CHAPTER ONE

Introduction

1 | P a g e Chapter-I: Introduction

Chapter -I

INTRODUCTION C

on

ten

ts

1.1 Coordination compounds:

1.2 A brief review of some metals of biological and chemical importance:

1.3 A brief review of Schiff base Ligands:

1.4 A brief review on Benzofuran and Naphthofuran:

1.1. Coordination Compounds:

Coordination Chemistry is the branch of science which deals with the

interaction of inorganic and organic ligands with central metal ions. It also studies the

synthesis, structures, physical, chemical and biological properties of the coordination

compounds. Coordination Chemistry is a dynamic and pioneering branch of science

and its study established much attention and offered inexhaustible results and hence this

has become an extremely important and attractive field for researchers. Coordination

compounds were known, but not understood in any sense till the beginning of the 20th

century, when Alfred Werner developed the basis of modern Coordination Chemistry.

It must be remembered that the Werner’s coordination theory in 1893 was put forward

before the electron had been discovered by J. J. Thompson in 1896, and therefore the

Electronic Theory of Valency. This theory and his painstaking work over the next 20

years won Alfred Werner the Nobel Prize in Chemistry in 1913 [1]. In recent years,

researchers have undertaken a number of methodologies towards the design and

synthesis of metal-organic coordination compounds [2]. The work on coordination

chemistry is the fundamental important topic of current interest.

Applications of coordination compounds are not only limited to synthesis and

stereochemistry but also for chemical, pharmaceutical, agriculture, cosmetics and

textile industries. Coordination compounds also play key role in Geoscience,

oceanography, agriculture and bio-inorganic chemistry as well. The Photolytic splitting

of water producing oxygen and hydrogen by metal complexes can be seen as one of the

important sources of renewable and nonpolluting energy, which may be an ultimate

solution to save the world from a severe energy crisis in the future due to non-

availability of fossil fuels. The knowledge of the factors that govern the stability and

2 | P a g e Chapter-I: Introduction

relativities of metal complex and the nature of the metal ligand bond provide a

fundamental basis for understanding the behavior of metal complexes.

In the modern world development of coordination chemistry has been

dominating among the research field in inorganic chemistry. Several coordination

compounds of transition and non-transition metal ions with a wide variety of ligands

have been reported.

The nature of the coordination compounds depends on the metal ion and donor

atom, the structure of the ligand and the metal-ligand interaction [3]. One of the most

important problems in coordination chemistry is 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 ions [4].

Tremendous growth of coordination chemistry is ranging areas from a purely

academic synthesis of 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 complexes [5-

7]. Thermal techniques such as TGA, DTA, DTG and DSC are also helpful for the

study of these complexes.

Synthetic and structural characterization of complex compounds is important

and has been spurred by the progress on the theory of electronic structure, later it has

provided insight into the pH metric, spectroscopic, magnetic, structural,

thermodynamic and kinetic properties of complexes. These developments of newer and

improved techniques as well as the easy availability of sophisticated analytical

instrument facility are mainly responsible for the Renaissance of coordination

chemistry. The Ligand Field Theory (LFT) and Molecular Orbital Theory (MOT) are

also of immense help to those, who is working in this rapidly growing field of inorganic

chemistry [8, 9]. 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 was explained by Bethe [10] in 1929. Physicists Vanvlenck [11] 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

3 | P a g e Chapter-I: Introduction

account the ligand orbitals, another approach is the so called angular overlap model

(AOM).

The wide application of coordination compounds leads 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. 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) supports to this view.

1.2. A brief review of some metals of biological and Chemical importance:

Cobalt: It is one of the first transition metals; it exhibits various oxidation states ranging

from +1 to +5. The most common oxidation states are +2 and +3. The cobalt literature

survey reveals that Co (II) is basically associated with different types of stereochemical

configurations such as tetrahedral, octahedral and square planar. Stable form of cobalt

is created in supernovas via the r-process [12]. Cobalt is a key constituent of

cobalamin/vitamin B12 (Figure1.1) Nicholls has reviewed the biological importance of

Cobalt compounds [13].

Figure-1.1 Cobalamin

Nickel: On earth the natural sources of nickel are found in combination with sulfur and

iron in pentlandite, with sulfur in millerite, with arsenic in the mineral nickel , and with

arsenic and sulfur in nickel galena [14,15]. Nickel plays important roles in the biology

of microorganisms and plants. The NiFe-hydrogenases contain nickel in addition

to iron-sulfur clusters. Such [NiFe]-hydrogenases characteristically oxidize H2. A

nickel-tetrapyrrole coenzyme, Cofactor F430 (Figure-1.2), is present in the

4 | P a g e Chapter-I: Introduction

methyl coenzyme M reductase, which powers methanogenic archaea [16]. 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 is dependent on the nature of the solvent, concentration and temperature.

Numerous interesting studies on Ni(II) complexes have been reported in literature [17-

20]. Five coordinated Ni(II) complexes with a trigonal bipyramidal [21] distorted

trigonal prismatic structure [22] and square pyramidal geometry [23] have also been

reported.

Figure-1.2: A nickel-tetrapyrrole coenzyme/Cofactor F430

Copper: Copper is synthesized in the universe in a massive stars [24] and it occurs in

the Earth's crust at a concentration of about 50 parts per million (ppm) [25]. It has a

single electron outside the completed 3d shell, exhibit oxidation states of +1, +2 and

+3. Among these di-positive state is the most important one for copper. The 3d9

configuration makes Cu (II) susceptible to Jahn-Teller distortion when placed in an

environment of cubic symmetry, i.e. regular octahedral or tetrahedral and this has

performed effect on its stereochemistry. All the hexacoordinated Cu (II) complex

structures of which have been established by X-ray technique [26] are found to be

affected from tetragonal distortion due to Jahn-Teller distortion. Copper proteins have

diverse roles in biological electron transport and oxygen transportation, processes that

exploit the easy interconversion of Cu(I) and Cu(II) [27]. Copper compounds have

applications in organic chemistry for oxidations, coupling reactions, halogenations etc.

