UV–vis spectra, magnetic moments, conductances, thermal analyses (DTA and TGA)

and electron spin resonance (ESR) measurements. The IR spectral data show that, the

ligandbehaves as a neutral bidentate type (15 and 16), monobasic bidentate type (6), or

monobasic tridentate type (5, 7, 8, 10, 11, 13, 14, 17–21) or dibasictridentate type 2–4,

9 and 12 towards the metal ion. Molar conductances in DMF solution indicate that, the

complexes are non-electrolytes. TheESR spectra of solid complexes (9 and 10) show

axial and non-axial types indicating a d(x2−y2) ground state with significant covalent

bond character.However, complexes (11 and 12), showisotropic type, indicating

manganese(II) octahedral geometry. Antibacterial and antifungal tests of the ligandand

its metal complexes are also carried out and it has been observed that the complexes are

more potent bactericides and fungicides than the ligand.

58

Salih Ilhan[20] et al have been proved that a new macrocyclic ligand, 1,3,5-

triaza-2,4:7,8:13,14-tribenzo-9,12-dioksa-cyclopentadeca-1,5-diene was synthesized by

reaction of 2,6-diaminopyridine and 1,2-bis(2-carboxyaldehyde phenoxy)ethane. Then,

its Cu(II), Ni(II), Pb(II), Co(III) and La(III) complexes weresynthesized by the template

effect by the reaction of 2,6-diaminopyridine and 1,2-bis(2-carboxyaldehyde phenoxy)

ethane and Cu(NO3)2.3H2O, Ni(NO3)2.6H2O, Pb(NO3)2, Co(NO3)2.6H2O,

La(NO3)3.6H2O, respectively. The ligand and its metal complexeshave been

characterized by elemental analysis, IR, 1H and 13C NMR, UV–Vis spectra, magnetic

susceptibility, thermal gravimetric analysis,conductivity measurements, mass spectra,

and cyclic voltammetry. All complexes are diamagnetic and Cu(II) complex is

binuclear.The Co(II) was oxidized to Co(III). The comparative electrochemical studies

show that the nickel complex exhibited a quasi-reversibleone-electron reduction

process, while copper and cobalt complexes gave irreversible reduction processes in

DMSO solution.

59

S. Sreedaran[21] et al have been proved that A series of novel unsymmetrical

dicompartmental binuclear nickel(II) complexes have been prepared by simple Schiff

base condensationof the compound 1,8-[bis(3-formyl-2-hydroxy-5-methyl)benzyl]-

l,4,8,11tetraazacyclotetradecane L with appropriate aliphatic or aromatic diamine,

nickel(II) perchlorate and triethylamine. All the complexes were characterized by

elemental and spectral analysis.Positive ion FAB mass spectra show the presence of

dinickel core in the complexes. The electronic spectra of the complexes show thed–d

transition in the range of 550–1040 nm. Electrochemical studies of the complexes show

two irreversible one electron reduction processaround E1pc ¼ -0:79 to -1:27 V and E2

pc ¼ -1:28 to -1:43 V. The reduction potential of the binuclear nickel(II) complexes

shiftstowards anodically upon increasing chain length of the macrocyclic ring. All the

nickel(II) complexes show two irreversible oxidation waves around 0.72 to +1.52 V.

The observed rate constant values for catalysis of the hydrolysis of 4-nitrophenyl

phosphate are inthe range of 9.20 -10-3–16.81 -10-3 min-1. The rate constant values for

the complexes containing aliphatic diimines are found tobe higher than that of the

complexes containing aromatic diimines. Spectral, electrochemical and catalytic studies

of the complexes werecompared on the basis of increasing chain length of the imine

compartment. All the complexes were screened for antifungal and anti bacterial

activity.

60

Hassan Keypour[22] et al have been proved that a series of Mn(II) macrocyclic

Schiff-base complexes [MnLn]2+ have been prepared via the Mn(II) templated [1+1]

cyclo condensation of 2,9-dicarboxaldehyde-1,10-phenanthroline with appropriate

linear and branched amines. In this way ligands the penta aza macrocycleL1 which is

15-membered and L2 which is 16-membered possessing no pendant arm, L6 is 15-

membered with one 2-aminoethyl pendant arm and L8 which is 18-membered hexa aza

macrocycle with two 2-aminoethyl pendant arms are formed. All the complexes have

beencharacterized using spectroscopic methods. The crystal structures of

[MnL8](ClO4)2 in EtOH were determined and indicate that in the solid state the

complex adopts a slightly distorted hexagonal bipyramid geometry with the Mn(II) ion

located within a hexa aza macrocycle with the two pendant amines coordinating in the

axial positions.

