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TRANSCRIPT
1
P. Krishnamoorthy, 2011
Chapter I
Introduction
Coordination and organometallic compounds
Coordination chemistry is undoubtedly the most active research area in inorganic
chemistry that spans the entire spectrum from theoretical works on bonding to the
synthesis of organometallic compounds. Several thousands of coordination complexes
have been synthesized and investigated during the past decades. Research on
coordination chemistry has emerged as an active and interesting field for chemists and
biologists due to the reason that coordination compounds are largely utilized in the
production of fragrances, semiconductors, pharmaceuticals, ceramic precursors etc.1 Ever
since the importance of coordination phenomenon in biological processes was realized,
large number of metal containing macromolecules have been synthesized and studied to
understand the mechanism of complex biological reactions that has resulted in the
emergence of an important branch of inorganic chemistry viz. bioinorganic chemistry.
Similarly, coordination of substrate molecules to metal ions in catalysis was well
understood and lot of research work is being carried out and published. Since structure
and reactivity are interdependent, studies on molecular structure of transition metal
complexes are of paramount importance to understand their properties. Excellent modern
theories available on metal ligand bonding aid the researchers in interpreting the
experimental data obtained using sophisticated instrumental techniques.
Metal complexes have played an important role since the early days of
coordination chemistry. Indeed, a great deal of work has been carried out on the synthesis
and characterization of transition metal compounds mainly due to their applications in
various fields. However, the ability of a metal ion to participate in bonding to all possible
coordination sites depends in part on its preferences for the donor atoms of the ligand, the
flexibility and conformational adaptability of the ligand used, as well as on the
competition from other Lewis acids and different entities capable of occupying the
coordination pocket.
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P. Krishnamoorthy, 2011
Medicinal inorganic chemistry is an area of growing interest owing to the fact that
inorganic pharmaceuticals play a key role in clinical therapy. For these inorganic
compounds, the metal serves as structural center for organizing the organic ligands in the
biologically relevant chemical space. Transition metals appear more appealing for this
purpose because they can support a multitude of coordination numbers and geometries
that go far beyond sp, sp2 and sp
3 hybridizations of carbon. Another key aspect for using
metal containing compounds as structural scaffolds is the kinetic stability of the
coordination sphere in the biological environment.
Transition metal complexes act as homogeneous catalysts in many industrially
important reactions such as hydrogenation, hydrosilation, hydroformylation,
polymerisation, isomerisation, acylation and oxidative hydrolysis of olefins. Binuclear
transition metal complexes have also received much attention in recent years as they may
serve as model for variety of biological reactions such as oxygen transport, oxygen
activation, photosynthesis water reduction, electron transfer process, metal-metal
interactions and multi centered catalysis.
Transition metal ions with different oxidations state have a strong role in redox
enzyme systems and may provide the basis of models for active sites. To mention a few,
nickel is an essential component in at least 4 types of enzymes viz. urease, carbon
monoxide dehydrogenase (CODH) or acetyl coenzyme A synthase, hydrogenase and
methyl-S-coenzyme M reductase. Some polydentate Co(II) complexes with ligands
capable of intercalation into DNA strands are capable of inducing DNA cleavage under
photochemical conditions. Since the recognition of Vitamin B12 and synthesis of
cobalmines, responsible for erythrocytes (RBC) formation in human body, there has been
much study of model systems. Copper complexes are known to play important role in the
active site of many copper proteins in vivo as well as in homogeneous and heterogeneous
catalysis for organic chemical reactions. A large body of evidence indicates that copper
chelation is an effective method to inhibit tumor growth and copper chelators have
become promising agents in the treatment of cancer. It has been found that some copper
chelators acquire more effective or novel bioactivity after forming complexes. Recent
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P. Krishnamoorthy, 2011
studies indicated that Cu2+
was critically needed for PDTC induced apoptosis in HL-60
cells and the copper complex of salicylaldehyde benzoylhydrazone (SBH) derivatives
showed increased potency of growth inhibition in several cancer cell lines, compared
with the metal-free organics. Copper-SBH complexes were significantly more cytotoxic
than complexes of other transitional metals (Cu > Ni > Zn > Mn > Fe > Cr > Co) in
MOLT-4 cells, an established human T-cell leukaemia cell line. It was noted that SBHs,
especially their copper complexes appeared to be unusually potent inhibitors of DNA
synthesis and cell growth in a variety of human cancer cell lines, including the human
lung epithelial cancer cell line, SKMES-1 and rodent cancer cell lines. A series of, novel
salicylaldehyde pyrazole hydrazone (SPH) derivatives were found capable of inhibiting
the growth of A549 lung carcinoma cells.
Hydrazones
In a brilliant series of investigations in the 1930‟s and the beginning of the
1940‟s, which were reviewed in,2-4
Pfeiffer and his co-workers developed principle
methods for synthesizing azomethine complexes and studied their physicochemical and
structural properties. The first paper describing a metal-containing product of the reaction
of ammonia with salicylaldehyde and cupric acetate appeared in 18405 and in subsequent
years, hundreds of papers on complexes of azomethine were published. Many of these
complexes were included in the review articles6-9
and the subject of azomethine was
represented by 15 papers in the proceedings of the 29th International Conference on
Coordination Chemistry (Lausanne, Switzerland, July1992).10
The architectural beauty of coordination complexes arises from the interesting
ligand systems containing different donor sites. Among the ligand systems, hydrazide and
hydrazone occupy special place because complexes of these compounds with transition
metals are nowadays extensively used for the treatment of several diseases, in synthetic
and analytical chemistry as novel heterogeneous catalysts in oxido-reduction processes
and various chemical and photochemical reactions as well as numerous industrial
applications of science and technology.11-15
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P. Krishnamoorthy, 2011
Aroyl hydrazones present a combination of donor sites such as protonated /
deprotonated amide oxygen and the imine nitrogen of hydrazone moiety, very often
additional donor site (usually N or O) is provided by the aldehyde or ketone forming the
Schiff base. Aroyl hydrazones have been proved to be a strong chelating agent for
transition metals,16-21
lanthanides22,23
as well as for main group elements.24,25
They have
also been shown to be useful molecules to build up controllable supramolecular
structures. Lehn and co-workers have demonstrated that suitably substituted hydrazones
are capable of coordinating metals to give multimetallic square grid complexes, whose
optical, photophysical and magnetic properties were modulated by the degree of
protonation of the ligands.26-28
Structure, bonding and stereochemistry of the acid hydrazones
Hydrazones contain two connected nitrogen atoms of different nature and a C=N
bond that is conjugated with a lone electron pair of the terminal nitrogen atom. These
structural fragments are mainly responsible for the physical and chemical properties of
hydrazones (Fig. 1.1). Both the nitrogen atoms of the hydrazone group are nucleophilic,
although the amino type nitrogen is more reactive. The carbon atom of hydrazone group
has both electrophilic and nucleophilic character.29,30
Fig. 1.1 Figure showing the reactivity of hydrazones.
The chelating behavior of hydrazones depends on their amido-iminol tautomerism
and in addition to this, the number and type of the substituents attached to the hydrazone
framework also influences the coordination mode. The functional grouping causes these
compounds to behave as bidentate ligands for metal ions and owing to the availability of
‒ NH‒ C=O group, acid hydrazones show keto-enol (amido-iminol) tautomerism (Fig.
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P. Krishnamoorthy, 2011
1.2). In aqueous or ethanolic solutions, these hydrazones show tautomeric structures
which can be coordinated to the metal ion, probably through the N-atom either alone or in
combination with O-atom of the enolic group.31
In solid state, hydrazones predominantly
exist in form (I) (amido), but in solution they exist in form (II) (iminol). In hydrazones, it
is well known that a proton transfer can occur between the hydrazinic-N and keto group
of hydrazide part. Therefore, tautomerisation equilibrium exists between amido form and
iminol form through intramolecular proton transfer. This proton transfer causes a change
in the π-electron configuration and thus increases conjugation.
