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Coordination Chemistry is one of the most advanced and active research fields
in inorganic Chemistry. This branch of Chemistry received much attention and
offered fruitful results and hence this has become extremely attractive field of
research. The first exploration of coordinated metal complexes dates back to the
nineteenth century, during the days of Alfred Werner
who is the father of
coordination chemistry. Thereafter, the inorganic chemistry witnessed a great
outflow of coordination compounds, with unique structural characteristics and diverse
applications. The rapid development in the field of coordination chemistry has been
dominating among the various research fields in inorganic chemistry.
Coordination compounds contain a central metal ion surrounded by a set of
molecules or ions known as ligands and capable of existing independently. A ligand
is a molecule or ion that can donate an electron pair to the central metal ion. If the
ligand binds to the central metal ion through more than one donor atoms, the resulting
compounds are said to be metal chelates. Such ligands are called polydentate or
chelating ligands. A metal complex containing the metal ion and only one type of
ligand molecule is referred as a binary system. On the other hand if the different
ligands are bound to the same metal ion, the complexes are called mixed ligand
complexes, which may be ternary or quaternary system depending on their
stoichiometry.
Metals play a very important role in biological life kingdom. It will not be an
exaggeration to say that metal complexes have vital role in modern scientific age to
achieve advancement in any chosen field of science such as agriculture, plant
nutrition and biological activity of living beings, industries and in medicine. The
correct proportion of metals is a must for normal growth and normal health, both, the
excess and deficiency of many metals, not synthesized in the body like other
nutrients, leads to metal poisoning, metabolic disorders and skeletal abnormalities.
Many of us heard the common and somewhat sarcastic statement, from our elders that
they have silver in the hair, gold in the teeth and lead in the bones. Strange as it may
seem at first sight, all three metals can have an effect on living systems.
Metal ions are generally positively charged and act as electrophiles, seeking
the possibility of sharing electron pairs with other atoms so that a bond or charge-
2
charge interaction can be formed. They behave rather like hydrogen ions (the poor
man's metal). Metal ions, however, often have positive charges greater than one, and
have a larger ionic volume so that they can accommodate many ligands around them
at the same time.
The nature of the coordination compounds depends on the metal ion and
donor atom, the structure of the ligand and the metal-ligand interaction1. One of the
most important problems in coordination chemistry has been the nature and strength
of metal-ligand bond. Normally the metal ion does not form bonds of equal strength
with two different donor atoms. Similarly, a particular donor atom does not form
bonds of the same strength with different metal ions2.
Tremendous growth of coordination chemistry is ranging in areas from purely
academic synthesis to large-scale industrial production due to the availability of
several modern physico-chemical techniques such as IR, 1HNMR, Mass, UV-Vis,
ESR, X-ray etc., which are of great help for elucidating the structures of metal
complexes3-5
. Thermal techniques such as TG, DTA, DTG and DSC are also helpful
for the study of these complexes.
The wide applications of coordination compounds lead scientists to conduct
research activities on these compounds. The extent of growth of coordination
chemistry gives an ample evidence for the importance of complex compounds in
biological, chemical and industrial fields.
Alfred Werner’s concept about coordination number and geometrical
arrangement were broadly accepted. However, there still remained the intriguing
questions about the nature of the bond which held the ligand to the metal ions. The
studies of Werner and his contemporaries followed by the concepts of Lewis6,
Langmuir7 and Sidgwick
8 who put forward the Effective Atomic Number (EAN) on
electron pair bond led to the idea that the ligands are the groups which donate
electron pairs to metal ions, thus forming a so called coordinated bond. Pauling9
extended the approach of bonding in complexes and gave a concept called valence
bond theory (VBT) of metal ligand bonding.
The VBT has great popularity during 1930 and 1940. After this in 1950 it was
supplemented by the crystal field theory (CFT). Previously the crystal field theory
3
was explained by Bethe10
in 1929. Physicists Vanvlenck11
and his research students
developed the crystal field theory and they rediscovered in 1950 with several
theoretical methods as ligand field theory (LFT). The LFT as it is used today has
evolved out of a purely electrostatic CFT. While the crystal field theory focus
attention completely on the metal ion d-orbitals, the molecular orbital theory (MOT)
takes into account the ligand orbitals. Another approach is the so called angular
overlap model (AOM).
Transition metals are characterized by their ability to form a wide range of
coordination compounds in which the octahedral, tetrahedral, square-planar and
square-pyramidal geometries are predominant. Several complexes of Co(II), Ni(II),
Cu(II), Zn(II), Cd(II) and Hg(II) are well known.
A brief review of some Metals:
Cobalt: It exhibits various oxidation states ranging from +1 to +5. The most
common oxidation states are +2 and +3. The cobalt compounds exhibits variable
coordination number, geometry, stability etc. Literature survey reveals that Co(II) is
basically associated with different type of stereochemical configurations such as
tetrahedral, octahedral and square planar. Nicholls has reviewed biological
importance of cobalt compounds12
.
Nickel: It exhibits various oxidation states ranging from +1 to +4. The most common
oxidation state is +2. Nickel(II) complexes exhibit mainly square-planar and
octahedral geometry, which depends on the nature of the solvent, concentration and
temperature. Numerous interesting studies on Ni(II) complexes have been reported in
literature13-16
. Five coordinated Ni(II) complexes with a trigonal bipyramidal17
,
distorted trigonal prismatic structure18
and square pyramidal geometry19
have also
been reported. Nickel is a necessary microelement for organisms, an activator for
many enzymes, such as arginase, acid phosphatase, decarboxylase, deoxyribonuclease
and peptidase, and promotes cytopoiesis.
Copper: It is having single electron outside the completed 3d shell, exhibits
oxidation states of +1, +2 and +3. The most common oxidation state is +2. The 3d9
configuration makes Cu(II) susceptible to Jahn-Teller distortion when placed in
environment of cubic symmetry i.e. regular octahedral or tetrahedral and this has
4
performed effect on its stereochemistry. All the hexacoordinated Cu(II) complex
structures of which have been established by X-ray technique20
are found to be
affected from tetragonal distortion due to Jahn-Teller distortion.