Hamdi Temel[23] et al have been proved that The newfive macrocyclic ligands

were synthesized by reaction of 2,6-diaminopyridine and various dialdehydes. Then,

their copper(II) perchloratecomplexes were synthesized by template effect by reaction

of 2,6-diaminopyridine, Cu(ClO4)2.6H2Oand aldehydes. The ligands and their

complexeshave been characterized by elemental analysis, IR, 1H and 13C NMR, UV–

vis spectra, magnetic susceptibility, conductivity measurements, massspectra. All

complexes are diamagnetic and binuclear. The diamagnetic behaviour of the binuclear

complexes may be explained by a very stronganti-ferromagnetic interaction in the Cu–

Cu pair.

61

Ali Akbar Khandar[24] et al have been proved that the reactions of NiX2 .6H2O

(X=Cl-, ClO4 NO3-) with a new macrocyclic Schiff base ligand (L = 8,9,18,19-

tetrahydro-7H,17Hdibenzo [f,o] [1,5,9,13] dioxadiaza cyclohexadecine-8,18-diol),

potentially hexadentate containing two alcoholic pendant arms, have beeninvestigated

by template condensation of 2-[3-(2formylphenoxy)-2-hydroxypropoxy]benzaldehyde

and 1,3-diamino-2-propanol. The isolation of a selection of 1:1 (metal:ligand)

complexes of nickel(II) has been carried out and IR and UV–Vis spectroscopy,

conductancemeasurements and X-ray determination have been employed to probe the

nature of the respective complexes in both solid and solutionstates. The UV–Vis spectra

and X-ray determination indicate that the complexes are of the type [NiLX]X, with a

distorted octahedralligand field. However, the perchlorate complex of Ni(II) is of the

[NiL(solv)]2+ form in solution. In all complexes, the potentially hexadentateligand

behaves as a pentadentate ligand.

62

Alexandre Martinez[25] et al have been proved that A series of chiral

macrocyclic Mn(III)Salen complexes has been prepared with two salicylidene moieties

linked in their 3 and 30positions by aliphatic polyether bridges of variable lengths or by

a more rigid aromatic junctionarm. X-ray structures of ligandprecursors and of complex

8 have been performed. All complexes have been used in the asymmetric epoxidation of

1,2-dihydronaphthalenewith NaOCl as oxygen atom donor and exhibited modest

enantiomeric excesses. Complex 10 was selected to be tested with two cis-disubstituted

olefins and several oxidants, namely NaOCl, PhIO and n-Bu4NHSO5. 2,20-

Dimethylchromene oxide wasobtained from 2,20-dimethylchromene with ee values of

56% and 74% when using 10 and NaOCl and PhIO, respectively.

Hisashi Shimakoshi[26] et al have been proved that New macrocyclic

dinucleating ligands have been easily synthesized by Schiff-base condensation reaction

with theappropriate aldehyde and amine using the boric ion template method. The

ligands have two N2O2 metal-binding sites which aredoubly linked to each other with

methylene spacers. The ligands chelate with Co2+

, Cu2+

and Ni2+

to form dimetallic

compoundsin high yields.

63

Gehad G. Mohamed[27] et al have been proved that Metal complexes of Schiff

base derived from condensation of o-vanilin (3-methoxysalicylaldehyde) and

sulfametrole [N1-(4-methoxy-1,2,5-thiadiazole-3-yl)sulfanilamide] (H2L) are reported

and characterized based on elemental analyses, IR, 1H NMR, solid reflectance,

magneticmoment, molar conductance, mass spectra, UV–vis and thermal analysis

(TGA). From the elemental analyses data, the complexes were proposedto have the

general formulae [M2X3(HL)(H2O)5]·yH2O (where M= Mn(II), Co(II), Ni(II), Cu(II),

Zn(II) and Cd(II), X= Cl, y = 0–3); [Fe2Cl5(HL)(H2O)3]·2H2O; [(FeSO4)2(H2L)(H2O)4]

and [(UO2)2(NO3)3(HL)(H2O)]·2H2O. The molar conductance data reveal that all the

metalchelates were non-electrolytes. The IR spectra show that, H2L is coordinated to

the metal ions in a tetradentate manner with ON and NO donor sitesof the azomethine-

