Post on 17-Jun-2020
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
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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
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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
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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
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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
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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
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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.
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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
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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
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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
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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,
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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
Refrences
1. Shouvik Chattopadhyay, Mau Sinha Ray, Siddhartha Chaudhuri, Gurucharan
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.
5. Gangadhar B. Bagihalli , Prakash Gouda Avaji, Sangamesh A. Patil, and Prema S.
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.
22. Hassan Keypour , Hamid Goudarziafshar , Alan K. Brisdon , Robin G. Pritchard ,
Majid Rezaeivala, Inorganica Chimica Acta 361 (2008) 1415–1420.
23. Hamdi Temel and Salih Ilhan , Spectrochimica Acta Part A 69 (2008) 896–903.
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.
31. Eren Keskio˘glu, Ayla Balaban G¨und¨uzalp ∗ , Servet C¸ ete, Fatma Hamurcu, and
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)
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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.