chapter-1shodhganga.inflibnet.ac.in/bitstream/10603/34765/7/07_chapter1.pdfmetal ions has aroused...

CHAPTER-1

INTRODUCTION

(Introduction) Chaptershy1 2009

D E P A R T M E N T O F C H E M I S T R Y ( S P U )

CHAPTER-1

INTRODUCTION 11 General introduction

In 1893 Alfred Werner (1866-1919) [1 2] challenged all previous

theories especially the reigning chain theory proposed by the Swede

Christian Wilhelm Blomstrand (1826-1897) [3 4] which was developed

and experimentally advanced by the Dane Sophus Mads Jorgensen (1837-

1914) [5] with a revolutionary new theory [6] According to Werners

own admission it was based on Jorgensenrsquos painstaking experimental

data In fact Jorgensenrsquos work bore the seeds of the chain theorys

destruction some of Jorgensenrsquos compounds later were crucial in

Werners proof of his coordination theory [7-9]

Werners theory abruptly broke with classical theories of valence

and structure postulating two types of valence primary of ionizable

valence (Hauptvalenz) and secondary or nonionizable valence

(Nebenvalenz) Every metal in a given oxidation state (primary valence)

also has a fixed coordination number (a specific number of secondary

valences that must be satisfied) Primary valences can be satisfied only by

anions but secondary valences can be satisfied by anions and neutral

molecules Secondary valences are directed in space around the central

metal atom The combined aggregate forms a complex which usually

exists as a discrete unit in solution The most common configurations are

`octahedral (coordination number six) and square-planar or tetrahedral

(coordination number four) Werners view of the two types of linkages -

ionogenic (ionizable) and nonionogenic (nonionizable) ndash clarified

ideas of chemical bonding a generation before Kossels and Lewiss views


D E P A R T M E N T O F C H E M I S T R Y ( S P U ) Page 2

(1916) lead to present concepts of ionic and covalent bonding

respectively

Walther Kosselrsquos ionic model (1916) was revitalized and

developed in to the crystal field theory (CFT) of coordination by Hans

Bathe and Jonh H Van Vleck Although used to some extent by

physicists until the 1950s When modified to include some degree of

covalence crystal field theory is usually know as ligand field theory

(LFT) or adjusted crystal field theory (ACFT) and is currently the best

and most popular method for treating spectra and other properties

quantitatively A simpler electrostatic theory is the valancendashshell

electron-pair repulsion (VSEPR) theory of directed valance proposed in

1957 by Ronald J Gillespie and late Ronald S Nyholm Both VBT and

CFT are only simplifications of the more general and more complicated

molecular orbital theory (MOT) which today offer the best interpretation

of the properties of coordination compound In future these theories may

probably be modified or there may arise a totally new one The

chronological list of some significant historically events in coordination

chemistry are shown in following Table

Some significant historically events in coordination chemistry in

twentieth-century

Year Scientist Events

1900 W J Pope S J Peachey

Resolution of optically active tin compound

1905 L A Chugdev Dimethylglyoximate test for nickel(first organic spot test reagent for a metal ion)

1905 H Grossmann Use of high ionic strength medium for studying complex constants

1907 L A Chugdev V Sokolov

First coordination compound containing an asymmetrical ligand stereospecificity

1913 A Werner Nobel Prize in Chemistry ldquofor his work on the linkage of atoms in moleculehelliprdquo



1915 L A Chugdev N A Vladimirov Chugdevrsquos salt [PtCl(NH3)5]Cl3

1926 J N Bronsted SN1CB mechanism (substitution

nucleophilic first order conjugate bonds)

1929-32

H Bethe R S Mulliken J H Van Vleck

Crystal field theory (ligand field theory)

1933 P Pfeiffer E Breith E Lubbe T Tasumaki

Oxygen-carrying chelate bis(salicylal)ethylenediiminecobalt(II)

1935 K A Jensen Dipole moments to determine structure of Pt(II) isomers

1938 R Tsuchida Spectrochemical series of ligands

1940 J H Van Vleck R Finkelstein

First application of electrostatic model to absorption bands of the ruby

1948 H Irving R J P Williams Stability order of complexes

1950

J Chatt Symposium on Coordination Chemistry (1st International Conference on Coordination Chemistry) Welwyn England

1952 M Wolfsberg L Helmholz

Molecular orbital model applied to transition metal complexes

1954 Y Tanabe S Sugano Calculation of energy level diagrams for octahedral d-group complexes

1955 J Chatt L A Duncanson L M Venanzi L E Orgel

π-Bonding theory of the trans effect

1955 F P Dwyer E C Gyarfas D P Mellor

Resolution of complex with hexadentate ligand ([Co(EDTA)]macr)

1956 D C Hodgkin Crystal structure of Co(III) complex of vitamin B12

1957 G Schwarzenbach L G Sillen

ldquoStability Constants of Metal-Ion Complexesrdquo

1958 C E Schaffer C K Jorgensen

Nephelauxetic series (interelectronic repulsion) of central atom and ligands

1959 E J Corey J C Bailer Jr

Conformational analysis of coordination compounds

1960 R B Woodward et al

Proof of structure of chlorophyll by total synthesis



1960-67

J C Bailar Jr M J S Crespi J Geldard

Action of biological systems on optically active complexes

1964 F A Cottan C B Harris

Binuclear metal cluster [ReC18]2- (quadruple bonds)

1965 B Rosenberg L Van Camp T Krigas

Biological effect of platinum complex (Cisplatin)

1967 F Basolo R G Pearson Mechanism of Inorganic Reactions

1973 E O Fischer G Wilkinson

Nobel Prize in Chemistry ldquofor their Pioneering workhellip on the chemistry ofhellip sandwich compoundsrdquo

1983 H Taube Nobel Prize in chemistry ldquofor his work on

the mechanisms of electron transfer reactions especially in metal complexesrdquo

1995-96

H B Gray et al Electrone-transfer and tunneling in proteins

1996 J K M Sanders et al Ligands as anchors in coordination templetes

1997 C Pigute G Bernardinelli G Hopfgartner

Multisite double and triple helical complexes

1997 B Linton AD Hamilton

Artificial receptors by metal-templated processes

12 Schiff bases Hugo (ugo) Schiff was a German chemist Schiff was a student of

Friedrich Wohler in Gottingen In 1879 he founded the chemical institute

of the University of Florence He discovered Schiff bases and had the

Schiff test named after him

Schiff base (or azomethine) is a functional group that contains a

carbon-nitrogen double bond with the nitrogen atom connected to an aryl

or alkyl group and not to hydrogen [10] Schiff bases are typically formed

by the condensation of primary amines and aldehydes The resultant

functional group R1HC=N-R2 is called imine and is particularly for its

binding to metal ions via the lone pair of N atom especially when used in

combination with one or more donor atoms to form polydentate chelating



ligands or macrocycles Ketones of course will also form imines of the

type R1R2C=N-R3 but the reactions tend to occur less readily than with

aldehydes Examples of few compounds of interest are given below



Reaction scheme of Schiff bases

Biological role of Schiff bases

Schiff bases form a significant class of compounds in medicinal

and pharmaceutical chemistry with several biological applications that

include antibacterial [11-16] antifungal [13-16] and antitumor activity

[17 18] They have been studied extensively as a class of ligands [19-21]

and are known to coordinate with metal ions through the azomethine

nitrogen atom

Recently there has been a considerable interest in the chemistry of

hydrazine and hydrazone compounds because of their potential

pharmacological applications [22] The remarkable biological activity of

acid hydrazides RndashCOndashNHndashNH2 their corresponding arylohydrazones

RndashCOndashNHndashN=CHR and also their mode of chelation with transition

metal ions has aroused interest in the past due to possible biomimetic

applications The coordination compounds of arylohydrazones have been

reported to act as enzyme inhibitors and are useful due to their

pharmacological applications [23]

Schiff base complexes play a vital role in designing metal

complexes related to synthetic and natural oxygen carriers [24] Metal

complexes make these compounds effective as stereospecific catalysts

towards oxidation reduction hydrolysis biological activity and other

transformations of organic and inorganic chemistry [25] In organic

compounds the presence of ndashC=Nndash along with other functional groups



form more stable complexes compared to compounds with only ndashC=Nndash

coordinating moiety

Similarly coumarin derivatives have been of great interest because

of their role in natural and synthetic organic chemistry Many products

which contain a coumarin subunit exhibit biological activity such as

molluscicides [26] anthelmintic hypnotic insecticidal [27] activity and

some are serving as anticoagulant agents [28] and fluorescent brighteners

So coumarins containing Schiff base are expected to have enhanced

antitumor and other biological activities It is well established that the

biological activity associated with the hydrazone compounds attributed to

the presence of the active pharmacophore (-CONH-N=C-) Hence many

hydrazone compounds containing this active moiety showed good

anticancer bioactivities according to the literature [29]