Copper compounds have applications in organic chemistry for oxidations,
coupling reactions, halogenations etc21
. Oxidation of phenol by copper amine
complexes22
provides model for the phenol-oxidizing enzymes. Copper is found to
play a significant role in biological processes, viz. Cu(DMG)2 shows high activity
against cancer23
and enhances the life span to the extent of 20 to 30%.
Zinc: It shows oxidation states of +1 and +2. Zn(I) do not occur in the normal
condition. Only spectroscopic species have been detected. Like Hg+2
, Zn+2
ion also
exists24
. Zn(II) complexes are essentially diamagnetic due to filled d10
configuration.
The complexes of Zn(II) can have coordination numbers 4, 5 and 6. It is invariably
seen that Zinc forms only tetrahedral complexes with coordination number 4. Five
coordinated complexes either posses square pyramidal or trigonal bipyramidal
structures with coordination number 5. Zn(II) complexes are octahedral when
coordination number is 6. Many polymeric structures involving bridging groups are
reported. Most of the zinc is utilized in the form of alloy to prepare containers, as its
toxicity is too low.
Zinc is the second most prevalent trace element, after iron, and is involved in
structure and function of over 300 enzymes. Zinc, a constituent of enzyme carbonic
anhydrous, which is involved in conversion of CO2 to carbonic acid in plants. It is
also found in horse-liver as alcohol dehydrogenase. Deficiency of Zinc in animals
results in stunted growth and male sexual immaturity. Zinc salts, primarily zinc
citrate, are widely used as antimicrobials. Zinc exhibits activity against oral
Streptococci, particularly Streptococcus mutans25
.
Zinc supplementation shows beneficial effects against infectious diseases,
especially diarrhea, and it has been shown that zinc supplementation can improve
mucosal innate immunity through induction of antimicrobial peptide secretion from
intestinal epithelial cells26
.
Cadmium: It shows +1 and +2 oxidation states. Cd(I) has been isolated in solid
state. Cd(II) is well known to form a large variety of compounds and complexes.
5
Four coordinated compounds are tetrahedral. Five coordinated complexes are not
found as frequently as in zinc. Six coordinated complexes have octahedral structures
and are commonly found.
Cadmium has not been found as essential trace element in biological system.
On the contrary, its presence in living organisms is highly toxic. It affects the kidney
and liver. Cadmium is used in control rods and shielding for nuclear reactors because
of its high neutron absorbing capacity.
A brief review of Schiff base ligands and their metal complexes:
Schiff base ligands are the condensation products of primary amines with
carbonyl compounds and they were first reported by Hugo Schiff in 186427
. These
compounds are named as azomethines, anils, or imines etc. Schiff bases have been
recently focused by Coordination Chemists as versatile spacers because of their
preparative accessibilities and structural varieties28, 29
.
Schiff base ligands have played an important role in the development of
coordination chemistry since the late nineteenth century. The finding that metal
complexes of these ligands are ubiquitous is a reflection of their facile synthesis, wide
application and accessibility of diverse structural modifications30
. Schiff base metal
complexes have been known since the mid nineteenth century31
and even before the
general preparation of the Schiff base ligands themselves. Schiff base metal
complexes have occupied a central place in the development of coordination
chemistry after the work of Jorgensen and Werner32
. However, there was no
comprehensive, systematic study until the preparative work of Pfeiffer and
associates33
. Pfeiffer and his co-workers34
reported a series of complexes derived
from Schiff bases of salicylaldehyde and its substituted analogues. In the past two
decades, the properties of Schiff base metal complexes stimulated much interest for
their contributions to single molecule-based magnetism, material science, catalysis of
many reactions like carbonylation, hydroformylation, oxidation, reduction and
epoxidation, their industrial applications, complexing ability towards some toxic
metals. The high affinity for the chelation of the Schiff bases towards the transition
metal ions is utilized in preparing their solid complexes35
. Schiff base complexes
containing nitrogen and oxygen as donor atoms play an important role in biological
6
systems and represent models for metalloproteins and metalloenzymes that catalyze
the reduction of nitrogen and oxygen36
.
Schiff bases are typically formed by the condensation of a primary amine and
an aldehyde / ketone. The resultant compound, R1R2C=NR3, is called a Schiff base
(named after Hugo Schiff), where R1 is an aryl group, R2 is a hydrogen atom and R3
is either an alkyl or aryl group. However, usually compounds where R3 is an alkyl or
aryl group and R2 is an alkyl or aromatic group are also regarded as Schiff bases.
Schiff bases that contain aryl substituents are substantially more stable and more
readily synthesized, while those which contain alkyl substituents are relatively
unstable. Schiff bases of aliphatic aldehydes are relatively unstable and readily
polymerizable37
, while those of aromatic aldehydes having effective conjugation are
more stable. In general, aldehydes react faster than ketones in condensation
reactions, leading to the formation of Schiff bases as the reaction centre of aldehyde
are sterically less hindered than that of ketone. Furthermore, the extra carbon of
ketone donates electron density to the azomethine carbon and thus makes the ketone
less electrophilic compared to aldehyde38
.
Schiff bases have exhibited higher coordination number and from kinetics and
thermodynamic point of view, they are important class of compounds, resulting in an
enormous number of publications and literature review, ranging from pure synthetic
work to physico-chemical and biochemically relevant studies of metal complexes and
found wide range of applications.
