i. general introduction to...

Synthesis and Characterization of Dithiocarbamate Complexes of Some 3d Metals and their Adducts with Nitrogen Donors 2013

Introduction []

I. GENERAL INTRODUCTION TO DITHIOCARBAMATES

Dithiocarbamates, the half amides of dithiocarbonic acids, were

discovered as a class of chemical compounds in the history of

organosulfur chemistry.1,2,3 These are a versatile class of monoanionic

1,1-dithio ligands and as they are easily prepared, a wide range of

chemistry has been developed around them.4 The structure of

dithiocarbamate group can be represented by the valence bond

formalism as shown below (Fig. 1). The resonance form (c) i.e. the

thioureide form results from the delocalization of nitrogen lone pair.4,5

C

S

S

R2N

_C

S

S

R2N C

S

S

_ _

_

R2N

(a) (b) (c)

+

Fig.1. Resonance forms of dithiocarbamate complexes

The extent to which the resonance form (c) contributes to the structure

and its effects on the physical and chemical properties of the dithio

compounds have been the subject of considerable study. The

contribution of the resonance form (c) to the structure of the

dithiocarbamate ligands and complexes was offered as a possible

explanation for the varying antifungal activities of these compounds. A

detailed infrared study of a great number of dithiocarbamate complexes

concluded that resonance form (c) does indeed contribute to the

structure to a considerable extent.6 The structures of the metal

dithiocarbamates are being investigated because of (i) the fact that most

of their detailed structures are unknown, (ii) the theoretical interests

arising from the sulfur containing four membered rings present in these

compounds, (iii) their biological (antifungal) activity and (iv) the lack of

correlation between structural properties and the known chemical and

physical properties of these compounds.1

The strong metal binding properties of the dithiocarbamates were

recognized early by the virtue of insolubility of the metal salts and the


Introduction []

capacity of the molecules to form chelate complexes. Dithiocarbamates

can function as unidentate, bidentate chelating as well as bidentate

bridging ligands as shown below7,8,9

R2N C

S

S

M

R2N C

S

S

M R2N C

S

S

M1

M2

In the chelating mode, they frequently stabilize the metal center in an

unusually high apparent formal oxidation state. They are capable of

stabilizing transition metals in a wide range of oxidation states, and in

by far the vast majority of instances, they act merely as non sterically

demanding ancillary ligands.5,10,11 A large number of compounds are

known where CS2 binds in 1-end on, 2-side or in 3-coordination

modes.7,12,13 The major advantage of using the small bite angle of

dithiocarbamato moiety as a stabilizing chelating ligand, is its unique

property to remain intact under a variety of conditions.14

Dithiocarbmates also have a property for stabilizing novel

stereochemical configurations, unusual mixed oxidation states (e.g. of

Cu), intermediate spin states (e.g. Fe(III), S = 3/2), and for forming a

variety of tris chelated complexes of Fe(II) which lie at the 2T2 - 6A1 spin

cross-over.

The ammonium salt of dithiocarbamic acid can be synthesized by the

following equation:

N

H

H

H + C2S N

H

H

C

S

S NH4+

_

Ammonium salt of Dithiocarbamic acid

H2O

The dithiocarbamate salts of the general formula (H2NR2+)(R2NCSS) can

be prepared by the reaction of carbon disulfide with primary or

secondary amines, both aliphatic and aromatic. The corresponding

alkali metal salts are obtained using an alkali hydroxide as the proton

acceptor corresponding to the reaction given below.

R2NH + CS2 + MOH R2NCSSM + H2OH2O


Introduction []

The main synthetic route to dithiocarbamates is based on the

interaction between the corresponding amine and carbon disulfide in

the presence of a strong base.15 The process can even take place in the

absence of a strong base, but in this case, the yield of dithiocarbamate

corresponds to about half the amount of the consumed amine. In the

presence of a strong base; indeed, the base catalyzed reaction makes an

essential contribution to the dithiocarbamate formation rate.16 The free

dithiocarbamic acids are unstable and very few have been isolated. The

simplest member of the series H2NCSSH can be obtained as an unstable

crystalline solid by the acidification of a concenterated solution of the

ammonium salt. The same salt hydrolizes according to the reaction and

the free amino group undergoes Schiff’s base condensation with ketones

and aldehydes. The dithiocarbamates derived from primary amines are

unstable, and in the presence of a base are converted to corresponding

isothiocyanates presumably according to the following reaction17

H2NCSSNH4 + H2O(NH4)2OCS2

RNCS + SHB

RHNCSS

The disubstituted dithiocarbamates are considerably more stable

although they too decompose under acidic conditions according to the

equation6

R2NCS2 R2NH + CS2

Generally the free dithiocarbamic acids are unstable since they are

susceptible to decomposition yielding free amine and carbon disulfide.

But the dithiocarbamic acid, 4-methylpiperazine-1-carbodithioic acid

(4-MPipzcdtH) derived from a saturated heterocyclic secondary amine,

1-methylpiperazine, has been isolated in its zwitter ionic form.18 It

involves the insertion of CS2 into the N_H bond of the saturated

heterocyclic secondary amine (1-Mpipz) and the resulting zwitter ion is

represented in Fig. 2.


Introduction []

N

N

..

H

H3C

+ CS2

N

N

C

S

SH

H3C

..

or

N

N C

S

S

H

CH3

Fig.2

Organic dithiocarbamates can also be made by one step reaction of

dialkylamine, carbon disulfide and an organic substrate. The organic

substrate is preferably an olefin, diene or epoxide. Organic

dithiocarbamates can also be made through two step reaction involving

ammonium or metal dithiocarbamate salts and organic halides.19 In

case of their ammonium salts, N-substituted dithiocarbamic acids,

RNHC(=S)SH or R2NC(=S)SH, are formed by the reaction of CS2 with

primary or secondary amine in alcoholic or aqueous solution before

they are further reacted with ammonia. In order to conserve the more

valuable amine, it is a common practice to use an alkali metal

hydroxide to form the salt.

RNH2 + CS2 + NaOH RNHC(=S)S_Na + H2O

The dithiocarbamic acid can be precipitated from an aqueous solution

of dithiocarbamate by adding strong mineral acid. The acids are quite

unstable but can be held below 5C for a short time. The most common

additive methylene-bis-dibutyldithiocarbamate is prepared from sodium

dibutyldithiocarbamate and methylene dichloride.2

2(C4H9)2NC(=S)S_Na + CH2Cl2 [(C4H9)2NC(=S)S]2CH2 + 2NaCl

A convenient, efficient and green procedure for the synthesis of S-aryl

dithiocarbamates has been developed by a simple one-pot condensation

of aryl diazonium fluoroborate, carbon disulfide and amine in the

absence of any transition metal catalyst in water at room temperature.


Introduction []

The reactions of a variety of substituted aryl diazonium fluoroborates,

and cyclic and open chain amines, have been addressed. The products

are purified by crystallization from ethanol and the process does not

involve any hazardous solvent.20

II. DITHIOCARBAMATES OF TRANSITION ELEMENTS

Sulfur is one of the most versatile elements in the main group

chemistry. It exhibits a remarkable property in its capacity for bonding

with other elements especially with transition elements. The chemistry

of transition metal-sulfur compounds has attracted much interest for

their importance in the field of metalloenzymes, material precursors,

and catalysts.21 Among the more frequently considered sulfur

containing ligands that have been studied in the past few years are

xanthates, dithiocarbamates and other similar ligands which form four-

membered chelate rings with sulfur as the sole donor atom such as

dithiocarboxylates, dithiophosphates, dithiophosphinates etc. Special

interest in the study of metal dithiocarbamates was aroused because of

the striking structural features presented by this class of compounds

and also because of its diversified applications.9,22 An extremely large

number of dithiocarbamate complexes with transition and non-

transition metal ions have been known.23-25

A large number of metal complexes with various aliphatic and aromatic

dithiocarbamate ligands have been synthesized and characterized in the

past few years.6,26 Cu(II)dithiocarbamates were first reported by Delpine

as water insoluble precipitates obtained when aqueous Cu(II) ions were

treated with aqueous solutions of the R2Dtc ligands. Copper forms

dithiocarbamate complexes in both +1 and +2 oxidation states. The

Cu(I) dithiocarbamates are pale yellow to reddish-yellow diamagnetic

solids and their melting points decrease with increasing size of the alkyl

groups on the ligands. The disubstituted dithiocarbamates of Cu(II) are

stable, water insoluble compounds and under acidic conditions do not

decompose to CS2 and the amine salt. Cu(II) reacts quantitatively with

the Pb(R2Dtc)2, Bi(R2Dtc)3 and Tl(R2Dtc)3 complexes to form the deep


Introduction []

red-brown Cu(R2Dtc)2 complexes. The magnetic susceptibilities of these

complexes are indicative of one unpaired spin. The crystal structure of

Cu(R2Dtc)2 complexes reveal that these are dimers with 5-coordinate

Cu(II) ions (Fig. 3). The axial interactions (CuS, 2.851{2} A) do not

persist in solution where such complexes are monomeric.6

R2N C

S

S

Cu

S

S

C NR2

R2N C

S

S

Cu

S

S

C NR2

Fig.3. Schematic structure of the Cu(R2Dtc)2 complexes

Three new dinuc1ear Cu(II) complexes of the general formula

[Cu2(Rdtc)tpmc](ClO4)3, where tpmc and Rdtc refer to N,N',N'',N'''-

tetrakis(2-pyridylmethyl)-1,4,8,1l-tetraazacyclotetradecane and 2-, 3-,

or 4-methylpiperidinedithiocarbamates (2-, 3- or 4-Mepipdtc),

respectively, have been prepared (Fig. 4). The complexes were

characterized by elemental analyses, conductometric measurements,

electronic, IR and mass spectroscopy. The complexes adopt an exo

coordination of Cu(II) ions and tpmc. The dithiocarbamate ion joins

through both the sulfur atoms acting as a bridging ligand.27

N

C

S S

Cu Cu

N N

NN

CH3

py

py

py

py

N

py =

Fig. 4. Structure of the [Cu2(Rdtc)tpmc](ClO4)3 complexes


Introduction []

Thiuram disulfides [R2NC(S)SSC(S)NR2] are the thiocarbamoyl esters of

dithiocarbamic acids and the interaction of copper(II) halides CuX2

(X=Cl or Br) with tetraalkylthiuram disulfides, R4tds (R = Me, Et or iPr)

in THF at ambient temperature yields Cu(III)dithiocarbamates,

X2Cu(R2dtc), as deeply coloured relatively air stable microcrystalline

solids, plus solutions which degrade rapidly in air to produce the

copper(II)bis(dithiocarbamate) complex.28

The dithiocarbamate compounds of Ag(I) and Au(I) were studied

thoroughly by Akerstorm. The Ag(I) complexes exist as hexamers while

the Au(I) complexes are dimeric in solution. The crystal structures of

[Ag-n-Pr2Dtc]6 and [AgEt2Dtc]6 and [Au-n-Pr2Dtc]2 have been

determined. The Au-Au distance of 2.76 A is even shorter than that in

the metal.6

The Au(I) and Au(III) complexes with dithiocarbamate ligands (DMDT =

N,N-dimethyldithiocarbamate, DMDTM = S-methyl-N,N-dimethyldithio

carbamate and ESDT = ethylsarcosinedithiocarbamate) have been

synthesized, purified and characterized by the means of elemental

analysis, conductivity measurements, mono and bi-dimensional NMR,

FT-IR and UV-Visible spectroscopy and thermal analysis. The

gold(III)DMDT derivatives have been obtained by the direct reaction in

water between KAuX4 and DMDT sodium salt in 1:1 molar ratio to give

the corresponding stoichiometric adducts [(DMDT)AuX2] (where X = Cl,

Br) (Fig. 5). The S-methylated complexes of the type [(MSDTM)AuX3]

and [(MSDTM)AuX] (X = Cl, Br) have also been prepared by the reaction

of DMDTM ligand with KAuX4 species in 1:1 and 2:1 molar ratio

respectively. In these complexes the dithiocarbamate ligand coordinates

the metal center through the thiocarbonyl sulfur-donating atom (Fig.