Various ketone Schiff bases and heterocyclic compounds are found

to be associated with diverse pharmacological activities including

antibacterial [30] antifungal [31] herbicidal [32] and antitubercular [33]

activities The heterocyclic compounds containing 124-triazole nucleus

have been incorporated into a wide variety of therapeutically interesting

drugs including H1H2 histamine receptor blockers CNS stimulants

anxieolytics and sedatives [34] It was also found that the thiadiazole

nucleus which incorporates a toxophoric N-C-S linkage exhibits a large

number of biological activities A number of 134-thiadiazole derivatives

have antitumor and pesticide activity Schiff bases led to heterocycles

having pharmaceutical importance like anticancer activity [35 36]

13 Quinolone Quinolone are an important group of antibiotics and very common

in clinical use They are chelating agents for varieties of metal ions

including transition and alkaline earth metal ions The first member of the



quinolone family introduced and kept forward for clinical practice was

nalidixic acid synthesized in 1962 by Lesher et al It was used for the

treatment of urinary tract infections [37] Fluoroquinolone represent an

important and a separate group of chemotherapeutic compounds which

exhibit high antibacterial activities Quinolones comprise a group of well-

known antibacterial agents and the first members being in clinical

practice over 40 years [38 39] They can act as antibacterial drugs that

effectively inhibit DNA replication and are commonly used in treatment

of many infections [40 41]

Family of quinolone drugs

1st generation Cinoxacin Flumequine Nalidixic acid Oxolinic acid Pipemidic acid Piromidic acid Rosoxacin

2nd generation Ciprofloxacin Enoxacin Fleroxacin Lomefloxacin Nadifloxacin Ofloxacin Norfloxacin Pefloxacin Rufloxacin

3rd generation Balofloxacin Grepafloxacin Levofloxacin Pazufloxacin Sparfloxacin Temafloxacin Tosufloxacin

4th generation Clinafloxacin Garenoxacin GemifloxacinMoxifloxacin Gatifloxacin Sitafloxacin Trovafloxacin Alatrofloxacin Prulifloxacin

Veterinary Danofloxacin Difloxacin Enrofloxacin IbafloxacinMarbofloxacin Orbifloxacin Pradofloxacin Sarafloxacin

Derivatives of compounds composed of 3-carboxy-4-oxo-14-

dihydroquinoline (ie 4-quinolones) are active against a wide range of

gram-positive and gram-negative organisms [42] Major increase in the

potency was obtained by addition of fluorine atom on 6th position of the

quinoline ring whereas addition of piperazinyl group on 7th position

enhanced permeability and potency [43] The ciprofloxacin (1-

cyclopropyl-6-fluoro-14-dihydro-4-oxo-7-(1-piperazinyl)- 3-quinoline



carboxylic acid) is widely use for clinical purpose It received Food and

Drug Administration approval in 1986 Ciprofloxacin is typically a

second-generation fluoroquinolone used clinically for more than decade

and sold for $US 15 billion in 1996 [44] In 2005 the US Food and

Drug Administration (US-FDA) changed the package insert for

ciprofloxacin to acknowledge the tendon ruptures and the development of

irreversible neurological conditions In connection with the outbreak of

suspected anthrax biological warfare many experts consider

ciprofloxacin the drug of choice for treating victims More than 15000

articles have been published about ciprofloxacin It is regularly found

among the top 100 most frequently prescribed drugs in North America

Quinolone antibacterial drugs have been frequently used to treat

various bacterial infections because of their activity against gram-positive

and gram-negative bacteria [45] Ciprofloxacin (Cip) is broad-spectrum

synthetic antibacterial agent used to treat infections of the skin sinuses

bone lung ear abdomen and bladder It can also be used to treat some

sexually transmitted infections pneumonia bronchitis and some types of

gonorrhea diarrhea typhoid fever prostate and urinary tract infections

caused by bacteria Resistance to the compounds is generally associated

with amino acid substitutions in portions of the GyrA (gyrase) and ParC

(topoisomerase IV) proteins called the quinolone resistance-determining

regions (QRDRs) [46]

Ciprofloxacin (Cip) is one of the quinolone antibacterial agents

used in the treatment of a wide range of infections that antagonize the A

subunit of DNA gyrase [46 47] It is active against the DNA gyrase

enzyme a type II topoisomerase DNA gyrase introduce negative

supercoils in DNA [48] by wrapping DNA around the enzyme Enzyme

then catalyzes the breaking of segment of DNA which is wrapped the



passage of a segment of the same DNA through the break and finally the

relegation of the break [49] In this way DNA lsquoknotsrsquo are resolved and

the DNA is exposed for replication processes Binding of fluoroquinolone

to DNA is relatively weak thus it is unlikely that their binding to DNA

triggers the formation of gyrasendashDNA complex [50-53] Likewise

binding of fluoroquinolone to gyrase is weak even though the presence

of mutated gyrase alleles in resistant bacteria clearly implicates gyrase in

the interactions [54-57] Numerous studies have shown that drug binding

to DNA [58-61] and gyrase is enhanced in the presence of metal ions and

metal ions are essential for antibacterial efficiency of drugndashDNA

interaction 14 Chemistry of transition metal ions

The name transition comes from their position in the periodic table

of elements In each of the four periods in which they occur these

elements represent the successive addition of electrons to the d atomic

orbitals of the atoms In this way the transition metals represent the

transition between group 2 elements and group 13 elements

More strictly IUPAC defines a transition metal as an element

whose atom has an incomplete d sub-shell or which can give rise to

cations with an incomplete d sub-shell Zinc has the electronic structure

[Ar] 3d10 4s2 When it forms ions it always loses the two 4s electrons to

give a 2+ ion with the electronic structure [Ar] 3d10 The zinc ion has full

d-levels and doesnt meet the definition either By contrast copper [Ar]

3d10 4s1 forms two ions In the Cu+ ion the electronic structure is [Ar]

3d10 However the more common Cu2+ ion has the structure [Ar] 3d9

Copper is definitely a transition metal because the Cu2+ ion has an

incomplete d-level



Most transition metals form more than one oxidation state As

opposed to group 1 and group 2 metals ions of the transition elements

may have multiple oxidation states since they can lose d electrons

without a high energetic penalty Manganese for example has two 4s

electrons and five 3d electrons which can be removed Loss of all of

these electrons leads to a +7 oxidation state Osmium and ruthenium

compounds are commonly found alone in stable +8 oxidation states

which is among the highest for isolatable compounds

The number of oxidation states of each ion increase up to

manganese after which they decrease Later transition metals have a

stronger attraction between protons and electrons (since there are more of

each present) which then would require more energy to remove the

electrons When the elements are in lower oxidation states they can be

found as simple ions However transition metals in higher oxidation

states are usually bonded covalently to electronegative elements like

oxygen or fluorine forming polyatomic ions such as chromate vanadate

or permanganate

Other properties with respect to the stability of oxidation states

Ions in higher oxidation states tend to make good oxidizing agents

whereas elements in low oxidation states become reducing agents

The +2 ions across the period start as strong reducing agents and

become more stable

The +3 ions start as stable and become more oxidizing across the

period

Coordination by ligands can play a part in determining color in a

transition compound due to changes in energy of the d orbitals Ligands

remove degeneracy of the orbitals and split them in to higher and lower

energy groups The energy gap between the lower and higher energy



orbitals will determine the color of light that is absorbed as

electromagnetic radiation is only absorbed if it has energy corresponding

to that gap When a legated ion absorbs light some of the electrons are

promoted to a higher energy orbital Since different frequency light is

absorbed different colors are observed

The color of a complex depends on

The nature of the metal ion specifically the number of electrons in

the d orbitals

The arrangement of the ligands around the metal ion (for example

geometrical isomers can display different colors)

The nature of the ligands surrounding the metal ion

The complex ion formed by the d block element zinc (though not

strictly a transition element) is colorless because the 3d orbitals are

full - no electrons are able to move up to the higher group

15 Biological role of cobalt zinc and vanadium Biological role of cobalt

Cobalt is a hard silvery-white metal that occurs in nature as cobalt-

58933 Cobalt is a constituent of the minerals cobaltite smaltite

erythrite and other ores and it is usually found in association with nickel

silver lead copper and iron Cobalt has both beneficial and harmful

effects on human health Cobalt is beneficial for humans because it is part

of vitamin B12 which is essential to maintain human health Cobalt

(016ndash10 mg cobaltkg of body weight) has also been used in treatment

of anemia (less than normal number of red blood cells) including in

pregnant women because it causes red blood cells to be produced Cobalt

also increases red blood cell production in healthy people but only at

very high exposure levels Cobalt is also essential for the health of

various animals such as cattle and sheep Exposure of humans and



animals to levels of cobalt normally found in the environment is not

harmful People exposed to 0007 mg cobaltm3 at work have also

developed allergies to cobalt that results in asthma and skin rashes The

general public however is not likely to be exposed to the same type or

amount of cobalt dust that caused these effects in workers

Like those of iron complexes of cobalt have been shown to be

capable of DNA modification by electron transfer mechanisms In one

case the highly inert cobalt(III) cage complex of the sarcophagane ligand

3610131619-hexaazabicyclo[666]icosane linked to polycyclic DNA-

intercalating groups such as anthracene can be photoactivated to induce

single-strand cleavage [62] In another a cobalt(II) peptide complex

modifies DNA by an O2-activated mechanism [63] The well known

alkynehexacarbonyldicobalt core containing a range of substituted

alkynes can demonstrate extreme cytotoxicity in some cases greater than

that of cisplatin in tumor cells Although the mechanism of this newly

discovered toxicity is as yet unknown it is associated with the complex

since the alkynes alone do not have this property [64] Complexation with

Co(III) has been used to mask the toxicity of a nitrogen mustard group

with the aim of selectively activating the mustard in hypoxic tumour

tissues by in vivo reduction of the cobalt centre The complex

[Co(DCD)(acac)(NO2)]ClO4 showed fivefold greater toxicity towards

hypoxic cells than towards normoxic cells [65]