[28] Oxidation of phenol by copper amine complexes [29], provides a 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 cancer [30] and enhances the life

span to the extent of 200 to 300% another important use of copper complexes is in the

catalysis [31] Considerable effort has now been focused on the development of new

anticancer drugs based on biocompatible copper(II) complexes, that bind to cleave

5 | P a g e Chapter-I: Introduction

DNA under physiological conditions. Also, these complexes must recognize nucleic

acids, particularly, in a sequence-specific fashion and then bind to them in a way that

alters their function. Copper complexes, which possess biologically accessible redox

potentials and demonstrate high nucleobase affinity, are potential reagents for cleavage

of DNA both oxidative and hydrolytically. The ability of copper complexes to cleave

DNA upon photo activation under physiological conditions has also received

considerable attention because of their possible utility in highly targeted Photodynamic

therapeutic applications [32]. Another natural occurrence of copper is

Hemocyanins/haemocyanins (Figure-1.3) a kind of proteins which transport oxygen in

some of the invertebrate animals. These proteins contain two copper atoms which

reversibly bind to a single oxygen molecule. They are secondary after hemoglobin in

frequency of use as an oxygen transport molecule. Unlike the hemoglobin in red blood

cells found in vertebrates, hemocyanins are not bound to blood cells but are instead

suspended directly in the hemolymph. Oxygenation causes a color change between the

colorless Cu(I) deoxygenated form and the blue Cu(II) oxygenated form.

Figure-1.3

Zinc: The element is normally found in association with other base metals such

as copper and lead in ores [33] It shows oxidation states of +1 and +2, Zn (I) do not

occur in the normal conditions, only spectroscopic species have been detected. Like

Hg+2, Zn+2 ions also exists [34]. 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 complex with coordination

number 4. Five coordinated complexes either possess 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

toxicity is too low. Zinc, a constituent of the enzyme carbonic anhydrous, which is

6 | P a g e Chapter-I: Introduction

involved in the conversion of CO2 to carbonic acid in plants. It is also found in the horse

- liver as alcohol dehydrogenase. Zinc gluconate/ zincum gluconicum (Figure-1.3) is

the zinc salt of gluconic acid. It is an ionic compound consisting of two moles of

gluconate for each mole of zinc. Zinc gluconate is a popular form for the delivery of

zinc as a dietary supplement [35]. Deficiency of Zinc in animals results in stunted

growth and male sexual immaturity, the toxicity of Zinc is very low. Complexes with

different substituents and bridging units, Zn (II) Schiff base complexes display

multiform photophysical properties. Use of maleonitrile as a bridging unit quenches

the quantum efficiency of square- planar Zn(II) Schiff base complexes. The synthetic

methodology used for the Zn complexes could be used in the preparation of Mg(II)

Schiff base derivatives [36].

Figure-1.3. Zinc gluconate structure

Cadmium: It founds at a concentration of 0.1 ppm of the Earth's crust as compared with

the more abundant 65 ppm zinc, cadmium is a very rare element and associated always

with zinc as (ZnS) sphalerite [37]. It shows +1 and +2 oxidation states, Cd (I) have

been isolated in the solid state. Cd(II) is well known to form a large variety of

compounds and complexes. 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 systems; on the contrary, its presence in

living organism 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. Silver and its salts have anti-bacterial properties and are used as disinfectants

due to their germicidal effects [38, 39] for example silver nitrate (AgNO3) in diluted

solution is administered to the eyes of newborn as a prophylactic agent against

gonorrheal infections [38-40]. Gold compounds, like Auronofin (2,3,4,6-tetra-o-

acetyl-1-thio--D-glucopyranosido-S) triethyl phosphrine gold [41,42] are applied as

oral drugs against rheumatoid arthritis [43,44]. Cisplatin, Cis-(NH3)2 PtCl2, which is

successfully employed worldwide as an anticancer drug or lithium carbonate which is

given to patient with certain mental disorders [45]. Lead is one of the oldest metal

7 | P a g e Chapter-I: Introduction

known to man and its toxicity was recorded already by Greek and Arab Scholars [46]

lead interest with the metabolism and action of essential metals, particularly Ca, Fe, and

Zn, lead(II) can act as an effective substitute. It is harmful mainly through its

neurotoxicological effects [47].

The studies of Alfred Werner and his contemporaries followed by the ideas of

Lewis [48], Langmuir [49] and Sidgwick [50], who put forward the Effective Atomic

Number (EAN) on electron pair bond led to the idea that ligands are the groups which

donate electron pairs to the metal ions, thus forming so called coordinate bond. This

approach to bonding in complexes was extended by Pauling [51] and developed the

Valence Bond Theory (VBT) of metal ligand bonding. This theory virtually exclusive

popular during 1930 and 1940s. But in 1950s, it was supplemented by the Crystal Field

Theory (CFT). The CFT was first expounded in 1929 by H. Bethe [10].

1.3.A brief review of Schiff base Ligands:

Schiff base ligands and their metal complexes plays an important role in the

development of coordination chemistry, related to catalysis, Fluorescence study,

enzymatic reactions, magnetism, molecular architectures, food industry, dye industry,

analytical chemistry, anti-bacterial, anti-fungicidal and agrochemical activity [52-62].

Schiff base ligands derived from the condensation of Salicylaldehyde, acetophenones,

coumarins and their substituted compounds with primary amines represent an important

class of chelating ligands and their metal complexes have been widely studied [63,64].

It has long been known that, metal ions involved in biological processes of life

and has been the subject of interest. The modes of action of these metal ions are often

complex, but are believed to involve bonding to the hetero atoms of heterocyclic

residues of biological molecules viz. Proteins, enzymes, nucleic acids, etc. [65].

Schiff bases have exhibited higher coordination number and from kinetics and

thermodynamic point of view, they are an 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 a wide range of applications [66-69].

Hydrazides and Thiazoles represent a very interesting class of compounds

because of their wide applications in pharmaceutical, analytical and industrial aspects,

e.g., as an antibacterial, antifungal, anti-inflammatory, antitubercular, anti-HIV, anti-

8 | P a g e Chapter-I: Introduction

degenerative activities and herbicides [70-76]. In recent years thiozole based chemi-

sensors have been investigated and showed to be successfully applicable in biological

systems [77, 78]. Numerous Thiazole and Hydrazide derivatives of Schiff base

ligands and their transition metal complexes have been investigated by various

physico-chemical techniques [79-82].

Azomethines and their complexing capabilities have been enlightened in many

review articles [83-86]. 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 separated from imines, oximes, etc.

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 has been tried for their complexation and the structures were deduced

with the aid of analytical, physico-chemical and spectral data.

Monodentate Schiff bases:

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 of the other group is required to stabilize the metal - nitrogen bond. Aryl

groups are attached to either O or N generally stabilizes the Schiff base by resonance.

Monoamine Schiff base as N-benzylidene-aniline derivatives, Figure-1.4 are well

known in the literature [87].

Figure-1.4 Where R1 = R2 = H, Cl, CH3, OCH3 and NO2.

Bidentate Schiff bases:

Bidentate Schiff bases are the most useful ligands for preparing metal complexes.

Potential bidentate ligands depending on their donor atom set has been given below.