R2
N
R1
HN
R3
O
R2
N
R1
N
R3
OH
Amido form (I) Iminol form (II)
Fig. 1.2 Tautomerisation of hydrazone ligands.
In general, hydrazones act as a bidentate chelating ligand by utilizing the
available amide oxygen and azomethine nitrogen donor sites by which a five membered
chelate ring is produced and some of the examples are provided in Fig. 1.3.32-34
Uninegative bidentateNeutral bidentate Uninegative bidentate
N
HN
O
M
N
N
O
M
HN
HN
O
M
Fig. 1.3 General bidentate coordination mode of acid hydrazones.
Further, the chelation can be increased by increasing the number of coordination
sites on the hydrazone framework. If a heterocyclic ring or phenolic moiety is attached to
the hydrazone framework as shown in Fig. 1.4, it can coordinate to the metal center with
increased denticity.35-39
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P. Krishnamoorthy, 2011
Neutral tridentate
N
HN
O
MN
N
N
O
MN
N
HN
OM O
NN
OM O
Mononegative tridentate Binegative tridentate
Mononegative tridentate
Fig. 1.4 Examples of tridentate behaviour of hydrazone ligands.
It is evident that the stereochemistry of the ligand is much decided by the steric
effects of the various substituents in the hydrazone moiety and most of them are in cis
form while coordinating to the metal ions. This phenomenon is assumed to be due to
better electron delocalisation in the chelate ring system that increases the stability upon
coordination with metal atoms. Hydrazones may also act as a unidentate ligand by
bonding through enolate oxygen when they are existing in a trans form.40
The amido form itself exists in syn or anti conformation depending on the groups
attached with the azomethine bond (Fig. 1.5). In the syn form, as far as the azomethine
bond is concerned two bulkier groups (R2 and R3) are on the same side, while in anti
form the bulkier groups are on opposite side.
R2
N
R1
HN
R3
O
R1
N
R2
N
R3
OH
syn form anti form
Fig. 1.5 Geometrical isomers of hydrazone system.
In addition to the steric effects of the various substituents in the hydrazone
moiety, additional interactions such as intramolecular hydrogen bonding also play a role
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P. Krishnamoorthy, 2011
to decide the stereochemistry of hydrazones. It is observed that the syn nature of the bond
usually transforms to anti geometry, while coordinating to metal ions.41,42
Transition metal hydrazone complexes: Applications
The coordination chemistry of hydrazones as ligand is an intensive area of study
and numerous transition metal complexes of them have been investigated.43
Earlier,
investigations on the hydrazone complexes were focused mainly on the synthesis and
structural characterization, but nowadays these metal complexes were reported to serve
some applications in various fields like non-linear optics, sensors, medicine etc.
In bioactivities
Metal complexes containing site-specific substructures and multiple reactive sites
constitute a group of promising candidates for nuclease activity because of their
electronic and structural advantages. Most of the first row transition metals either alone
or in their complex form are biologically essential with a number of known bioactivities.
Among them, nickel, cobalt and copper are especially notable as they involve in many
biological processes.44-53
It is well known that cancer is currently the second leading
cause of death in industrialized countries, accounting for roughly a quarter of total
numbers.54
Hence, development of new anticancer therapies is one of the fundamental
goals in medicinal chemistry. The interactions between biomacromolecules and drugs
have attracted special interest among both chemistry and biology researchers recently.55-
57 DNA is one of the main molecular targets in the design of anticancer compounds
58 and
the interaction between nucleic acids and other molecules is a fundamental issue in life
science that relates the replication, transcription, mutation of genes and related variations
of species in character, origin of some diseases and mechanism of interaction of some
DNA-targeted drugs.59-62
Further, it has been demonstrated that free radicals can damage
proteins, lipids and DNA of bio-tissues leading to increased rates of cancer and
fortunately antioxidants can prevent this damage due to their free radical scavenging
activity.63,64
Hence, it is very important to develop compounds with strong DNA binding,
antioxidant and cytotoxic properties for effective cancer therapy. As known well, serum
albumins are the class of proteins involved in the transport of metal ions and metal
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P. Krishnamoorthy, 2011
complexes along with drugs through the blood stream.65
Many drugs, including
anticoagulants, tranquilizers, antiinflammatory and general anaesthetics are transported in
the blood via combination with albumin.66,67
The nature and magnitude of drug-albumin
interaction significantly influence the pharmacokinetics of drugs and thus the binding
parameters are useful in studying protein-drug binding as they greatly influence
absorption, distribution, metabolism and excretion properties of typical drugs.
In molecular sensors
Recently, the development of molecular sensors has attracted lot of research
activities for their use in processes that include food, clinical, environmental analysis and
analytical applications. It was reported that a potentiometric aluminium sensor based on
N,N'-bis(salicylidene)-1,2-cyclohexanediamine as a neutral carrier in poly(vinyl chloride)
matrix was successfully applied for direct determination of aluminium(III) in biological,
industrial and environmental samples 68
in the pH range of 2.0-9.0. It has been used as an
indicator electrode in potentiometric titration of aluminium ion with EDTA. The Schiff
base, N,N′,N″,N′′′-1,5,8,12-tetraazadodecane-bis(salicylaldiminato), has been used as an
ionophore for preparing Mn2+
selective sensor69
over a number of alkali, alkaline and
heavy metal ions for the determination of manganese in various samples by direct
potentiometry.
In non-linear optical devices
Non-linear optics (NLO) deals with the interactions of applied electromagnetic
fields materials to generate new electromagnetic fields, altered in frequency, phase, or
other physical properties. Such materials that are able to manipulate photonic signals
efficiently are of importance in optical communication, optical computing and dynamic
image processing.70-74
In this connection, transition metal complexes have emerged as
potential building blocks for nonlinear optical materials due to various excited states
present in these systems as well as their ability to tailor metal-ligand interactions.75-80
Compared to the more common organic molecules, metal complexes offer a large variety
of novel structures, the possibility of enhanced thermal stability and a diversity of tunable
electronic behaviours by virtue of the coordinated metal center and hence they may find
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P. Krishnamoorthy, 2011
use as NLO materials with unique magnetic and electrochemical properties.81-83
Investigations on NLO properties of metal complexes are being pursued by several
research groups.84-90
Di Bella and co-workers reported that bis(salicylaldiminato) metal
Schiff base complexes exhibit good second order NLO properties.91-97
Based on the above facts, studies on the chelating properties of hydrazone ligands
and the effect of coordination of them on the composition and geometry of the complexes
containing cobalt(II), nickel(II) and copper(I/II) ions were undertaken as the subject of
the present work. Additionally, comparison on the biological properties of hydrazone
complexes with respect to DNA / BSA interactions, free radical scavenging and
cytotoxicity under in vitro conditions have been carried out.
Survey of the previous work
Though voluminous reports are available in the literature on the chemistry and
other aspects of metal hydrazone complexes, some of them relevant to our work alone
were reviewed and presented in this part of the Introduction chapter.
Yi-Heng Lu et al.98 reported the synthesis and characterization of Co(II)
complexes containing salicyladehyde benzoylhydrazone (SBH) and established that the
ligand has three sites suitable for coordination bond formation. The UV-visible
absorption spectra using deconvolution method showed that the structure of complex in
solution is different from that in solid crystals. The nature of complexes in solution
depends on acidity of the phenolic proton of SBH and on the medium. In neutral or
slightly acidic medium, the SBH is a non-charged bidentate ligand and the free hydroxyl
group on the SBH molecule makes it possible to form hydrogen bonds in solution. In
basic medium, the SBH is a uninegatively charged tridentate ligand.