5).29 The gold(III)ESDT derivatives have been prepared by a template

reaction between KAuX4, ESHCl (ethylsarcosinehydrochloride), CS2 and

NaOH in 1:2:2:2 molar ratio, leading to pure 1:1 metal-to-ligand species

of the type [(ESDT)AuX2] (X = Cl, Br). The gold(I) analogue [(ESDT)Au]2

has been synthesized by the same template reaction following the

complete reduction of KAuX4 to KAuX2 (Fig. 5).29


Introduction []

N

H3C

H3C

C

S

S

Au

X

X

N

H3C

H3C

C

S

S CH3

Au

XX

X

N C

H3C

H3C

S

S

Au

X

CH3

CH3CH2O

C

O

CH2 N

CH3

C

S

S

Au

X

X

CH3CH2O

C

O

CH2 N

CH3

C

S

S

Au

Au

S

S

C N

CH3

CH2

C

O

OCH2CH3

[(DMDTM)AuCl][(DMDTM)AuBr]

[(DMDTM)AuCl3]

[(DMDTM)AuBr3]

[(ESDT)AuCl2]

[(ESDT)AuBr2]

[(ESDT)Au]2

[(DMDT)AuCl2]

[(DMDT)AuBr2]

Fig.5. Chemical Drawings of the Gold Complexes

A novel route for the synthesis of Ni(II)dithiocarbamate complexes is by

the reaction of di--hydroxobis[bis(pentafluorophenyl)nickelate(II)] ion

with amines (pyrrolidine, propylamine, dimethylamine, diethylamine,

piperidine and morpholine) in the presence of CS2 to give corresponding

complexes of the type [(C6F5)2Ni(S2CX)], X = NEt2, NHEt, NMe2, etc.30

The nickel(II)diethyldithiocarbamate complexes of the composition [Ni(-

SR)(Et2dtc)]2, (R = Ph, C6H4Me-p, Et, t-Bu, CH2Ph) are binuclear with a

square planar arrangement of donor atoms around nickel in which

dithiocarbamates are chelated to the metal centers as terminal bridges

between two Ni(II) ions.31 Binuclear Ni(II)dithiocarbamates, with

aromatic monothiols as bridging ligands, of the composition [Ni(-

L)(Rdtc)]2, [dtc = S2CN, R = C4H8O(morph), C5H10(pip), C4H8(pld); HL =

thiophenol, 4-methylthiopenol or 2-thionaphthol] and [Ni(-L)(HR1dtc)]2,

{R1= C11H11N2O (aap)} have been prepared and characterized by

elemental analyses, IR and electron spectroscopy, magnetochemical and

conductivity measurements and thermal analysis. The methods used


Introduction []

indicate that the complexes are diamagnetic, complex non-electrolytes

with two square-planar NiS4 chromophores.32 Ni(II), Pd(II) and Pt(II)

complexes of 4-aminophenyl ammoniumdithiocarbamate have also been

synthesized and characterized.33

Some new coordination compounds of the composition

[Ni(cetdtc)(triphosII)]X (cetdtc = cyclohexylethyldithiocarbamate; dtc =

S2CNˉ; triphosII = C41H39P3 = 1,1,1-tris(diphenylphosphinomethyl)

ethane; X = Clˉ, PF6ˉ, BPh4ˉ, ClO4ˉ; Ph = phenyl) and [Ni(pe2dtc)

(triphosII)]X (pe2dtc = di(pentyl)dithiocarbamate; X = Clˉ, ClO4ˉ) have

been synthesised (Fig. 6). The isolated complexes have been

characterised by elemental analysis, IR and UV/VIS spectroscopy,

thermal analysis, magnetochemical and conductivity measurements. All

complexes are diamagnetic, 1:1 electrolytes, with pentacoordinated

nickel in the NiS2P3 chromophore.34

H3C C P Ni

H2

CH2

C

H2C

S

S

C N

R1

R2

X

P

P

Ph Ph

Ph Ph

Ph

Ph

Fig.6. Structure for the complexes of composition [Ni(R1R2dtc)(triphosII)]X (R1 =

cyclohexyl, pentyl; R2 = ethyl, pentyl; X= Clˉ, PF6ˉ, BPh4ˉ, ClO4ˉ; Ph = phenyl)

Mixed ligand complexes involving four amino acid dithiocarbamates

[(RR'dtc = glydtc) (R = H; R' = H), methdtc (R = H; R' = C3H7S), sardtc (R

= Me; R' = H) and trydtc (R = H; R' = C9H8N)], substituted phosphines

[PPh3, Ph2PCH2CH2PPh2(dppe)] and nickel(II) are reported. All are

diamagnetic. Thermal analyses of the complexes are in accordance with

the proposed formulae. Thermal decomposition of the dithiocarbamate

moiety proceeds through the formation of Ni(SCN)2.35

A series of novel octahedral nickel(II) dithiocarbamate complexes

involving bidentate nitrogen-donor ligands (bpy = 2,2'-bipyridine, phen

= 1,10-phenanthroline,) or a tetradentate ligand (cyclam = 1,4,8,11-


Introduction []

tetraazacyclodecane) of the composition [Ni(BzMetdtc)(phen)2]ClO4,

[Ni(Pe2dtc)(phen)2]ClO4, [Ni(Bzppzdtc)(phen)2]ClO4.CHCl3, [Ni(Bzppzdtc)

(phen)2](SCN), [Ni(BzMetdtc)(bpy)2]ClO4.2H2O, [Ni(Pe2dtc)(cyclam)]ClO4,

[Ni(BzMetdtc)2(cyclam)], [Ni(Bz2dtc)2(cyclam)] and [Ni(Bz2dtc)2(phen)]

{where BzMetdtc = N,N-benzyl-methyldithiocarbamate(1-) anion, Pe2dtc

= N,N-dipentyldithiocarbamate(1-) anion, Bz2dtc = N,N-dibenzyl

dithiocarbamate(1-) anion, Bzppzdtc = 4-benzylpiperazinedithio

carbamate(1-) anion}, have been synthesized. Spectroscopic (electronic

and infrared), magnetic moment and molar conductivity data, and

thermal behaviour of the complexes are discussed. Single crystal X-ray

analysis of [Ni(Bzppzdtc)(phen)2]ClO4.CHCl3 and [Ni(Bz2dtc)2(cyclam)]

confirmed a distorted octahedral arrangement in the vicinity of the

nickel atom with a N4S2 donor set. They represent the first X-ray

structures of such type of complexes.36

Generally, it is well known that square-planar dithiocarbamates (dtc) of

nickel(II) of the type [Ni(dtc)2] react very unreadily with nitrogen-donor

ligands. To date, only a few data regarding this topic have been found in

the literature. However, octahedral complexes [Ni(H2dtc)2(c-pic)2],

[Ni(H2dtc)2-(py)2] and [Ni(HRdtc)2(c-pic)2] (R = chlorophenyl; cpic = c-

picoline, py = pyridine) have been synthesized by the reactions of the

mentioned Ni(II)-dithiocarbamates with monodentate N-donor ligands.37

The complexes are found to be paramagnetic. Moreover, it is found that

[Ni(Et2dtc)2] (Et = ethyl) forms adducts with pyridine and c-picoline at

liquid nitrogen temperature.38

Dithiocarbamate complexes of Co(II) and Co(III) have been reported but

Co(II)dithiocarbamates are extremely unstable and oxidize readily to

Co(III)dithiocarbamates.6 The synthesis and characterization of Co(III)

tris complexes of N-alkylcyclohexyldithiocarbamates has been done.39

The tris complexes of Co(III)dithiocarbamates derived from glycine, DL-

alanine, DL-valine and L-leucine have also been reported. An octahedral

skeleton with D3 symmetry was proposed for the complexes.

The chemistry of divalent and trivalent iron dithiocarbamate complexes

has been studied in considerable detail. In case of


Introduction []

tris(dialkyldithiocarbamate)Fe(III) complexes a trigonally distorted

octahedral structure has been shown. However, when one or two

dithiocarbamate groups are substituted by other bidentate ligands the

extent of distortion increases. The molecular and crystal structure of

monochlorobis(diethyldithiocarbamate)Fe(III) reveals that it has a

square pyramidal structure. Mixed ligand complexes of iron(III) derived

from piperidine and morpholine dithiocarboxylic acids and

glycine/oxine/acetylacetone/dithiozone have been prepared and

characterized.40,41 Tris complexes of Fe(IV) with 4-methylpiperazine-1-

carbodithiolate have been synthesized by the oxidation of

Fe(Mepipzcdt)3 with Fe(ClO4)3.9H2O. The complex was characterized by

various physico-chemical techniques.42

Self-assembled symmetrical metal dithiocarbamates of the type

M2(hdtc)2, [where M = Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) and

hdtc = (S2N2C3H4)2CH2], with a closed ring system, have been prepared

by a convenient one pot synthesis in moderate yields (Fig. 7).

H2

C

C C

N N

NHNH

C C

S S S S

M M

H3C CH3

S S S S

C C

NH

N

HN

N

C C

C

H2

CH3H3C

C

H2

C

C

CH3H3C

+

O O

4

NH2

NH2

+ +

4 HCl

4 CS22 MCl2

Fig.7. Tempelate synthesis of metal dithiocarbamates of the type M2(hdtc)2, where

M = Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II) and hdtc = (S2N2C3H4)2CH2


Introduction []

On the basis of elemental analyses, IR, TGA and magnetic susceptibility

measurements, a square planar geometry has been proposed for Co(II),

Ni(II), and Cu(II) dithiocarbamates, while tetrahedral geometry has been

suggested for Zn(II), Cd(II) and Hg(II) complexes. The dithiocarbamate

moiety is observed to be symmetrically bonded to the metal ion via both

sulfur atoms of the NCS2 group. Since the dithiocarbamates are

covalently bonded to the metal ions they are non-conducting in

solution.43

A condensation reaction was carried out between acetylacetone,

ethylenediamine and carbon disulfide in a single step leading to the

formation of a ring like complex (Fig. 8 and Fig. 9).

H2

C

C C

N N

HNNH

C C

S S S S

M M

H3C CH3

S S S S

C C

NH

N

HN

N

C C

C

H2

CH3H3C

C

H2

C

C

CH3H3C

+

O O

4NH2

H2C+ +

4 HCl

4 CS2 2 MCl2CH2

NH2

CH2

CH2

H2C

H2C

CH2

CH2

H2C

H2C

Fig.8. Structure of [M2(etdtc)2] where M = Mn(II), Fe(II), Co(II), Ni(II),

Cu(II), Zn(II), Cd(II), Hg(II) and etdtc = S4N4C11H18

These metal dithiocarbamates have been characterized by

spectroscopic, TGA/DSC, magnetic susceptibility and conductivity data.

The complexes, [Mn2(etdtc)2], [Fe2(etdtc)2], [Co2(etdtc)2], [Zn2(etdtc)2],

[Cd2(etdtc)2] and [Hg2(etdtc)2] have been suggested to be tetrahedral


Introduction []

while [Ni2(etdtc)2] and [Cu2(etdtc)2] have square planar geometry.

[Cr(etdtc)Cl]2 and [Fe(etdtc)Cl]2 have chlorine bridged distorted

octahedral geometry. The dithiocarbamato moiety has been observed to

be symmetrically bonded in all the cases.44

C

H2

C

C

CH3H3C

+

O O

4NH2

H2C+ +

4 HCl

4 CS2 2 MCl3CH2

NH2

2

H2

C

C C

N N

HNNH

C C

S S S S

M M

H3C CH3

S S S S

C C

NH

N

HN

N

C C

C

H2

CH3H3C

CH2

CH2

H2C

H2C

CH2

CH2

H2C

H2C

Cl

Cl

Fig.9. Structure of [M1(etdtc)Cl]2,

where M1 = Cr(III) and Fe(III) and etdtc = S4N4C11H18

The complexes of 4-methylpiperazine-1-carbodithioic acid (4-MPipzcdtH)

with transition metal ions viz. Fe(III), Co(II), Ni(II) and Cu(II) with

perchlorate as counter anion have been synthesized. The process of

synthesis involves the treatment of 4-MPipzcdtH with the ethanolic

solution of M(ClO4)n.xH2O (for M = Co(II), Ni(II), Cu(II), n = 2 and x = 6

and for Fe(III), n = 3 and x = 9). The general reaction and proposed

structures of the complexes are shown below (Fig. 11). The complexes

are moisture sensitive and, therefore, were stored under vacuum. The

complexes have fairly good solubility in methanol, ethanol and acetone.