O, N and N, N donor atom set:

A number of metal complexes were synthesized by using Schiff bases having

N, O and N, N donor sets. Since in N, O donor set oxygen is often represented by -OH

9 | P a g e Chapter-I: Introduction

group. These Schiff bases generally acts as chelating mono amines. Hydrazides have

been synthesized and complexed with transition metals, both -NH2 and C=O groups

are involved in the bond formation [88], Figure-1.5.

Figure-1.5

Also, there are a number of examples for potential bidentate ligands with N, O donor

sets derived [89] from 2-hydroxy aldehyde Figure-1.6 and N, N donor sets p-anilines

Figure-1.7.

Figure-1.6

Figure-1.7

Singh et. al. [90], have synthesized 2-furoyl hydrazones of 2-acetyl thiophene

and 2-acetyl furan Figure-1.8 and Figure-1.9 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

following ligands.

Figure-1.8

Figure-1.9

Mononuclear Co(II), Ni(II), Cu(II) and Zn(II) complexes of bidentate Schiff base 4-(1-

methyl-1-mesylcyclobutane-3-yl)-2-(2, 4-dihydroxybenzyli-dene hydrazino) thiazole

(Figure-1.10) have been reported by Alladin et. al. [91]. These complexes have been

characterized by Microanalysis, IR, UV-Vis., 1HNMR and magnetic susceptibility

measurements.

10 | P a g e Chapter-I: Introduction

Figure-1.10

One of the most important and frequently used in the literature, for the development

of the pyrazole ring system is carbonylhydrazide (CO=NHNH2). Based on this we

evolved a synthetic strategy, which involves the modification of the carbonyl hydrazide

group located on furan moiety of the benzofuran nucleus into the desired benzofuran

ring system. The benzofuran-2-carboxylhydrazide. (Figure-1.12) and 3-methoxy

benzofuran-2-carboxyl hydrazide (Figure-1.11) have been synthesized as described by

Tanaka [92].

Figure-1.11

Figure-1.12

Hiremath et. al. [93], have reported the complexes of 3-acetylamino-2-benzofu-

ran carboxamide [L], 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 indicate that 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.

M. Nagar et.al [94] have reported complexes of the type ML2Cl2 (Figure-1.13)

where Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II) and L= cis-3,7-dimethyl-2,6-

octadiensemicarbazone. Structures of the synthesized complexes were determined on

the basis of elemental analysis, molar conductivity, magnetic measurements, IR and

electronic, as well as NMR spectra. L acts as a bidentate ligand in all the complexes.

Figure-1.13

11 | P a g e Chapter-I: Introduction

M. B. Halli et.al.[95], have reported complexes of the type MLCl2,

where, M=Co(II), Ni(II), Zn(II), Cd(II) and Hg(II) where L =3,7-dimethylocta-2,4,6-

trien-1-ylidene)naphtho[2,1-b]furan-2-carbohydrazide (Figure-1.14) and are

characterized by elemental analysis, electrical conductance, magnetic moment, IR and

electronic spectral data. These results indicated that Co(II), Ni(II) and Cu(II) Zn(II)

and Cd(II) complexes are dimeric octahedral in naturel. The ligand behaves as

bidentate in all the complexes.

Figure-1.14

D. Khalaji et. al. [96]. have synthesized bidentate Schiff base ligands of N,N′-

bis(2,3,4-trimethoxybenzylidene)-1,2-diaminoethane, and its corresponding zinc(II)

and mercury(II) complexes and characterized by elemental analyses (CHN), FTIR and

proton NMR spectroscopy. The thermal behaviors of complexes were studied using

Thermogravimetry in order to evaluate their thermal stability and thermal

decomposition pathways. The crystal structures were determined from single crystal X-

ray diffraction. The coordination polyhedron about the zinc(II) center in complex is

best described as a distorted tetrahedron (Figure-1.15).

Figure-1.15

J. Zhang. et al. [97] have reported two cobalt(III) complexes with the Schiff

bases 4-X-2-(cyclopentyliminomethyl)phenol (Figure-1.16) (X = chloro and bromo)

were synthesized and structural characterized by elemental analysis (CHN), FT-IR

spectra, and single crystal X-ray diffraction. The Co atom in each complex is six-

12 | P a g e Chapter-I: Introduction

coordinated in an octahedral geometry by three O atoms and three N atoms from three

Schiff base ligands.

Figure-1.16. The Schiff bases [X = Cl/Br]

Tridentate Schiff bases:

There are a large number of tridentate Schiff bases containing NNO, NNS,

NOO, NSO donor sets [98]. 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 (Figure-1.17) and

(Figure-118).

Figure-1.17 and 1.18

Co(II), Ni(II), Cu(II) and Cd(II) complexes of tridentate Schiff base (Figure-1.19) have

been reported by N. Nawar and others [99]. These complexes have been characterized

by elemental analysis, IR, Mass, 1HNMR, Electronic Spectra and magnetic

susceptibility measurements, spectrophotometric and potentiometric studies. Also,

they have studied antimicrobial activity.

Figure-1.19

Abdel et. al. [100] have reported synthesis of five mononuclear complexes

(Figure-1.20) of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) with the tridentate Schiff base

N-(2-hydroxy-5-bromobenzylidene)-2-hydroxyaniline. The complexes were fully

characterized by elemental analyses, FT- IR, 1H NMR, EPR, FAB mass spectra,

13 | P a g e Chapter-I: Introduction

electronic spectra, molar conductivity, magnetic susceptibility measurements and

thermogravimetric analyses (TGA). Structural compositions were assigned by mass

spectral studies. Four-coordinate geometry has been assigned to these complexes

tentatively.

Figure-1.20

Pyridine-2-carboxaldehydearylhydrazone (Figure-1.21) possessing pyridine N, imine

N and the amide O forms two five membered chelate rings upon complexation with

metal ions. The reaction of one mole of [C ((O2CCH))2]H2O and two moles of Schiff

bases in methanol, the complexes of general formula [CuL] [101]. Generally, hexa-

coordinated complexes undergo tetragonal distortion from the octahedral symmetry

Figure-1.21

due to the Jahn-Teller distortion. The structure of the above reported hexacoordinated

Cu (II) complex [Cu (pabh) 2] (Figure-1.22) 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 inconsistent with its structure.

Figure-1.22

14 | P a g e Chapter-I: Introduction

M. B. Halli et. al. [62], have reported the complexes of the type of ML2 Figure-1.23

where L=2-hydroxyquinoline-3-yl)methylene) methylene)benzofuran-2-

carbohydrazide with Co(II), Ni(II) and Co(II) metal ions and characterized on the basis

of elemental analysis, IR, electronic spectra, magnetic moments and conductance

measurement studies.