N
HN
OO Co
OAc
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Introduction
P. Krishnamoorthy, 2011
Recently, the first Co(III)/Co(III) ionic complex with hydrazone and azide
ligands, [Co(L)2]+[Co(L)(N3)3]
-·CH3OH was structurally and electrochemically
characterized by Bikasa et al.99 in which HL = N'-[(1E)-1-pyridin-2-ylethylidene]-2-
furohydrazide was used as a ligand. In the cation [Co(L)2]+, two units of furanhydrazone,
each of them with three donor atoms constitute a meridional arrangement around the
cobalt atom. The coordination polyhedron is a CoO2N4 distorted octahedron for the
cation and a CoON5 distorted octahedron for the anion. Cyclic voltammetric experiments
of the [Co(L)2]+[Co(L)(N3)3]
- in DMSO revealed the reduction of ligand at -1.56 V and
two reduction potentials at -0.81 and -1.28 V respectively, for two different Co(III) ions.
N
CH3
NN
O
O
CoN
CH3
NN
O
O
N
CH3
NN
O
O
Co
N
N
N
N
N
N
N3
+ -
A novel ligand 2-acetyl-2-thiazoline acetylhydrazone (ATHAc) and two new
chloride-bridged dimeric nickel(II) complexes containing thiazoline hydrazone derivative
ligands, [{Ni(ATsc)(MeOH)}2(μ-Cl)2]Cl2 (1) (ATsc = 2-acetyl-2-thiazoline
semicarbazone) and [{Ni(ATHAc)(H2O)}2(μ-Cl)2]Cl2 (2) were prepared and structurally
characterized using elemental analysis, single crystal X-ray diffraction, IR and UV-
SN
H3CN
N
R
O
Ni
O HH
SN
CH3
N
N
R
O
Ni
OHH
Cl
Cl
2
visible spectroscopy by Vinuelas-Zahinos et al.100 The coordination geometry around
each nickel ion was described as a distorted octahedron coordinated to one thiazoline
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Introduction
P. Krishnamoorthy, 2011
nitrogen atom, one imine nitrogen atom, one carbonyl oxygen atom, one oxygen atom
(from a methanol molecule in 1 and from a water molecule in 2) and two bridging
chloride ligands.
From the reaction between Cu(II) and Ni(II) salts and the Schiff base 6-amino-5-
formyl-1,3-dimethyluracil-benzoylhydrazone (H2BEZDO), in dimethylformamide
(DMF)-water and ammonia media, the complexes [Ni(BEZDO)]·H2O·NH3 (1),
[Cu(BEZDO)]·H2O·NH3 (2) and [Cu(BEZDO)(H2O)]·H2O (3) containing the dianionic
organic ligand have been obtained. These compounds have been studied by IR, electronic
and EPR spectroscopy and magnetic measurements. The structure of
[Cu(BEZDO)(H2O)]H2O has been solved by means of X-ray diffraction method. The
coordination environment around the Cu(II) was a square-plane structure in which the
Schiff base acts as tridentate ligand through the N(6), N(51) and O(52) atoms, making
both a five and six membered chelate rings. The coordination sphere is completed with
the oxygen atom of a water molecule.101
NN
ONH
Cu
OHH
O
O
H3C
CH3
3
Galic et al.102
reported the solution and solid-state complexation behaviour of first
series transition metal cations, Cd(II) and Al(III) with two aroylhydrazones derived from
nicotinic acid hydrazide and salicylaldehyde or o-vanillin at 25 °C in buffered dioxane /
water 1 / 1 mixture (pH, 5.8) by means of spectrophotometric and spectrofluorimetric
titrations. The addition of Mn(II) or Cd(II) ions to hydrazone solutions had no effect on
their absorption spectra whereas the addition of Ni(II) and Cr(III) immediately caused
precipitation.
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Introduction
P. Krishnamoorthy, 2011
NN
OO
N
M
R
NN
OO
N
M
R
where, M = Cu(II) (or) Ni(II) (or) Zn(II); R = H (or) CH3
Three new diorganotin(IV) complexes of the general formula R2Sn[3-(OMe)-2-
OC6H3CH=N–N=C(O)Ph] (R = Ph, Ia; R = Me, Ib; R = n-Bu, Ic) have been synthesised
from the corresponding diorganotin(IV) dichlorides and the ligand, N'-(2-hydroxy-3-
methoxybenzylidene)benzohydrazide in methanol at room temperature in the presence of
trimethylamine.103
All the complexes have been characterized by elemental analysis, IR
and 1H,
13C,
15N,
119Sn NMR spectra and their structures have been confirmed by single
crystal X-ray diffraction analysis of the representative compound Ia in which the ligand
N'-(2-hydroxy-3-methoxybenzylidene)benzohydrazide (H2L) coordinates to the metal
centre in the enolate form via the phenolic O, imino N and enolic O atoms. In the
complex Ia, the central tin atom adopted a distorted trigonal bipyramidal coordination
geometry with the oxygen atoms in axial positions, while the imino nitrogen atom of the
Schiff base and the two phenyl groups occupy the equatorial sites.
O
NN
OSn
R ROCH3
where, R = CH3 (or) CH3CH2CH2CH3 (or) C6H5
A new aroyl hydrazone, N-2-hydroxy-4-methoxybenzaldehyde-N-4-nitrobenzoyl
hydrazone [H2L], its binuclear [Cu2L2] (1) and mixed ligand copper(II) mononuclear
complexes [CuLpy] (2) [py = pyridine] have been prepared by Raj et al.104 The structures
determined by single crystal X-ray diffraction showed that the ligand molecule exits in
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Introduction
P. Krishnamoorthy, 2011
the keto form in the solid state, while at the time of complexation, it tautomerises into the
ligand molecule i.e., both the phenolic and the enolic protons.
NN
OO Cu
NO2
H3CO
NN
OO
O2N
OCH3Cu
NN
OO Cu
NO2
H3CO
N
21
“Tritopic” picolinic dihydrazone ligands with tridentate coordination pockets
were designed to produce homoleptic [3×3] nonanuclear square grid complexes on
reaction with transition metal salts and many structurally documented examples have
been obtained with Mn(II), Cu(II) and Zn(II) ions. However, other oligomeric complexes
with smaller nuclearities have also been identified structurally in some reactions
involving Fe(II), Co(II), Ni(II) and Cu(II) with certain tritopic ligands. This illustrates the
dynamic nature of the metal-ligand interaction and the conformationally flexible nature
of the ligands and points to the possible involvement of some of these species as
intermediates in the [3×3] grid formation process. Examples of mononuclear, dinuclear,
hexanuclear, heptanuclear and nonanuclear species involving Fe(II), Co(II), Ni(II) and
Cu(II) salts with a series of potentially heptadentate picolinic dihydrazone ligands with
pyrazine, pyrimidine and pyridine end groups were described in the same study.105
Cobalt(III) complexes of diacetyl monooxime benzoyl hydrazone (dmoBH2) and
diacetyl monooxime isonicotinoyl hydrazone (dmoInH2) have been synthesized and
characterized by elemental analyses and spectroscopic methods by Naskar et al.106 The
X-ray crystal structure of the hydrazone ligands, as well as that of the cobalt(III) complex
[CoIII
(dmoInH)2]Cl·2H2O (1) were also reported in which the amide and the oxime
hydrogens are deprotonated for both the ligands, while the isonicotine nitrogens are
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Introduction
P. Krishnamoorthy, 2011
protonated. In the [CoIII
(dmoBH)2]Cl (2) complex, only the amide nitrogens are
deprotonated. It was shown that the additional hydrogen bonding capability of the
H3CN
N
NO
N+
CoH3C
O-
N+
NO
NCH3
CH3N
-O
Cl-
1
H H
isonicotine nitrogen resulted in different conformation and supramolecular structure for
dmoInH2, compared to dmoBH2, in the solid state. Comparing the structure of the
[CoIII
(dmoInH)2]Cl·2H2O with that of the Zn(II) complex of the same ligand reported
earlier, it is seen that the metal ion has a profound influence on the supramolecular
structure due to change in geometrical dispositions of the chelate rings.