Introduction []

All of the complexes do not melt but decompose between 140 and

240C.18

MXn.xH2O + nN

N

H3C

C

S

S

H

.. _[M(LH)n]Xn + xH2O

(LH)

N

N

N

NC

S

S

MS

S

C

CH3

H3C

H

H

+X_

+X

_

M = Co(II), Ni(II), Cu(II) and X = ClO4

H3C

H

N

N

+ClO4

_C

S

S

Fe

S

S

S

S

C

C

N

NH

CH3+ClO4

_

N

N+

ClO4

_

CH3

H

Fig.11. General Reaction and Proposed Structures of the Complexes

In view of the diverse applications of the dithiocarbamates and various

biological aspects of pyridine it is found worthwhile to study complexes

containing both sulfur and pyridine.45,46 Although the reports on metal

complexes containing dithiocarbamates are extensive, the studies on

transition metal complexes containing both dithiocarbamate moiety and

pyridine ligand are scarce.47,48 However, complexes of the type

[Mpy2(dedtc)2] and [Mpy2(dpdtc)2], where M = Mn(II), Fe(II), Co(II), Ni(II),

Cu(II), Zn(II), py = pyridine, dedtc = diethyldithiocarbamate and dpdtc =

diphenyldithiocarbamate, have been synthesized (Fig. 10). These

complexes have been characterized by elemental analysis, magnetic

susceptibility, TGA/DSC and infrared in the solid and electronic


Introduction []

spectroscopy and conductivity measurement studies in solution. The

dithiocarbamato moiety has been found to be symmetrically bonded to

the metal. The complexes have a distorted octahedral structure.49

N

R

R

C

S

S

MCl Cl2NaCl

Na

N

R

R

C

S

S

M

S

S

C N

R

R

2 +

N

N

N

N

Fig.10. Synthesis of the Complexes Mpy2(dedtc)2, where M = Mn(II), Fe(II),

Co(II), Ni(II) and Cu(II), py = C5H5N and R = C2H5 or C6H5

As compared to other metal ions (especially Cu and Ni) very few

dithiocarbamate complexes of vanadium have been reported. These

complexes involve the VO2+ ion and R2dtc ligands. A number of vanadyl

complexes of the type VO(R2dtc)2 with R2 = Me2, Et2, i-Pr2 and pyrrol

have been reported.50,51 These compounds are monomeric,

paramagnetic species (eff = 1.69-1.77 B.M.) and have tetragonal

pyramidal structure. Their electronic spectra have been assigned on the

basis of an MO scheme. A procedure of deoxygenation of VO2+

complexes of the type VO(S2CNEt2)2 by its reaction with appropriate

Ac.X (X = Cl, Br) in CH2Cl2 has been reported. The complexes formed

are cis-dihalobis(dialkyldithiocarbamato)vanadium(IV).52

A series of oxovanadium(IV)dithiocarbamate adducts and derivatives

with pyridine and cyclohexyl, di-iso-butyl, di-n-propyl, aniline,

morpholine, piperidine and di-iso-propyl amines have been synthesized.

These complexes were assigned the formulae [VOL2].py (L = cyclohexyl,

di-iso-butyl, di-n-propyl and aniline dithiocarbamates) and

[VO(OH)(L)(py)2]OH.H2O (L = morpholine, piperidine and di-iso-propyl

dithiocarbamates).53 Oxovanadium(IV) complexes with dithiocarbamates

show a square pyramidal structure, which can react with Lewis bases to

form mainly stable adducts, in which the base occupies the sixth

coordination position in an octahedral complex, as in the

oxovanadium(IV)xanthates and dithiocarboxylates.54-58 So the adduct


Introduction []

formula [VOL2].B (L = bidentate ligand, B = base) has been assigned to

them. On the basis of the various studies, a six-coordinated distorted

octahedral structure for the adducts [VO(L)2].py and possible six-

coordinated structure for the derivatives [VO(OH)(L)(py)2]OH.H2O has

been assigned. The stoichiometry in the adducts is 1:1 (base:complex)

and in the derivatives is 2:1 (base:metal).53

The vanadium(III) complexes, V(S2CNMe2)3 and V(S2CNiPr2)3 have also

been prepared and characterized by IR, electronic and 1HNMR spectral

analysis. The complexes show reversible thermochromic behaviour.59

R1

R2

N C

S

S

V

OS

S

C N

R1

R2

VO-DMD: R1=R2= _CH3

VO-DED: R1=R2= _CH2CH3

VO-PYD: R1=R2= _CH2CH2_

VO-MGD: R1= _CH3

R2= _CH2CH(OH)CH(OH)CH(OH)CH(OH)CH2(OH)

VO-SAD: R1= _CH3, R2= _CH2_COO-

Fig.12. Structures of vanadyl-dithiocarbamate complexes:

VO-DMD, VO-DED, VO-PYD, VO-MGD and VO-SAD.

Five vanadyl dithiocarbamate complexes with VO(S4) coordination mode

have been prepared and their structures have been determined by

elemental analysis, visible absorption, IR and electron spin resonance

spectra. The five complexes are bis(N,N-dimethyldithio

carbamate)oxovanadium(IV) (VO-DMD), bis(N,N-diethyldithiocarbamate)

oxovanadium(IV) (VO-DED), bis(pyrrolidine-N-dithiocarbamate)oxo

vanadium(IV) (VO-PYD), bis(N-methyl,N'-D-glucamine-dithiocarbamate)

oxovanadium(IV) (VO-MGD) and bis(sarcosine-N-dithiocarbamate)oxo

vanadium(IV) (VO-SAD) (Fig. 12). Their insulin mimetic activities were

evaluated by in vitro and in vivo experiments. On the basis of various

results, the VO-PYD complex is indicated to be a good agent to treat

insulin dependent diabetes in the experimental animals.60

The ability of thiuram disulfide to afford metal dithiocarbamates in

abnormally high oxidation states has been recognized for several years

now. This capability stems from the presence of potential

dithiocarbamate ligands which can delocalize positive charge from the


Introduction []

metal towards the periphery of the complex.61 The literature shows

many examples of this.62 Some examples from the recent years are

the synthesis of [V2(m-S2)2(Et2dtc)4] from VS43 and Et4tds, and the

reaction of thiuram disulfides and [HB(Me2pz)3W(CO)3] to afford

[HB(Me2pz)3W(CO)2R2dtc] and [HB(Me2pz)3WII(CO)2(S)WIV(R2dtc)2

(thiocarboxamido)] (where HB(Me2pz)3 = 3,5-dimethylpyrazol-1-yl

borate).63 Other products arising from this extremely complicated

reaction are W(R2dtc)4+ and HB(Me2pz)3W(S)R2dtc.64

A number of Cr(III)dithiocarbamates have been prepared by reacting

anhydrous CrCl3 and an alkali dithiocarbamate in dry, organic solvent.

For example, Cr(H2Dtc)3, Cr(HMeDtc)3, Cr(HEtDtc)3, Cr(H-i-BuDtc)3,

Cr(Et2Dtc)3, Cr(n-Bu2Dtc)3, Cr(Me2Dtc)3 and Cr(PyrrolDtc)3. The

chemistry of molybdenum dithiocarbamate complexes has been

investigated in considerable detail. The dithiocarbamate complexes of

Mo(VI) have been isolated and are of the form MoO2(n-Bu2Dtc)2 and

MoO2(pyrrolDtc)2. The synthesis of these complexes involves the

acidification of aqueous solutions of MoO42 and R2Dtc ions by either

hydrochloric or nitric acid. The dithiocarbamates of Mn(II), Mn(III) and

Mn(IV) have been reported.6

Tetrakis-dithiocarbamates of Ti(IV), Zr(IV) and Hf(IV) have been obtained

by the reaction of M(NR2)4 complexes with CS2. The complexes M(R2Dtc)4

(M = Ti, Zr; R = Me, Et, n-Pr) are monomeric (except for the Me

derivative). An interesting series of (C5H5)2TiR2Dtc complexes have also

been reported (Fig. 13).

S , Ti , C

Fig.13. Proposed structure for the (C5H5)2TiR2Dtc complexes

The ruthenium complexes with dithio ligands are rare.65 However

arene-ruthenium complexes with bidentate dithiocarbamate ligands


Introduction []

have been synthesized. One such complex has been prepared by the

treatment of [(6-p-cymene)RuCl2]2 with sodium diethyldithiocarbamate,

Et2NCS2Na.3H2O (Fig. 14). The molecular structure of this complex

consists of discrete monomeric molecules with distorted octahedral

configuration around Ru atom, having p-cymene ring at one face. The

(6-p-cymene)Ru fragment is coordinated by S atoms of a symmetrically

chelating diethyldithiocarbamate group and a terminal chloride ligand.

The ruthenium atom is situated 1.749(2) A from the center of the

planar aromatic in the pcymene moiety. All the RuC bond distances

are in the range 2.1604(17)-2.2319(17) A. The two RuS distances are

essentially the same [2.3925(5) and 2.3978(5) A]. The RuCl bond

length is 2.4276(5) A.66

Ru

S

S

C

N

Cl

EtEt

Fig.14. [Ru(C5H10NS2)Cl(6-C10H14)]

Dithiocarbamate complexes of niobium [Nb(S2CN(CH3)2)4] and tantalum

[Ta(S2CN(CH3)2)5] have been synthesized by the insertion of CS2 into

NbN bonds of dimethylamine complexes of niobium and tantalum. The

compounds having formulae MS(2-SCNEt2)(2-S2CNEt2)2, (M = niobium

or tantalum), have been prepared from the reaction of NaS2CNEt2 with

M2Cl6(SC4H8)3. These compounds were characterized using

spectroscopic methods and X-ray crystallography. The coordination

sphere of the metal(V) atom consists of a lone sulfur atom, two chelating

dithiocarbamate ligands, and one thiocarbamyl ligand bound through

both the carbon and sulfur atoms. The resulting structure is a seven-

coordinate pentagonal bipyramid having a lone sulfur atom and a sulfur

from one of the dithiocarbamate ligands occupying the polar


Introduction []

positions.67 The reaction of [NbVO(S2CNEt2)3] with boron sulfide was

investigated under a variety of conditions. The major product in all the

cases was yellow [NbVS(S2CNEt2)3]. In dichloromethane at room

temperature, orange [NbV(S2)(S2CNEt2)3] and orange-brown [Nb2IV(-

S2)2(S2CNEt2)4] were also formed.68

III. APPLICATIONS OF DITHIOCARBAMATES

Special interest in the study of metal dithiocarbamates was aroused due

to the striking structural features presented by this class of compounds

and also due to their potential biological activity and practical

applications in the fields of rubber technology and agriculture.69-72 They

have diverse applications acting as high pressure lubricants in

industry, fungicides and pesticides, and also as accelerators in

vulcanization.73,74 Dithiocarbamates used in the process of

vulcanization of rubber compounds form a group of ultra-accelerators of

the curing process.75 Moreover they act as therapeutic agents for

alcoholism and metal intoxication.1 Now a days they have been reported

to treat acquired immune depressive syndrome and cancer.76-79 They

have also been used as photo-sensitisers in dye-sensitised solar cells.80

Disulfiram or tetraethylthiuram disulfide (Fig. 15), which is a

dithiocarbamate was first synthesized in 1881 and used to accelerate

the vulcanization of rubber. It was only in the 1930s that disulfiram

found a medicinal use as a scabiescide and subsequently, as a

vermicide because it was toxic to lower animal forms due to its ability to

chelate copper; an essential component of the respiratory chain of these

organisms.81

N C S S C

S S

N

CH2CH3

CH2CH3

H3CH2C

H3CH2C

Fig.15. Disulfiram or tetraethylthiuram disulfide

In 1948 it was proposed that disulfiram can be used in the treatment of

chronic alcoholism as alcohol aversion therapy.82 This was proved


Introduction []

successful and disulfiram under the trade name Antabuse, continues to

be used clinically to this day.83 Moreover disulfiram is finding

increasing use in cocaine addiction and narcotic addiction.84,85

The use of disulfiram as a scabiescide and vermicide suggests that

dithiocarbamates exert antifungal action by chelating metals that are

indispensable components of the respiratory chains of lower organisms.