Figure-1.23

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 behavior. Tetradentate Schiff bases of ethylene diamine are given

below: (Figure-1.24 and Figure-1.25.)

Figure-1.24 Figure-1.25

Dubsky and Sokola [102] have reported the reactions of salicylaldehyde with

diamines. These display show Tetradentate behavior by forming square-planar

complexes (Figure-1.26) with Ni(II) and Cu(II). They form inner complexes. The

complexes of transition and non-transition metals with Schiff bases derived from

aliphatic diamines have received considerable attention in these years [103].

15 | P a g e Chapter-I: Introduction

Figure-1.26

Carrigan and co-workers [104] have carried out electron spin resonance

spectral analysis of Cu(II) complexes of bis(mercaptobenzylidene)diamine (Figure-

1.27) and have reported the configuration around the Cu(II) ion, viz. square-planar.

They have calculated the various parameters using computer simulated programs.

Figure-1.27 Figure-1.28

Sacconi and Bertini [105] have reported similar type of ligands while trying to

prepare a Cu(II) complex containing ethylenediamine and acetyl acetone Figure-1.26.

Morgan and Mainsmith [106] obtained a green complex having the following structure.

This complex was synthesized by Combos as early in 1889.

Pfeiffer [107] has extended the field to the various aromatic diamines, like the

derivatives of bis(salicylidene)ethylenediamine, o-phenylenediamine derivatives yield

metal complexes (Figure-1.29) containing two six membered and one five membered

ring [108].

Figure-1.29. Where = Co(II), Ni(II), or Cu(II)

Mevlut Bayrakcı. et. al [109] reported the Schiff base metal complexes of

Co(II), Ni(II), Cu(II), Zn(II) (Figure-1.30) synthesized from 4,4'-((1E,1'E)-((4,4'-

bis((E)-(2,5-dihydroxybenzylidene)amino)-[1,1'-biphenyl] 3,3'diyl) bis

16 | P a g e Chapter-I: Introduction

(azanylylidene))bis (methanylylidene))bis(benzene-1,3-diol). Analytical and spectral

data reveals the tetradentate nature of the synthesized ligand.

Figure-1.30

N. Raman et. al. [110] have reported a tetradentate Schiff base ligand de- rived

from 3- benzalideneacetoacetanilide and N-(2-aminoethyl)-1,3- propanediamine The

nature of the complexes (Figure-1.31) and the geometry have been inferred from their

microanalytical data , magnetic susceptibility measurements , IR , UV - Vis , 1 H NMR

, ESR , and mass spectral techniques.

Figure-1.31. (ligand L and its X= Cu(II), Ni(II) Co(II) and Zn(II) complexes.

1.4. A brief review on Benzofuran and Naphthofuran:

Benzofuran compounds are distributed widely in the nature and most of them occur

in plant kingdom these compounds having Benzofuran nucleus (Figure-1.32) are

extremely important and useful in many areas of agriculture, Pharmaceutical chemistry,

Industrial chemistry, Biology [111-116] etc., The compounds with benzofuran moiety

have stimulated huge curiosity to the chemists for their biological significance and are

good chelating agents, with many analytical applications both in qualitative and

quantitative analysis. The vast interest in synthetic products containing benzofuran

nucleus has resulted in the progress of benzofuran chemistry in a remarkable fashion

during the last several ages. A numerous studies demonstrated that on complexation

with metals, benzofuran products show superior biological and catalytic activity. It was

also reported that halide substitution on the aromatic ring significantly increased the

17 | P a g e Chapter-I: Introduction

antibacterial activity [117]. This Antimicrobial property of the compound either kills

the microbe or prevents their reproduction by hindering active sites [118].

Figure-1.32

Benzofuran compounds ranges from a simple molecule such as 5-

methoxybenzofuran (Figure-1.33) to a highly complex molecule like morphine A and

B, much more synthetic work has been carried out so far. Recently Shigetoshi Kadota

et. al. [119] have discovered benzofuran derivatives, Propolis-benzofurans A (1) and B

(2), which were isolated from the methanol extract of Brazilian Propolis, together with

two known isoprenylated compounds (E) -3-[2,3-dihydro-2-(1- methylethenyl) -7-

prenyl-5-benzofuranyl] -2-propenoic acid and (E) -3-{4-hydroxy-3-[(E) -4-(2,3-

dihydrocinnamoyloxy) -3-methyl 2-butenyl] -5-prenylphenyl} -2-propenoic acid.

These compounds were elucidated on the basis of spectral analysis. Both the new

compounds exhibited mild cytotoxicity toward highly liver-metastatic murine colon 26-

L5 carcinoma and human HT-1080 fibrosarcoma cells.

Figure-1.33.

These furan containing polycyclic (Figure-1.34 and Figure-1.35) compounds

may provide high HOMO levels and have useful utility in the Organic light emitting

diodes (OLEDs) [120] and organic field-effect transistors (OFETs) [121].

Figure-1.34. Where R= H/Me/Ph2N-C6H4/(p-tol)2-N-C6H4

18 | P a g e Chapter-I: Introduction

Figure-1.35. R=H/n-C8H17

Amiodarone,(2-{4-[(2-butyl-1-benzofuran-3-yl)carbonyl]-2,6-diiodophenoxy}

ethyl) diethylamine) [122], (Figure-1.36) was first introduced in Europe as an

antifungal agent [123], but was later found to be highly effective antiarrhythmic drug

[124, 125]. It has been designated as “Ideal antiarrhythmic drug” because of its high

degree of efficacy wide spectrum arrhythmias and also because of initial patient

acceptance [126]. In December 1985 amiodarone [127] (cordarone) was approved in

the United States [128] for treatment of life threatening ventricular tachyarrhythmia’s.

Figure-1.36

Baker’s yeast / Saccharomyces cerevisiae [129], comprises a benzofuran

derivative, which acts as an antioxidant and prevents, hemorrhaging liver necrosis in

rats and hemolysis of red cells in vitamin E deficient rats [130].

Egonoki (Styrax Japonicus) seed oil which commonly found in Japan contains

a benzofuran derivative called “Egonol” (Figure-1.37). It is an effective synergist for

rotenone pyrethrum against houseflies, mosquitoes, aphids and many other insects

[112].

Figure-1.37

Moracins/Mori Cortex (Radicis, the root bark of some Morus species,)( Figure-

1.38) a Benzofuran analogue possesses excellent antibacterial and antifungal activities it

19 | P a g e Chapter-I: Introduction

has been used in oriental medicine as an antidiabetic, diuretic, expectorant and laxative

agent [131]. Moncrieff [132] have studied the elementary compound provalin in

furocoumarin, which is used as medicine for the treatment of Leukoderma.