Biological role of zinc

Zinc is one of the most common elements in the earths crust It is

found in air soil water and is present in all foods It is one of the most

abundant trace elements in the human body It is typically taken in by

ingestion of food and water although it can also enter the lungs by

inhaling air including that contaminated with zinc dust or fumes from



smelting or welding activities The amount of zinc that can pass directly

through the skin is very small Absorption of zinc into the bloodstream

following ingestion is normally regulated by homeostatic mechanisms so

the balance between zinc intake and excretion is controlled Absorption

from the gastrointestinal tract is 20 to 30 in people with diets containing

adequate levels of zinc but it can reach 80 in those with low levels of

zinc in their diets or body tissues Zinc is normally excreted in the urine

and feces with small amounts excreted in sweat About 90 of what is

retained is found in muscles and bones

Zinc is an essential element in our diet Too little zinc can cause

problems and too much zinc is also harmful Harmful effects generally

begin at levels 10-15 times higher than the amount needed for good

health Large doses taken by mouth even for a short time can cause

stomach cramps nausea and vomiting Taken longer it can cause anemia

and decrease the levels of your good cholesterol Rats that were fed large

amounts of zinc became infertile Inhaling large amounts of zinc (as dusts

or fumes) can cause a specific short-term disease called metal fume fever

Putting low levels of zinc acetate and zinc chloride on the skin of rabbits

guinea pigs and mice caused skin irritation Skin irritation may probably

occur in people

Biological role of vanadium

Vanadium is a natural element in the earth It is a white to gray

metal often found as crystals Vanadium occurs naturally in fuel oils and

coal The design and application of vanadium complexes as insulin

mimetics and the possible mechanisms involved have been reviewed by

leaders in the field [66-71] New complexes synthesized targeting the

applications include VO2+ complexes of aspirin [72] and pyridinone [73]

Other potential pharmaceutical uses of VO2+ complexes are being



explored complexes such as [VO(SO4)(phen)2] have been shown to

induce apoptosis in tumour cell lines [74 75] On the other hand the new

VO2+ complex [VO(oda)(H2O)2] appears to inhibit nitric oxide-induced

apoptosis [76]

The biological effects biodistribution pharmacological activity

and toxicology of vanadium are areas of increasing research interest So

far the best evidence for a biological role of vanadium comes from

bacteria (the so-called alternative nitrogenases in which vanadium

replaces molybdenum in the FeMo-cofactor of some Azotobacter species)

[77 78 80-83] and from plants (vanadium dependent haloperoxidases

found in some algae lichens and fungi) [77 78 82-84]

The experiments with laboratory animals have shown that

vanadium deprivation enhances abortion rates reduces milk levels during

lactation and produces thyroidal disorders It has also been suggested that

vanadium participates in the regulation of ATP-ases phosphoryl

transferases adenylate cyclase and protein kinases and potentiate

different growth factors [79 83 85 86]

Environmental contamination by vanadium has dramatically

increased during the last decades especially in the most developed

countries due to the widespread use of fossil fuels many of which

liberate finely particulate V2O5 to the atmosphere during combustion [87ndash

89] Therefore and also owing to the emerging interest in the

pharmacological effects of some of its compounds [90-94] the toxicology

and detoxification of vanadium constitute areas of increasing research

interest Vanadium toxicity has been reported in experimental animals

and in humans The degree of toxicity depends on the route of

incorporation valence and chemical form of the element and is also to

some extent species-dependent [95 96]



In general it increases as valence increases pentavalent vanadium

being the most toxic [96 97] Although under normal natural conditions

toxic effects do not occur frequently at high doses or as a consequence of

chronic exposure it is a relatively toxic element for human [98] The

upper respiratory tract is the main target in occupational exposure

Vanadium compounds especially V2O5 are strong irritants of the airways

and eyes Acute and chronic exposure gives rise to conjunctivitis rhinitis

and to bronchitis bronchospasms and asthma-like diseases [95 96] It

can also produce fatigue cardiac palpitation gastrointestinal distress

kidney damage and even neurological disorders In human acute toxicity

has been observed in vanadium miners and industrial workers exposed to

high doses of vanadium The classic symptoms of this malady referred to

as lsquogreen tonguersquo syndrome are a green coloration of the tongue

accompanied by some of the above-mentioned disorders [79 95 96]

A series of drugs that are capable of chelating metal ions in vivo

have been developed not only to eliminate excess of essential metals but

also to prevent possible damage caused by nonessential toxic elements

This is the basis of the so called chelation therapies and constitutes the

chemical detoxification ways [99] Chelation therapy occupies a central

place in modern medicine and pharmacology as extensive clinical

experience and continuous studies with laboratory animals demonstrate

that acute or chronic human intoxications with a variety of metals can be

considerably improved by administration of a suitable chelating agent

[99 100-103] Chelating agents usually diminishes metal toxicity by

complexation and subsequent excretion of the generated complex or

preventing the absorption of the toxic species

In the case of vanadium the biologically most relevant species ie

V3+ VO2+ VO3+ and VO2+ can be classified as hard acids [99 104]



Therefore one may expect that the best chelating agents for these species

are ligands that offer oxygen or nitrogen donors (hard bases in the SHAB

classification) Most of the so far known and well-established chelating

agents employed in the clinical practice have been tested with varying

success for vanadium detoxification generally with laboratory animal

experiments [96] Well-known chelating agents such as

ethylenediaminetetraaceticacid (EDTA) and related

polyaminopolycarboxylic acids have been profusely investigated EDTA

in particular shows a good chelating behavior for both vanadium(V) and

vanadium(IV) species [96] In the case of sulfur containing chelating

agents such as 23-disulfanylpropanol (BAL) l-cysteine or d-

penicillamine (2) conflicting reports are found in the literature

concerning its efficacy in the case of acute intoxications [96]

16 Deoxyribonucleic acid [DNA]

The determination of the structure of DNA by Watson and Crick in

1953 [105] is often said to mark the birth of modern molecular biology

and is of high importance since it provides the foundation for the central

molecule of life The strands of DNA are composed of an alternating

sugar-phosphate backbone comprising deoxyribose sugar groups and

phosphodiester groups A series of heteroaromatic bases project from the

sugar molecules in this backbone There are two types of bases that occur

in DNA the purine bases guanine (G) and adenine (A) and the

pyrimidine bases cytosine (C) and thymine (T) The two anti-parallel

strands of nucleic acid that form DNA can assume several distinct

conformations [106] The three most commonly occurring conformations

are A- B- and Z-DNA (Figure 1) B-DNA is regarded as the native form

as it is found in eukaryotes (ie humans) and bacteria under normal

physiological conditions



(a) (b) (c)

Figure 1 The three structures of DNA showing the right-handed (a) A-

form and (b) B-form and (c) the left-handed Z-form

There are several major features of B-DNA It consists of two anti-

parallel polynucleotide strands that wrap around a common axis and each

other with a right-handed twist in such a way that they cannot be

separated without unwinding the helix (plectonemic coiling) The planes

of the bases are nearly perpendicular to the axis of the double helix Each

base hydrogen bonds to a base on the opposite strand (Watson-Crick base

pairing Figure 2) to form a planar base pair thus holding the two DNA

strands together The DNA double helix is further stabilized by π-π

stacking interactions between the aromatic rings of the base pairs [107]



Figure 2 A dinucleotide segment showing the hydrogen bonds between

the A-T and C-G base pairs and the 3-5 direction of the strands from

the perspective of the minor groove

The characteristics of A- B- and Z- DNA are summarized in

following Table

Comparison of the microscopic structural features of A- B- and Z-

DNA [55]

Parameter A-DNA B-DNA Z-DNAHelical sense Right handed Right handed Left handed

Diameter ~26 Aring ~20 Aring ~18 Aring Base pairs per helical

turn 11 10 12

Helical twist per base pair 33deg 36deg 60deg

Helix pitch (rise per turn)

28 Aring 34 Aring 45 Aring

Helix rise per base pair 26 Aring 34 Aring 37 Aring

Major groove Narrow deep Wide deep Flat

Minor groove Wide shallow Narrow deep Narrow deep



Under normal physiological conditions B-DNA has a helical rise per

base pair of 34 Aring and each base has a helical twist 36deg from the previous

base The double helix has 10 bases per turn and a diameter of 20 Aring

[108] The asymmetry of the bases gives rise to minor and major grooves

along the DNA helix

Interaction of small molecules with DNA

There are four different ways in which molecules can interact with

DNA covalent and coordinate covalent binding groove binding

electrostatic binding and intercalation The widely used anticancer drug

cisplatin obtains its cytotoxicity by forming coordinate covalent DNA

intrastrand and interstrand cross-links as well as protein-DNA cross links

in the cellular genome [109-113] The complex mer-[Ru(tpy)Cl3] (tpy =

22prime6prime2primeprime-terpyridine) has been found to be active as a cytostatic drug in