Disulfiram and other dithiocarbamates have been reported to show a

significant potential in the treatment of human cancers. It has also

been reported to induce apoptosis, show metal ion dependant

antineoplastic activity and assert angiogenesis. Thus disulfiram has an

important role as an adjuvant in the chemotherapy of human cancers

and in the treatment of drug resistant fungal infection.86

Gold(III) complexes with dithiocarbamate ligands, DMDT = N,N-

dimethyldithiocarbamate and ESDT = ethylsarcosinedithiocarbamate

are reported to have antitumor activity.87 These dithiocarbamates have

superior chemotherapeutic index in terms of increased bioavailability,

higher cytotoxicity and lower side effects than cisplatin which is one of

the most widely employed anticancer drug.

Diethyldithiocarbamate and two different substituted analogues of this

compound were evaluated for anticandidial effect. These compounds

were tested for their in vitro inhibitory effect on the growth of Candida

strains and it was observed that sodium diethyldithiocarbamate and

sodium dimethyldithiocarbamate produced inhibitory effects

comparable to amphotericin-B, a drug clinically used to treat

candidiasis. The in vivo effects of these dithiocarbamates were also

encouraging with N-methyl-D-glucaminedithiocarbamate being the most

effective.86 The synthetic utility of dithiocarbamato moiety (MS2CNR2)

is due to the inclusion of a variety of organic substituents (R) in the

stable ligand.

Now a days copper(II)dithiocarbamate is successfully used as a single

source precursor for the growth of semiconducting copper sulfide thin

films.88 The iron(II), iron(III) dithiocarbamates have been studied for

their spin-cross over phenomenon, radical traps for NO, and as


Introduction []

antioxidants and pro-oxidants in biological systems.8,89,90

Diethyldithiocarbamates are also known to inhibit the activity of

Cu/Zn-superoxidedismutase (SOD) through the withdrawal of copper

from the protein both in vivo and in vitro.91 Some dialkyl substituted

dithiocarbamates have proved to be an efficient anti-alkylating, anti-HIV

and froath floatation agents.92 The optical and electrochemical

properties of dithiocarbamates can effectively be used to construct

sensors for guest molecules and macromolecules.93,94

Pyrrolidinedithiocarbamate complexes are widely used in solvent

extraction and other analytical procedures, because of their resistance

to acidic media. The piperidinedithiocarbamate complexes of Zinc and

Cadmium are largely applied as curing agents in rubber processing and

in photographic films.95,96

Tin dithiocarbamates have been examined for their antitumor activity

and to obtain molecular precursors for tin sulfide films, that find

applications as photovoltaic materials, holographic recording systems

and solar control devices.97,98 In fact, dithiocarbamate derivatives of tin

are considered as the most promising species for metal chalcogenide

deposition.98 Dithiocarbamates are employed in the construction of

nano sized resorcarene based assemblies due to their coordinating

properties.99 They are exploited as molecular receptors in which metal

ions or multiple substrate molecules can be bound, stored or

transported to the required active sites.100,101 Re and Tc

dithiocarbamtaes play a vital role in the design and synthesis of new

radiopharmaceuticals for nuclear medicine.102,103 Te(IV)

dithiocarbamates are used as accelerators in rubber vulcanization.104

Mixed dithiocarbamates of Zn and Cd are used to obtain films of ZnS

and CdS.105

IV. COORDINATION CHEMISTRY OF VANADIUM(IV)

Vanadium occurs with an abundance of 0.014% in the earth’s crust

and is widespread.106 The element is the second most abundant

transition metal in the oceans (50 nM).106 Some aquatic organisms are


Introduction []

known to accumulate vanadium. Vanadium was discovered by Andres

Manuel del Rio, a Mexican chemist in 1801. Unfortunately, a French

chemist incorrectly declared that Del Rio’s new element was only

impure chromium. The element was rediscovered by Nils Gabriel

Sefstrom in 1830. Pure vanadium is a bright white metal, and is soft

and ductile but traces of impurities make it hard and brittle. It is solid

at room temperature and melts at 1910C. Natural vanadium is a

mixture of two isotopes, 51V (99.76%) and 50V (0.24%), the latter being

slightly radioactive has a half-life of 3.9 1017 years. Vanadium is

primarily obtained from the minerals vanadinite [Pb5(VO)3Cl] and

carnotite [K2(UO2)2(VO4)2] by heating crushed ore in the presence of

carbon and chlorine to produce vanadium trichloride. The vanadium

trichloride is then heated with magnesium in an argon atmosphere. It is

also present in some crude oils in the form of organic complexes.

Vanadium has good corrosion resistance to alkalis, sulfuric acid,

hydrochloric acid and salt water due to the formation of a surface film

of oxide. At room temperature it is not affected by air, water or acids,

other than HF with which it forms complexes. However, the metal

dissolves in oxidizing acids such as hot concentrated H2SO4, HNO3 and

aqua regia. The metal has good structural strength and a low fission

neutron cross section making it useful in nuclear applications. At

elevated temperatures vanadium reacts with air or oxygen to form

oxides of the type V2O3, VO2 and V2O5. The metal also reacts with N2

and C at high temperatures forming interstitial nitrides VN and carbides

VC and VC2 respectively. On heating with H2, the element forms non

stoichiometric hydrides. It also forms halides in different oxidation

states such as VF5, VCl4, VBr3 and VI3.

Vanadium can exist in eight oxidation states ranging from 3 to +5 with

the exception of –2.107 The maximum oxidation state for vanadium is

+5. Oxidation states +2 and +3 for vanadium are reducing, +4 is stable

and +5 slightly oxidizing. The coordination chemistry of vanadium is

strongly influenced by the oxidation/reduction properties of the metal

center and the chemistry of vanadium ions in aqueous solution is


Introduction []

limited to oxidation states of +2, +3, +4 and +5. Vanadium compounds

of oxidation state of +2 and +3 are unstable to air and their compounds

are predominantly octahedral. Many oxovanadium(V) complexes contain

the VO2+ entity and the cis geometry in dioxo complexes has been

confirmed by structural determination.108 The oxo complexes of the

halides, alkoxides, peroxides, hydroxamates and amino carboxylates

have been characterized.109 The oxidation of ligands by vanadium(V)

prevents the isolation of a larger number of complexes. On the other

hand, the oxidizing properties of vanadium(V) compounds are useful for

many preparative reactions, namely for the catalysis of oxidations such

as oxidation of SO2 to SO3 in the industrial production of sulphuric

acid.

Vanadium(IV) is the most stable oxidation state under ordinary

conditions and majority of vanadium(IV) compounds contain the VO2+

unit which can persist through a variety of reactions and in all physical

states. The VO2+ ion forms stable anionic, cationic and neutral

complexes with several types of ligands and has one coordination

position occupied by the vanadyl oxygen. These vanadyl complexes are

generally green or blue-green in colour.

V

O O

O O

C

C

H3C

C

H3C

C

C

C

CH3

CH3

O

HH

Fig.16. Square pyramidal structure of VO(acac)2

A wide variety of oxovanaduim(IV) complexes have been prepared and

characterized.107,110 They are very frequently five coordinate having a

well established square pyramidal geometry with the oxovanadium(IV)

oxygen at apical position and the vanadium atom lying above the plane

defined by the donor atoms of the equatorial ligands. These square

pyramidal complexes generally exhibit strong tendency to remain five

coordinate.110 [VO(acac)2] is the prime example of this geometry (Fig.


Introduction []

16). However a sixth ligand may be weakly bonded trans to V=O to

produce a distorted octahedral structure.

Inspite of the evident proclivity of VO2+ to form square pyramidal or

distorted octahedral complexes, it must not be assumed that 5-

coordination inevitably results in the former shape. [VOCl2(NMe3)2] is in

fact trigonal bipyramidal (Fig. 17).

V

N

O

N

Cl

CH3

CH3

H3C

CH3

CH3

H3C

Cl

Fig.17. The Trigonal bipyramidal structure of [VOCl2(NMe3)2]

A novel oxovanadium(IV) complex was obtained by the reaction of

vanadyl acetylacetonate with oxazine (Fig. 18a). Another

oxovanadium(IV) complex was obtained by the reaction of vanadyl

acetylacetonate with oxazoline ligand in absolute alcohol (Fig. 18b).111

In both the complexes the geometry around vanadium center is

distorted square pyramidal with two units of bidentate (N, O)

oxazoline/oxazine ligand trans coordinated in equatorial plane and axial

terminal oxygen atom.

R1 = R2 = CH3

O

N

OR2

R1

V

O

N

OR2

R1

O

NO

O

V

O O

NO

a b

Fig.18. Oxovanadium(IV) complexes obtained by the reaction of

vanadylacetylacetonate with oxazine and oxazoline ligands


Introduction []

The oxovanadium(IV) complexes of the type [VO(L)]SO4 have been

prepared using an in situ method of synthesis with ligands derived from

the condensation of di-2-thienylethanedione with 1,2-diaminobenzene

or 2,3-diaminopyridine (Fig. 19).

V

ON

NH2 H2N

N

C CSS

NN

SO4V

ON

NH2 H2N

N

C CSS

SO4

Fig.19. Structure of [VO(L)]SO4

These parent complexes have been further reacted with β-diketones to

yield macrocyclic complexes of the type [VO(mac)]SO4 (where mac =

macrocyclic ligands derived by condensation of amino group of parent

complex with β-diketones), wherein the VO2+ cation acts as a template

(Fig. 20). Tentative structures of these complexes have been proposed

on the basis of elemental analysis, electrical conductance, magnetic

moments and spectral (infrared, electronic and electron spin resonance)

data. The oxovanadium(IV) complexes are five coordinated wherein the

tetraaza macrocyclic ligands act as tetradentate chelating agents.112

V

ON

N N

N

C C

C CCH2

R R'

SS

NN

SO4V

ON

N N

N

C C

C CCH2

R R'

SS

SO4

Where R R' β-Diketone

CH3 CH3 Acetylacetone

C6H5 CH3 Benzoylacetone

C4H3S CF3 Thenoyltrifluoroacetone

C6H5 C6H5 Dibenzoylmethane

Fig.20. Structure of [VO(mac)]SO4


Introduction []

A thiol containing vanadium(IV) complex has been prepared by using a

one pot method (Fig. 21).113 The presence of vanadium cannot only

catalyze the formation of the Schiff’s base, but also stabilize the ligand

against isomerisation. In this compound the vanadium ion is in a

distorted tetragonal pyramidal environment consisting of two imine

nitrogens and two thiophenolates in the basal plane, from which it is

displaced by 0.668 A.

S

N

VS

N

O

Fig.21. VIV

O(tsalen)

The oxovanadium(IV) complexes (1-4) with 2-methyl-3-(pyridine-2-yl

methyleneamino)quinazolin-4(3H)-one (L1) or 3-(2-hydroxy-3-methoxy

benzylideneamino)-2-methylquinolin-4(3H)-one (L2) were synthesized

and characterized by elemental analysis, IR, 1H-NMR, electronic

spectra, molar conductance and thermal studies. Based on the above

spectral studies, the complexes have the general formula [VO(L1)2] (1),

[VO(L1)phen] (2), [VO(L2)2] (3) and [VO(L2)phen] (4) (Fig. 22).114

V

O

O

O

N

N

N

N

N

CH N

CH

N

V

O

ON

N

N

CH N

NN

V

O

O

O

N

N

N

N

N

CH

CH

1 2

HO OCH3

OHH3COV

O

ON

N

N

CH

NN

43

OCH3

Fig.22. Structures of [VO(L1)2] (1), [VO(L

1)phen] (2),

[VO(L2)2] (3) and [VO(L2)phen] (4) Complexes


Introduction []

A vanadium(IV)-oxocorrolazine complex, vanadyloctakis(para-tert-

butylphenyl)corrolazine, (TBP)8Cz(H)VIVO (Fig. 23). The complex has

been synthesized and characterized by spectroscopic and

electrochemical methods and acid/base reactivity as a neutral

vanadium(IV) species, with the corrolazine ligand containing a single

labile proton.115

V

N N

N N

O

NN

( H+ )

R

R

R R

R

R

R

R

N

Fig.23. Vanadyl Octakis(para-tert-butylphenyl)corrolazine

Three novel vanadium complexes [VIVO(acac)(Hhasc)] (1), [VIVO2(H2hasc)]

(2), and [VVO2(Hhasc)] (3), have been prepared from [VO(acac)2] and the

ligand H2hasc (where H2hasc = 2-Hydroxyacetophenone semicarbazone

and acac = acetylacetonate ion) by varying the reaction conditions as

shown in Fig. 24.116 The complexes have been characterized by various

analytical methods which include FTIR, 1H-, 13C-, 51V-NMR and EPR

spectroscopies, elemental analysis and X-ray diffractometry from single

crystals. The crystal and molecular structures of [VIVO2(H2hasc)] and

[VVO2(Hhasc)] were determined. In [VIVO2(H2hasc)], the (VO2)2+ core is

coordinated to a neutral O,N,O-tridentate unit of the H2hasc ligand,

with the vanadium atom showing a square pyramidal coordination

sphere. In the crystal of [VVO2(Hhasc)] two symmetry independent (VO2)+

cores are observed. Each of them coordinates to a mono deprotonated

Hhasc─ unit, in a O,N,O-tridentate mode. One assumes a square

pyramidal geometry for the pentacoordinate vanadium(V) center. An

additional interaction is observed for the other one, involving the

phenolate oxygen atom from a symmetry related unit, resulting in a

[5+1]-coordination number for the transition metal atom.