Figure-1.38. Basic scaffold of moracin

Sridhar et.al. [133], have synthesized 3-methyl/5-methoxybenzofuran-2-

carbamate and carbamide derivatives are well known biodynamic agents possessing

various pharmacological properties. The presence of the nitro group in the benzofuran

derivatives is more important for paraciticidal properties of Benzofuran [134,135].

Vaidya et. al. [136], have synthesized some aryl and aryloxy 1-5-nitrofuran-2-

carbomates having antibacterial and antifungal activities. (Figure-1.39 and 1.40)

Figure-1.39 and 1.40

Benzofuran, Naphthofuran and Furanochromens are well recognized to possess

numerous pharmacological properties, eg. Natural furochrome Khellin (Figure-1.41)

known possess many physiological activity. It exhibits high anti-atherosclerotic and

lipid altering activity, it is one of the active constituent of modern medicines [137]

Spath and Gruber [137], have reported that Khellin (Figure-1.42) has a

selective antispasmodic effect upon the ureter bronchial muscles, gall bladder and bile

duct. Choline is found to be a potent coronary vasodilators [138], inhibitors, gastric

ulcers and intestinal activity. It is useful in the treatment of heart disease and whooping

cough [139].

20 | P a g e Chapter-I: Introduction

Figure-1.41, 1.42

Naphthofuran nuclei are key structural moieties found in a large number of

biologically important natural products. Cumhur kirilmis et al., [140] have shown that

many of the natural naphthofurans, such as (±)-Laevigatin, (+)-Heritol and

Balsaminone-A (Figure-1.43 to 1.45) possess interesting pharmacological and

cytotoxic properties.

Figure-1.43. (±)Laevigatin,

Figure-1.44. (+)-Heritol

Figure-1.45.Balsaminone-A

Kentaro Nakanishi et. al. [120] have reported construction of dinaphtho[2,1-

b;2′,3′-d]furan-6-ol (Figure-1.46) via a dehydration reaction involving two molecules

of 2,3-dihydroxynaphthalene in the presence of a strong acid. Starting from the

dinaphthofuran, a various butterfly shaped compounds were synthesized. The optical

properties of these compounds were investigated with special attention to the dihedral

angle formed by adjacent dinaphthofuran rings and/or the sizes of the fused aromatic

rings.

Figure-1.46

21 | P a g e Chapter-I: Introduction

Basavaraj Padmashali et al., [141] have synthesized a large number of

naphthofuran derivatives having various biological activities like anthelmintic,

anticonvulsant and antipyretic. They also act as fluorescent dyes and probes as well as

photosensitizers. Kumaraswamy and Vaidya [142], Kumaraswamy et al [143], and

Nagendra Prasad et al.,[144] have shown that Naphthofuran when condensed with

various heterocycles exhibit a wide spectrum of activities. Bukhari et al.,[145]

Basavaraj Padmashali and Vaidya [146] have synthesized many heterocycles and metal

containing compounds have exhibited various antioxidant activities, more importantly

naphthofuran derivatives have been proven to be a potent antioxidant agents.

Recently from our lab P, Vithal Reddy (Figure-1.47 & 1.48) [147], V. B.

Patil(Figure-1.49) [148] and R. Sahebgouda (Figure-1.50) [149] have synthesized

series of various Schiff base Ligand and their Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and

Hg(II) metal complexes from benzofuran and Naphthofuran derivatives. These

products have been characterized on the basis of analytical and various spectral studies.

The synthesized compounds show outstanding microbial and DNA cleavage activity.

Figure-(1.47)

Where R = H, Br or CH3

Figure-(1.48)

22 | P a g e Chapter-I: Introduction

Figure-(1.49)

Figure-(1.50)

Where R = -CH3/-H, Ar = 2-acetylpyridine / 2-acetylthiophene / acetophenone / p-

methoxyacetophenone / p-chloroacetophenone / 3-methyl-2-thiophenecarboxaldehyde

/ 4-methylthiobenzaldehyde and 3-ethoxy-4-hydroxybenzaldehyde.

From above literature it is clear that the Benzofuran and Naphthofuran Schiff

base and their metal complexes are vital and useful compounds in chemistry and related

areas. Hence we decided to synthesize and characterize the Schiff base and their metal

complexes derived from Benzofuran and Naphthofuran.

23 | P a g e Chapter-I: Introduction

Present research:

The major objectives of the present research are:

Synthesis of Ligands L-I to L-VIII and their Co(II), Ni(II), Cu(II), Zn(II), Cd(II),

and Hg(II) metal complexes.

We have synthesized the following ligands.

1. L-I: 5-bromo-3-((2-hydroxybenzylidene)amino)benzofuran-2-carboxamide.

2. L-II: 5-bromo-3-(3,7-dimethylocta-2,6-dien-1-ylidene)amino) benzofuran –

2-carboxamide.

3. L-III: 5-bromo-3-(((2-hydroxynaphthalen-1yl)methylene)amino)benzofuran-

2-carboxamide.

4. L-IV: 5-bromo-3-((2-hydroxy-5-(phenyldiazenyl) benzylidene)amino)

benzofuran-2-carboxamide.

5. L-V: Methylthio(enzylidene)naphtho[2,1-b]furan-2-carbohydrazide.

6. L-VI: 2-hydroxy-5-(phenyldiazenyl)benzylidene)naphtho[2,1-b]furan-2-

carbohydrazide.

7. L-VII: 3-oxoindolin-2-yl)methylene)naphtho[2,1-b]furan-2 carbohydrazide.

8. L-VIII: Hydroxy-3-methoxybenzylidene)naphtho[2,1-b]furan-2-

carbohydrazide.

Elucidation of the structure of the synthesized ligands and their metal complexes on

the basis of an elemental analysis and various spectral techniques viz. IR, 1HNMR,

Mass, UV-Vis., ESR and X-ray diffraction etc.

Evaluation of the biological activity viz. Antibacterial, antifungal and DNA

cleavage activities of the synthesized ligands and their metal complexes.

To develop methodology for the synthesis of novel heterocyclic Schiff base ligands

derived from Benzofuran, Naphthofuran and various aldehydes which have been

utilized in the present research work. These studies will be systematically presented

in the succeeding chapters of the thesis.

24 | P a g e Chapter-I: Introduction

REFERENCES:

1. J. D. Lee., Concise Inorganic Chemistry, 5th Ed., Blackwell Publishing company

(1996) p195.

2. A. Werner, Z. Anorg. Chem., 3 (1893) 367.

3. R. S. Nyholm, Proc. Chem. Soc., (1961) 273.

4. R. J. Sanderson, “Chemical Periodicity”, East-West Press, Pvt. Ltd., New Delhi,

(1969).