L1210 murine leukaemia cells with an activity comparable to that of

cisplatin [114] mer-[Ru(tpy)Cl3] is able to bind two sequential guanine

residues in a trans-configuration forming coordinate covalent interstrand

cross-links with DNA Electrostatic or external binding occurs when

cations or cationic molecules are attracted to the anionic surface of DNA

Ions and charged metal complexes such as Na+ associate electrostatically

with DNA by forming ionic or hydrogen bonds along the outside of the

DNA double helix [115 116]

Groove binding involves the direct interactions of generally

elongated crescent shaped molecules with the edges of the base pairs in

either the major or minor grooves and is dependent on the size hydration

and electrostatic potential of both DNA grooves The exact location of

binding is largely dependent on a favourable combination of these

interactions as well as the potential for hydrogen bonding The organic

anti-tumour drug netropsin has been shown (Figure 3) to bind within the



DNA minor groove [117] The drug is held in place by amide hydrogen

bonds to adenine N-3 and thymine O-2 atoms [117] Once bound it

widens the groove slightly but does not unwind or elongate the double

helix

Figure 3 Netropsin bound to double-stranded B-DNA

The DNA is shown with smooth ribbons stick bonds and special

representations of the sugars and bases Netropsin is coloured by element

and shown in the ball-and-stick representation with a transparent pink

molecular surface [118]

Intercalating molecules associate with DNA (from either the major

or minor groove) through the insertion of their planar fused aromatic

moiety between the base pairs of DNA This interaction is stabilized by

stacking between the aromatic moiety of the intercalator and the DNA

base pairs Optimal intercalating molecules are planar and contain three

or four fused aromatic rings with a surface area of 28 Aring2 [119]

Intercalating molecules generally contain charged groups or metal ions

which make intercalation more favourable through electrostatic

interactions between the intercalating molecule and the DNA [119] The

insertion of an intercalator forces the base pairs apart increasing the base-

to-base distance from 34 Aring to 68 Aring The consequences of this increase

in inter-base distance are unwinding and extension of the DNA backbone



and loss of the regular helical structure Unlike covalent binding

intercalation is reversible [120]

Transition metal complexes containing fused planar aromatic

systems have been shown to be successful intercalators [121 122] Some

organic molecules such as dipyrido[32-a23-c]phenazine (dppz) are

unlikely to intercalate due to lack of functional groups capable of

electrostatic interactions with the DNA however once dppz is

coordinated to a transition metal such as ruthenium the resulting

positively charged metal complex intercalates with DNA [123-125]

17 Metal complexes as chemotherapeutic agent Medicinal application of metals can be traced back almost 5000

years [126] Over the years there has been a continuous interest in the

chemistry of metal complexes of biologically important ligands The

study of such complexes may lead to a greater understanding of the role

of the ligand in biological systems and may also contribute to the

development of new metal-based chemotherapeutic agents Most studies

have concentrated on the first-row transition metals [127 128] and

relatively few studies have concerned barbituric acid complexes of the

platinum-group metals [129] or silver and gold [130]

Many activities of metal ions in biology have stimulated the

development of metal-based therapeutics Cisplatin as one of the leading

metal-based drugs is widely used in treatment of cancer being especially

effective against genitourinary tumors such as testicular Significant side

effects and drug resistance however have limited its clinical

applications Biological carriers conjugated to cisplatin analogs have

improved specificity for tumor tissue thereby reducing side effects and

drug resistance Platinum complexes with distinctively different DNA

binding modes from that of cisplatin also exhibit promising



pharmacological properties Ruthenium and gold complexes with

antitumor activity have also evolved Other metal-based

chemotherapeutic compounds have been investigated for potential

medicinal applications including superoxide dismutase mimics and

metal-based NO donorsscavengers These compounds have the potential

to modulate the biological properties of superoxide anion and nitric

oxide

Metal centers being positively charged are favored to bind to

negatively charged biomolecules the constituents of proteins and nucleic

acids offer excellent ligands for binding to metal ions The

pharmaceutical use of metal complexes therefore has excellent potential

A broad array of medicinal applications of metal complexes has been

investigated and several recent reviews summarize advances in these

fields [131-135] Some selected compounds that are currently used in

clinical diagnosis Designing ligands that will interact with free or

protein-bound metal ions is also a recent focus of medicinal inorganic

research [136-138] For example chelating ligands for copper and zinc

are being investigated as a potential treatment for Alzheimers disease

[139] Developing metal complexes as drugs however is not an easy

task Accumulation of metal ions in the body can lead to deleterious

effects Thus biodistribution and clearance of the metal complex as well

as its pharmacological specificity are to be considered Favorable

physiological responses of the candidate drugs need to be demonstrated

by in vitro study with targeted biomolecules and tissues as well as in vivo

investigation with animal models before they enter clinical trials A

mechanistic understanding of how metal complexes achieve their

activities is crucial to their clinical success as well as to the rational

design of new compounds with improved potency



Several Ru(II) arene compounds with the formula [RuII(η6-

arene)(en)X]+ (X = Cl- or I- arene = p-cumene or biphenyl en =

ethylenediamine or N-ethylethylenediamine) were demonstrated to inhibit

the proliferation of human ovarian cancer cells Some of the IC50 values

were comparable with that of carboplatin [140] These complexes do not

inhibit topoisomerase II activity One representative compound binds

strongly to DNA forming monofunctional adducts selectively with

guanine bases Further studies lead to the synthesis of thirteen Ru(II)

analogs six of which are quite active against human ovarian cancer cells

No cross-resistance was observed in cisplatin-resistant cells Cross-

resistance did occur however with the multi-drug-resistant cell line

2780AD possibly mediated through the P-gP efflux mechanism [141]

Gold complexes are well known pharmaceuticals the main clinical

application being to treat rheumatoid arthritis They are also active as

antitumor agents [142] Tetrahedral Au(I) complexes with 12-

bis(diphenylphosphino)ethane and 12-bis(dipyridylphosphino)ethane

ligands display a wide spectrum of antitumor activity in-vivo especially

in some cisplatin-resistant cell lines Mechanistic studies suggest that in

contrast to cisplatin DNA is not the primary target of these complexes

Rather their cytotoxicity is mediated by their ability to alter

mitochondrial function and inhibit protein synthesis Very recently a

hydrophilic tetrakis[(tris(hydroxymethyl)phophine)]gold(I) complex was

reported to be cytotoxic to several tumor cell lines With HCT-15 cells

derived from human colon carcinoma cell cycle studies revealed that

inhibition of cell growth may result from elongation of the G-1 phase of

the cell cycle [143] Au(I) complex having both monophosphine and

diphosphine ligands have been prepared that is highly cytotoxic against

several tumor cell lines Its IC50 values are in the micromole range [144]



The available treatment is based on organic pentavalent antimony

compounds that produce severe side effects such as cardiotoxicity

reversible renal insufficiency pancreatitis anemia leucopenia rashes

headache abdominal pain nausea vomiting thrombocytopenia and

transaminase elevation [145]

The parasites of the genus Leishmania along with those of the

genus Trypanosoma belong to order Kinetoplastide and are considered to

behave in a way similar to tumoral cells with regard to drug sensitivity

and cell multiplication [146147] Cisplatin and other metal-containing

antitumoral compounds have been tested against Leishmania spp with

interesting results in the search for new and more effective

chemotherapeutic treatments Based on these results and because it is

known that this kind of compound interacts with DNA it has been

proposed that all DNA-interacting compounds might show activity

against protozoa [148]

Additionally in the development of new pharmaceutics against

tropical diseases some effort have been directed to the synthesis and

characterization of complexes of transition metals with different organic

drugs such as pentadiamine chloroquine clotrimazole and ketoconazole

as ligands and that have been evaluated against malaria trypanosomiasis

and leishmaniasis [149-154] The strategy in pursuing the search for new

drugs that combine high activity and low toxicity has been the

coordination of planar ligands to palladium This may result in an

interesting biological activity because of the possible ability of the new

metal complexes to inhibit DNA replication through single or

simultaneous interactions such as intercalation andor covalent

coordination to DNA [155 156]



It has been reported that palladium complexes such as trans-

palladium complex containing a bulky amine ligand showed a higher

activity against the L929 cell line when compared with carboplatin [157]

Also trans-[PdCl2(L)2] where L is a highly substituted pyrazole ligand

was more cytotoxic than cis-platinum with the same ligand although less

cytotoxic than cisplatin [153] Additionally the cytotoxic activity of

chloroquine clotrimazole thiosemicarbazones and their palladium

complexes was tested against human tumor cell lines with encouraging

results [158-161]