Introduction []

Fig.24. Scheme for the preparation of [VIV

O(acac)(Hhasc)] (1),

[VIV

O2(H2hasc)] (2), and [VVO2(Hhasc)] (3)

The synthesis of a V(ONS)2 vanadium complex has also been

successfully achieved by using an indirect method (Fig. 25).

[VOCl2(thf)2] was first reacted with o-mercapto-aniline and possibly

forms VIV intermediate. After the addition of o-hydroxy-naphthaldehyde,

V(ONS)2 was formed. Here, vanadium is in a highly distorted trigonal

prismatic environment.117

N

O

V

NS

O

S

Fig.25. VIV

(ONS)2 Vanadium complex

The non-oxovanadium(IV) complexes of the composition [VCl2-n(acac)2

(OAr)n] and [VCl2-n(acac)2(OAr')n] (where OAr = 2-Phenylphenol, OAr' = 4-

Phenylphenol, acac = acetylacetonate ion and n = 1, 2) have been

synthesized by the reaction of [VCl(acac)2] with sodium salt of respective

phenols.118 The complexes have been characterized by elemental

analysis, molar conductance measurements, molecular weight

determinations and infrared, electronic and FAB-MS spectral and


Introduction []

magnetic moment studies. Based upon these studies monomeric

distorted octahedral structures for the complexes have been proposed

(Fig. 26).

Cl

V

OAr

acacacac

[VCl(acac)2(OAr)] and [VCl(acac)2(OAr')]

OAr

V

OAr

acacacac

[V(acac)2(OAr)2] and [V(acac)2(OAr')2]

Fig.26

Novel mononuclear oxovanadium(IV) complexes [VO(L1)2·H2O], [VO(L2)2·

H2O] and [VO(L3)2·H2O] were prepared by the condensation of 1 mol of

VOSO4·5H2O with 2 mol of ligand HL1, HL2 or HL3 (where HL1 = 4-[(2-

hydroxy-ethylamino)-methylene]-5-methyl-2-phenyl-2,4-dihydropyrazol-

3- one; HL2 = 4-[(2-hydroxy-ethylamino)-methylene]-5-methyl-2-p-tolyl-

2,4-dihydro-pyrazol-3-one; HL3 = 4-{4-[(2-hydroxy-ethyl-amino)-methyl]

-3-methyl-5-oxo-4,5-dihydropyrazol-1-yl}benzenesulfonic acid). The

resulting complexes were characterized by elemental analyses, molar

conductance, magnetic and decomposition temperature measurements,

electron spin resonance, FAB mass, IR and electronic spectral studies.

From TGA, DTA and DSC, the thermal behaviour and degradation

kinetic were studied. Electronic spectra and magnetic susceptibility

measurements indicate distorted octahedral stereochemistry of

oxovanadium(IV) complexes (Fig. 27).119

V

OON

O N

OH2

NN

N

N

X

X

CH3

H

H

OH

HO

H3C

Fig.27. General structure of Schiff base complexes of oxovanadium(IV)


Introduction []

V. BIOLOGICAL ROLE OF VANADIUM AND ITS COMPLEXES

The growing interest in vanadium chemistry has been inspired by the

discovery of its bioinorganic functions.120,121 The diversified roles of

vanadium among others in biological systems are primarily responsible

for stimulating a recent increasing interest in vanadium coordination

chemistry.122-126 The coordination chemistry of vanadium is of great

current interest because of the discovery of its presence in abiotic as

well as biotic systems.127 Vanadium(V) complexes are known as

potential inhibitors of various enzymes. Recent advances in catalytic

and medicinal properties of vanadium complexes have stimulated their

design and synthesis. Another important impetus to the coordination

chemistry of vanadium in the context of medical application has arisen

from the ability of vanadium complexes to promote the insulin mimetic

activity in patho-physiological state of diabetes mellitus in humans.128

Besides the anti-diabetic effects for which it is now so well known,

vanadium compounds also exhibits a number of other therapeutic

effects including anti-tumour, anti-inflammatory and antibacterial

activities.129-133

The coordination chemistry of vanadium with sulfur containing ligands

is an emerging field of interest with relevance to several disparate

biological systems.122,134,135 The presence of vanadium-sulfur bonding

in the active site of certain nitrogenase enzymes has been well

established and vanadium-sulfur coordination also appears to be

pivotal to the well known tyrosine kinase or tyrosine phosphatase

inhibition through binding to cystine at the putative active site.136-138

Vanadium, participates in enzymatic reactions such as nitrogen fixation

by vanadium nitrogenases and halogenation of a variety of organic

substrates by haloperoxidases.125,139-141 Haloperoxidases also exhibit a

sulfide-peroxidases activity and, in their apo form, phosphatase activity.

The use of oxovanadium complexes in oxidation and oxo transfer

catalysis has been noted.142,143 The vanadium dependant nitrogenase

enzyme from nitrogen fixing bacteria of the genus Azotobactor features

vanadium in medium oxidation states of V(II)-V(IV) and is postulated to


Introduction []

bind and reduce dinitrogen.120,121 Vanadium in medium oxidation

states, is the constituent of iron-vanadium cofactor, bonded to three

bridging sulfides, a hystidine and the vicinal carboxylate and alkoxide of

homocitrate. Vanadium dependant haloperoxidases, from marine

seaweeds, terrestrial lichens and moulds, features vanadium in its

highest oxidation state of V(V) in the active center, where it possesses a

trigonal bipyramidal geometry in the resting state, being surrounded by

three (equatorial) oxygen donors and axial oxygen and nitrogen

(hystidine residue) donors.144-147

The complex VO(acetylacetonato)[(R)(S)-N,N-bis-(2-oxiethyl)-1-

phenylaminoethane] has been synthesized and characterized. The

complex has been found to catalyze the oxidation of organic sulfides to

sulfoxides by peroxides.148

The potential medicinal application such as the treatment of diabetes

type I (insulin deficiency) and II (insulin resistance) has further

stimulated research into vanadium coordination compounds. Diabetes

is a mammalian disease in which the amount of glucose in the blood

plasma is abnormally high.149 The condition can be acutely life-

threatening, since patients with diabetes suffer from a number of

secondary complications, such as atherosclerosis, microangiopathy,

renal disease, cardiac disease and diabetic retinopathy and other vision

disorders including blindness. Millions of sufferers control diabetes by

daily insulin administration and/or a special diet. Insulin

supplementation is the easiest method to control chronic diabetes;

however, insulin is not orally active and must be taken by injection. In

addition, insulin is essentially inactive in type II diabetes, which is by

far the most frequent type of this disease. The development of insulin-

mimetic compounds for oral administration would thus be very

useful.150 In fact, vanadium compounds have a long history as insulin

mimetic agents.151-153 Vanadium compounds stimulate glucose

metabolism without affecting the concentration of insulin. This makes

them promising candidates for the treatment of type II diabetic

individuals (which include the majority of people diagnosed with


Introduction []

diabetes) where hyperinsulinemia is of concern because of secondary

complications resulting from excess insulin. Sodium vanadate was

reported to have an oral insulin-like effect in human diabetes in 1899.

However, it is only in the last decade or so that the pharmacological

potential of vanadium has been systematically explored. Aside of

vanadium complexes, many other metal compounds, such as derived

from molybdenum, tungsten and zinc have been tried, both in vivo and

in vitro, but none have rivaled vanadium salts as effective insulin

substitutes.154,155 A possible reason could lie in the structural

resemblance between vanadate and phosphate, which leads vanadium

complexes to have the ability either to inhibit the protein tyrosine

phosphatase or to activate the insulin receptor kinase and/or glucose

carrier, thus triggering glucose intake into cells.

Since 1980, considerable evidence has been provided that vanadium

salts, specifically tetravalent vanadyl, usually found as the divalent

cation VO2+, and pentavalent vanadate, H2VO4, have the ability to

mimic insulin action in a number of isolated cell systems and produce

dramatic glucose lowering effects when given orally to animal models of

both type I and type II diabetes mellitus.156 Sodium orthovanadate has

been found to stimulate glucose uptake and glucose oxidation in rat

adipocytes, stimulate glycogen synthesis in rat diaphragm and liver and

inhibit hepatic gluconeogenesis.157 A very exciting finding was that

vanadate could be administered orally, with a long-term insulin mimetic

effect, in vivo. Oral vanadium(V) treatment of diabetic animals partially

or completely restored liver and muscle enzyme activities in glycolysis,

without stimulating increased insulin synthesis.158-160 In addition, it

has been shown that oral administration of vanadyl sulfate also lowers

blood glucose and blood lipids in STZ (streptozotocin) induced diabetic

rats and prevents secondary complications of diabetes such as

cataracts and cardiac dysfunction. The insulin enhancing properties of

VO2+ and VO2+ chelates in diabetic laboratory animals and humans

have commanded widespread scientific attention because of the

potential for improved therapy through drug design.161-166 Although the


Introduction []

molecular basis is not known, it is established that the insulin-mimetic

action of VO2+ chelates, measured as lowering of serum glucose levels in

animals or as glucose uptake or lipogenesis in adipocytes, greatly

exceeds that of inorganic VO2+.167-170 Inorganic vanadium compounds,

although they are effective, have poor gastrointestinal absorption and

require high doses for therapeutic efficacy.136 As far as toxicity is

concerned vanadyl ion (VO2+) is superior to vanadate in that it is less

toxic.

In consideration of the low intestinal absorption of vanadyl and high

toxicity of vanadate (vanadate is an effective inhibitor of many

phosphate-metabolizing enzymes); a search for alternative vanadium

compounds containing organic ligands has been initiated. The recent

successes achieved with organic transition metal complexes suggest

that modifications of the metal ion chemistry by the organic ligands not

only increased efficacy but also decreased toxicity.