5. H. A. O. Hill and P. Day, “Physical Methods in Advanced Inorganic Chemistry”,

Inter science, New York, (1968).

6. B. N. Figgis and J. Lewis, “Progress in Inorganic Chemistry”, Vol. VI,

Interscience, New York (1964).

7. I. S. Griffith, J. Chem. Phys., 41 (1964) 516.

8. R. G. Shulman and S. Sugano, J. Chem. Phys., 42 (1965) 39.

9. J. P. Dahl and C. J. Balhansan. “Adv. Quantum Chem.”, 4 (1968) 170.

10. H. Bethe, Ann. Physik., 3 (1929) 208; Z. Physik., 60 (1930) 218.

11. J. H. Ven Velck, Phys. Red., 41 (1932) 208; J. Chem. Phys., 3 (1935) 603, 807.

12. D.A. Ptitsyn; V. M. Chechetkin, "Creation of the Iron-Group Elements in a

Supernova Explosion". Soviet Astronomy Letters 6 (1980): 61–64.

13. D. Nicholls, “Comprehensive Inorganic Chemistry”, 3, Pergaman Press, New

York, (1973).

14. A. Sigel, H. Sigel, R.K.O. Sigel, Nickel and Its Surprising Impact in Nature: Metal

Ions in Life Sciences, Wiley, 2007

15. L. Banci, Metallomics and the Cell, Springer Netherlands, 2013. ISBN:

9789400755604

16. Ragsdale, in:, P.M.H. Kroneck, M.E.S. Torres (Eds.), Met. Biogeochem. Gaseous

Compd. Environ. SE - 6, Springer Netherlands, 2014, pp. 125–145.

17. S. L. Holt (Jr), R. T. Bouchard and R. L. Carline, J. Am. Chem. Soc., 86 (1964)

519.

18. F. A. Cotton and D. M. L. Goodgame, J. Am. Chem. Soc., 82 (1960) 5771-5774.

19. S. Buflgani, L. M. Vallarino and T. V. Quagliano, Inorg. Chem., 3 (1964) 480.

20. D. M. L. Goodgame and M. Goodgame, J. Chem. Soc., (1963) 207.

21. M. Ciampolini and G. D. Speroni, Inorg. Chem., 5 (1966) 45.

22. E. B. Fleischer, B. J. Hathway and P. Nicholls, J. Chem. Soc., (1971) 1280.

23. L. Sacconi, P. L. Orioli and M. Divaria, J. Am. Chem. Soc., 87 (1965) 2059.

24. D. Romano, F. Matteucci, Mon. Not. R. Astron. Soc. Lett. 378 (2007) L59–L63.

25. J. Emsley, Nature’s Building Blocks: An A-Z Guide to the Elements, Oxford

University Press, 2001.

26. I. M. Procter, B. J. Hathway and P. Nicholls, J. Chem. Soc., A (1968) 1678.

27. G. Yee, W. Tolman, in:, P.M.H. Kroneck, M.E. Sosa Torres (Eds.), Sustain. Life

Planet Earth Met. Mastering Dioxygen Other Chewy Gases SE - 5, Springer

International Publishing, 2015, pp. 131–204.

28. M. Fieser “Reagents for Organic Synthesis”, 12, Wiley, New York, (1967).

29. D. G. Hewitt, Chem. Commun., (1970) 227.

30. M. J. Cleare, Coord. Chem. Rev., 12 (1974) 349.

31. J. Guan, J. Liu, J. Trans. Met. Chem. 39(2014) 233–238.

25 | P a g e Chapter-I: Introduction

32. Mallayan Palaniandavar et. al. J. Inorg. Chem. 46(20) (2007).

33. The R. S. Lehto, A. Clifford, A, Hampel., The Encyclopedia of the Chemical

Element. New York: Reinhold Book Corporation. (1968) 822-830.

34. D. H. Kerridge and S. A. Tariq, J. Chem. Soc., A (1967).

35. Robert A. DiSilvestro., Handbook of Minerals as Nutritional Supplements (Crc

Series in Modern Nutrition Science) (2004).

36. Y. C. Lin et. al., Dalton Trans., 2007, 781–791.

37. K. Hans Wedepohl., “The composition of the continental crust". Geochimica et

Cosmochimica Acta 59(7) (1995): 1217–1232.

38. G.F. Nordberg and Gerhardson; in handbook on “Toxicity in inorganic

compounds” ed. H. G. Sigel, A. Sigel, Marcel Dekker, New York, 619-624 (1988).

39. P. J. Doherty and D. F. Williams; in “Hand book on Metals in clinical and

analytical chemistry”, ed. H.G. Seiter, A. Sigel, Marcel Dekker, New York, 563

(1994).

40. Z. Guo and P. J. Sadler; “Metals in Medicine”, Angew, Chem. Int. Ed. Engl., 38,

1512 (1999).

41. K. C. Dash and H. Schmidbaur; Met. Ions Biol. Syst. (Inorganic Drugs in

Deficiency and Diseases), 14, 179-205 (1982).

42. K. Ishida and H. Orimo; in “Hand book on Metals in Clinical chemistry”, ed. B.

Lippert, VHCA, Zurich, and Wiley-VCH, Weinheim, 1-563. (1999).

43. B. Lippert, VHCA, Zurich, and Wiley-VCH, Weinherin “Cisplatin; Chemistry and

Biochemistry of a Leading anticancer Drug” (1999) 1-563.

44. J. P. Whitehead and S.J. Lippard; Met. Ion Biol. Syst., 32, (1996) 687-726.

45. N. J. Birch; “Lithium in psychiatry”, Met. Ions Biol. Syst., (Inorganic drugs

In deficiency and diseased, 14 (1982) 257-313.

46. R. B. Martin; “Bioinorganic chemistry of metal ions, in toxicity”, Met. Ions

Biol. Syst., (concept on metal ion toxicity) 20, (1986)21-65.

47. R. A. Goyer; in “Hand book on Toxicity of Inorganic Compounds”, ed. H. G.

Seiler, H. Sigel and A. Sigel, Marcel Dekker; New York 359 (1988).

48. G. N. Lewis, J. Am. Chem. Soc., 38 (1961) 762.

49. Langmuir, J. Am. Chem. Soc., 41 (1919): 1543.

50. N. V. Sidgwick, “The Electronic Theory of Valency”, Oxford University Press,

London and New York, (1927).

51. N. Pauling, “The nature of the Chemical Bond”, Cornell University Press, Ithaca,

New York, (1939).