Schiff bases are generally bidentate, tridentate, tetradentate or polydentate
ligands capable of forming very stable complexes with transition metals. They can
only act as coordinating ligands if they bear a functional group, usually the hydroxyl,
sufficiently near the site of condensation in such a way that a five or six membered
ring can be formed when reacting with a metal ion. Schiff bases derived from
aromatic amines and aromatic aldehydes have a wide variety of applications in many
fields, e.g., biological, inorganic and analytical chemistry39, 40
. Schiff bases are used
in optical and electrochemical sensors, as well as in various chromatographic
methods, to enable detection of enhanced selectivity and sensitivity41-43
. Among the
organic reagents actually used, Schiff bases possess excellent characteristics,
7
structural similarities with natural biological substances, relatively simple preparation
procedures and the synthetic flexibility that enables design of suitable structural
properties44, 45
. Schiff bases are also effective inhibitors and could be adsorbed on the
surface of metals46
.
Schiff bases offer opportunities for inducing substrate chirality, tuning the
metal centered electronic factor, enhancing solubility and either performing
homogenous or heterogeneous catalyses and include diversified subjects comprising
their various aspects in bio-coordination and bio-inorganic chemistry. Schiff bases
are widely applicable in analytical determination, using reactions of condensation of
primary amines and carbonyl compounds in which the azomethine bond is formed
(determination of compounds with an amino or carbonyl group) using complex
formation reactions (determination of amines, carbonyl compounds and metal ions) or
utilizing the variation in their spectroscopic characteristics following changes in pH
and solvent47
. Schiff bases are widely studied in coordination chemistry as they
easily form stable complexes with most transition metal ions48, 49
. Many biologically
important Schiff bases have been reported in the literature possessing, antimicrobial,
anticonvulsant, antitumor and anti HIV activities50-55
which may be due to the
presence of azomethine linkage56-58
. The applications of Schiff bases and their
importance in the field of coordination chemistry have generated a great deal of
interest in the synthesis of new metal complexes.
Schiff base transition metal complexes are one of the most adaptable and
thoroughly studies systems59, 60
. They are of both stereochemical and
magnetochemical interest due to their preparative accessibility, diversity and
structural variability61
. Metal complexes play an essential role in agriculture,
pharmaceutical and industrial chemistry62
. Heteronuclear Schiff base complexes have
found applications as magnetic materials, catalysts and in the field of bio-
engineering63, 64
.
Transition metal complexes have attracted attentions of inorganic, metallo-
organic as well as bio-inorganic chemists because of their extensive applications in
wide ranging areas from materials to biological sciences65
. It is well known that N
and S atoms play a key role in the coordination of metals at the active sites of
8
numerous metallobiomolecules66
. Schiff base metal complexes have been widely
studied because they serve as models for biologically important species and find
applications in biomimetic catalytic reactions. Chelating ligands containing N, S and
O donor atoms show broad biological activity and are of special interest because of
the variety of ways in which they are bonded to metal ions. It is known that the
existence of metal ions bonded to biologically active compounds may enhance their
activities67, 68
. Transition metal complexes have emerged as potential building blocks
for nonlinear optical materials due to the various excited states present in these
systems as well as due to their ability to tailor metal-organic-ligand interactions69-71
.
Inorganic complexes can be used in footprinting studies, as sequence specific DNA
binding agents, as diagnostic agents in medicinal applications, and for genomic
research.
The studies on Schiff base complexes provide insight into coordination sphere
effects caused by the different ligands employed, such as the influence of the total
charge, the steric hindrance and electronic effects of the ligands on the structures,
properties and reactivity of the complexes.
During the last decades there has been curiosity owing to the interaction of
small molecules with DNA72
. The reaction of metal complexes with DNA has been
extensively studied in relation to the progress of development of new reagents in the
field of medicine and biotechnology. Numerous biological experiments have
demonstrated that DNA is the primary intracellular target of anticancer drugs,
interaction between small molecules and DNA can cause damage in cancer cells,
blocking the division and resulting in cell death 73
. DNA or deoxyribonucleic acid is
the primary target molecule in humans and almost all living organisms. The most
accepted model for the structure of DNA molecule is the double helix model
proposed by Watson and Crick in the year 1953 for which they were awarded a nobel
prize in 1962.
Binding studies of transition metal complexes have played a vital role in the
development of DNA molecule probes and chemotherapeutics74
. The interaction of
transition metal complexes with nucleic acids is a major area of research due to the
utility of these complexes in the design and development of synthetic restriction
9
enzymes, chemotherapeutic agents, foot printing agents, spectroscopic probes, site-
specific cleavers and molecular photo switches75
.
Azomethines and their complexing capabilities have been enlightened in
many review articles76-79
. Hydrazones are the special group of compounds of Schiff
bases. They are characterized by the presence of >C=N-N< group. The presence of
two inter-linked nitrogen atoms separates from imines, oximes, etc. Many
hydrazones and their metal complexes have biological and pharmaceutical activities
such as anticancer, antitumor and antioxidative activities as well as inhibition of lipid
peroxidation etc80-82
. Many drugs may possess modified toxicological and
pharmacological properties when administered in the form of complexes. The most
widely studied metal in this respect is Copper(II), which proved to be beneficial in
diseases such as tuberculosis, gastric ulcers and rheumatoid arthritis83, 84
.
Hydrazides represent a very interesting class of compounds because of their
wide applications in pharmaceutical, analytical and industrial aspects, e.g., as
antibacterial, antifungal, anti-inflammatory, antitubercular, anti-HIV, anti-
degenerative activities and herbicides
85-90. Numerous hydrazide derivatives of Schiff
base ligands and their transition metal complexes have been investigated by various
physico-chemical techniques91-94
.
The basic strength of C=N group is not sufficient to obtain stable complexes
by coordination of the imino nitrogen atom to the metal ion. Hence, the presence of
at least one other group is required to stabilize metal-nitrogen bond95
. This is evident
from the literature review that, a different type of potential Schiff bases on the basis
of their donor atoms set has been attempted. Based on the donating sites, further
Schiff bases are classified as monodentate, bidentate, tridentate, tetradentate and
polydentate ligands containing O, N and S donor atoms. Such type of donor site
ligands have been tried for their complexation and the structures were deduced with
the aid of analytical, physico-chemical and spectral data.