Most of the compounds reported contain bidentate ligands and have a

1:2 metal-to-ligand stoichiometry. Such as bis(acetylacetonato)

oxovanadium(IV), [VO(acac)2], which potentiates the tyrosine

phosphorylation activity of the insulin receptor and synthesis of

glycogen in 3T3-L1 adipocytes.170 Other examples are the vanadyl

complexes with maltol and ethylmaltol (approved food additives),

namely, bis(maltolato)oxovanadium(IV) (BMOV) and bis(ethylmaltolato)

oxovanadium(IV) (BEOV) which are several times more potent than

vanadyl sulfate.170 BMOV has been shown to have a strong glucose-

lowering effect; in the in vivo studies; it is roughly three times more

effective than uncomplexed vanadyl (in the form of vanadyl sulfate),

with no evidence of toxicity.171

A series of complexes with VIVO(N2O2) coordination mode have been

prepared, in order to study the structure-activity relationship of anti-

diabetic vanadyl complexes. Among these VO(picolinate)2 (VOPA) has

been very effective in normalizing the glucose levels of STZ-induced

diabetic rats when given intraperitoneally or orally.172 In the in vivo

testing, it has been found that VOPA has modest glucose lowering


Introduction []

activity, without accompanying plasma insulin elevation or food intake

suppression.173

In addition, a great attention has been paid to the organic vanadium

complexes containing polydentate ligands and having 1:1

stoichiometry.174,175 Dipicolinic acid has been successfully tested in this

respect recently.175 The respective vanadium complex is desirable

because of its low toxicity and its amphophilic nature. The synthesis

and structure of [VO2dipic] were reported previously; vanadium is five

coordinate.175 Differing from all known effective insulin-mimetic organic

vanadium compounds, which have neutral charge, [VO2dipic] is

anionic. Vanadium(V)-dipicolinate is a more potent inhibitor for

phosphatases than the corresponding vanadium(IV) complex and is also

effective as an oral agent.175,176 The compound has been successfully

applied orally to diabetic cats.177

Vanadate inhibits many phosphate-metabolizing enzymes, such as

phosphatases, kinases and ribonucleases, and it stimulates a few other

enzymes, e.g. certain phosphamutases. In addition vanadate has shown

a great utility as a tool in molecular biology for recognizing and

understanding the structure of phosphate binding proteins, and as a

mediator of catalytic photo-cleavage of the peptide backbone.178-180

An additional medicinal aspect with respect to vanadium chemistry is

the inhibitory action towards phosphatases not only by simple

vanadates, but also by highly condensed form of vanadate, viz.

decavanadate, which forms as the pH drops below 6.3. Decavanadates

like other polyoxometallates (POMs) have also been shown to be potent

anti-viral and -retroviral agents, leaving apart their importance as redox

catalysts in oxo transfer reactions. Many different kinds of POMs have

been tested in vivo and in vitro and found to be biologically active. For

example, the vanadate dimer H2V2O72 has been found to be both an

inhibitor and an activator for dehydrogenases, isomerases and

phosphatases.181,182 The vanadate tetramer V4O124 inhibits

dehydrogenases and aldolases.181-183 The vanadate tetramer also

appears to be the active species in the photolytically-induced cleavage of


Introduction []

myosin at the phosphate binding sites, despite of the fact that the

tetramer only has the modest affinity for this protein.184,185 Vanadate

decamers HXV10O28(6X) show high affinity for selected kinases,

phosphorylases and reverse transcriptase, as illustrated by the potent

inhibition of phosphofructokinase.186,187 Decavanadate has previously

been used to facilitate crystallization of proteins and the Ca2+ transport

by ATPase and adenylate kinase.188,189

VI. COORDINATION CHEMISTRY OF NICKEL(II)

Nickel is a silvery-white metal with a slight golden tinge. Nickel was first

isolated and classified as a chemical element in 1751 by Axel Fredrik

Cronstedt, who initially mistook its ore for a copper mineral. It is one of

the only four elements that are magnetic at or near room temperature,

the others being iron, cobalt and gadolinium. Nickel is transition metal

and is hard and ductile. Naturally occurring nickel is composed of 5

stable isotopes; 58Ni, 60Ni, 61Ni, 62Ni and 64Ni with 58Ni being the most

abundant (68.077% natural abundance).

The coordination chemistry of nickel spans a wide and interesting

variety of coordination numbers, geometries and oxidation states.190

Nickel complexes are known with oxidation states ranging from -1 to +4.

However the most common oxidation state of nickel is +2. Divalent

nickel forms a large number of complexes encompassing coordination

numbers 4, 5 and 6, and all main structural types, which include

square planar, square pyramidal, tetrahedral, octahedral and trigonal

bipyramidal. The coordination number of Ni(II) rarely exceeds 6 and its

principal stereochemistries are octahedral and square planar with

rather fewer examples of trigonal bipyramidal, square pyramidal and

tetrahedral. Nickel(II) is a d8 system so octahedral and tetrahedral

complexes will have 2 unpaired electrons and square planar complexes

usually will have none. With regard to Lewis acidity, Ni(II) is considered

to be a borderline metal ion. This is because it binds to both soft and

hard ligands and sometimes, albeit rarely, to both in the same

complex.190

http://en.wikipedia.org/wiki/Axel_Fredrik_Cronstedt

http://en.wikipedia.org/wiki/Axel_Fredrik_Cronstedt

http://en.wikipedia.org/wiki/Ore

http://en.wikipedia.org/wiki/Cobalt

http://en.wikipedia.org/wiki/Gadolinium

http://en.wikipedia.org/wiki/Ductility

http://en.wikipedia.org/wiki/Isotope

http://en.wikipedia.org/wiki/Natural_abundance

http://en.wikipedia.org/wiki/Oxidation_state


Introduction []

The four coordinate Nickel(II) complexes exhibit two different

geometries: tetrahedral and square planar. The tetrahedral complexes of

Ni(II) have two unpaired electrons and are paramagnetic while its

square planar complexes usually have no unpaired electron and hence

are diamagnetic. Among four-coordinate nickel(II) complexes, those with

strong field ligands tend to be square planar and those with weak field

ligands tend to be tetrahedral. But complexes of Ni(II) with square

planar geometry form more stable complexes and are preferred because

the d8 configuration of Ni2+ with eight d electrons can occupy the four

planar bonding orbitals more readily than the higher energy

antibonding orbitals in tetrahedral coordination. Although less

numerous than square planar complexes, tetrahedral complexes of

nickel(II) also occur. The simplest of these are the complexes

Ni[(C6H5)3P]2X2 ( X = Clˉ, Brˉ, Iˉ, NO3ˉ), [(C6H5)3AsCH3]2.NiX4 (X = Clˉ,

Brˉ, Iˉ) and Ni[(C6H5)3MO]2X2 (M = P, X = Clˉ, Brˉ, Iˉ; M = As, X = Clˉ,

Brˉ) which are almost certainly tetrahedral or pseudo-tetrahedral.191-193

New metal complexes with general composition [M(L)2] of the ligand 2-

thioacetic acid benzothiozole with the metal ions Ni(II), Cu(II), Zn(II),

Cd(II) and Sn(II) have been prepared and characterized by FTIR

spectroscopy, electronic spectroscopy, 1H-NMR, magnetic susceptibility

and conductivity measurements. On the basis of spectral studies,

square planar geometry has been assigned for Cu(II) complexes but

other complexes were proposed to be tetrahedral (Fig. 28).194

N

S S

O

O

M

O

O N

SS

Fig.28. Structure of [M(L)2] where M= Ni(II), Cu(II), Zn(II), Cd(II)

and Sn(II), L=2- thioacetic acid benzothiazole

5-isopropyl- and 5-t-butyl-5H-dibenzophosphole forms four coordinate

complexes of the type (phos)2MX2. The nickel(II)dihalide complexes of

this type have a tetrahedral structure as indicated by their magnetic

and spectroscopic properties. 2,8-(Dimethoxy-5-phenyl-5H-dibenzo


Introduction []

phosphole) also forms four coordinate, tetrahedral, nickel(II)dihalide

complexes. The seven-membered cyclic triarylphosphine, {10,11-

dihydro-5-phenyl-5H-dibenzo[b,f]phosphepin(V)} on the other hand

forms diamagnetic, square-planar nickel(II)dihalide complexes.195

The compound, (2,6-diacetylpyridinebis{[2-(hydroxyimino)propanoyl]

hydrazone}(2-))nickel(II)dimethylsulfoxide solvate monohydrate,

[Ni(C15H17N7O4)]C2H6OS.H2O, represents an example of square-planar

N(4) coordination via N atoms with four different functions, namely

amide, azomethine, hydroxyimino and pyridine. The coordination

polyhedron of the central Ni atom has a slightly distorted square-planar

geometry. The 2,6-diacetylpyridinebis{[2-(hydroxyimino)propanoyl]

hydrazone} ligand forms one six- and two five-membered chelate rings,

and a pseudo-chelate ring through an intra-molecular hydrogen bond

with an amide group as donor and a deprotonated hydroxyimino group

as acceptor, resulting in a pseudomacrocyclic arrangement.196

Two Ni(II) complexes having general formula [Ni(bhac)L] with tridentate

ONO-donor acetylacetonebenzoylhydrazone (H2bhac) and monodentate

N-donor heterocycles [L = 3,5-dimethylpyrazole (Hdmpz) and imidazone

(Himdz)] are reported. The complexes were synthesized in ethanolic

media by reacting Ni(O2CCH3)2.4H2O, H2bhac and L in 1:1:1 molar ratio

and characterized by analytical, magnetic and spectroscopic methods.

In each complex a square planar geometry is found around the metal

ion.197

Ni

S

S

PPh2

Ph2P

Fig.29. [Ni(SC6H4R-4)2(dppe)]

The complexes, [Ni(SC6H4R-4)2(dppe)] (R = MeO, Me, H, Cl or NO2 and

dppe = Ph2PCH2CH2PPh2) were prepared and characterized by elemental

analysis and 1H and 31P NMR spectroscopies, together with the X-ray


Introduction []

crystal structures for the R = H, Cl and Me derivatives. The structures

show that the geometry about the nickel in [Ni(SC6H4R-4)2(dppe)] is best

described as distorted square planar (Fig. 29).198

Four nickel(II) complexes having formula [Ni(L)(L')] (where L' =

MePhCHNH2, iPrNH2, Py and PPh3) have been reported along with an

H2L, Schiff-base ligand obtained from the monocondensation of

diaminomaleonitrile and 4-(diethylamino)salicylaldehyde. The crystal

structures have been solved for H2L, [Ni(L)(MePhCHNH2)] and

[Ni(L)(iPrNH2)] and it is found that upon complexation an unusual nickel

amido (―NH―NiII) bond is formed by the deprotonation of the primary

amine of H2L. The structural studies show that these Ni(II) complexes

have nearly square planar structures (Fig. 30).199

Ni

NH

L'

ONNC

NC

N

L' =N

H2NCH3

H

H2N

P

Fig.30. Molecular structure of the [Ni(L)(L')] complexes

A series of complexes with general formula NiLX2 [where X = Cl; L = 2-

(2-pyridyl)benzimidazole ligand] have been synthesized and

characterized by elemental analysis and 1H-NMR spectroscopy.200 The

complexes have square planar geometry and were prepared in two

steps. First step involves the condensation of one equivalent of

appropriate o-phenylenediamine with one equivalent of picolinic acid to

form ligand (A). The complexes (B) were synthesised in the second step

by dissolving nickel chloride in ethanol followed by the addition of one


Introduction []

equivalent of ligand in ethanol. Treatment of these complexes with

methylaluminoxane leads to active catalysts for ethylene oligomerization

for the olefins from C4 to C6 as oligomers (Fig. 31).

N

NH2

NH2

R1

R2

+

CO2H N

HNR1

R2N

N

HNR1

R2N

Metal Salt

NiCl2.6H2O N

HNR1

R2N

Ni

Cl Cl

A

BA

Fig.31. Scheme for formation of NiLX2, where R1= R2= H or CH3

Some five-coordinate complexes are known but are rare. It is well

known that the electronic ground state of nickel(II) in five-coordinate

complexes is influenced to a great extent by the nature of the donor

atoms and bulkiness of the ligand.201 The essential condition required

for the formation of five coordinated Ni(II) complexes is its

stereochemical nature. The ligand must be such that the bulk and

disposition of its part allow only five coordinating centers to approach

the central metal ion closely. If the ligand is polydentate, any five

coordinate complex it forms will have an additional stability due to

structural rigidity.202 Five-coordinate nickel(II) complexes can have

either square pyramidal or trigonal bipyramidal geometries. Within

these two geometrical types the metal ion may be either high spin (S =

1) or low spin (S = 0).203

A thiocyanate-bridged dinuclear nickel(II) complex, having the

composition [Ni2(C11H11Br2N2O)2(NCS)2] has been synthesised. The

asymmetric unit contains two molecules. Both nickel atoms in each

molecule have a square pyramidal coordination geometry and each

center is bound by one oxygen atom and two nitrogen atoms of one


Introduction []

Schiff base ligand and by one nitrogen atom from the bridging

thiocyanate ligand, which defines the basal plane nitrogen atoms from

the bridging thiocyanate ligands occupying the apical positions (Fig.