Synthesis, structural investigation by elemental analyses, magnetic susceptibility
measurements, electronic, IR, NMR and EPR spectral techniques and corrosion inhibition
studies on cobalt(II), nickel(II), copper(II) and zinc(II) complexes with 2-acetylthiophene
benzoylhydrazone (Hatbh) was investigated by Singh et al.107 The molecular structures of
ligand and its copper(II) complex have been determined by single crystal X-ray
diffraction technique. The Cu(II) complex possesses a CuN2O2 chromophore with a
considerable delocalization of charge. The structure of the complex was stabilized by
intermolecular – stacking and C–H··· interactions. Hatbh acts as a monobasic
bidentate ligand in all the complexes bonding through a deprotonated C–O- and C=N
groups. Electronic spectral studies indicated an octahedral geometry for the Ni(II)
complex while square planar geometry for the Co(II) and Cu(II) complexes. EPR
spectrum of the Cu(II) complex exhibits a square planar geometry in both solid and in
DMSO solution. The trend g|| > g > 2.0023 indicates the presence of an unpaired electron
15
Introduction
P. Krishnamoorthy, 2011
in the dx2
-y2 orbital of Cu(II). The electrochemical study of Cu(II) complex revealed a
metal based reversible redox behavior.
CH3
NN
O
S
Cu
H3C
NN
O
S
A new series of macrocyclic unsymmetrical binuclear copper(II) [CuLa,b
]
complexes was prepared by Sengottuvelan et al.108 using 6,6′-piperazine-1,4-
diyldimethylenebis(4-methyl-2-formyl)phenol (La) and 6,6′-piperazine-1,4-
diyldimethylenebis(4-bromo-2-formyl)phenol (Lb) and [Cu(oxen)](ClO4)2 or
[Cu(oxpn)](ClO4)2 (where oxen = N,N′-bis(2-aminoethyl)oxamide and oxpn = N,N′-bis(3-
aminopropyl)oxamide). The binuclear copper(II) complexes contain three different
compartments: the first compartment has two piperazinyl nitrogens and two phenolic
oxygens (N2O2), the second compartment has two phenolic oxygens and two imine
nitrogens (O2N2) and the third compartment has two imine nitrogens and two amide
nitrogens (N4) as coordinating sites. Apart from the three compartments, the complex has
two oxamide oxygen atoms for further coordination. The copper(II) ion in the complex is
2+
where, L1a: R = (CH2)2, X = CH3; L1b: R = (CH2)2, X = Br;
L2a: R = (CH2)3, X = CH3; L2b: R = (CH2)3, X = Br
ON N
O NNCu
OHN
NH
O
(R)
(R)
Cu
X
X
(ClO4-)2
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Introduction
P. Krishnamoorthy, 2011
tetracoordinated with two tertiary nitrogen atoms and two phenoxy oxygen atoms
coordinated in the equatorial plane to the copper(II) ion and the geometry around the
copper nuclei is distorted square planar. Both mono and binuclear copper(II) complexes
were characterized by elemental, electronic, EPR, etc., Further, the electrochemical
studies of the mono- and binuclear copper(II) complexes were also are discussed.
Dioxo- and oxovanadium(V) complexes of biomimetic, ONO and NNS donor
hydrazone ligands and their catalytic reactivity was reported by Monfared et al.109
Oxo-
and dioxovanadium(V) complexes of hydrazone ONO donor ligands with the formula
[VVO(μ2-OCH3)(L
1)]2 (1) and [V
VO2(L
2)]·H2O (2) were synthesized by the reaction of
[VO(acac)2] with proton transfer complexes of benzenetricarboxylic acid /
benzoylhydrazide and benzenetricarboxylic acid / isonicotinohydrazide, respectively
(H2L1 = monocondensation of benzoylhydrazide and acetylacetone, H2L
2 =
monocondensation of isonicotinohydrazide and acetylacetone). Dioxo complex of V(V),
[VO2(L3)] (3), was synthesized by the reaction of equimolar amounts of VO(acac)2, 2-
acetylpyridine and thiosemicarbazide (H2L3 = hydrazone Schiff base of acetylpyridine
and thiosemicarbazide and Hacac = acetylacetone) and characterized by FT-IR, UV-
visible and NMR spectroscopic methods. The crystal structures of 1 and 2 were
determined by X-ray analyses. The 1H NMR spectrum of the complex 1 in CDCl3
solution indicated that this dimeric complex is converted appreciably into its respective
monomeric form. The catalytic potential of the complexes has been tested for the
oxidation of alkene, alkane and aromatic hydrocarbons using H2O2 as the terminal
oxidant.
H3C
NN
OO
CH3
V
O
OCH3
CH3
NN
OO
H3C
V
O
H3COH3C
NN
OO
NH+CH3
V
OO
1
3
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Introduction
P. Krishnamoorthy, 2011
New macrocyclic binuclear nickel(II) complexes have been synthesized by using
the bicompartmental mononuclear complex [NiL] [3,3′-((1E,7E)-3,6-dioxa-2, 7-
diazaocta-1,7-diene-1,8-diyl)bis(3-formyl-5-methyl-2-diolato)nickel(II)] with various
diamines like 1,2-bis(aminooxy)ethane (L1), 1,2-diamino ethane (L
2), 1,3-diamino
propane (L3), 1,4-diamino butane (L
4), 1,2-diamino benzene (L
5) and 1,8-diamino
naphthalene (L6). The complexes were characterized by elemental analysis and
spectroscopic methods. The molecular structures of the symmetrical binuclear complex
[Ni2L1(H2O)4](ClO4)2 (1) and unsymmetrical binuclear complex [Ni2L
3(H2O)4](ClO
4)2·(H2O)4 (3) were determined by single-crystal X-ray diffraction which reveled that
geometry around both the nickel(II) ions in each molecule is a slightly distorted
octahedral. The influence of the coordination geometry and the ring size of the
binucleating ligands on the electronic, redox, phosphate hydrolysis, DNA binding and
cleavage properties have been studied.110
A novel difunctional acylhydrazone has been synthesized by the reaction of 5-
methylisoxazole-4-carboyl hydrazine with benzaldehyde and characterized by X-ray
crystallography and spectroscopy by Jin et al.111 Moreover, the spectroscopic properties
were evaluated through density functional theory (DFT) and time-dependent density
functional theory (TD DFT) calculations. In addition, the results of antibacterial activities
indicated that the title compound has certain modest antibacterial activity as well as the
broad-spectrum bacteriostasis, which can be supported by the molecular electrostatic
potential (MEP). Therefore, it is concluded that the title compound possess both
antibacterial activity and photoluminescent property, which has potential applications in
many fields such as material science and photodynamic therapy.