N, phenolic-OH, enolic sulphonamide-OH and thiadiazole-N. From the magnetic and

solid reflectance spectra, it is found thatthe geometrical structures of these complexes

are octahedral. The thermal behaviour of these chelates shows that the hydrated

complexes losseswater molecules of hydration in the first step followed immediately by

decomposition of the anions and ligand molecules in the subsequent steps.The

activation thermodynamic parameters, such as, E*,-H*,-S* and -G* are calculated from

the DrTG curves using Coats–Redfern method. Thesynthesized ligand, in comparison to

their metal complexes also were screened for their antibacterial activity against

bacterial species, Escherichiacoli, Salmonella typhi, Bacillus subtillus, Staphylococcus

64

aureus and Fungi (Aspergillus terreus and Aspergillus flavus). The activity data

showthat the metal complexes to be more potent/antimicrobial than the parent Shciff

base ligand against one or more microbial species.

M. Sivasankaran Nair[28] et al have been proved that Co(II), Ni(II), Cu(II) and

Zn(II) complexes of the Schiff base derived from vanillin and dl-_-aminobutyric acid

were synthesized and characterizedby elemental analysis, IR, electronic spectra,

conductance measurements, magnetic measurements, powder XRD and biological

activity. Theanalytical data show the composition of the metal complex to be

[ML(H2O)], where L is the Schiff base ligand. The conductance data indicatethat all the

complexes are non-electrolytes. IR results demonstrate the tridentate binding of the

Schiff base ligand involving azomethine nitrogen,phenolic oxygen and carboxylato

oxygen atoms. The IR data also indicate the coordination of a water molecule with the

metal ion in the complex.The electronic spectral measurements show that Co(II) and

Ni(II) complexes have tetrahedral geometry, while Cu(II) complex has square

planargeometry. The powder XRD studies indicate that Co(II) and Cu(II) complexes are

amorphous, whereas Ni(II) and Zn(II) complexes are crystallinein nature. Magnetic

65

measurements show that Co(II), Ni(II) and Cu(II) complexes have paramagnetic

behaviour. Antibacterial results indicated thatthe metal complexes are more active than

the ligand.

S.M. Ben-saber[29] have been proved that Complexes of Iron, Cobalt, Nickel

and Zinc ions with the Schiff base derived from p-dimethylaminobenzaldehyde and o-

aminobenzoic acidwere synthesized and investigated by several techniques using

elemental analyse (C,H,N), molar conductance measurements, infrared andelectronic

spectra. The elemental analysis data suggest the stoichiometry to be 1:1 [M:L] ratio

formation. The molar conductance measurementsreveal the presence of non-electrolytic

nature complexes. Infrared spectral data agreed with the coordination to the central

metal ions throughboth the nitrogen atom of the azomethine and oxygen atom of the

carboxyl group of the 2-aminobenzoic acid moiety. The electronic spectral datasuggest

the existence of octahedral geometry for Fe(III) complex, square planar geometry for

Co(II) and Ni(II) complexes and tetrahedralgeometry for Zn(II) complex.

66

Moamen S. Refat[30] et al have been proved that Complexes of ruthenium(III)

with N,N-disalicylidene-l,2-phenylenediamine (H2dsp), N,N-disalicylidene-3,4-

diaminotoluene (H2dst), 4-nitro-N,N-disalicylidene-1,2-phenylenediamine (H2ndsp) and

N,N-disalicylidene ethylene diamine (H2salen) have been prepared and characterized by

elemental analysis, molar conductivity, spectral methods (mid-infrared, 1H NMR and

UV–vis spectra) and simultaneous thermal analysis(TG and DTG) techniques. The

molar conductance measurements proved that all these complexes are non-electrolytes.

The electronic spectra measurements were used to infer the structures. The IR spectra of

the ligands and their complexes are used to identify the type of bonding. The kinetic

thermodynamic parameters such as: E*, -H*, -S* and -G* are estimated from the DTG

curves. The four ligands and their complexeshave been studied for their possible

biological antifungal activity.