Synthesis of possible chemotherapeutic agents against

schistosomiasis leads to investigate compounds formed between

antimony(III)chloride and thiourea as well as the complexes formed

between NNrsquo-dialkyloxamides NNrsquo-dialkyldithiooxamides NNrsquo-

dialkylmalonamides NNrsquo-dialkyldi-thiomalonmides NNrsquo-

dialkylsuccinamides and toluene 34-dithiol with Group VB and Group

IV metal halides [162-164]

The synthesized chemical compounds which may be used for the

treatment of infectious diseases are known as chemotherapeutic agents

Every year thousand of compounds are synthesized with an aim to find a

potential chemotherapeutic agent combat pathogenic microorganisms

18 Literature survey on the complexes Quinolone are antimicrobial agents with a broad range of activity

against both gram-negative and gram-positive bacteria [165166] The

first member of the quinolone carboxylic acid family of antimicrobials

introduced into clinical practice was nalidixic acid used in the treatment

of urinary tract infections [37] The ciprofloxacin and norfloxacin have

been used to treat resistant microbial infections [167] The mechanism of

ciprofloxacin action involves inhibition of bacterial DNA gyrase which



is essential for DNA replication [168] Complexation of ciprofloxacin

with the metal cations and how this complexation affects ciprofloxacin

bioavailability and antimicrobial activity have been extensively studied

by Turel et al [169] Ma et al have reported that the presence of metal

ions results in a higher ciprofloxacin uptake by bacterial cells compared

to that of the drug alone [170] and it was also found that different metal

cations reduce its in-vitro antibacterial activity to varying extents [171]

Lomaestro and Bailie have reported that reduction in bioavailability is a

consequence of metal complex formation in the gastric system using

carboxylate functional groups of the molecule [172] Also it was reported

by Polk et al that zinc reduced bioavailability by an average of 24

[173] Mendoza et al have designed and synthesized series of ternary

complexes of quinolone as an attempt to understand how coordination

affects the activity of quinolone [174] Method for the determination of

fluoroquinolone (levofloxacin ciprofloxacin norfloxacin) by ion pair

complex formation with cobalt (II) tetrathiocyanate was reported by El-

Brashy et al [175] First nanosized neutral cavity of vanadium based

copolymer of norfloxacin was reported by Chen et al [176] Complexes of

Co(II) Ni(II) Cu(II)and Zn(II) with bidentate Schiff bases derived using

heterocyclic ketone and their antimicrobial study have been done by

Singh et al [177] Crystal structure stacking effect and antibacterial

studies of quaternary copper(II) complex with quinolone have been

studied by Guangguo et al [178] Perchlorate complexes of ciprofloxacin

and norfloxacin with magnesium calcium and barium have been studied

by Jamil Al-Mustafa [179] Toxicological studies of some iron(III)

complexes with ciprofloxacin have been studied by Obaleye et al and

concluded that the toxic effect of drugs like ciprofloxacin can be reduce

by complexation [180] The process of complexation completely



inhibited the crystallinity of ciprofloxacin which is helpful in control

release therapy which was studied by Pisal et al [181] Effect of pH on

complexation of ciprofloxacin and Zn(II) under aqueous condition was

studied by Marija Zupancic [182]

The Fe(III) Ni(II) Co(II) and Cu(II) complexes with thiazoline

and their fungicidal activity have been evaluated by Sangal et al [183]

Eight salicylhydroxamic acids and their metal chelates with Cu(II)

Ni(II) Co(II) Fe(III) Mn(II) and Zn(II) have been screened for their

antifungal activities by Khadikar et al [184] Saidul et al have studied

anti-microbial activity of some mixed-ligand complexes of Co(II) and

Fe(III) ion with maleicacid (MEH2) as primary and heterocyclic bases

viz quinoline(Q) iso-quionoline(IQ) 8-hydroxyquinoline(8-HQ)

pyridine(py) 2-aminopyridine(2apy) and 4-picoline (4-pico) as secondary

ligands [185] Sissi et al have determine the binding constant for drug-

DNA- Mg+2 ternary complex using flourometric titration and compared

with the binding constant of quinolone alone [60] Son et al have

reported that the binding mode of quinolone to DNA was just a like

classical intercalator [53] Mode of DNA binding of Zn(II) complex was

determine using absorption titration and fluorescence spectroscopy by

Wang et al [186] L-N Ji et al have studied intercalative mode of

Ru(II)Co(III) complexes using absorption spectroscopy emission

spectroscopy and cyclic voltametry [187] In pioneering research

Friedman et al [188] have demonstrated that complexes containing dppz

bind to DNA by intercalation with a binding constant (Kb) greater than

106 M-1 The complexes [Ru(phen)2(dppz)]2+ and [Ru(bpy)2(dppz)]2+ have

also been shown to act as ldquomolecular light switchesrdquo for DNA



19 Present work The research work describe in this thesis is in connection with the

synthesis spectroscopic thermal and magnetic studies of Co(II) Zn(II)

dimeric quinolone complexes with ciprofloxacin and neutral bidentate

ligands and monomeric VO(IV) complexes with a amino acids and

ciprofloxacin Antibacterial activity has been assayed against three

Gram(-ve) and two Gram(+ve) microorganisms using the doubling dilution

technique Binding of DNA with the complex has been investigated using

spectroscopic method and viscosity measurements Gel electrophoresis

technique has been used for the DNA cleavage activity of compounds

The entire work of the thesis is divided into four chapters

Chapter-1 Introduction

In this chapter general overview on coordination compound Schiff

bases quinolone chemistry of transition metal ions biological role of

cobalt zinc and vanadium metal ions DNA coordination compounds as

chemotherapeutic agents and literature survey on quinolone metal

complexes are discussed

Chapter-2 Synthesis and characterization of ligands

This chapter is divided into two parts first part deals with the

synthesis of the neutral bidentate ligands

The following ligands have been used for the synthesis of dimeric mixed

ligand complexes of cobalt(II) and zinc(II)

(I) NN-Dicyclohexylidene-benzene-12-diamine (A1~dcbd) (II) NN-Bis-(4-methoxy-benzylidene)-benzene-12-diamine

(A2~bmbbd) (III) NN-Bis-(3-chloro-phenyl)-12-diphenyl-ethane-12-diimine

(A3~bcpded) (IV) Bis(benzylidene)ethylenediamine (A4~benen) (V) NN-Bis-(4-methoxy-phenyl)-12-diphenyl-ethane-12-

diimine (A5~bmpded)



(VI) 2 2rsquo-Bipyridylamine (A6~bipym) (VII) NN-Bis-(phenyl)-12-dimethyl- ethane-12-diimine

(A7~bpdmed) (VIII) 4-Methoxy-N-(thiophene-2-ylmethylene)aniline (A8~mtma) (IX) 3-Amino-2-phenyl-3H-quinazolin-4-one (A9~apq) (X) NN-Bis-(1-phenylethylidene)-ethane-12-diamine

(A10~bpeed) (XI) NN-Dicyclohexylidene-napthalene-18-diamine (A11~dcnd) (XII) NN-(12-Diphenyl-ethane-12-diylidene)dianiline

(A12~dpeda) (XIII) NN-Bis-(4-methoxy-phenyl)-12-dimethyl-ethane-12-

diimine (A13~bmpdme) (XIV) NN-Bis-(4-methoxybenzylidene)ethane-12-diamine

(A14~bmbed) (XV) NN-Bis-(1-phenylethylidene)-benzene-12-diamine

(A15~bpebd) (XVI) 1 8-Diaminonaphthalene (A16~dan) (XVII) o-Phenylenediamine (A17~opd) (XVIII) Ethylenediamine (A18~en)

Following uninegative bidentate ligands have been used for the synthesis of monomeric oxovanadium(IV) complexes

(I) Anthranilic acid (L1) (II) Glycine (L2) (III) β-Alanine (L3) (IV) L-Asparagine (L4) (V) DL-Serine (L5) (VI) o-Aminophenol (L6) (VII) DL-Valine (L7) (VIII) DL-Alanine (L8) (IX) L-Leucine (L9)