32).204-209

Ni Ni

NCS

NCS

N

O

N

Br

Br

O

N

N

Br

Br

Fig.32. Structure of [Ni2(C11H11Br2N2O)2(NCS)2] complex

A mononuclear Ni(II) complex with the ligand bppppa (N,N-bis[(6-phenyl

-2-pyridyl)methyl]-N-[(6-pivaloylamido-2-pyridyl)methyl]amine) ligand

has been synthesized and characterized by X-ray crystallography, 1H1

NMR, UV-Vis and infrared spectroscopy, and elemental analysis. The

complex has the empirical formula [(bppppa)Ni](ClO4)2 (Fig. 33). In solid

state the metal center has coordination number five and the cation also

has a sixth weak interaction involving a perchlorate anion. Thus this

Ni(II) complex assumes a geometry half way between square pyramidal

and trigonal bipyramidal.210

Ni

O

N

NN

N

HN

Ph Ph

2+

(ClO4-)2

Fig.33. [(bppppa)Ni](ClO4)2

Ni(II) forms octahedral complexes with the coordination number six.

Octahedral complexes can be prepared from both strong field and weak


Introduction []

field ligands (or a mixture of both). The octahedral complexes are often

prepared in aqueous solution by the replacement of coordinated water

with neutral or anionic ligands. These complexes are characteristically

blue or purple in contrast to the bright green colour of

hexaaquanickel(II) ion. On the treatment of aqueous solution of

nickel(II) thiocyanate with alkali metal thiocyanate solution, green

hydrated complex salt like K4[Ni(NCS)6].4H2O is obtained in which

nickel is octahedrally coordinated.

Two dicationic dinuclear complexes having formula [Ni(µ-Cl)2(N,OH)2]Cl2

(where N,OH = 2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-propan-2-ol; [1],

N,OH = 2-pyridin-2-yl-propan-2-ol; [2]) have been prepared (Fig. 34).

These paramagnetic complexes are characterized by single-crystal X-ray

diffraction in the solid state and in solution which revealed agreement

between the octahedral coordination spheres found in solution and in

the solid state. The N-donor atoms of each chelating ligand are in

mutual cis position, and the OH donors are mutually trans situated.211

Ni Ni

Cl

Cl

OH HO

N

N

N

N

OH HO

O

O

O

O

2+

2Cl-

Ni Ni

Cl

Cl

OH HO

OH HO

N N

N N

2+

2Cl-

1 2

Fig.34. [Ni(µ-Cl)2(N,OH)2]Cl2

A novel mononuclear Ni(II) complex containing a neutral bidentate

acetohydroxamic acid ligand, [(bppppa)Ni(HONHC(O)CH3)](ClO4)2 has

been synthesized and characterized (Fig. 35).212 The same complex has

also been prepared by the reactivity of [(bppppa)Ni](ClO4)2 with one

equivalent of acetohydroxamic acid in CD3CN solution. This six

coordinate Ni(II) complex has pseudo-octahedral stereochemistry.210


Introduction []

NiNN

O O

O

N

N H

H

NH

N

2+(ClO4

-)2

Fig.35. [(bppppa)Ni(HONHC(O)CH3)](ClO4)2

A low spin diamagnetic square planar complex Ni(tmhd)2 (tmhd =

2,2,6,6-tetramethyl-3,5-heptanedionate) adds a bidentate ligand L—L

(L—L = {BPY = 2,2'-bipyridine, TEME = tetramethylethylenediamine,

TEMP = tetramethylpropylenediamine and MAO = 1-dimethylamino-2-

methoxy-ethane}) and forms a paramagnetic octahedral complex

[Ni(tmhd)2L—L] (Fig. 36). The flexible N—N ligand TEME, the rigid N—N

ligand BPY and the flexible N—O ligand MAO form five membered

chelate rings. On the other hand the N—N ligand TEMP forms six

membered chelate ring.213

Ni

O O

O O

+ L L Ni

O

O

O

O

L

L

L__L : BPY = 2,2'-bipyridine; TEME = tetramethylethylenediamine; TEMP =

tetramethylpropylenediamine; MAO = 1-dimethylamino-2-methoxy-ethane

Ni(tmhd)2 L__L+ = Ni(tmhd)2(L__L)

Fig.36. Scheme for the preparation of Paramagnetic

Octrahedral Complex Ni(tmhd)2L—L from Ni(tmhd)2

A new complex with composition [Ni(L1)(L2)(H2O)]ClO4 (where L1=2-(2'-

pyridyl)-benzothiazole), L2=N-[(1)-pyridylmethylidenebenzohydrazone),

has been synthesized and characterized by various physico-chemical


Introduction []

techniques. The Ni atom is coordinated through azomethine nitrogen,

pyridine nitrogen and carbonyl oxygen of L2 and two nitrogen atoms of

L1. The X-ray data of the coordination sphere shows that the Ni(II)

center has a N4O2 coordination moiety with distorted octahedral

geometry. The L2 coordinates to the nickel atom as a uninegatively

charged chelating agent in its deprotonated hydrazone form via the

ketonic oxygen atom, azomethine nitrogen atom and the pyridine

nitrogen atom. Additionally, the pyridyl planes in the complex are

engaged in intra- and intermolecular hydrogen bonding. This complex is

a fairly good biological agent and exhibits excellent hydrogen bonding

making it suitable candidate in medicine and biochemistry.214 The

complex was prepared by the scheme as shown below (Fig. 37).

NHN

N

Ni(NO3)2.6H2O

N

S

N

N

S

N

Ni

N

NN

O

H2O+NaClO4

ClO4

+

+

Methanol

Fig.37. Scheme for the preparation of [Ni(L1)(L2)(H2O)]ClO4

Mixed ligand Ni(II) complexes of the type [M(Q)(L).2H2O] have been

synthesized by using 8-hydroxyquinoline (HQ) as a primary ligand and

N- and/or O- donor amino acids (HL) such as L-serine, L-isoleucine, L-

proline, 4-hydroxy-L-proline and L-threonine as secondary ligands. The

metal complexes have been characterized on the basis of elemental

analysis, electrical conductance, room temperature magnetic

susceptibility measurements, spectral and thermal studies. The

electrical conductance studies of the complexes in methanol at 10–3 M

concentration indicate their non-electrolytic nature. Room temperature

magnetic susceptibility measurements revealed paramagnetic nature of

the complexes. An octahedral structure has been proposed for these

complexes (Fig. 38).215


Introduction []

Ni

N

O

O

H2N

OH2

OH2

O

Ni

N

O

O

NH

R

OH2

OH2

O

R

R = __CH2OH : [Ni(Q)(Ser).2H2O] Complex

R = __CH__CH2__CH3 : [Ni(Q)(Iso).2H2O] Complex

CH3

R = __CH__CH3 : [Ni(Q)(Thr).2H2O] Complex

OH

R = H : [Ni(Q)(Pro).2H2O] Complex

R = __OH : [Ni(Q)(HPro).2H2O] Complex

Fig.38. Mixed Ligand Ni(II) Complexes of the type [M(Q)(L).2H2O]

Ethanol adducts of bis(3-R-penta-2,4-dionato)nickel(II) have been

prepared by the recrystallization of the corresponding

bis(acetylacetonato)nickel(II) species from ethanol, and their crystal

structures have been determined by X-ray diffraction (Fig. 39). The

nickel atom has an octahedral environment, with the four oxygen atoms

of the pentadionato fragment lying in the equatorial plane and two

ethanol oxygen atoms in the axial positions.216

Ni

O O

O O

RR

H3C

H3C

CH3

CH3

2EtOHNi

O O

O O

RR

H3C

H3C

CH3

CH3

OH

OH

Et

Et

where R = __CH3, __(CH2)4__CH=CH2 or __Ph

Fig.39. Ethanol adducts of bis(3-R-penta-2,4-dionato)nickel(II)

VII. BIOLOGICAL ROLE OF NICKEL AND ITS COMPLEXES

Nickel(II), like other ions of first transition series, has the ability to

complex, chelate or bind with many substances of biological interest.

Thus it is not surprising that nickel is an ubiquitous element found in

all biological materials. Various authors have tabulated nickel content

in numerous plants, microorganisms and animals. Except for some


Introduction []

nickel-accumulating plants and marine species, nickel levels in nearly

all biological materials are in the range of nanograms per gram to a few

micrograms per gram.

The chemistry of nickel complexes with redox-active ligands represents

one of the promising developments of nickel coordination chemistry

with their potential applications in the area of nanotechnology.217 Due

to their peculiar physical properties, there is a rapidly growing interest

in ligand redox-active transition metal complexes as building blocks for

new magnetic and conducting molecular materials.218-231

Nickel(II) compounds which can be reversibly reduced to nickel(I)

species have been attracting attention as models of redox active nickel-

containing enzymes and as electrocatalysts.232-236 Nickel complexes

occur in several nickel-containing enzymes which have been proposed

to be involved in catalytic reaction.237,238 Nickel is found in the active

site of eight metalloenzymes.239 Of this group, nickel is redox active in

carbon monoxide dehydrogenase, acetyl-CoA synthase, iron-nickel

hydrogenase, superoxide dismutase and methyl coenzyme M reductase.

For the other three enzymes (urease, glyoxalase I and acireductone

dioxygenase) the oxidation state of the nickel center is +2 and does not

change during catalysis. Instead the nickel center(s) in these enzymes

is/are proposed to be a Lewis acid that coordinates and facilitates

deprotonation of a substrate (or inhibitor), or lowers the pKa of water to

produce a Ni(II)-OH species.

Urease is produced by plants, algae, fungi and bacteria, and it catalyzes

the hydrolytic decomposition of urea. Due to its nickel content, urease

is a unique example among the hydrolytic enzymes, which typically

contains zinc as the essential cofactor. In this context, the question of

the role of nickel in the catalytic mechanism remains intriguing for the

bioinorganic community. An approach towards addressing this issue

has involved attempts to substitute nickel with other divalent metal

ions, such as Zn2+, Co2+ and Mn2+.240 Removal of both Ni2+ ions by

treating the enzyme with EDTA at low pH causes irreversible

denaturation of the protein.241


Introduction []

Glyoxalase I catalyzes a key step of the cellular detoxification pathway

for α-ketoaldehydes in bacteria, animals and humans.242 The first step

of this pathway is a nonenzymatic reaction of the α-ketoaldehyde {e.g.

methylglyoxal (MG)} and glutathione (GSH) which results in the

formation of a hemithioacetal. Glyoxalase I (GlxI) catalyzes the

isomerization of the hemithioacetal to a thioester product.

Subsequently, the glyoxalase II enzyme (GlxII) promotes the hydrolysis

of the thioester, producing the corresponding α-hydroxy acid and GSH.

These two enzymes are referred to as the glyoxalase system. Two

distinct classes of GlxI enzymes have been identified to date.243 A zinc

dependent glyoxalase I (e.g. human and rat liver GlxI) is a prevalent

form of the enzyme and has been extensively studied. However more

recent studies revealed that various bacterial GlxI enzymes exhibit

maximal activity in the presence of Ni2+ (E. coli, as well as Y. pestis, P.

aeruginosa and N. meningitis).243-245 GlxI from the human parasite L.

major was also found to be Ni-dependant.246

Acireductone dioxygenase (ARD) enzymes are associated with the

methionine salvage pathway (MSP), an ubiquitous biological cycle.247

ARDs catalyze oxygen dependent aliphatic C-C bond cleavage in 1,2-di

hydroxy-3-oxo-5-(methylthio)pent-1-ene (acireductone). Over-expression

of the ARD gene in E. coli produces two ARD enzymes, one containing

Fe2+ and a second containing Ni2+ as the metal cofactor.248 A unique

feature of the reactions catalyzed by these enzymes is that the

regioselectivity of the carbon-carbon bond cleavage depends on the

metal ion bound in the active site. While Ni2+-ARD catalyzes a reaction

that is a shunt out of the methionine salvage pathway, Fe2+-ARD

operates on pathway enabling the recovery of methionine.248-250

The Ni2+-ARD reaction gives as products methylthiopropionic acid,

formate and carbon monoxide. None of these products is a precursor for

methionine, and more importantly methylthiopropionic acid is cytotoxic.