Eren Keskio˘glu [31] et al have been proved that A series of metal complexes

were synthesized from equimolar amounts of Schiff bases: 1,4-bis[3-(2-hydroxy-1-

naphthaldimine)propyl] piperazine (bappnaf) and 1,8-bis[3-(2-hydroxy-1-

naphthaldimine)-p-menthane (damnaf) with metal chlorides. All of synthesized

67

compoundswere characterized by elemental analyses, spectral (UV–vis, IR, 1H-13C

NMR, LC–MS) and thermal (TGA-DTA) methods, magnetic and

conductancemeasurements. Schiff base complexes supposed in tetragonal geometry

have the general formula [M(bappnaf or damnaf)]Cl·nH2O, whereM= Cr(III), Co(III)

and n = 2, 3. But also Fe(III) complexes have octahedral geometry by the coordination

of two water molecules and the formulais [Fe(bappnaf or damnaf)(H2O)2]Cl. The

changes in the selected vibration bands in FT-IR indicate that Schiff bases behave as

(ONNO) tetradentateligands and coordinate to metal ions from two phenolic oxygen

atoms and two azomethine nitrogen atoms. Conductance measurements suggest

1:1electrolytic nature of the metal complexes. The synthesized compounds except

bappnaf ligand have the antimicrobial activity against the bacteria:Escherichia coli

(ATCC 11230), Yersinia enterocolitica (ATCC 1501), Bacillus magaterium (RSKK

5117), Bacillus subtilis (RSKK 244), Bacilluscereus (RSKK 863) and the fungi:

Candida albicans (ATCC 10239). These results have been considerably interest in

piperazine derivatives dueto their significant applications in antimicrobial studies.

U.M. Rabie[32] et al have been proved that Three dissymmetrical Schiff bases

have been prepared by the condensation of 2-hydroxyacetophenone, ethylenediamine

68

and severalaldehydes. The electronic transitions within these Schiff bases molecules

and the effect of solvents of different polarities on these transitionshave been

investigated by UV/vis spectroscopy. Schiff bases complexes, binary 1:1 (metal:ligand)

and ternary 1:1:1 (metal:ligand:Lewis base, where Lewis base = imidazole or pyridine),

with transition metals, Co(II), Ni(II), Cu(II), and Zn(II) have been synthesized and

characterized by elemental analysis, molar conductivity and electronic absorption and

IR spectra. Further, the stoichiometricratios of the complexes in solutions and the

formation constants of the interaction of Schiff base ligands with metal ions havebeen

determined.

Shouvik Chattopadhyay[33] et al have been proved that The 1:1 condensation

of 2,4-pentanedione and 1,2-diaminopropane gives a mixture two positional isomers of

tridentate mono-condensed product 7-amino-4-methyl-5-aza-3-octene-2-one (HAMAO)

and 7-amino-4,6-dimethyl-5-aza-3-heptene-2-one (HADAH) thatreacted readily with

Ni(II) thiocyanate to yield exclusively a single product, [Ni(AMAO)NCS] (1) in which

the methyl substituent ofdiamine is „remote‟ from the imino nitrogen. The mixture of

terdentate ligands has been used for further condensation with pyridine-2-

carboxaldehyde or 2-acetylpyridine to obtain the unsymmetrical tetradentate Schiff base

ligands. The tetradentate ligands formedby the condensation of it and pyridine-2-

carboxaldehyde readily yielded complexes with Cu(II) and Ni(II) (2 and 3,

69

respectively). Crystal structure analysis shows that in 2 the condensation site of the

diamine with 2,4-pentanedione is the same as in 1 but that in 3 is different(the methyl

group of the diamine is located in the vicinity of 2,4-pentanedione), i.e., the tetradentate

ligand is in two different isomericforms in complexes 2 and 3. Another tetradentate

ligand, obtained by the condensation of the tridentate ligands and 2-

acetylpyridineyielded a Ni(II) complex (4) where the methyl group is in the vicinity of

2,4-pentanedione as in 3. The isomerization in the Ni(II) complexeshas been studied by

NMR spectroscopy.