N NH
O
N
O
H3C
A new bis-phenanthroline dicopper(II) complex has been synthesized and
characterized by elemental analysis and spectroscopic methods by Anbu et al.112
The
molecular structure of the dinuclear Cu(II) complex [Cu2(μ-CH3COO)(μ-H2O)(μ-
18
Introduction
P. Krishnamoorthy, 2011
OH)(phen)2]2+
(phen = 1,10-phenanthroline) (1) was determined by single crystal X-ray
diffraction technique. The coordination environment around each Cu(II) ion in complex 1
was described as slightly distorted square pyramidal geometry. The electronic, redox,
phosphate hydrolysis, DNA binding and DNA cleavage have been studied. The
antiproliferative effect of complex 1 was confirmed by the lactate dehydrogenase (LDH)
enzyme level in MCF-7 cancer cell lysate and content media. The dicopper(II) complex
inhibited the LDH enzyme as well as the growth of the human breast cancer MCF7 cell
line in minimum concentration level.
A series of mono and binuclear copper(II) complexes, of general formulae
[CuL](ClO4) and [Cu2L](ClO4)2, respectively, have been synthesized from lateral
macrocyclic ligands that have different compartments, originated from their
corresponding precursor compounds 3,4:9,10-dibenzo-1,12-[N,N′-bis{(3-formyl-2-
hydroxy-5-methyl)-benzyl}diaza]-5,8-dioxacyclotetradecane (PC-1) and
3,4:9,10-dibenzo-1,12-[N,N′-bis{(3-formyl-2-hydroxy-5-methyl)-benzyl}diaza]-5,8-
dioxacyclopentadecane) (PC-2). The structure of the precursor compound PC-1,
O N O
CH3
N
O N O N
CH3
Cu(CH2)m (CH2)nCu
ClO4
+
where, L1a: m = 2, n = 2; L1b: m = 2, n = 3; L1c: m = 2, n = 4;
L2a: m = 3, n = 2; L2b: m = 3, n = 3; L2c: m = 3, n = 4
(ClO4-)2
mononuclear copper(II) complex [CuL1a
](ClO4) and binuclear copper(II) complex
[Cu2L2c
](ClO4)2 were determined using single crystal XRD. In addition, electrochemical,
magnetic moment and EPR studies evidenced the mono and binuclear nature of them.
19
Introduction
P. Krishnamoorthy, 2011
The observed initial rate constant values of catechol oxidation, using complexes as
catalysts, range from 4.89×10-3
to 5.32×10-2
min-1
and were higher for binuclear
complexes than for the corresponding mononuclear complexes.113
Five new copper(I) complexes containing PPh3 and [2,3]-pyrazino-[1,10]
phenanthroline-2,3-dicarbonitrile (C16H6N6) [Cu(PPh3)(C16H6N6)Cl]·H2O (1),
[Cu(PPh3)(C16H6N6)Br]·CH3CN (2), [Cu(PPh3)(C16H6N6)I]·CH3CN (3),
[Cu(PPh3)(C16H6N6)(CN)]·0.5 CH2Cl2 (4) and Cu(PPh3)(C16H6N6)(SCN) (5) have been
synthesized for the first time114
by the reactions of CuX (X = Cl, Br, I, CN, SCN) with
the bidentate ligand C16H6N6 and the monodentate ligand PPh3 in the molar ratio of 1:1:1
in the mixed solvent of CH2Cl2 and CH3CN (5 mL / 5 mL). They are characterized by X-
ray crystallography, luminescence, IR, 1H NMR and
31P NMR. All the complexes exhibit
intense luminescence in solid state at room temperature.
The macrocyclic symmetrical and a series of unsymmetrical binuclear copper(II)
complexes have been synthesized by using mononuclear complex [CuL] [3,30-((1E,7E)-
3,6-dioxa-2,7-diazaocta-1,7-diene-1,8- diyl)bis(3-formyl-5-methyl-2-diolato)copper(II)].
Another compartment of the [CuL] have been condensed with various diamines like 1,2-
bis(aminooxy)ethane (L1), 1,2-diamino ethane (L
2a), 1,3-diamino propane (L
2b), 1,4-
diamino butane (L2c
), 1,2-diamino benzene (L2d
), 1,8-diamino naphthalene (L2e
) and
characterized by elemental analysis, spectroscopic and X-ray crystallographic methods.
The influence of the coordination geometry and the ring size of the binucleating ligands
on the electronic, redox, magnetic, catecholase activity, DNA binding and cleavage
properties have been studied. The molecular structures of the symmetrical binuclear
complex [Cu2L1(H2O)2](ClO4)2 (1) and unsymmetrical binuclear complex
[Cu2L2b
(ClO4)(H2O)]ClO4 (2b) were determined by X-ray crystallography. The aromatic
diamine condensed macrocyclic ligands of copper(II) complexes display better DNA
interaction and significant chemical nuclease activity than the aliphatic diamine
condensed macrocyclic Cu(II) complexes115
.
20
Introduction
P. Krishnamoorthy, 2011
Two types of copper(II) and nickel(II) complexes derived from benzophenone
anthranoylhydrazone (L1), 2-acetonaftanone anthranoylhydrazone (L2), 4-
phenylacetonaftonone anthranoylhydrazone (L3), benzophenone salicyloylhydrazone
(L4), 2-acetonaftanon salicyloylhydrazone (L5), 4-phenylacetonaftanon
salicyloylhydrazone (L6) and bidentate heterocyclic base [1,10-phenanthroline (phen)]
with general stoichiometry [M(L)2] and [ML(phen)]Cl have been synthesized and
characterized by Gup et al.116
Cytotoxicity, quantitative structure-activity relationships of salicylaldehyde
benzoylhydrazone analogs and their transition metal complexes have been discussed by
Ainscough et al.117 For this discussion, a series of salicylaldehyde benzoylhydrazone
derivatives, their copper(II) complexes and a range of transition metal complexes of the
unsubstituted ligand have been synthesized and evaluated for cytotoxicity against a
human adenocarcinoma cell line. The QSAR analysis revealed a strong correlation
between the ligand cytotoxicity with electronic and transport factors that can be modeled
by treating each „half‟ of the molecule as an isolated unit. Activity increases when
substituents in the benzoyl ring were electron withdrawing whereas for the
salicylaldehyde ring electron donation was required. However, the activity of the
transition metal complexes of the unsubstituted ligand mirrored charge density on the
metal.
O
N
HN
OCu
Cl
R1
R2
The key role of hydrogen bonding in the nuclearity of three copper(II) complexes
with hydrazone derived ligands and nitrogen donor heterocycles were reported by Shit et
al.118 Three new Cu(II) complexes of formula [Cu(L
1)(pyz)(CH3OH)]ClO4 (1),
[Cu(L1)(4,4'-bpy)(ClO4)]·0.5H2O (2) and [{Cu(L
2)(ClO4)}2(μ-4,4'-bpy)] (3) have been
synthesised by using pyrazine (pyz) and 4,4'-bipyridine(4,4'-bpy) and tridentate O,N,O-
donor hydrazone ligands, L1H and L
2H, obtained by the condensation of 1,1,1-trifluoro-
21
Introduction
P. Krishnamoorthy, 2011
2,4-pentanedione with salicyloylhydrazide and benzhydrazide, respectively. The ligands
and their complexes have been characterized by elemental analyses, FT-IR and UV-
visible spectroscopies. Single crystal X-ray structure analysis revealed the metal ion in a
slightly distorted square pyramidal geometry in all the complexes. However, complexes 1
and 2 are mononuclear with pyz and 4,4'-bpy, respectively showing an unusual
monodentate behavior while complex 3 is dinuclear with 4,4'-bpy adopting the typical
bridging coordination mode.