Second part of this chapter concerns with characterization of

ligands The above listed ligands have been characterized with help of

elemental analysis infrared spectroscopy 1H NMR and 13C NMR

spectroscopy



Chapter-3 Synthesis and characterization of complexes

This chapter deals with the synthesis and characterization of

dimeric and monomeric mixed-ligand complexes In the first section

experimental procedure for the synthesis of Co(II) Zn(II) and VO(IV)

complexes are discussed General reaction schemes for synthesis of

mixed-ligand complexes of Co(II) Zn(II) and VO(IV) are as follow

Co(NO3)2 6H2O + Cip + An rarr [Co2(Cip)2(An)2(pip)(H2O)2]3H2O

Zn(OAc)2 H2O + Cip + An rarr [Zn2(Cip)2(An)2(pip)(H2O)2]3H2O

VOSO4 3H2O + Cip + Ln rarr [VO (Cip)(Ln)]2H2O

Where Cip = ciprofloxacin An = A1- A18 neutral bidentate ligands and

Ln = L1-L9 uninegative bidentate ligands

Second section represents the characterization of monomeric and

dimeric mixed ligand complexes The complexes have been characterized

by elemental analysis IR reflectance and UV-Vis spectroscopy

magnetic measurements and thermogravimery analyses The

coordination of the metal to the ligand has been interpreted by

comparison of IR and UV-Vis spectra Elemental analyses provide us

information about the how much percentage of elements is present in the

compounds TGA of complexes expose the detail of decomposition

lattice and coordinated water molecules present in the complexes The

reflectance spectra and magnetic measurements of the complexes provide

structural information such as geometry and magnetic nature The Co(II)

and VO(IV) complexes are paramagnetic in nature while Zn(II)

complexes are diamagnetic An octahedral geometry for Co(II) and Zn(II)

complexes while distorted square pyramidal structure for VO(IV) have

been suggested



Chapter-4 Biological aspects of the compounds

This chapter is divided into three major parts

First part deals with the antimicrobial activity [minimum inhibitory

concentration] Antibacterial activity has been assayed against three

Gram(-ve) ie E coli and P aeruginosa S merscences and two Gram(+ve)

ie S aureus B subtilis microorganisms using the doubling dilution

technique The results show a significant increase in antibacterial activity

compared with parental ligands and metal salts

Second part deals with the DNA binding activity of the complexes

with Sperm hearing DNA Binding of DNA with the complex was

investigated using spectroscopic method and viscosity measurements

The results showed that these complexes bind to DNA by intercalation

mode and their intrinsic binding constants (Kb) are in range 50 x 102 - 66

x 105 M-1 The complexes possess good binding properties than metal

salts and ligands

Third part represents the DNA cleavage activity of compound

towards plasmid pBR322 DNA Gel electrophoresis technique has been

used for this study All the mixed ligand complexes show higher nuclease

activity compare to parental ligands and metal salts



REFERENCE

[1] Kauffman GB Alfred Werner Founder of Coordination Chemistryrdquo Springer-Verlag Berlin New York 1966

[2] Kauffman GB in Dictionary of Scientific Biography Gillispie CC ed Charles Scribners Sons New York 1976 Vol 14 pp 264

[3] Blomstrand CW Ber 1871 4 40 [4] Kauffman GB in Dictionary of Scientific Biography Gillispie CC

ed Charles Scribners Sons New York 1970 Vol 2 pp 199-200 Annals of Science 1975 32 12 Centaurus 1977 21 44

[5] Kauffman GB in Dictionary of Scientific Biography Gillispie CC ed Charles Scribners Sons New York 1973 Vol 7 pp 179-180

[6] Werner A Z Anorg Chem1893 3 267 [7] Kauffman GB J Chem Educ 1959 36 521 Chymia 1960 6 180 [8] Kauffman GB Chemistry 1966 39(12) 14 [9] Kauffman GB Educ Chem 1967 4 11 [10] International Union of Pure and Applied Chemistry Schiff base Compendium of Chemical Terminology [11] Abu-Hussen AAA J Coord Chem 2006 59 157 [12] Sithambaram Karthikeyan M Jagadesh Prasad D Poojary B Subramanya BK Bioorg Med Chem 2006 14 7482 [13] Singh K Barwa MS Tyagi P Eur J Med Chem 2006 41 1 [14] Pannerselvam P Nair RR Vijayalakshmi G Subramanian EH Sridhar SK Eur J Med Chem 2005 40 225 [15] Sridhar SK Saravan M Ramesh A Eur J Med Chem 2001 36

615 [16] Pandeya SN Sriram D Nath G Declercq E Eur J Pharmacol 1999 9 25 [17] Mladenova R Ignatova M Manolova N Petrova T Rashkov I Eur Polym J 2002 38 989 [18] Walsh OM Meegan MJ Prendergast RM Nakib TA Eur J Med Chem 1996 31 989 [19] Arora K Sharma KP Synth React Inorg Met-Org Chem 2003 32

913 [20] Vigato PA Tamburini S Coord Chem Rev 2004 248 1717 [21] Katsuki T Coord Chem Rev 1995 140 189 [22] Chohan ZH Sherazi SKA Metal-Based Drugs 1997 4(6) 327 [23] Agarwal RK Singh L Sharma DK Singh R Tur J Chem 2005

29(3) 309 [24] Thangadurai TD Gowri M Natarajan K Synth React Inorg Met-

Org Chem 2002 32 329 [25] Ramesh R Sivagamasundari M Synth React Inorg Met-Org

Chem 2003 33 899



[26] Schonberg A Latif N J Am Chem Soc 1954 76 6208 [27] Mitra AK Misra SK Patra A Synth Commun 1980 10 915 [28] Singer LA Kong NP J Am Chem Soc 1966 88 5213 [29] Jin L Chen J Song B Chen Z Yang S Li Q Hu D Xu R Bioorg Med Chem Lett 2006 16 5036 [30] Bhamaria RP Bellare RA Deliwala CV Indian J Exp Biol 1968 6

62 [31] Chen H Rhodes J J Mol Med 1996 74 497 [32] Holla BS Rao BS Shridhara K Akberali PM Farmaco 2000 55

338 [33] Islam MR Mirza AH Huda QMN Khan BR J Bangladesh Chem

Soc 1989 2 87 [34] Heindel ND Reid JR J Hetero Chem 1980 17 1087 [35] Islam MR Huda QMN Duddeck H Indian J Chem 1990 29B 376 [36] Shaha GC Khair K Islam MR Chowdhury MSK Indian J Chem

1992 31 B 547 [37] Lesher GY Froelich EJ Gruett MD Bailey JH Brundage RP J

Med Pharm Chem 1962 5 1063 [38] Mitscher LA Chem Rev 2005 105(2) 559 [39] Andriole VT (Ed) ldquoThe Quinolonesrdquo 3rd ed Academic Press San

Diego 2000 [40] Turel I Coord Chem Rev2002 232 27 [41] King DE Malone R Lilley SH Am Fam Physician 2000 61 2741 [42] Koga H Itoh A Murayama S Suzue S Irikura T J Med Chem

1980 23 1358 [43] Lomaestro BM Bailie GR Ann Pharmacotheraphy 1991 25 1249 [44] Gorbach SL Nelson KW in Wilson APR Gruumlneberg RN Maxim

Medical Oxford 1997 pp 1 [45] Wolfson JS Hooper DC Clin Microbiol Rev 1989 2 378 [46] Yoshida H Bogaki M Nakamura M Nakamura S Antimicrob

Agents Chemother 1990 34 1271 [47] Trucksis M Wolfson JS Hooper DC J Bacteriol 1991 173(18)

5854 [48] Gellert M Mizuuchi K OrsquoDea MH Nash HA Proc Natl Acad Sci

USA 1976 73 3872 [49] Shen LL Chu DTW Curr Pharm Des 1996 2 195 [50] Shen LL Pernet AG Proc Natl Acad Sci USA 1985 82 307 [51] Bailly C Colson P Houssier C Biochem Biophys Res Commun

1998 243 844 [52] Son GS Yeo JA Kim JM Kim SK Moon HR Nam W Biophys

Chemist 1998 74 225 [53] Son GS Yeo JA Kim JM Kim SK Holmeacuten A Akerman B N ordeacuten B J Am Chem Soc 1998120 6451



[54] Fisher LM Lawrence JM Jostly IC Hopewell R Margerrison EE Cullen ME Am J Med 1989 87 2Sndash8S

[55] Fung-Tomc J Kolek B Bonner DP Antimicrob Agents Chemother 1993 37 1289

[56] Niccolai D Tarsi L Thomas RJ Chem Commun 1997 1997 2333 [57] Hammonds TR Foster SR Maxwell A J Mol Biol 2000 300 481 [58] Fan J-Y Sun D Yu H Kerwin SM Hurley LH J Med Chem 1995

38 408 [59] Palu` G Valisena S Ciarrocchi G Gatto B Palumbo M Proc Natl

Acad Sci USA 1992 89 9671 [60] Sissi C Andreolli M Cecchetti V Fravolini A Gatto B Palumbo M

Bioorg Med Chem 1998 6 1555 [61] Sissi C Perdona E Domenici E Feriani A Howells AJ Maxwell A

Palumbo M J Mol Biol 2001 311 195 [62] Moghaddas S Hendry P Geue RJ Qin C Bygott AMT Sargeson

AM Dixon NE J Chem Soc Dalton Trans 2000 2085 [63] Ananias DC Long EC J Am Chem Soc 2000 122 10460 [64] Schmidt K Jung M Keilitz R Gust R Inorg Chim Acta 2000 306

6 [65] Ware DC Brothers PJ Clark GR Denny WA Palmer BD Wilson

WR J Chem Soc Dalton Trans 2000 925 [66] Thompson KH Orvig C J Chem Soc Dalton Trans 2000 2885 [67] Rehder D Conte V J Inorg Biochem 2000 80 vii [68] Kiss E Garribba E Micera G Kiss T Sakurai H J Inorg Biochem

2000 78 97 [69] Crans DC Yang LQ Jakusch T Kiss T Inorg Chem 2000 39

4409 [70] Buglyo P Kiss E Fabian I Kiss T Sanna D Garriba E Micera G

Inorg Chim Acta 2000 306 174 [71] Amin SS Cryer K Zhang BY Dutta SK Eaton SS Anderson OP