`

Mau Sinha Ray[34] et al have been proved that the mononuclear copper(II)

complexes, [CuL1](ClO4) (1), and [CuL2](ClO4) (2) with unsymmetrical quadridentate

Schiff baseligands derived from the 1:1:1 condensation of 2,4-pentanedione, pyridine-

2-carboxaldehyde and 1,2-ethanediamine (HL1) or 1,3-propanediamine (HL2) have

been prepared and characterised. Complex 2 undergoes Cu(II)/H_ catalysed

rearrangement to[CuL3](ClO4)2 (3) where L3 is a symmetrical tetradentate Schiff base

involving 1,3-propanediamine and pyridine-2carboxaldehyde.Structures of all the three

compounds have been verified by single crystal X-ray analysis. The geometry around

Cu(II) is square planarin 1 and 2 whereas that in 3 is distorted octahedral with two

axially coordinated perchlorate ions.

70

Masaaki Kojima[35] et al have been proved that This article describes the

crystal structures of several vanadium complexes containing tetradentate Schiff base

ligands, and theirproperties and reactivities in the solid state. [VO{sal-(R,R)-stien}]

(H2sal-(R,R)-stien_/N,N-disalicylidene-(R,R)-1,2-diphenyl-1,2-ethanediamine)

crystallized in two different forms, green (from dichloromethane and chloroform) and

orange (fromacetonitrile). X-ray structure analysis revealed that the green form contains

mononuclear square-pyramidal molecules of thecomplex, whereas the orange form has

a polynuclear linear chain structure. The green crystals turn orange when heated at 120

8Cfor a few minutes (thermochromism). Both forms are vapochromic, the orange

crystals turning green on exposure to chloroform vapor, and the green crystals turning

orange on exposure to acetonitrile vapor. The color of the orange complex changes to

green ongrinding (mechanochromism). [VO{3-EtOsal-(R,R)-2,4-ptn}] (H23-EtOsal-

(R,R)-2,4-ptn_/N,N-di-3-ethoxysalicylidene-(R,R)-2,4-pentanediamine)also crystallizes

in two different forms, green and orange. The polymeric orange crystals turn into

themonomeric green form upon heating at 170 8C for 10 min. The mechanism of this

conversion was studied using X-ray structure analysis and thermal analysis. Thermal

isomerization in the solid state between a pair of diastereomers, I and II, of

theoxovanadium(IV) complex with an unsymmetrical tetradentate Schiff base ligand,

[VO{3-EtOsal,sal-(R,R)-chxn}] (H23-EtOsal,sal-(R,R)-chxn-/N-salicylidene-N?-3-

ethoxysalicylidene-(R,R)-1,2-cyclohexanediamine), was studied at 195 8C. The two

diastereomerswere separated using column chromatography, and each crystallized in

two different colors: green (monomeric) and orange(polymeric). The orange complexes,

71

I (orange) and II (orange), turned green on heating at 195 8C for a few minutes. All four

complexes, I (green), II (green), I (orange), and II (orange), undergo isomerization at

195 8C to yield an equilibrium mixture, I:II:/1:1. On heating [VO(3-EtOsal-meso-

stien)] (H23-EtOsal-meso-stien/N,N-di-3-ethoxysalicylidene-(R,S)(S,R)-1,2-diphenyl-

1,2-ethanediamine) at 190 8C for 8 h, dehydrogenation took place at the two benzylic

carbon atom sites to form a C C double bond.

72

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Mukhopadhyay, Gabriele Bocelli , Andrea Cantoni , and Ashutosh Ghosh,

Inorganica Chimica Acta, 359 (2006) 1367–1375.

2. Mau Sinha Ray , Rahul Bhattacharya , Siddhartha Chaudhuri , Lara Righi, Gabriele

Bocelli, Gurucharan Mukhopadhyay , and Ashutosh Ghosh, Polyhedron, 22 (2003)

617-/624.

3. Masaaki Kojima, Hideki Taguchi , Masanobu Tsuchimoto and Kiyohiko Nakajima,

Coordination Chemistry Reviews 237 (2003) 183-196.

4. Xiu R. Bu, Carl R. Jackson, Donald Van Derveer, Xiao Z. You, Quin J. Meng” and

Rei X. Wang” Pol.vhedron Vol. 16, No. 17, (1997) pp 2991-3001.

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Badami European Journal of Medicinal Chemistry xx (2008) 1-11.