O
HNN
H3C
O
F
FF
Cu
NO4Cl
N
3
O
NHN
CH3
OF
F
F
Cu
ClO4
OH
O
NHN
CH3
O
F
FF
Cu
N
N
OH CH3
ClO4-
OH
O
NHN
CH3
O
F
FF
Cu
N
OH CH3
ClO4-
N
12
Wang et al.119 reported the synthesis, characterisation and calf-thymus DNA
interaction studies of neutral mononuclear Ln(III) complexes with 7-methoxychrom-one-
3-carbaldehyde-isonicotinoyl hydrazone ligand. The antioxidant activities of the ligand
and its Ln(III) complexes were also investigated.
Schleife et al.120 investigated the metal complexation properties of a
functionalized N3O2 donor ligand H2L2, where H2L2 stands for 2,6-diacetyl-4-
22
Introduction
P. Krishnamoorthy, 2011
carboxymethyl-pyridine bis(benzoylhydrazone). The ligand H2L2 is observed to react
essentially in the same fashion as its unmodified parent H2L1 producing mixed-ligand
[M(H2L2)(Cl2)] complexes (M = MnII (1), Co
II (3)) upon treatment with MCl2.
Complexes [M(HL2)(H2O) (EtOH)]BPh4; (M = MnII (2), M = Co
II (4)), incorporating the
supporting ligand in the partially deprotonated form (HL2)-, are formed by salt
elimination of the [M(H2L2)(Cl2)] compounds with NaBPh4. Compounds 2 and 4 are
isostructural featuring distorted pentagonal-bipyramidal coordinated MnII and Co
II ions,
with the H2O and EtOH ligands bound in axial positions.
HN
O
N
H3CN
CH3
NNH
O
O O-
M
Cl Cl
HN
O
N
H3CN
CH3
NN
O
O O-
M
OH2EtOH
where, M = Mn(II) (or) Co(II)
(BPh4)-+
1 (or) 3 2 (or) 4
The reactions between bis(acetylacetonato)dioxomolybdenum(VI) and Schiff base
ligands derived from 5-chlorosalicylaldehyde or 3-ethoxy-salicylaldehye and 3-methoxy-
benzoic hydrazide (m-anisic hydrazide), 2-furoic hydrazide or 2,4-dihydroxy-benzoic
hydrazide in the presence of donor solvents yielded cis-dioxomolybdenum(VI)
complexes with the general formula MoO2L(D), where L = tridentate Schiff base ligand
and D = dimethylsulfoxide, hexamethylphosphoramide, dimethylformamide, imidazole
or methanol. The complexes were characterized by elemental analysis, electronic spectra,
IR, 1H and
13C NMR spectroscopies, thermogravimetric analysis, cyclic voltammetry and
the molecular structures of five of the dioxomolybdenum complexes were elucidated by
single crystal X-ray diffraction studies.121
In general, the complexes adopt an octahedral
environment around the Mo center with a cis-oxo configuration. The other coordination
sites are occupied by the imino nitrogen, phenoxyl oxygen, hydroxyl oxygen of the
tridentate Schiff base and the donor atom of the solvent molecule. The structural data
23
Introduction
P. Krishnamoorthy, 2011
revealed that the labile coordination site, which is occupied by N or O atoms from the
donor solvents, has a longer Mo–O or Mo–N bond distance.
NN
O
Cl
O Mo
O OO
P N(CH3)3
(H3C)3N N(CH3)3
ONN R
O
Cl
O Mo
O OO
S
H3C
CH3
where, R = 3-(CH3O)C6H4 (1) (or) 2-(C4H3O) (2)
(or) 2,4-(OH)2C6H3) (3)
NN
OO Mo
O ODOC2H5
OCH3
where, D = HMPA (5) (or) DMSO (6) (or) DMF (7) (or) Imz (8) (or) MeOH (9)
4
Two new copper(II) complexes have been synthesized by reacting 2-oxo-1,2-
dihydroquinoline-3-carbaldehyde-(benzoyl)-hydrazone (H2L) with CuCl2·2H2O or
Cu(NO3)2·3H2O.122
The structure of the complexes have been determined by single
crystal X-ray diffraction studies. Results obtained using spectroscopic methods strongly
suggested that the ligand and its Cu(II) complexes interacted with calf thymus DNA
through intercalation. In the case of protein binding, the obtained results indicated that all
the three compounds could quench the intrinsic fluorescence of bovine serum albumin
through static quenching process. In addition, antioxidant activity tests showed that H2L
and its copper(II) complexes possess significant scavenging effect against free radicals.
Further, the two copper(II) complexes exhibited effective cytotoxic activity against a
panel of human cancer cell lines.
Six new copper complexes of di-2-pyridyl ketone nicotinoylhydrazone and their
versatile binding properties (HDKN) have been studied by Mangalam et al.123 The
24
Introduction
P. Krishnamoorthy, 2011
complexes have been characterized by a variety of spectroscopic techniques and the
structure of [Cu(DKN)2]·H2O (1) determined by single crystal X-ray diffraction was
proved to be distorted octahedral geometry. The EPR spectra of compounds
[Cu2(DKN)2(μ-N3)2] (2) and [Cu2(DKN)2(μ-NCS)2] (3) in polycrystalline state suggested
a dimeric structure as they exhibited a half field signal, which indicate the presence of a
weak interaction between two Cu(II) ions in these complexes.
NN
O
N
Cu
NN
O
N
1
A new series of stable transition metal complexes of the formula [M(L)X·S] (
where M = Cu(II), Ni(II), Co(III), Cr(III) and Fe(III) and L is the deprotonated ligand of
4-hydroxy-coumarin-3-thiocarbohydrazone, X = Cl-, NO3
- or CH3COO
- and S = H2O and
/ or EtOH) have been prepared.124
The ligand HL acts as a monobasic tridentate ONS
donor in all metal complexes and coordinated through the phenolic OH, azomethine
nitrogen and thione sulfur. The formed complexes after releasing the solvent were
investigated and their structures are suggested to have square planar or octahedral
arrangement. Pharmacodynamic of cobalt(III) complex on some biochemical parameters
and histological studies in serum and heart tissue in rats have been studied. Although the
complexes demonstrated a significant effect at low dose than the high dose, the ligand
showed significant good effects in both high and low doses on the biochemical analysis
in serum and heart tissue. Cobalt complex was screened in order to evaluate its antifungal
activity against the filamentous fungi Aspergillus niger, Aspergillus fumigatus and
Aspergillus flavus and antibacterial activity against the Candida albicans, Escherichia
coli, Klebseilla pneumoniae and Pseudomonas aeruginosa.
25
Introduction
P. Krishnamoorthy, 2011
The coordination behavior of a new dihydrazone ligand, 2,6-bis[(3-
methoxysalicylidene) hydrazinocarbonyl]pyridine towards manganese(II), cobalt(II),
nickel(II), copper(II), zinc(II) and cadmium(II) has been described by Vadavia et al.125
The metal complexes were characterized by magnetic moments, conductivity
measurements, spectral (IR, NMR, UV-visible, FAB mass and EPR) and thermal studies.
IR spectral studies revealed the nonadentate behavior of the ligand. The X-band EPR
spectra of copper(II) complex at both room temperature and liquid nitrogen temperature
showed unresolved broad signals with giso = 2.106. Cyclic voltammetric studies of
copper(II) complex at different scan rates revealed that all the electrochemical reactions
are irreversible in nature.
O
H3CO
NN
ON
N
O
N
OCH3
OM
Cl ClH2O
MM
OH2 OH2
OH2
H2OH2O
H2O
where, M = Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II)
Six copper(II) complexes of 2-hydroxy-4-methoxybenzaldehyde
nicotinoylhydrazone (H2hmbn), 2-hydroxy-4-methoxyacetophenone nicotinoylhydrazone
(H2hman), 2-hydroxy-4-methoxybenzaldehyde benzoylhydrazone (H2hmbb) and 2-
hydroxy-4-methoxyacetophenone benzoylhydrazone (H2hmab) have been synthesized by
Mathew et al.126
The complexes viz. [Cu(hmbn)]2·2H2O (1), [Cu(hman)]2 (2),
[Cu(hmbb)]2·2H2O (3), [Cu(hmbb)phen]·1(1/2)H2O (4), [Cu(hmbb)(bipy)·H2O] (5) and
[Cu(hmab)phen] (6) were characterized by different physicochemical techniques. The
crystal structure of complex 6 showed that it possesses a distorted square pyramidal
geometry with π–π stacking interactions and significant C–H···π interactions.