Miller SM Reul BA Brichard SM Crans DC Inorg Chem 2000 39 406

[72] Etcheverry SB Williams PAM Barrio DA Salice VC Ferrer E Gand Cortizo AM J Inorg Biochem 2000 80 169

[73] Rangel M Trans Met Chem 2001 26 219 [74] Dong YH Narla RK Sudbeck E Uckun FM J Inorg Biochem

2000 78 321 [75] DrsquoCruz OJ Dong YH Uckun FM Anti-Cancer Drugs 2000 11 849 [76] Rio D del Galindo A Tejedo J Bedoya FJ Ienco A Mealli C Inorg

Chem Commun 2000 3 32 [77] Slebodnick C Hamstra BJ Pecoraro VL Struct Bonding 1997 89

51 [78] Baran EJ An Soc Cientίf Argent 1998 228 61 [79] Baran EJ J Braz Chem Soc 2003 14 878



[80] Eady RR Chem Rev 1996 96 3013 [81] Masepohl B Schneider K Drepper T Muumlller A Klipp W Ed Leigh

GJ Elsevier New York 2002 pp 191 [82] Baran EJ in lsquoAdvances in Plant Physiologyrsquo Vol 10 Ed

Hemantaranjan H Scientific Publishers Jodhpur 2008 pp 357 [83] Crans DC Smee JJ Gaidamauskas E Yang L Chem Rev 2004 104

849 [84] Butler A Baldwin AH Struct Bonding 1997 89 109 [85] Nielsen FH FASEB J 1991 5 3 [86] Plass W Angew Chem Int Ed 1999 38 909 [87] Nriagu JO Pirrone N in lsquoVanadium in the Environment Part I

Chemistry and Biochemistryrsquo Ed Nriagu JO John Wiley amp Sons New York1998 pp 25

[88] Mamane Y Pirrone N Chemistry and Biochemistry Part I Ed Nriagu JO John Wiley amp Sons New York 1998 pp 37

[89] Baran V Baran EJ An Acad Nac Cs Ex Fίs Nat 2002 54 171 [90] Baran EJ Acta Farm Bonaerense 1997 16 43 [91] Djordjevic C in lsquoMetal Ions in Biological Systemsrsquo Vol 31 Eds

Sigel H Sigel A Marcel Dekker New York 1995 pp 595 [92] Thompson KH Orvig C J Chem Soc Dalton Trans 2000 2885 [93] Thompson KH Orvig C Coord Chem Rev 2001 219221 1033 [94] Rehder D Inorg Chem Comm 2003 6 604 [95] Faulkner-Hudson TG lsquoVanadium Toxicology and Biological

Significancersquo Elsevier Amsterdam1964 [96] Baran EJ in lsquoVanadium in the Environment Part II Health Effectsrsquo

Ed Nriagu JO John Wiley amp Sons New York 1998 pp 317 [97] Nechay BR Nanninga LB Nechay PSE Post RL Grantham JJ

Macara IG Kubena LF Phillips TD Nielsen FH Fed Proc 1986 45 123

[98] Nielsen FH in lsquoMetal Ions in Biological Systemsrsquo Vol 31 Eds Sigel H Sigel A Marcel Dekker New York 1995 pp 543

[99] Taylor DM Williams DR lsquoTrace Element Medicine and Chelation Therapyrsquo Royal Society of Chemistry Cambridge 1995

[100] Baran EJ lsquoQuίmica Bioinorgaacutenicarsquo McGraw-Hill Interamericana de Espaňa SA Madrid 1995

[101] Andersen O Chem Rev 1999 99 2683 [102] Andersen O Mini-Rev Med Chem 2004 4 11 [103] Blanusa M Varnai VM Piasek M Kostial K Curr Med Chem

2005 12 2771 [104] Porterfield WW lsquoInorganic Chemistry A Unified Approachrsquo 2nd ed

Academic Press San Diego 1993 [105] Watson JD Crick FHC Nature 1953 171 737 [106] Felsenfeld G Scientific American 1985 253 58 [107] Sundquist WI Lippard SJ Coord Chem Rev 1990 100 293



[108] Voet D Voet JG Biochemistry 2nd ed Wiley 1995 pp 1361 [109] Perego P Gatti L Caserini C Supino R Colangelo D Leone R

Spinelli S Farrell N Zunino F J Inorg Biochem 1999 77 59 [110] Rauter H Di Domenico R Menta E Oliva A Qu Y Farrell N Inorg

Chem 1997 36 3919 [111] Wu PK Qu Y van Houten B Farrell N J Inorg Biochem 1994 54

207 [112] Eastman A Chemico-Biological Interactions 1987 61 241 [113] Eastman A Pharmacology and Therapeutics 1987 34 155 [114] Van Vliet PM Toekimin SMS Haasnoot JG Reedijk J Novakova O

Vrana O Brabec V Inorg Chim Acta 1995 231 57 [115] Gessner RV Quigley GJ Wang AHJ Van der Marel GA Van Boom

JH Rich A Biochemistry 1985 24 237 [116] OSullivan WJ Perrin DD Biochemistry 1964 3 18 [117] Kopka ML Yoon C Goodsell D Pjura P Dickerson RE J Mol

Bio 1985 183 553 [118] The Regents of the University of California

httpwwwcglucsfeduchimeraImageGallery (02112005) [119] Lerman LS J Mol Bio 1961 3 18 [120] Jennette KW Lippard SJ Vassiliades GA Bauer WR Proceedings of

the National Academy of Sciences of the United States of America 1974 71 3839

[121] Aldrich-Wright JR Greguric ID Lau CHY Pellegrini P Collins JG Rec Res Dev Inorg Chem 1998 1 13

[122] Erkkila KE Odom DT Barton JK ChemRev 1999 99 2777 [123] Dupureur CM Barton JK Inorg Chem 1997 36 33 [124] Friedman AE Chambron JC Sauvage JP Turro NJ Barton JK J

Am Chem Soc 1990 112 4960 [125] Hiort C Lincoln P Nordeacuten B J AmChem Soc 1993 115 3448 [126] Orvig C Abrams MJ Chem Rev 1999 99 2201 [127] Cotton FA Falvello LR Schwotzer W Murillo CA Valle-Bourrouet

G InorgChimActa 1991190 89 [128] Fazakerley GV Linder PW Nassimbeni LR Rodgers AL Inorg

Chim Acta 1974 9 193 [129] Sinn E Flynnjun CM Martin RB J Am Chem Soc 1978 100 489 [130] Bonatti F Burini A Rosa P Pietroni BR Bovio B J Organomet

Chem 1986 317 121 [131] Sakurai H Kojima Y Yoshikawa Y Kawabe K Yasui H Coord

Chem Rev 2002 226 187 [132] Sadler PJ Li H Sun H Coord Chem Rev 1999 185-186 689 [133] Ali H van Lier JE Chem Rev 1999 99 2379 [134] Louie AY Meade TJ Chem Rev 1999 99 2711 [135] Volkert WA Hoffman TJ Chem Rev 1999 99 2269 [136] Sarkar B Chem Rev 1999 99 2535



[137] Liu ZD Hider RC Coord Chem Rev 2002 232 151 [138] Whittaker M Floyd CD Brown P Gearing AJH Chem Rev 1999

99 2735 [139] Bush AI Neurobrol Aging 2002 23 1031 [140] Morris RE Aird RE Murdoch PS Chen H Cummings J Hughes NO Parsons S Parkin A Boyd G Jodrell DI Sadler PJ J Med Chem 2001 44 3616 [141] Aird RECummings J Ritchie AA Muir M Morris RE Chen H

Sadler PJ Jodrell DI Br J Cancer 2002 86 1652 [142] McKeage MJ Maharaj L Berners-Price SJ Coord Chem Rev 2002

232 127 [143] Pillarsetty N Katti KK Hoffman TJ Volkert WA Katti KV Kamei

H Koide T J Med Chem 2003 46 1130 [144] Caruso F Rossi M Tanski J Pettinari C Marchetti F J Med Chem

2003 46 1737 [145] Olliaro P Bryceson A Today 1993 9 323 [146] Kinnamon K Steck EA Rane DS Antimicrob Agents Chemother

1979 15 157 [147] Farrell NP Willianson J MacLaren DJM Biochem Pharmacol

1984 33 961 [148] Brown R In Critical Reports on Applied Chemistry Chemotherapy

of Tropical Diseases Hooper M ed John Wiley amp Sons Chichester 1987 72

[149] Mbongo N Loiseau PM Craciunescu DG Robert-Gero M Acta Tropica 1998 70 239

[150] Saacutenchez-Delgado RA Lazardi K Rincoacuten L Urbina JA Hubert AJ Noels AF J Med Chem 1993 36 2041

[151] Navarro M Peacuterez H Saacutenchez-Delgado RA J Med Chem 1997 40 1937

[152] Saacutenchez-Delgado RA Navarro M Lazardi K Atencio R Capparelli M Vargas F Urbina JA Bouillez A Hubert AJ Noels AF Inorg Chim Acta 1998 275 528