52. W. Zeng, J. Li, Z. Mao, Z. Hong. S. Qin. Adved Synth. Catalysis, 346 (2004): 1385.

53. K. Nejati, Z. Rezvani, M. Seyedahmadian, Dye. Pigment. 83 (2009) 304–311

54. B. N. Reddy, P. G. Avaji, P. S. Badami, S. A. Patil, J. Coord. Chem. 61 (2008):

1827–1838.

55. P. Giorgio Cozzi, Chem. Soc. Rev., 33 (2004): 410-421

56. P. G. Lacroix, Eur. J. Inorg. Chem. (2001): 339-348.

57. P. Mukherjee, M. G. B. Drew, C. J. G. Omez-Garcı´a, A Ghosh, Inorg. Chem. 48

(2009): 5848–5860.

26 | P a g e Chapter-I: Introduction

58. Lee, Annette T., and Anthony Cerami. "Role of glycation in aging" Annals of the

New York Academy of Sciences 663.1 (1992): 63-70.

59. Prakash, Anant, and D. Adhikari, Inter. J. Chem. Tech. Res. 4 (2011): 1891-1896.

60. V. Gupta, A Kumar, K. Singh et. Al. Analytica chimica acta 575(2) (2006) 198-

204.

61. Yuan, R., Chai, Y., Liu, D., Gao et. Al. Analytical Chemistry, 65(19),(1993) 2572-

2575

62. M. B. Halli, K. Mallikarjun, S.S. Suryakanth et.al. World. J. Pharm. Pharma.

Sci. 3(7) (2015): 1499-1512.

63. N. Ramarao, P. Venkateshwar Rao, G. Venkat Reddy et. Al. Indian J. Chem., 26A

(1987) 887.

64. A. R. Shankar, S. Mandal, et.al. J. Indian Chem. Soc., 83 (2006) 185-190.

65. Z. Lu You and Qing-Zhu Jiao, Synth. React. Inorg. Met-Org. and Nano-Met.

Chem., 36 (2006) 713-717.

66. B. Erwin, C. Omoshile, Hydrogen isotope-pe-exchange in Pt-II thiazole

complexes. J. Chem. Soc., Perkin Trans 2 (1995) 1333-1338.

67. A. H. Rahama and E. M. Khandel, J. Indian Chem. Soc., 58 (1981) 404.

68. S. B. Kadin, J. Med. Chem., 15 (1972) 551.

69. S. Gaur, Asian J. Chem., 15 (1) (2003) 250.

70. M. J. Geni, C. Biles, B. J. Keiser, et. al. J. Med. Chem., 43 (5) (2000) 1034.

71. Z. Y. Yang, Synth. React. Inorg. Met-Org. Chem., 30 (2000) 1265.

72. L. F. Wang, Y. Zhu, Z. Y. Yang et. al. Polyhedron, 10 (1991) 2477.

73. D. H. Brown, W. E. Smith and J. W. Teape, J. Med. Chem., 23 (1980) 729.

74. A. Bravo and J. R. Anacona J. Coord. Chem., 44 (1988) 173.

75. J. R. Anacona and E. M. Figueroa, J. Coord. Chem., 48 (1999) 181.

76. J. A. Bakir, Jeragh and Ali El-Dissouky, J. Coord. Chem., 58 (12) (2005) 1029.

77. A. S. N. Murthy, A. R. Reddy. Proc. Indian Acad. Sci. Chem. Sci., 90 (1981) 519-

526.

78. X. Y. Qiu, W. S. Lie, F. Y. Hao, et. al. Syn. React. Inorg. Met-Org. Nano-Met.

Chem., 36 (2006) 595-597.

79. M. B. Halli, A. C. Hiremath, N. V. Huggi, Indian J. Chem., 40A (2001) 645-647.

80. K. Hussain Reddy, P. Samhsiva Reddy, J. Indian Chem. Soc., 79 (2002) 132-134.

81. Z. Y. Yang, Synth. React. Inorg. Met-Org. Chem., 32 (2002) 903.

82. Sulekh Chandra and Sangeetika, J. Indian, Chem. Soc., 81 (2004) 203.

83. J. P. Tandon and R. V. Singh., Quart. Chem. Rev., 1 (1984) 88.

84. V. Casellato, P. A. Vigoto, M. Vidali., Coord. Chem. Rev., 23 (1977) 31.

85. N. S. Dixit, C. C. Patel., J. Indian. Chem. Soc., 54 (1977) 176.

86. M. Calligaris, G. Nardin, L. Randacio., Coord. Chem. Rev., 7 (1972) 385.

87. J. W. Smith “The Chemistry of the Carbon-Nitrogen Double Bond.”

Ed. S. Patai Wiley-Interscience, New York (1970) 239.

88. B. R. Havinale, Ph. D. Thesis, “Studies on Some Metal Complexes.”

Karnataka University, Dharwad (1976).

89. P. L. Oriodi, M. D. Vaive, L. Succoni, Inorg. Chem., 5 (1966) 400.

90. Singh and P. Srivastava, Trans. Met. Chem., 11, (1986) 963.

91. C. Alladdin, I. Yilmaj, A. Ozman et. al. Trans. Met. Chem., 27 (2002) 171-176.

92. S. Tanaka., J. Chem. Soc. Japan., (Pure Chem. Sect), 73 (1953) 282.

27 | P a g e Chapter-I: Introduction

93. A. C. Hiremath, M. B. Halli and N. V. Huggi., J. Indian. Chem. Soc., 61 (1984) 191.

94. M. Nagar, R. Sharma, J. Phosp. Sulfur Silicon., 181(12),(2006) 2863-2875.

95. M. B. Halli, R. B. Sumathi, Arab. J. Chem. (Accepted manuscript) (2013).

96. A. D. Khalaji, S. J. Akerdi, G. Grivani, et. al, Russ. J. Coord. Chem. 37(8) (2011):

578-584.

97. J. Zhang, F. Pan, H. Cheng,et. al. Synth. Reac. Inorg. Met-Org. Nan-Met. Chem.

40 (2010):211–215.

98. R. R. Gagne, R. P. Kreh, J. A. Dadge. J. Am. Chem. Soc., 101 (1979).

99. N. Nawar, M. A. Khattab, M. M. Bekheit et. al., Ind. J. Chem.35 (1996) 308.

100. A. Abdel Aziz, Synth. React. Inorganic, Met. Nano-Metal Chem. 44 (2013) 1137–

1153.

101. M. Calligaris and L. Randccio “Comprehensive Coordination Chemistry” Ed.

G. Willkison, R.D. Gillard and J.A. Mc Cleverty Pergamon, Oxford, 1987, 2,

Chapt.20.1.