26
Introduction
P. Krishnamoorthy, 2011
CH3
NN
O
H3CO
O
CuN
N
6
A number of indolo[3,2-c]quinolines were synthesized and modified at the lactam
unit to provide a peripheral binding site to accommodate metal ions.127
Potentially
tridentate ligands HL1a
-HL4a
and HL1b
-HL4b
were reacted with copper(II) chloride in
isopropanol/methanol to afford novel five-coordinate copper(II) complexes
[Cu(HL1a-4a
)Cl2] and [Cu(HL1b-4b
)Cl2]. In addition, a new complex [Cu(HL5b
)Cl2] and
two previously reported compounds [Cu(HL6a
)Cl2] and [Cu(HL6b
)Cl2] with modified
paullone ligands HL5b
, HL6a
and HL6b
which can be regarded as close analogues of
indoloquinolines HL1b
, HL4a
and HL4b
in which the pyridine ring was formally
substituted by a seven-membered azepine ring, were synthesized and compared. The new
ligands and copper(II) complexes were characterized by 1H and
13C NMR, IR and
electronic absorption spectroscopy, ESI mass spectrometry, magnetic susceptibility
measurements in solution at 298 K ([Cu(HL1a
)Cl2] and [Cu(HL4b
)Cl2]) and X-ray
crystallography ([Cu(HL3b
)Cl2]·3DMF, [Cu(HL4b
)Cl2]·2.4DMF, HL5b
and
[Cu(HL5b
)Cl2]·0.5CH3OH). All complexes were tested for cytotoxicity in the human
cancer cell lines CH1 (ovarian carcinoma), A549 (non-small cell lung cancer) and
SW480 (colon carcinoma). The compounds are highly cytotoxic, with IC50 values
ranging from nanomolar to very low micromolar concentrations. Substitution of the
seven-membered azepine ring in paullones by a pyridine ring resulted in a six to nine fold
increase of cytotoxicity in SW480 cells. Electron-releasing or electron-withdrawing
substituents in position 8 of the indoloquinoline backbone do not exert any effect on
cytotoxicity of copper(II) complexes, whereas copper(II) compounds with Schiff bases
obtained from 2-acetylpyridine and indoloquinoline hydrazines are 10 to 50 times more
27
Introduction
P. Krishnamoorthy, 2011
cytotoxic than those with ligands prepared from 2-formylpyridine and indoloquinoline
hydrazines.
Complexes of Co(II), Ni(II), Cu(II), Mn(II), Cd(II), Zn(II), Hg(II) and U(IV)O2
with N′-(1-(4-hydroxyphenyl)-ethylidene)-2-oxo-2-(phenylamino)acetohydrazide
H3OPAH) are reported and have been characterized by various spectroscopic techniques
like IR, UV-visible, 1H NMR and EPR as well as magnetic and thermal (TG and DTA)
measurements.128
It was found that the ligand behaves as a neutral bidentate,
monoanionic tridentate or tetradentate and dianionic tetradentate. An octahedral
geometry for [Mn(H3OPAH)2Cl2], [Co2(H2OPAH)2Cl2(H2O)4] and
[(UO2)2(HOPAH)(OAc)2(H2O)2] complexes, a square planar geometry for
[Cu2(H2OPAH)Cl3(H2O)]·H2O complex, a tetrahedral structure for [Cd(H3OPAH)Cl2],
[Zn(H3OPAH)(OAc)2] and [Hg(H3OPAH)Cl2]H2O complexes. The binuclear
[Ni2(HOPAH)Cl2(H2O)2]·H2O complex contains a mixed geometry of both tetrahedral
and square planar structures.
The design of novel Fe chelators with high Fe mobilization efficacy and low
toxicity remains an important priority for the treatment of Fe overload disease. Some
new methyl pyrazinylketone isonicotinoyl hydrazone (HMPIH) analogs were designed
and synthesised based on previously investigated aroylhydrazone chelators. The HMPIH
series demonstrated high Fe mobilization efficacy from cells and showed limited to
moderate antiproliferative activity. Importantly, this novel series demonstrated
irreversible electrochemistry which was attributed to the electron-withdrawing effects of
the non-coordinated pyrazine N-atom. The latter functionality played a major role in
forming redox-inactive complexes that prevent reactive oxygen species generation. In
fact, the Fe complexes of the HMPIH series prevented the oxidation of ascorbate and
hydroxylation of benzoate. It was determined that the incorporation of electron-
withdrawing groups is an important feature in the design of N,N,O-aroylhydrazones as
candidate drugs for the treatment of Fe overload disease.129
28
Introduction
P. Krishnamoorthy, 2011
A novel hydrazone, N′-(2,4-dimethoxy benzylidene)-2-hydroxybenzohydrazide
(DBH), which is an analogue of isonicotinic acid (3-hydroxy-naphthalen-2-ylmethylene)-
hydrazide possessing potent anticancer activity has been synthesized and characterized.
The interaction between DBH and bovine serum albumin (BSA) was investigated
systematically by fluorescence, molecular docking, circular dichroism, UV-visible
absorption and electrochemical impedance spectroscopy methods under physiological
conditions. The fluorescence quenching observed is attributed to the formation of a
complex between BSA and DBH and the reverse temperature effect of the fluorescence
quenching has been found and discussed. The effects of iron on the system of DBH-BSA
have also been investigated and found that iron could compete against BSA to bind DBH.
All of these results are supported by a docking study using a BSA crystal model. It is
shown that DBH can efficiently bind with BSA and be transported to the focuses
needed.130
The syntheses and characterization of six copper(II) complexes of 2-
benzoylpyridine benzhydrazone (BPB) in the form of [Cu(BPB)2], [Cu(BPB)Cl]·H2O,
[Cu(BPB)Br], [Cu2(BPB)2](ClO4)2·4H2O, [Cu(BPB)N3]·H2O and [Cu(BPB)NCS]·
H2O·CH3OH were reported by Mangalam et al.131
The crystal structural analysis revealed
that the hydrazone adopts the E conformation about the azo bond and attached to the
metal through the Npy–Nazo–O chelating system.
A new series of homo, heterodinuclear and homotrinuclear copper(II) complexes
containing a new Schiff base ligand (L) and 1,10-phenanthroline were synthesized. Based
on the results of elemental analyses, FT-IR, 1H and
13C NMR spectra, conductivity
measurements and magnetic susceptibility measurements, the complexes were assigned
general compositions {[Cu(L)(H2O)M(phen)2](ClO4)2 [M = Cu(II), Mn(II), Co(II)]} and
{[Cu3(L)2(H2O)2](ClO4)2} with metal:L:phen ratio of 2:1:2 for the dinuclear copper(II)
complexes whereas the metal:L ratio for the trinuclear copper(II) complex was 3:2. The
interaction between these complexes and DNA has also been investigated by agarose gel
electrophoresis and it was found that the homo and heterodinuclear copper complexes can
cleave supercoiled pBR322 DNA to nicked and linear forms in the presence of H2O2.132
29
Introduction
P. Krishnamoorthy, 2011
Nickel, copper and zinc complexes of both isatin (H2L1) and N-methylisatin 3-
picolinoyl hydrazone (HL2) were synthesized and characterized by means of
spectroscopic techniques including X-ray diffractometry by Maria et al.133 Biological
studies carried out in vitro on human leukemic cell lines TOM 1 and NB4, have shown
that both ligands and some copper and nickel complexes are active to inhibit cell
proliferation.