6. Esref Tas, Ahmet Kilic, Nazli Konak , and Ismail Yilmaz , Polyhedron 27 (2008)

1024–1032.

7. Michelle K. Taylor , Katherine D. Trotter , John Reglinski ,,Leonard E.A. Berlouis,

Alan R. Kennedy , Corinne M. Spickett , and Rebecca J. Sowden, Inorganica

Chimica Acta xxx (2008) xxx–xxx.

8. Rongqing Li , Thomas A. Mulder , Udo Beckmann , Peter D.W. Boyd , and Sally

Brooker Inorganica Chimica Acta 357 (2004) 3360–3368.

9. Makoto Itagaki, Koji Hagiya, Masashi Kamitamari, Katsuhisa Masumoto, Katsuhiro

Suenobu and Yohsuke Yamamoto, Tetrahedron 60 (2004) 7835–7843.

10. Ahmed A. Soliman , and Gehad G. Mohamed , Thermochimica Acta 421 (2004)

151–159.

11. Martin Breza, and Stanislav Biskupic, Journal of Molecular Structure:

THEOCHEM 760 (2006) 141–145.

73

12. Jian Lv , Tingting Liu , Sulan Cai , Xin Wang , Lei Liu , and Yongmei Wang ,

Journal of Inorganic Biochemistry, 100 (2006) 1888–1896.

13. Mannar R. Maurya, Anil K. Chandrakar , and Shri Chand Journal of Molecular

Catalysis A: Chemical 270 (2007) 225–235.

14. M. Tuncel, A.Ozbulbul, and S Serın, Reactive & Functional Polymers 68 (2008)

292–306.

15. Davar M. Boghaei, and Mehrnaz Gharagozlou, Spectrochimica Acta Part A 67

(2007) 944–949.

16. X.-H. Lu, Q.-H. Xia , H.-J. Zhan,H.-X. Yuan , C.-P. Ye , K.-X. Su, and G. Xua

Journal of Molecular Catalysis A: Chemical 250 (2006) 62–69.

17. Nuanphun Chantarasiri, Vithaya Ruangpornvisuti, Nongnuj Muangsin, Hussadee

Detsen,Thussanee Mananunsap, Chureephon Batiya, and Narongsak Chaichit

Journal of Molecular Structure 701 (2004) 93–103.

18. J. Costa Pessoa, I. Cavaco, I. Correia, D. Costa, R.T. Henriques , and R.D. Gillard

Inorganica Chimica Acta 305 (2000) 7–13.

19. Abdou Saad El-Tabl , Fathey A. El-Saied ,Winfried Plass , and Ahmed Noman Al-

Hakimi Spectrochimica Acta Part A xxx (2008) xxx–xxx

20. Salih Ilhan, Hamdi Temel, Ismail Yilmaz, and Memet S-ekerci, Polyhedron 26

(2007) 2795–2802.

21. S. Sreedaran, K. Shanmuga Bharathi, A. Kalilur Rahiman, K. Rajesh, G. Nirmala,

L. Jagadish, V. Kaviyarasan and V. Narayanan, Polyhedron 27 (2008) 1867–1874.

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Majid Rezaeivala, Inorganica Chimica Acta 361 (2008) 1415–1420.

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24. Ali Akbar Khandar a, Seyed Abolfazl Hosseini-Yazdi, Masomeh Khatamian,

Patrick McArdle and Seyed Amir Zarei Polyhedron 26 (2007) 33–38.

74

25. Alexandre Martinez, Catherine Hemmert, Heinz Gornitzka ,and Bernard Meunier

Journal of Organometallic Chemistry 690 (2005) 2163–2171.

26. Hisashi Shimakoshi, Hiroki Takemoto, Isao Aritome and Yoshio Hisaeda,

Tetrahedron Letters, 43 (2002) 4809–4812.

27. Gehad G. Mohameda, and Carmen M. Sharaby Spectrochimica Acta Part A 66

(2007) 949–958.

28. M. Sivasankaran Nair, and R. Selwin Joseyphus, Spectrochimica Acta Part A xxx

(2007) xxx–xxx.

29. S.M. Ben-saber, A.A. Maihub, S.S. Hudere, and M.M. El-ajaily, Microchemical

Journal 81 (2005) 191 – 194.