Bidentate Schiff’s bases:
Bidentate Schiff’s bases are the most useful ligands for preparing metal
complexes. Potential bidentate ligands depending on their donor atom set has been
given below.
10
N, O and N, N donor atom set:
Number of metal complexes were synthesized by using Schiff’s bases having
N, O and N, N donor sets. Since in N, O donor set oxygen is often represented by -
OH group. These Schiff’s bases generally act as chelating mono amines.
Tetradentate Schiff’s bases with N2O2 donor set have been widely studied for
their ability to coordinate with metal ions.
Hydrazides have been synthesized and complexed with transition metals, both
-NH2 and C=O groups are involved in the bond formation96
Fig. I (1).
There are number of examples for potential bidentate ligands with N, O donor
sets97
derived from 2-hydroxy aldehyde Fig. I (2) and N, N donor sets derived from
p-anilines Fig. I (3).
Singh et al98
., have synthesized 2-furoyl hydrazones of 2-acetyl thiophene and
2-acetyl furan Fig. I (4) and Fig. I (5) and their Cu(II), Co(II), Ni(II), Zn(II) and
Mn(II) complexes. Later on they have also synthesized Fe(III) complexes with the
same ligand99
.
O
N
NH2
H
Fig. I (1)
OH
N
R
H
N
N
R
H
Fig. I (2) Fig. I (3)
Where R = H, Cl or CH3
Fig. I (4) Fig. I (5)
O
N
O
N
H
(E)
S
H3C
O
N
O
N
H
(E)
O
H3C
11
Aurora et al100
., have synthesized N-(2-furanylmethylene)-3-aminodibenzofuran Fig.
I (6) and their Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) complexes.
Fig. I (6)
Spinu et al101
., have synthesized N-(2-thienylmethylidene)-2-aminopyridine Fig. I (7)
and their Fe(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes. The complexes
have been characterized by elemental analysis, IR, 1HNMR, electronic spectra and
magnetic susceptibility measurements. These results suggest a distorted octahedral
geometry for the Fe(II), Co(II), Ni(II) and Cu(II) complexes and a tetrahedral
geometry for the Zn(II) and Cd(II) complexes.
Fig. I (7)
The Co(II), Mn(II) and Zn(II) complexes of bidentate Schiff base Fig. I (8)
derived from aniline and salicylaldehyde have been reported by Rehman102
and
others. These complexes have been characterized by elemental analysis and spectral
techniques. The results obtained showed that the complexes have octahedral
geometry.
Fig. I (8)
One of the most important and frequently used in the literature, for the
development of pyrazole ring system is carbonylhydrazide (CO=NHNH2). Based
on this, we evolved a synthetic strategy, which involves the modification of carbonyl
O
N
HC
O
S CH
N N
C N
H
OH
12
hydrazide group located on furan moiety of benzofuran nucleus into the desired
benzofuran ring system.
Hiremath et al103
., have reported the complexes of 3-acetylamino-2-benzofu-
ran carboxamide Fig. I (9) with Co(II), Ni(II), Cu(II), Cd(II) and Hg(II) metal ions
and characterized on the basis of elemental analysis, IR, electronic spectra, magnetic
moments and conductance measurement studies. These results indicated the
polymeric octahedral structure for the Cu(II), Ni(II) and Co(II) complexes and
monomeric octahedral structure for Cd(II) and Hg(II) complexes.
Fig. I (9)
Halli et al104
., have reported complexes of the type MLCl2, where, M = Co(II),
Ni(II), Cu(II), Zn(II) and Cd(II) and L = 3-amino-2-acetylbenzofuran and
characterized by elemental analysis, electrical conductance, magnetic moment, IR,
mass, 1HNMR and electronic spectral data. These results indicated that Co(II), Ni(II)
and Cu(II) complexes are polymeric octahedral in nature while Zn(II) and Cd(II)
complexes are monomeric tetrahedral. The ligand behaves as bidentate in all the
complexes.
Sheela et al105
., have reported Cu(II), Ni(II), Co(II), Zn(II), Cd(II), VO(IV)
and UO2(VI) complexes of bidentate Schiff base derived from 4-amino-N-
guanylbenzenesulfonamide and salicylaldehyde. The structural features of the
complexes have been confirmed by microanalytical data, IR, UV-Vis, 1HNMR, FAB
mass and ESR spectral techniques. Spectroscopic and other analytical studies reveal
the square-planar geometry for copper, square-pyramidal geometry for oxovanadium,
seven-coordinate UO2(VI) complex and octahedral geometry for other complexes
Fig. I (10).
O CONH2
NHCOCH3
13
Where M = Co(II), Ni(II), Zn(II), Cd(II) or Mn(II)
Fig. I (10)
Garnovski et al106
., have reported complexes of naphthalene carbonyl
derivatives, Fig. I (11) where R = H, R1 = iodo-2 and R = Me, R1 = (i-C3H7)2.
Fig. I (11)
Cu(II) complexes of bidentate Schiff base 4-methoxy-2-(1H-benzimidazol-2-
yl)-phenol and its methyl / chloro / nitro derivatives Fig. I (12) have been reported by
Tavman et al107
.,
O
N
S
NH
C
OO
H2N NH
M
O
N
S
HN
C
O O
NH2HN
OH2
OH2
O
R
N
R1
O
R
N
R1
Cu
14
Fig. I (12)
Synthesis, physico-chemical investigations and biological studies on Mn(II),
Co(II), Ni(II), Cu(II) and Zn(II) complexes with p-amino acetophenone isonicotinoyl
hydrazone have been reported by Singh and others108
. The results obtained by
spectral and other physico-chemical techniques showed that the complexes have
octahedral geometry Fig. I (13).