102. J. V. Dubsky and A Sokol, Collect Czeeck, Chem. Communo., 3 (1932) 548.

103. R. V. Singh and J.P. Tandon, Indian J. Chem., 16A (1982) 84.

104. M. F. Carrigan, K. S. Murray, B. O. West and J. R. Pilbrow, Aust. J. Chem., 30 (1977)

2455.

105. L. Sacconi, J. Bertini and G.P. Speroni, Inorg. Chem., 11 (1972) 1323.

106. G. T. Morgan and J. D. Mainsmith, J. Chem. Soc., (1925) 2030.

107. P. Pfeiffer, Annalen der Chemie. 503 (1933) 84-130.

108. R. L. Dutta and M. M. Hossain, Indian. J. Chem., 21A (1982) 746.

109. Bayrakc, Mevlüt, Synth. React. Inorg. Met-Org. Nan.-Met. Chem. 41(2011):

484-490

110. Raman, N., Raja, S. J., Joseph, J., & Raja, J. D. Russ. J. Coord.

Chem., 33(1) (2007) 7-11.

111. Nguyen, T. Dat., Phan, V. Kiem., et. al. Arch. Pharm. Res. 27 (2004) 1106-1108.

112. Mastubara, H., Botyk Kogaku. 1954, 19, 15.

113. B.C. Echezona., J. E. Asiegubu.,Izuagba., A. A. African Crop Science Journal 18

(2010) 97-105.

114. Shinichiro, Ono, Tomohiro., et. al., Chem. Pharm. Bull. 47(12)(1999)1694-1712.

115. S. Kumar, D. N. Dhar, P. N. Saxena, J. Sci. Ind. Res. 68 (2009)181-187.

116. Arifa, K. Banu, Aruna, Devraj. J. Pharm. Sci. Innov. (2013) 22-25.

117. L. Shi, H. M. Ge, S. H. Tan et. al., Eur. J. Med. Chem. 42 (2007) 558-564.

118. Mishra, A.P. J. Indian Chem. Soc.1999, 46, 3537

119. H. Arjun, Y. Banskota, K. Tezuka et. al. J. Nat. Prod., 63 (9) (2000): 1277–

1279.

120. N. Kentaro, S. Takahiro, K. Kouji, T. et. al., J. Org. Chem. 79 (2014) 2625−2631.

121. C. Mitsui, J. Soeda, K. Miwa et. al., J. Am. Chem. Soc.134 (2012) 5448−5451.

122. B. E. Sobel and E-Braunwald, “In Principles and Internal Medicine”, J. D. Wilson

Eds. Mc Graw Hill (1983) 176.

123. M. Vastasaeger, P. Gillot and G. Rasson, Acta Cardiol., 22 (1967) 483.

124. B. N. Singh and E. M. Vaughan-Williams, Br. J. Pharmacol., 39 (1970) 483.

28 | P a g e Chapter-I: Introduction

125. K. Nademanee, J. A. Hendrickson, D. S. Cannom, et. al. Am. Heart. J., 101 (1981)

759.

126. I. Sigehu, I. Kikoo, MonKajelo and Y. Hisao, Japan Pat., (1972) 72 05 253; Chem.

Abstr., (1972) 14049h.

127. J. W. Mason, New Eng. J. Med., 316 (1987) 455.

128. M. B. Rosenbaum, P. A. Chiale, D. Ryba et. al. Am. M. J. Cardiol., 34 (1974) 5.

129. Y. Linda; Cauvain, P. Stanley. (2007). Technology of Bread making. Berlin:

Springer. p. 79. ISBN 0-387-38563-0.

130. M. Forbes, F. Zilliken, G. Robert et. al. J. Am. Chem. Soc., 80, 385 (1985).

131. R. Naik, D. S. Harmalkar, X. Xu, K. Jang, et. al. Eur. J. of Med. Chem. 90

(2015) 379-393

132. R. W. Moncrieff Mfg., “Chemist. Aerosol New”, 37, (1966), 45; Chem. Abstr., 65

(1966) 8665g.

133. D. R. Sridhar, C. V. R. Sastry, K. B. Lal et. al. J. Indian. Chem. Soc., 55, (1978),

910

134. R. Rene, D. Loice, Picure, C. Raymond et. al. Chem. Abstr., 75, (1971), 62485 U.

135. S. B. Kadin, J. Med. Chem., 15 (1972) 551.

136. V. P. Vaidya, H M Vagdevi, K M Mahadevan et. al. Ind. J. Chem. 43B.

(2004)1537-1543.

137. E.Spath . W. Gruber, Berichte der deutschen chemischen Gesellschaft (A and B

Series) 71(1), pp106–113, 5. Januar 1938 DOI: 10.1002/cber.19380710118

138. R. L. Farrond and S. M. Harwath., Am. J. Physiol., 196 (1959) 391

139. N. P. Buu Hoi, E. Bisanji, R. Royer et. al. J. Chem. Soc., (1957); 625; Chem. Abstr.,

51 (1957) 10469.

140. C. Kirilmis¸M. Koca, Suleyman Servi et. al. Turk J Chem 33 (2009) 375 – 384.

141. P. Basavaraj, V. P. Vaidya, K. M. Mahadevan et. al. Indian. J. Chem., 44 (2005)

1446.

142. D. Ramesh, V.P. Vaidya, M.N. Kumaraswamy et. al., Int. J. Pharm. Chem. Bio.

Sci., 4 (2014) 298–306.

143. M. N. Kumaraswamy, C. Chandrashekhar, H. Shivakumar, et.al., Indian J. Pharm.

Sci. 70 (2008) 715–720.

144. M. N. Nagendra Prasad, H. K. Vivek, A. Prasad et.al., J. Chem. Pharm. Res. 2,

(2010) 567–574

145. B. S. Bukhari, S. Memon, M. M. Tahir, M. I. Bhanger, 2008. J. Mol. Struct. 892,

39–46.

146. B. Padmashali, V. P. Vaidya, Indian J. Heterocycl. Chem. 12(2002) 89–94.

147. Dr. P. Vithal Reddy, Ph. D. Thesis, “Physico-chemical and equilibrium studies

on metal complexes”, Gulbarga University, Kalaburagi, Karnataka (Ind.) (2007).

148. Dr. V. B. Patil Ph.D Thesis., “Synthesis and characterization of metal complexes

with schiff’s bases” Gulbarga University, Kalaburagi, Karnataka (Ind.) (2011).

149. Dr. Ravindra Sahebgouda., Ph. D. Thesis, “Studies on metal complexes derived

from Schiff’s base ligands” Gulbarga University, Kalaburagi, Karnataka

(Ind.)(2014).