N
R O
NN
N
O
N
RO
NN
N
O
M
R = H (or) CH3
Srinivasan et al.134 studied the spectral and redox properties of mixed ligand
complexes of cobalt(III) phenanthroline / bipyridyl-benzoylhydrazones [Co(N-
N)2L](ClO4)2·H2O [where L = anionic form of para-substituted benzaldehyde-
benzoylhydrazone (BHBR); R = H, Me, OMe, OH, Cl or NO2; N-N = 2,2′-bipyridine
(bpy) or 1,10-phenanthroline (phen)] along with their DNA binding and antimicrobial
activity. Binding of these complexes with herring sperm DNA displayed a lower binding
constant value of these complexes with respect to the [Co(phen/bpy)3]3+
due to the polar
interaction of the substituted benzoylhydrazone moiety with the sugar-phosphate
backbone of the DNA. The experimental results indicated that phenanthroline mixed
ligand complexes bound to DNA through an intercalative mode more effectively than
their bipyridine counterparts. These complexes were also found to have good
antimicrobial activity.
30
Introduction
P. Krishnamoorthy, 2011
N
N
O
CoN
NN
N
2(ClO4)-
R
where, R = H (or) Me (or) OMe (or) OH (or) Cl (or) NO2
Anticancer activity, structure and theoretical calculation of N-(1-phenyl-3-methyl-
4-propyl-pyrazolone-5)-salicylidene hydrazone (H2L) and its copper(II) complex
[Cu2L2CH3OH]·2CH3OH has been studied by Zhang et al.135 The crystallographic
structural analysis of the complex revealed that the two Cu centers display two different
coordination patterns. The pharmacological result showed that the coordination effect
improves the antitumor activity of the ligand. The calculated Fukui function for H2L and
its deprotonated form L2 predicts that the most probable reactive sites for electrophilic
attack are oxygen atoms and the theoretical data were in good agreement with the
experimental data.
O
N N
O
N N
O
O
CuCuOH3C
H
Binuclear complexes [Zn2(HL1)2(CH3COO)2] (1) and [Zn2(L
2)2] (2) were
synthesized with salicylaldehyde semicarbazones (H2L1) and salicylaldehyde-4-
chlorobenzoyl hydrazone (H2L2) respectively by Parrilha et al.136
Upon recrystallization
of previously prepared [Zn2(HL2)2(Cl)2] (3) in 1:9 DMSO:acetone crystals of
31
Introduction
P. Krishnamoorthy, 2011
[Zn2(L2)2(H2O)2]·[Zn2(L
2)2(DMSO)4] (3a) were obtained. The crystal structure of 3a was
also determined. All crystal structures revealed the presence of phenoxo-bridged
binuclear zinc(II) complexes.
ONN
H2N O
Zn
OS
CH3
H3C
O NN
NH2O
Zn
OS
H3C
CH3
1
Complexation of iron(III) with the heterodonor chelating agent 3,5-di-tert-
butylsalicylidene benzoylhydrazine (H2(3,5-tBu2)salbh), in the absence or presence of a
base afforded the complex cation [Fe{H(3,5-tBu2)salbh}2]
+(1) or the neutral compound
[Fe{H(3,5-tBu2)-salbh}{(3,5-
tBu2)salbh}] (2) respectively as revealed by single-crystal
X-ray analyses. Such a synthetic and crystallographic demonstration of the coordination
versatility of an aroylhydrazone towards iron is uncommon. The oxidation and spin states
of the iron have been verified with magnetic and spectroscopic measurements.137
Bu2t
N
HN
OO
Fe
tBu2
NN
OOtBu2
tBu2
Bu2t
N
HN
OO
Fe
tBu2
NNH
OOtBu2
tBu2
1 2
Novel Ln(III) complexes with hesperetin-4-one-(benzoyl) hydrazone (H4L) have
been synthesized and characterized.138
Electronic absorption spectroscopy, fluorescence
spectra, ethidium bromide displacement experiments, iodide quenching experiments, salt
32
Introduction
P. Krishnamoorthy, 2011
O
HN N
O
OH
OH
OHH3CO
LnO
NHN
O
HO
HO
HO OCH3
O
ON O
O
ONO
NO3-
where, Ln = La (or) Sm (or) Dy (or) Yb (or) Nd
.
+
effect and viscosity measurements indicated that the ligand and Ln(III) complexes,
especially the Nd(III) complex strongly bind to calf thymus DNA presumably via an
intercalation mechanism. The intrinsic binding constants of the Nd(III) complex and
ligand with DNA were 2.39×106 and 2.7×10
5 M
-1, respectively. Further,, the in vitro
antioxidant activity of the ligand and Ln(III) complexes was determined by superoxide
and hydroxyl radical scavenging method indicated that the ligand and Ln(III) complexes
have the activity to suppress O2-. and HO
. and the Ln(III) complexes were more effective
than the free ligand.
A macrocyclic hydrazone Schiff base synthesized by reacting 1,4-dicarbonyl
phenyl dihydrazide with 2,6-diformyl-4-methyl phenol was treated with Co(II), Ni(II)
and Cu(II) salts and the new complexes have been characterized by elemental analyses,
IR, 1H NMR, UV-visible, FAB mass, EPR spectra, fluorescence, thermal, magnetic and
molar conductance data.139
The electrochemical behavior of the copper(II) complex was
investigated by cyclic voltammetry. EPR spectra of the complex showed the presence of
33
Introduction
P. Krishnamoorthy, 2011
O
CH3
NNH
O
NHN
O
O
CH3
NHN
O
NNH
O
M M
Cl
Cl
.(H2O)2
where, M = Co(II) or Cu(II)
O
CH3
NNH
O
NHN
O
O
CH3
NHN
O
NNH
O
Ni Ni
Cl
Cl
.(H2O)2
E
E
where, E = H2O
a considerable covalent character in the metal-ligand bond. The brine shrimp bioassay
was also carried out to study their in vitro cytotoxic properties. The Schiff base and its
complexes have also been screened for their antibacterial and antifungal activities
(Escherichia coli, Staphylococcus aureus, Shigella dysentery, Micrococcus, Bacillus
subtilis, Bacillus cereus, Pseudomonas aeruginosa, Aspergillus niger, Penicillium and
Candida albicans) by MIC method.
Two novel 2-oxo-quinoline-3-carbaldehyde-(4'-hydroxybenzoyl) hydrazone
thiosemicarbazone ligands and their corresponding water soluble Cu(II) complexes were
synthesized and characterised by single crystal X-ray diffraction.140
Interaction of these
Cu(II) complexes with calf thymus DNA (CT DNA) was investigated by electronic
absorption spectroscopy, fluorescence spectroscopy and viscosity measurement. Further,
the in vitro antioxidant activity of the above complexes were determined using hydroxyl
and superoxide radicals.
Metal complexes of 2-methyl-1H-benzimidazole-5-carboxylic acid hydrazide and
its Schiff base, 2-methyl-N-(propan-2-ylidene)-1H-benzimidazole-5-carbohydrazide with
copper, silver, nickel, iron and manganese were prepared and their antitumor activity has
34
Introduction
P. Krishnamoorthy, 2011
been studied. Among the complexes, the silver containing one displayed cytotoxicity
(IC50 = 2 μM) against both human lung cancer cell line A549 and human breast cancer
cell line MCF 7.141
35
Introduction
P. Krishnamoorthy, 2011
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