Where M = Mn(II), Co(II), Ni(II), Cu(II) or Zn(II)
Fig. I (13)
Dhumwad et al109
., have reported the synthesis and characterization of Co(II), Ni(II),
Cu(II), and Zn(II) complexes with Schiff base, 7-hydroxy-4-methyl-8-((pyridine-3-
ylimino)methyl)-2H-chromen-2-one Fig. I (14). All the complexes exhibited an
octahedral geometry with a slight distortion in Cu(II) complexes.
N
HN
OCH3
N
NH
O
H3CO
Cu O
R
R
N C
HN
O
N
CH3C
NH2
M
Cl
Cl
OH2
OH2
15
Fig. I (14)
Tridentate Schiff bases:
There are large number of tridentate Schiff bases containing NNO, NNS,
NOO, NSO donor sets110
. These may be generally derived from the bidentate
analogous by the addition of another donor group. It must be pointed out that the
oxygen donor atom of such ligands may often act as bridge between two metal
centers giving polynuclear complexes of some tridentate ligands Fig. I (15) and
Fig. I (16).
The Co(II), Ni(II), Cu(II) and Cd(II) complexes of tridentate Schiff base Fig. I
(17) have been reported by Nawar and others111
. These complexes have been
characterized by elemental analysis, IR, 1HNMR, Mass, Electronic Spectra and
magnetic susceptibility measurements, spectrophotometric and potentiometric studies.
NH2
N
CH3
HN
O
Fig. I (17)
Fig. I (15) Fig. I (16)
N
N
N
H
N
N
N
H
XH
Where X=O or S
16
Pyridine-2-carboxaldehyde arylhydrazone Fig. I (18), possessing pyridine N, imine N
and the amide O forms two five membered chelate rings upon complexation with
metal ion.
Reaction of one mole of [Cu(O2CCH3)2].H2O and two moles of Schiff bases
in methanol afford the complexes of general formula [CuL2]112
. Generally, hexa-
coordinated complexes undergo tetragonal distortion from the octahedral symmetry
due to the Jahn-Teller distortion. Structure of the reported hexacoordinated Cu(II)
complex [Cu(pabh)2] Fig. I (19) is proved by its single crystal X-ray data. The
magnetic moment value for these complexes was found to be in the range 1.90 - 2.08
B.M. From the crystal structure data, it was found that there is a tetragonal
compression along the N2-Cu-N5 axis and the CuN4O2 coordination sphere in the
[Cu(pabh)2] complex which is rhombically distorted. Its EPR spectrum results are in
consistent with its structure.
Naik et al113
., have reported the synthesis, spectroscopic and thermal studies
of Co(II), Ni(II) and Cu(II) complexes of the hydrazone Fig. I (20) derived from 2-
benzimidazolyl mercaptoaceto hydrazide and o-hydroxy aromatic aldehydes.
Fig. I (18)
HN
N
C
NO
CH3
N
N
C
NO
N
N
C
N O
Cu
CH3
CH3
Fig. I (19)
17
Where R = H, Cl, Br or CH3.
Fig. I (20)
The Co(II), Ni(II), Cu(II) and Cd(II) complexes of tridentate Schiff base,
4-[2-(aminomethyl)pyridylisonitroacetyl)diphenylether Fig. I (21) have been reported
by Coskun and Yilmaz114
.
Where M = Co(II), Ni(II), Cu(II) or Cd(II)
Fig. I (21)
Gudasi et al.115,116
,
have reported Co(II), Ni(II), Cu(II), Zn(II), Cd(II),
Oxovanadium(IV) and Ln(III) complexes with 2-(3-coumarinyl)imidazole[1-2a]
pyridine (CIP), Fig. I (22) which were found to possess good antifungal and
antibacterial activity.
Sanjay Annarao117
have reported the synthesis of 3-acetyl coumarine
semicarbazone Fig. I (23) and 3-acetyl coumarine thiosemicarbazone Fig. I (24) and
their Zn(II), Cd(II) and Hg(II) complexes. Based on the elemental, spectral, magnetic
N
N
SH2C C
O
HN N C
H
HO RH
O C C
O N
NH
O
H2C N
OCC
ON
HN
O
CH2N
M
O O
N
N
Fig. I (22)
18
and solubility studies the Co(II), Ni(II) and Cu(II) complexes are predicted octahedral
geometry and Zn(II), Cd(II) and Hg(II) complexes are tetrahedral geometry.
They have also screened all the ligands and their complexes for bacterial and
fungal activity.
Vidyanand K. Revankar et al118
., have synthesized a series of Co(II), Ni(II),
Cu(II) and Zn(II) complexes of quinoline-thiosemicarbazone Schiff base Fig. I (25)
with ONS donor atoms. The ligand and complexes were characterized by elemental
analysis and various spectral studies. Based on these studies, all the complexes have
been assigned octahedral geometry except the Cu(II) complexes which possess square
pyramidal structure. Further, the Schiff base has exhibited good antimicrobial
activity and the complexes have shown higher activity than the ligand.
Fig. I (25)
Tetradentate Schiff bases:
Tetradentate Schiff bases with N2O2 donor set have been widely studied for
their ability to coordinate with metal ions. The properties of complexes obtained by
these ligands are determined by an electronic nature of the ligands as well as by their
conformational behaviour119
. Dubsky and Sokol120
have reported the reactions of
salicylaldehyde with diamines. These display tetradentate behavior by forming
square-planar complexes Fig. I (26) with Ni(II) and Cu(II).
Fig. I (24) Fig. I (23)
O O
N(E)
CH3
N
O
NH2
H
O
(Z)
O
N(E)
CH3
N
S
NH2
H
19
Carrigan and co-workers121
have carried out electron spin resonance spectral
analysis of Cu(II) complexes of bis(mercaptobenzylidene)diamine Fig. I (27) and
have reported square-planar configuration around the Cu(II) ion. Sacconi and
Bertini122
have reported similar type of ligands while trying to prepare a Cu(II)
complex containing ethylenediamine and acetyl acetone Fig. I (28).