[153] Navarro M Lehmann T Cisneros-Fajardo EJ Fuentes A Sanchez-Delgado RA Silva P Urbina JA Polyhedron 2000 19 2319

[154] Navarro M Cisneros-Fajardo EJ Lehmann T Sanchez-Delgado RA Atencio R Silva P Lira R Urbina JA Inorg Chem 2000 40 6879

[155] Erkkila KE Odom DT Barton KJ J Chem Rev 1999 99 2777 [156] Farrell N In Trans Met Comp Drugs and Chemother Age in Cat

Met Compl James BR Ugo R ed Kluwer Dordrecht 1989 ch1-4 [157] Abu-Surrah AS Al-Allaf TAK Rashan LJ Klinga M Leskela M

Eur J Med Chem 2002 37 919 [158] Budzisz E Krajewska U Rozalski M Szulawska A Czyz M

Nmawrot B Eur J Pharmacol 2004 502 59



[159] Navarro M Prieto-Pentildea N Colmenares I Gonzalez T Arsenak M Taylor P J Inorg Biochem 2006 100 152

[160] Rebolledo AP Vieites M Gambino D Piro OE Castellano E Zani CL Souza-Fagundes EM Teixeira LR Batista AA Beraldo H J Inorg Biochem 2005 99 698

[161] Goacutemez-Quiroga A Navarro-Ranninger C Coord Chem Rev 2004 248 119

[162] Wandiga SO J Chem Soc Dalton Trans 1975 1894 [163] Wandiga SO Jenkins LJ Willey GR J Inorg Nucl Chem 1979

41(7) 941 [164] Wandiga SO Pure Appl Chem 1999 71(6) 1019 [165] Hooper D Drugs 1999 58 6 [166] King A Phillip I J Antimicrob Chemother 1986 18 1 [167] Kalley SG Bertram MA Young LS J Antimicrob Chemother

1986 17 281 [168] Shen LL Mitscher LA Sharma P Donnell TJ Chu DWT Cooper

CS Rosen T Pernet AG Biochemistry 1989 28 3886 [169] Turel I Leban I Bukovec N J Inorg Biochem 1994 56 273 [170] Ma HHM Chiu FCK Li RC Pharm Res 1997 14 366 [171] Adepoju-Bello AA Eboka CJ J Pharm Sci Pharm Pract 1997

3(1) 35 [172] Lomaestro BM Bailie GR Ann Pharmacother 1991 25 1249 [173] Polk RE Healy DP Sahai J Drwal L Antimicrob Agents

Chemother 1991 35 1004 [174] Mendoza-Diaz G Perez-Alonso R Mantinez-Agilera LMR Inorg

Chim Acta 1987 138 41 [175] El-Brashy AM Metwally ME El-Sepai FA J Chin Chem Soc

2005 52 77 [176] Chen ZF Liang H Hu HM Li Y Xiong RG You XZ Inorg Chem

Comm 2003 6 241 [177] Singh K Barwa MS Tyagi P Eur J Med Chem 2006 41 147 [178] Wu G Wang G Fu X Zhu L Molecules 2003 8 287 [179] Al-Mustafa J Acta Chim Slov 2002 49 457 [180] Obaleye JA Akinremi CA Balogu EA Adebayo JO Afri J Biotech 2007 6(24) 2826 [181] Pisal S Rana Z Nalawade P Mahadik K Kadam S AAPS Pharm

SciTech 2004 5(4) Article 62 [182] Zupancic M Turel I Bukovec P White AJP David JW Croa Chem

Acta 2001 74(1) 61 [183] Sangal SK Herjinider K J Indian Chem 1994 71 621 [184] Khadikar PV Saxena R Khaddar T Feraqui MA J India Chem Soc

1994 56 215 [185] Saidul Islam M Belayet Hossain Md Yeamin Reza Md J Med Sci

2003 3(4) 289



[186] Wang J Shuai L Xiao X Zeng Y Li Z Matsumura-Inoue T J Inorg Biochem 2005 99 883

[187] Ji L-N Zou X-H Liu J-G Coord Chem Rev 2001 216-217513 [188] Friedman AE Chambron JC Sauvage JP Turro NJ Barton JK J Am

Chem Soc 1990 112 4962



CHAPTER-1

INTRODUCTION 11 General introduction

In 1893 Alfred Werner (1866-1919) [1 2] challenged all previous

theories especially the reigning chain theory proposed by the Swede

Christian Wilhelm Blomstrand (1826-1897) [3 4] which was developed

and experimentally advanced by the Dane Sophus Mads Jorgensen (1837-

1914) [5] with a revolutionary new theory [6] According to Werners

own admission it was based on Jorgensenrsquos painstaking experimental

data In fact Jorgensenrsquos work bore the seeds of the chain theorys

destruction some of Jorgensenrsquos compounds later were crucial in

Werners proof of his coordination theory [7-9]

Werners theory abruptly broke with classical theories of valence

and structure postulating two types of valence primary of ionizable

valence (Hauptvalenz) and secondary or nonionizable valence

(Nebenvalenz) Every metal in a given oxidation state (primary valence)

also has a fixed coordination number (a specific number of secondary

valences that must be satisfied) Primary valences can be satisfied only by

anions but secondary valences can be satisfied by anions and neutral

molecules Secondary valences are directed in space around the central

metal atom The combined aggregate forms a complex which usually

exists as a discrete unit in solution The most common configurations are

`octahedral (coordination number six) and square-planar or tetrahedral

(coordination number four) Werners view of the two types of linkages -

ionogenic (ionizable) and nonionogenic (nonionizable) ndash clarified

ideas of chemical bonding a generation before Kossels and Lewiss views




respectively


















twentieth-century














1929-32










1950




















1960-67












1995-96
































nitrogen atom



















coordinating moiety











































































































incomplete d-level



















or permanganate





become more stable


period














the d orbitals







































































occur in people














apoptosis [76]























































































(a) (b) (c)


















following Table


DNA [55]



turn 11 10 12













along the DNA helix





























helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962




respectively


















twentieth-century














1929-32










1950




















1960-67












1995-96
































nitrogen atom



















coordinating moiety











































































































incomplete d-level



















or permanganate





become more stable


period














the d orbitals







































































occur in people














apoptosis [76]























































































(a) (b) (c)


















following Table


DNA [55]



turn 11 10 12













along the DNA helix





























helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962






1929-32










1950




















1960-67












1995-96
































nitrogen atom



















coordinating moiety











































































































incomplete d-level



















or permanganate





become more stable


period














the d orbitals







































































occur in people














apoptosis [76]























































































(a) (b) (c)


















following Table


DNA [55]



turn 11 10 12













along the DNA helix





























helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962



1960-67












1995-96
































nitrogen atom



















coordinating moiety











































































































incomplete d-level



















or permanganate





become more stable


period














the d orbitals







































































occur in people














apoptosis [76]























































































(a) (b) (c)


















following Table


DNA [55]



turn 11 10 12













along the DNA helix





























helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962















nitrogen atom



















coordinating moiety











































































































incomplete d-level



















or permanganate





become more stable


period














the d orbitals







































































occur in people














apoptosis [76]























































































(a) (b) (c)


















following Table


DNA [55]



turn 11 10 12













along the DNA helix





























helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962




coordinating moiety











































































































incomplete d-level



















or permanganate





become more stable


period














the d orbitals







































































occur in people














apoptosis [76]























































































(a) (b) (c)


















following Table


DNA [55]



turn 11 10 12













along the DNA helix





























helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962


















































































incomplete d-level



















or permanganate





become more stable


period














the d orbitals







































































occur in people














apoptosis [76]























































































(a) (b) (c)


















following Table


DNA [55]



turn 11 10 12













along the DNA helix





























helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962



















or permanganate





become more stable


period














the d orbitals







































































occur in people














apoptosis [76]























































































(a) (b) (c)


















following Table


DNA [55]



turn 11 10 12













along the DNA helix





























helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962










the d orbitals







































































occur in people














apoptosis [76]























































































(a) (b) (c)


















following Table


DNA [55]



turn 11 10 12













along the DNA helix





























helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962




















































occur in people














apoptosis [76]























































































(a) (b) (c)


















following Table


DNA [55]



turn 11 10 12













along the DNA helix





























helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962






apoptosis [76]























































































(a) (b) (c)


















following Table


DNA [55]



turn 11 10 12













along the DNA helix





























helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962































































(a) (b) (c)


















following Table


DNA [55]



turn 11 10 12













along the DNA helix





























helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962







following Table


DNA [55]



turn 11 10 12













along the DNA helix





























helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962







along the DNA helix





























helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962






helix























































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962






































oxide



























































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962






































































results [158-161]







































































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962





















































































diimine (A5~bmpded)















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962















spectroscopy




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962




























been suggested

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962

















salts and ligands







REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962



REFERENCE











Chem 2003 33 899

















































































































2003 3(4) 289





Chem Soc 1990 112 4962

















































































































2003 3(4) 289





Chem Soc 1990 112 4962





Chem Soc 1990 112 4962

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