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Spectrochimica Acta Part A xxx (2007) xxx–xxx.

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Birg¨ul Erk Spectrochimica Acta Part A xxx (2007) xxx–xxx.

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Mukhopadhyay, Gabriele Bocelli , Andrea Cantoni , and Ashutosh Ghosh

Inorganica Chimica Acta 359 (2006) 1367–1375.

34. Mau Sinha Ray, Rahul Bhattacharya , Siddhartha Chaudhuri , Lara Righi , Gabriele

Bocelli , Gurucharan Mukhopadhyay, and Ashutosh Ghosh, Polyhedron 22 (2003)

617-624.

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Coordination Chemistry Reviews 237 (2003) 183-/196.

75

1.11 SCOPE AND OBJECTIVES OF THIS WORK

Schiff base ligands are widely used as analytical reactants. They are considered

privileged ligands because they are easily prepared by the Condensation between

aldehyde and amine. Since they allow simple and inexpensive determination of several

organic and inorganic substances. Macrocyclic Schiff base ligands are able to

coordinate many different metals and to stabilize them in various oxidation state.

Synthesis of new Schiff base and their metal complexes played an important

role in their development of coordination chemistry as they readily form stable

complexes with most of the transition metals. In the past two decades properties of

Schiff base metal complexes stimulated much interest for their noteworthy

contributions to single molecule based magnetism, material, science catalysis of many

reactions and their industrial applications. In addition some of the complexes containing

N and O donor atoms effective as stero Specific catalyst for oxidation, reduction,

hydrolysis, biological activity and other transformations of organic and inorganic

chemistry.

Further more tetradentate Schiff base Complexes are increasingly important for

designing metal complexes related to synthetic and natural oxygen carrier. This

attention is still growing so that a considerable research effort is today devoted to the

synthesis of new schiff base complexes with transition metal ions to for their develop

applications in the area of material and pharmaceutical chemistry .

Copper is an important trace element in plants and animals and is involved in

mixed ligand complex formation in a number of biological process. Cu complexes

containing schiff base ligand are of great interest, since they exhibit numerous

biological activity such as antitumor, antimicrobial activity. Manganese plays an

76

important role in the biochemistry of many organism various oxidation of Mn is

receiving much attention in many enzymatic reaction

Nickel is an essential trace element for many species. Nickel complexes in the

presence of oxidants have been extensively used for DNA cleavage reactions. Zinc

plays an important role in biological studies. A potential implication of zinc as an thero

protective agent. Recently a second motif for DNA binding protein “zinc finger”

emerged from sequence analysis of TF111A4, a factor involved in the control of RNA.

Zinc decreases C–reactive protein, lipid peroxidation and inflammatory cyclokines in

elderly subject, a potential implications of zinc as an thero protective agent, zinc and

immune function the biological basis of altered resistance to infection zinc chelates

inhibit cotaxin Ranles and MCP-1 protection in stimulated human airway; epitheliams

and fibroblasts.

The main aim of the present work in this thesis is to study the coordination

behavior of Schiff base that incorporate binding sites towards the metal complexes with

Cu, Zn, Ni and Mn.

The new Schiff base synthesized from the reactions of 2-Hydroxy1-

Naphthaldehyde with 1,8-diaminonaphthalene, 5-amino1-naphthol, 8-amino2-naphthol,

4-bromo 1-Naphthylamine and their metal complexes have been studied by various

physicochemical methods to evaluate their relative thermal stability and examine their

antimicrobial activity.

Objectives of the Study

1) Synthesis of mononuclear Cu(II), Zn(II), Ni(II) and Mn(II) Schiff base complexes

derived from 2-Hydroxy1-Naphthaldehyde with 1,8-diaminonaphthalene/

5-amino1-naphthol/ 8-amino2-naphthol/ 4-bromo-1-naphthylamine.

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2) To characterize the Schiff bases and their metal complexes using various analytical

and spectral techniques such as IR Elemental analysis, UV-visible spectroscopy,

NMR spectra, CV, molar conductance, thermal, ICP, magnetic, EPR studies.

3) DNA Cleavage studies

The cleavage study was monitored by gel electrophoresis method.

4) Antimicrobial activity

The in vitro biological screening effects of the synthesised compounds were tested

against the some Gram positive and Gram negative bacteria by the well diffusion

method.