Fig. I (27) and Fig. I (28)
Zacharios and others123
have reported the reactions of salicylaldehyde with
o-phenylenediamine. These display tetradentate behavior by forming metal
complexes Fig. I (29) containing two six membered and one five membered ring.
Some neutral tetradentate N2O2 type complexes of Co(II) have been reported
by Naeimi and others124
. The complexes have been synthesized using Schiff bases
C N N C
O O
H H
M
Fig. I (26)
Where M = Ni(II) or Cu(II)
N N
O O
M
Fig. I (29)
Where M = Co(II), Ni(II) or Cu(II)
C N N C
S S
Cu
H H
C N N C
H2C
C O
CH2
CO
Me Me
MeMe
Cu
20
formed by condensation of 5-nitro-salicylaldehyde with various diamines in alcohol.
The results obtained by spectral and other physico-chemical techniques showed that
the complexes have square-planar geometry Fig. I (30).
Fig. I (30)
Singh et al125
., have reported the synthesis, spectroscopic and biological activity
studies of Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes of tetradentate Schiff
base Fig. I (31).
Where M = Co(II), Ni(II), Cu(II), Zn(II) or Cd(II)
Fig. I (31)
A brief review on Naphthofurans and Benzofurans:
Naphthofuran nuclei are key structural moieties found in a large number of
biologically important natural products. They have been isolated from many natural
sources like Fusarium oxysporum, Gossypium barbadense. Their plant extracts are
being used for traditional medicines126
. Many of the natural naphthofurans, such as
(±)-laevigatin, (+)-heritol and balsaminone A possess interesting pharmacological and
cytotoxic properties127
. A large number of naphthofuran derivatives possess various
biological activities like anthelmentic, anticonvulsant and antipyretic128
. They also
act as fluorescent dyes and probes as well as photosensitizers. Naphthofurans when
condensed with various heterocycles exhibit wide spectrum of activities129-131
.
Naphthofuran derivatives have been proven to be potent antioxidant agents132
. While,
N
R
N
O O
O2N NO2
Co
R = (CH2)2 ; (CH2)3 ; (CH2)4 ; (CH2)6 ; (CH2)8 ; ;
O
;
SO O
;
Where
H2C CC
C
N H
N H
M
X
X
H2C C
NH
HN
O
O
21
mansonone D133
and Dunnione134
, the members of naphthofuran family are vital
biologically active agents.
Benzofuran compounds are abundantly present in nature, particularly among
the plant kingdom, often such natural products possessing benzofuran nucleus Fig. I
(32) are endowed with useful pharmacological properties. The compounds with
benzofuran moiety have aroused enormous interest to the chemists for their biological
importance and are good chelating agents, with many analytical applications both in
qualitative and quantitative analysis. The wide interest in synthetic products
containing benzofuran nucleus has resulted in the development of benzofuran
chemistry in a spectacular fashion during the last several years.
Benzofuran compounds occur in nature in a variety of structural forms which
ranges from a simple molecule such as 5-methoxybenzofuran Fig. I (33) to a highly
complicated molecule like morphine A and B, much more synthetic work has been
carried out so for135-137
.
Amiodarone138
, (2-Butyl-benzofuran-3-yl)-[4-(2-diethylamino-ethoxy)-3, 5-di
iodo-phenyl]-methanone Fig. I (34) was first introduced in Europe as an antianginal
agent139
, but was later found to be highly effective antiarrhythmic drug140, 141
. It has
been designated as “Ideal antiarrhythmic drug” because of its high degree of efficacy,
wide spectrum arrhythmias and also because of initial patient acceptance142
. In 1985
amiodarone143
(cordarone) was approved in the United States144
for treatment of life
threatening ventricular tachyarrhythmias.
O
Fig. I (32)
O
H3CO
Fig. I (33)
Fig. I (34)
On-Bu
O
I
I
O
N
CH3
CH3
22
Baker’s yeast contains a benzofuran derivative, which acts as an antioxidant and
prevents, hemorrhaging liver necrosis in rats and haemolysis of red cells in Vitamin-E
deficient rats145
.
The seed oil of plant “Egonoki” which is much common in Japan is known to
contain a benzofuran derivative called “Egonol”. It is an effective synergist for
rotenone pyrethrum against houseflies, mosquitoes, aphids and many other insects146
.
Joseph147
has prepared 2-acetylbenzofuran Fig. I (35) which acts as diuretic and
choleritic agents.
Sridhar et al148
, have synthesized 3-methyl / 5-methoxybenzofuran-2-
carbamate and carbamide derivatives which are well known biodynamic agents
possessing various pharmacological properties. The presence of nitro group in the
benzofuran derivatives is more important for paraciticidal properties of benzofuran149,
150. Khellin, a furochrome is well known for its physiological activity.
A number of chelate compounds have been reported151
on benzofuran
derivatives of the type Fig. I (36) with Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) metal
ions. These complexes have been characterized by infrared and electronic spectra
and magnetic moment measurements.
Where Z = O or S and R = aryl or alkyl group
Fig. I (36)
Shivakumar et al152
., have reported the synthesis, spectroscopic and biological
activity studies of the hydrazones derived from Co(II), Ni(II), Cu(II) Zn(II), Cd(II)
and Hg(II) complexes derived from benzofuran-2-carbohydrazide and benzaldehyde /
3, 4-dimethoxybenzaldehyde. Spectroscopic and other analytical studies reveal the
O
O
CH3
Fig. I (35)
O
Z
NHR
23
chloride-bridged polymeric octahedral geometry for Co(II), Ni(II) and Cu(II)
complexes and tetrahedral geometry for Zn(II), Cd(II) and Hg(II) complexes.
In view of various applications and biological importance of the Schiff base
ligands and their metal complexes, in the present investigation we thought it is
worthwhile to synthesize the Schiff base ligands by the condensation of
naphthofuran-2-carbohydrazide with cinnamaldehyde / diacetylmonoxime / citral / 8-
formyl-7-hydroxy-4-methylcoumarin / 2-chloro-3-formylquinoline and their metal
complexes by using metal ions like Co(II), Ni(II), Cu(II), Cd(II), Zn(II) and Hg(II).
The synthesized Schiff base ligands are as follows.
1. (N'-3-phenylallylidene)naphtho[2,1-b] furan-2-carbohydrazide (PNFC)
2. N'-(3-(hydroxyimino)butan-2-ylidene)naphtho[2,1-b]furan-2-carbohydrazide (DNFC)
3. (N'-3,7-dimethylocta-2,6-dienylidene)naphtho[2,1-b]furan-2-carbohydrazide
(DMNFC) 4. N'-((7-hydroxy-4-methyl-2-oxo-2H-chromen-8-yl)methylene)naphtho[2,1-b]furan-2
carbohydrazide (HNFC)
5. N'-((2-chloroquinolin-3-yl)methylene)naphtho[2,1-b]furan-2-carbohydrazide (CNFC)
All the metal complexes have been characterized on the basis of elemental
analysis, spectral studies, magnetic susceptibility, conductivity measurements, XRD
and thermal analysis. All the ligands and their metal complexes were screened for
their antibacterial and antifungal activities. DNA cleavage activity was carried out
for all the metal complexes. Some of the ligands and their metal complexes were
tested for their antioxidant activity. The details are discussed in the succeeding
chapters.
A brief review on Mixed-Ligand Complexes:
The complexes in which the metal ion is simultaneously bonded to two or
more different complexing reagents (ligands) are known as ‘Mixed-Ligand’
complexes. If more than one kind of ligand and more than two different metal ions
are present, they may exhibit polynuclear complexes153
. The areas of mixed ligand
are homo / hetero binuclear complexation and have been extensive growth stimulated
by interest in the area such as metallo-enzymes154
, homogeneous / heterogeneous
catalysis155
, electrical conductance and magnetic exchange processes. The design and
synthesis of mixed ligand metal complexes have shown a spectacular progress and
24
drawing the attention of coordination and bioinorganic chemists. The coordination
chemistry of amino acid Schiff base ligand is of considerable interest due to their
biological importance. Especially, because it has been reported that, the mixed-ligand
complexes of amino acid Schiff base ligands with transition elements are used as
radiotracers in nuclear medicine156
as antitumor157
agents. Mixed ligand complexes
of Schiff base ligands play a vital role due to their biological158, 159
and industrial160
importance and are useful in the storage and transport of active substances through
membranes161
. They have found useful applications in the microelectronic industry
and chemical vapour deposition of metals162
.
Mixed ligand complexes are also used in the storage and transport of additive
substances through the membrane and the phenomenon strongly depend on the
formation of such species and the nature of the metal ion involved. Mixed chelation
appears in biological fluids as millions of potential ligands likely to compete for
metal ions found in-vivo i.e. Na, K, Mg, Ca, Mn, Fe, Co, Cu, Zn and Mo.
As the present work deals with the mixed ligand complexes involving
benzofuran nucleus, it is appropriate to include a brief discussion on the chemistry of
secondary ligands.
Saidul Islam et al163
., have reported new mixed ligand complexes of Cu(II)
and Pd(II) with homophthalic acid and nitrogen containing heterocyclic bases and
characterized them by spectral studies and suggested the square planar structure for
the Fig. I (37) complexes.
Where M = Cu(II) or Pd(II)
Fig. I (37)
Cakir164
has reported the interaction of acetylsalicylic acid and nicotinamide
with Co(II) and Ni(II) ions which were investigated using square wave and cyclic
O
O
O
O
N
N
M
25
voltametry techniques. In mixed ligand complexes, nicotinamide bonds to metal ions
with pyridine N atom while salicylate ligands are bonded by O atoms of the
carboxylate group Fig. I (38).
Augushin et al165
., have reported square pyramidal mononuclear Cu(II)
complexes containing [Cu(AA)(BB′)]
+ moieties, were AA = acetyl acetone, BB
′ =
4, 4′-dimethyl(2, 2
′-bipyridine) and assigned the following structure, Fig. I (39).
Prasad et al166
., have synthesized mixed ligand complexes of the metal ions
like Mg(II), Ca(II), Sr(II) and Ba(II) with 2-hydroxy-1-naphthaldehyde and
2-hydroxy benzophenone, 5-bromo / 5-chloro salicylaldehyde in 1:1:1 molar ratio and
characterized by analytical and spectral studies. The metal atom appears to be hexa-
coordinated and the probable geometry is octahedral, Fig. I (40) and Fig. I (41).
N
O
NH2
M O
O
HON
O
NH2
O
O
OH
H2O
H2O
Where M = Co or Ni
Fig. I (38)
Cu
O
CH2
O
CH3
CH3
N
N
H3C
H3CFig. I (39)
26
Sastri and others167
have reported mixed ligand complexes of Co(III) and Ni(II)
namely [Co(phen)2(qdppz)]3+
, [Ni(phen)2(qdppz)]2+
, [Co(phen)2(dicnq)]3+
and
[Ni(phen)2(dicnq)]2+
where phen = 1, 10-phenanthroline, qdppz = naptho[2, 3-
a]dipyrido[3, 2-h:2′, 3
′-f]phenazine-5, 18-dione and dicnq = dicyanidipyrido
quinoxaline. The complexes have been characterized by elemental analysis, IR, UV-
Vis, 1HNMR, FAB-MS, cyclic voltametry and magnetic susceptibility methods
Fig. I (42) and Fig. I (43).
Where M = Co(III) or Ni(II)
Fig. I (42)
N
N
N
N
N
N
M
N
N
O
O
n+
O
O
C6H5
O
O
H
M
H2O
H2O
O
O
H
O
O
H
M
H2O
H2O
R
Fig. I (40) Fig. I (41)
Where M = Mg, Ca, Sr or Ba Where M = Mg, Ca, Sr or Ba
R = Br or Cl
27
Where M = Co(III) or Ni(II)
Fig. I (43)
Sawant et al168
., have reported mixed ligand complexes of primary ligand 2-
phenyl-3-(benzyl-amino)-1,2-dihydroquinazolin-4(3H)one and secondary ligands
such as ethylenediamine and 1, 10-Phenanthroline with metal ions Mn(II), Co(II) and
Ni(II). Based on the physico-chemical, spectroscopic and thermal studies they
proposed octahedral geometry for all the complexes Fig. I (44) and Fig. I (45).
Where M = Mn(II), Co(II) or Ni(II)
Fig. I (44) and Fig. I (45)
Garnovski et al169
., have reported nickel(II) complexes of the type Fig. I (46)
and Fig. I (47) with two different N, O chelate environments of salicyliminate and β-
ketiminate combined in the same molecule.
HN N
O
N
M
X
X
N
N
HN N
O
N
M
X
X
H2N
H2N
N
N
N
N
N
N
M
N
N CN
CN
n+
28
Fig. I (46) and Fig. I (47)
Azza et al170
., have reported Cu(II) mixed ligand complexes of 3-acetylcoumarine (3-
ACoum) and dinitrogen bases (L), with the general formula Cu(3-ACoum)(L)Xn
where n = 2, L = N, N, N′, N
′′- tetraethylenediamine, 1, 10-Phenanthroline and 2, 2
′-
bipyridine and X = ClO4¯, BF4¯ or NO3¯. The complexes have been characterized by
elemental analysis, IR, UV-Vis, ESR, magnetic susceptibility and conductivity
measurements Fig. I (48).
Where X = ClO4¯, BF4¯ or NO3¯ and n = 2
Fig. I (48)
El-ajaily and others171
have reported Co(III) mixed ligand complexes derived from
catechol and 2-aminopyridine / 2-aminobenzothiazole. The complexes have been
characterized by elemental analysis, IR, UV-Vis, ESR, molar conductivity and
thermogravimetric analysis Fig. I (49) and Fig. I (50).
Fig. I (49) and Fig. I (50)
O
N N
O
Me
C(O)MeNi
O
N N
O
Me
Ni
Me
HO
O
O
O
N
N
Cu Xn
N
NH2
CoO
O
Cl
H2O
2H2O Co
O
O
N
S NH2
Cl
H2O
2H2O;
29
From our laboratory Shivakumar172
has synthesized mixed ligand complexes
of primary ligand [3, 4, 5-trimethoxyphenylmethine]carbohydrazone and secondary
ligands such as 1, 10-Phen, 2, 2′-Bipy, Acac etc with metal ions Co(II), Ni(II) and
Cu(II). The elemental analysis and physico-chemical studies reveal octahedral
geometry for all the complexes Fig. I (51) and Fig. I (52).
Recently from our laboratory, Jumnal173
has synthesized mixed ligand complexes of
primary ligand Benzofuran [Indole-2, 3-dione] carbohydrazone and secondary ligands
such as orthophenylene diamine (opd), 2-aminopyridine (ampy), acetylacetone (acac) etc
with metal ions Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II). The analytical data
and spectral studies reveal octahedral geometry for all the complexes Fig. I (53) and
Fig. I (54).
Where M = Co(II), Ni(II), Cu(II), Zn(II), Cd(II) or Hg(II)
Fig. I (53)
Fig. I (52)
HN
O
N
OCH3
OCH3
OCH3M
N
N
Cl
Cl
O
Fig. I (51)
Where M = Co, Ni or Cu
HN
O
N
OCH3
OCH3
OCH3M
N
N
Cl
Cl
O
O
C
HN
N
O
NH
O
M
H2N NH2
ClCl
30
Where M = Co(II), Ni(II), Cu(II), Zn(II), Cd(II) or Hg(II)
Fig. I (54)
The present work deals with the synthesis of mixed ligand complexes using
the following primary and secondary ligands with metal ions viz. Co(II), Ni(II),
Cu(II), Cd(II), Zn(II) and Hg(II).
Primary ligand:
1. N'-((benzo[d][1,3]dioxol-6-yl)methylene)benzofuran-2-carbohydrazide
(BMBFC)
Secondary ligands:
1. 2-Aminothiophenol (2-atp)
2. 2-Aminophenol (2-amp)
3. 8-Hydroxyquinoline (8-hq)
4. 1,10-Phenanthroline (phen)
All the metal complexes have been characterized on the basis of elemental
analysis, spectral studies, magnetic susceptibility, conductivity measurements, XRD
and thermal analysis. All the ligands and their metal complexes were screened for
their antibacterial, antifungal and antioxidant activities. DNA cleavage activity was
carried out for all the metal complexes. The details are discussed in the succeeding
chapters.
O
C
HN
N
O
NH
O
M ClCl
C
CH
C
OO
H3C CH3
31
Present work:
The major objectives of the present work are:
1. To develop methodology for the synthesis of novel heterocyclic Schiff’s base
ligands derived from naphthofuran, benzofuran, coumarin, quinoline etc
moieties which have been utilized in the present research work.
2. To synthesize Co(II), Ni(II), Cu(II), Cd(II), Zn(II) and Hg(II) metal complexes
derived from the ligands containing above moieties.
3. To elucidate the structure of the synthesized ligands and their metal complexes
based on the elemental analysis and various spectral techniques viz. IR,
1HNMR, Mass, UV-Vis., Thermal, ESR and X-ray diffraction etc.
4. To evaluate the antibacterial and antifungal activities of the synthesized ligands
and their metal complexes.
5. To study the DNA cleavage ability of all the synthesized metal complexes
6. To test antioxidant activity of some of the Schiff base and their metal complexes
etc
These studies will be systematically presented in seven chapters (Chapter I-
VII) of the thesis.
32
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