Alternatively, carbon monoxide has been found to play a role as a

neurotransmitter in mammals.251 It is proposed that the activity of Ni2+-

containing ARD might aid in the regulation of methionine levels,


Introduction []

however the precise function of this enzyme is still unclear.252 Moreover,

nickel-containing acireductone dioxygenase is the only known example

of nickel-containing dioxygenase.252

Nickel-dioxygen intermediates obtained by the reaction of low-valent Ni

complexes with O2 and H2O2 play a role in several stoichiometric and

catalytic reactions. For example, Ni2+ azamacrocycles react with O2 to

yield putative Ni/O2 intermediates capable of H-atom abstraction.253-258

Also bis-µ-oxo and bis-µ-1,2-superoxo bridged (Ni3+)2 dimers have been

shown to be competent of carrying out diverse organic

functionalizations through intra- or inter-molecular H-atom

abstraction.259,260 Thus nickel-dioxygen species possess significant

potential for use as oxidation catalysts.

VIII. COORDINATION CHEMISTRY OF COPPER(II)

Copper (Cu), element 29, is a member of the first transition series and

therefore can form coloured complexes due to partially filled 3d orbitals.

As expected for a typical transition element, Cu is a metal; can serve as

a catalyst (e.g. in the oxidation of organic molecules by O2); exists in a

variety of oxidation states ranging from 0 in the metal to +4; and gives

rise to ions which readily form complexes, yielding an extensive variety

of coordination compounds.261 By far the most common oxidation states

for Cu are +1 and +2 states. The +3 state is not common and +4 state

(e.g. Cs2[CuF6]) extremely limited.

Cu(I), having a closed shell configuration, [Ar]3d10, is diamagnetic. Since

it has no vacant d orbital, it cannot undergo d-d transitions. Hence,

Cu(I) compounds are usually colourless. However, there are some that

are coloured, due to charge-transfer transitions {both ligand to metal

charge transfer (LMCT) and metal to ligand charge transfer (MLCT)} or

intraligand-orbital transitions.108,261 Although the intraligand-orbital

transitions do not involve the metal center directly, any intra-ligand

absorptions are often strongly modified on complexing the ligand to the

metal center.261 However most Cu(I) compounds are readily oxidized to

Cu(II) compounds.108


Introduction []

The single unpaired electron in the case of Cu(II) ([Ar]3d9) makes it

paramagnetic. Cu(II) compounds therefore show EPR signals, and in

nuclear magnetic resonance spectroscopy the binding of Cu(II) to

ligands result in paramagnetic line broadening and shift effects for the

ligand resonances. Virtually all Cu(II) complexes or compounds are blue

or green in colour.108 The d-d spectra, although composed of broad,

overlapping bands, yield considerable information concerning

coordination and site symmetry.

The d9 configuration makes Cu(II) subject to Jhan-Teller distortion if

placed in an environment of cubic i.e., regular octahedral or tetrahedral

symmetry and this has profound effect on all its stereochemistry. With

Cu(II) and any other d9 system, the octahedral configuration is unstable

because of the ambiguity which results from incomplete occupation of

the eg degenerate orbital. For Cu(I) with a d10 configuration, all the d

orbitals are filled in all the common stereochemistries and hence

regular octahedral and tetrahedral symmetries are possible.

Cu(II) is classified as a borderline hard acid; N-type, O-type, and Clˉ

ligands dominate its chemistry, although a fair number of complexes

with S ligands are known. Cu(II) readily forms coordination complexes

involving mainly the coordination numbers 4, 5, and 6. These

complexes are mostly distorted due to Jahn-Teller effect, as discussed

above. Thus, even near regular tetrahedral geometry is unknown, and

instances of regular octahedral geometry are rare. A majority of 6-

coordinate Cu(II) complexes involve elongated tetragonal or rhombic

octahedral structure, with a few involving a compressed tetragonal (or

rhombic) octahedral structure.

The 4-coordinate Cu(II) complexes have either tetrahedral geometry,

which involve significant compression along the S4 symmetry axis and

regular square planar geometry. Even the latter often involves a slight

tetrahedral distortion.

Three new mono-, di-, and trinuclear copper(II) complexes of the Schiff

base ligand, 2-{(E)-[(6-{[(1E)-(2-hydroxyphenyl)methylene]amino}-pyridin

-2-yl)imino]-methyl}phenol (H2PySAL), with formula [Cu(H2PySAL)]Cl2


Introduction []

(1), [Cu2(PySAL)(Phen)]Cl2 (2) and [Cu3(PySAL)2]Cl2 (3), were prepared

and characterized by elemental analyses, magnetic moment, and IR,

UV-Vis, and mass spectral studies (Fig. 40). The spectroscopic data of

the complexes indicate that the copper(II) ions are coordinated by the

oxygen atoms and nitrogen atoms of the ligand. In the dinuclear

complex, the first Cu(II) ion was complexed with oxygen and nitrogen

atoms of the Schiff base ligand while the second Cu(II) ion is bridged by

the dianionic oxygen atoms of the phenolate group and linked to the

nitrogen atoms of 1,10-phenanthroline ligand. The magnetic moment

data of these copper(II) complexes suggest square-planar geometry for

them.262

Cu

NO

NO

N

Cl2.H2O

Cu

NO

NO

N Cu

N

N

Cl2

1 2

Cu

NO

NO

N Cu

NO

NO

NCuCl2

3

Fig.40. Proposed Structures of Copper(II)

Complexes of Schiff Base Ligand (H2PySAL)

The preparation of copper(II) complexes having formula [Cu(L)X] (HL =

N-(2-pyridylmethyl)-3-methoxysalicylaldiminato and X = Clˉ, Brˉ) has

been described. The compounds were characterized by elemental

analysis, spectral, magnetic and crystallographic studies. In both

compounds, the molecular structure of the Cu(II) ion involves a square-


Introduction []

planar CuN2OX chromophore, consisting of a deprotonated phenolate

oxygen, an imine nitrogen, the pyridine nitrogen and X.263

Cu(II) complexes of sulfamethazine ligand (4-amino-N-[4,6-dimethyl-2-

pyrimidinyl]benzenesulfonamide = HL) i.e., {[Cu2(CH3COO)2(L)2].2dmf}

(1) and {[Cu(L)2].2H2O}∞ (2) were prepared and characterized (Fig. 41).

In compound 1 two copper ions are linked by two syn-syn acetates and

two non linear NCN bridging groups pertaining to the deprotonated

sulfamethazine ligands. Each copper center presents a nearly square

planar geometry. However the copper in polymeric compound 2 is five

coordinate. The CuN5 chromophore has a highly distorted square

pyramidal geometry. In this compound a sulfamethazinate anion binds

to one copper through the sulfonamido and pyrimidine N atoms and to

an adjacent copper via the amino N atom.264

Cu CuH2O OH2

O O

O O

O O

OO

Cu Cu

O O

N N

O O

NN

Sulfamethazine

dmf

Fig.41. Reaction of Cu2(CH3COO)4(H2O)2 with Sulfamethazine

in dmf to form [Cu2(CH3COO)2(L)2].2dmf

Volatile low melting Cu(II) metal complexes

Cu[OC(CF3)2CH2C(Me)=NMe]2 and Cu[OC(CF3)2CH2CHMeNHMe]2 were

synthesized and characterized by spectroscopic methods (Fig. 42). A

single-crystal X-ray diffraction study of the complex

Cu[OC(CF3)2CH2C(Me)=NMe]2, shows anticipated N2O2 square planar

geometry with the imino alcoholate ligand arranged in all trans

orientation. In contrast, a highly distorted N2O2 geometry was observed

for the complex Cu[OC(CF3)2CH2CHMeNHMe]2 suggesting that the fully

saturated amino alcoholate ligand produces a much greater steric

congestion around the metal ion.265


Introduction []

Cu

N O

NOF3C

CF3

CF3

CF3

Me Me

MeMe

Cu

NH O

NHOF3C

CF3

F3C

CF3

Me Me

MeMe

Cu[OC(CF3)2CH2C(Me)=NMe]2 Cu[OC(CF3)2CH2CHMeNHMe]2

Fig.42.

5-coordinate Cu(II) complexes generally involve distorted square

pyramidal and distorted trigonal bipyramidal stereochemistry. In the

distorted square pyramidal geometry there is both an elongation of the

four-fold axis and a trigonal in-plane distortion or, less frequently, a

tetrahedral distortion. It rarely involves a regular square pyramidal

stereochemistry. Regular trigonal bipyramidal geometry can occur but

is more frequently distorted towards square pyramidal geometry.

Cu(OAc)2.H2O

N P

Ph

Ph

Ph

Me3Si

Cu

O

O

HN N

H

O

PPh3

Ph3P

O

Cu(OAc)2.H2O

Cu Cu

O O

O

O

O O

O

OHN N

H

PPh3

Ph3P

Cu(HNPPh3)2(OAc)2

[Cu(HNPPh3)(OAc)2]2

Fig.43. Scheme for the preparation of

Cu(HNPPh3)2(OAc)2 and [Cu(HNPPh3)(OAc)2]2

Copper acetate complexes of the type [Cu(HNPPh3)m(OAc)2]n have been

prepared and structurally characterized as a monomer (m = 2, n = 1)

and as a dimer (m = 1, n = 2) (Fig. 43). The complex,

Cu(HNPPh3)2(OAc)2, was obtained when a CH2Cl2 slurry of


Introduction []

Cu(OAc)2.H2O was treated with CH2Cl2 solution of Me3SiNPPh3. On the

other hand, when CH2Cl2 solution of analytically pure

Cu(HNPPh3)2(OAc)2 was treated with excess of Cu(OAc)2.H2O, the

complex, [Cu(HNPPh3)(OAc)2]2, was obtained as the sole product upon

recrystallization. The solid state structure of both the complexes was

determined by single-crystal X-ray diffraction study which reveals a

square-planar structure for the complex Cu(HNPPh3)2(OAc)2 and a

square-pyramidal structure for the complex [Cu(HNPPh3)(OAc)2]2.266

Hydroxo- and methoxo- bridged tetranuclear copper(II) complexes of the

tetramacrocyclic ligand 1,2,4,5-tetrakis-(1,4,7-triazacyclonon-1-yl

methyl)benzene (Ldur) have been prepared from

[Cu4Ldur(H2O)8](ClO4)8.9H2O (1). Addition of base to an aqueous solution

of (1) gave [Cu4Ldur(µ2-OH)4](ClO4)4 (2). Diffusion of MeOH into DMF

solution of (2) produces [Cu4Ldur(µ2-OMe)4](ClO4)4.HClO4.2/3MeOH (3), a

complex which hydrolyzes on exposure to moisture regenerating (2).

The Cu(II) centers in the complexes 2 and 3 exhibit distorted square

pyramidal coordination polyhedra, with the tertiary bridgehead

nitrogens occupying axial positions (Fig. 44).267

Cu

NHN

HN

HO OH

Cu

HN N

NH

[Cu4Ldur(µ2-OH)4]4+ (1) [Cu4Ldur(µ2-OMe)4]4+ (2)

Cu

NHN

HN

HO OH

Cu

N NH

NH

Cu

NHN

HN

HO OH

Cu

HN N

NH

Cu

NHN

HN

HO OH

Cu

N NH

NH

Fig.44. Hydroxo- and Methoxo- bridged Copper(II) complexes of Ldur

Novel N,N',N''-trialkylated derivatives of cis,cis-1,3,5-triaminocyclo

hexane (tach), designated tach-R3, were prepared through the alkylation

of N-protected tach with subsequent acid deprotection, to afford N-

methyl, N-ethyl, N-n-propyl derivatives as their trihydrobromide salts.

The tach-neopentyl3 and tach-furan3 derivatives were prepared by


Introduction []

formation of the imine from tach and pivaldehyde or furan-2-

carboxaldehyde, respectively, followed by the reduction of imine.

Complexes [Cu(tach-R3)Cl2] (R = Me, Et, n-Pr, CH2-2-thienyl and CH2-2-

furanyl) were prepared from CuCl2 in MeOH or MeOH—Et2O solvent.

Crystallographic characterization of [Cu(tach-Et3)Br0.8Cl1.2] reveals a

square-based pyramidal CuN3X2 coordination sphere in which one

nitrogen donor occupies the apical position at slightly longer distance

than those of the basal nitrogens. The solution-phase and solid-phase

structures of [Cu(tach-R3)Cl2] have been studied extensively by EPR and

visible-near-IR spectroscopies. The square-based pyramidal structure is

retained in solution, according to correspondence of solution and solid-

state data (Fig. 45). In aqueous solution, halide is replaced by water, as

indicated by the high energy UV-visible spectral shifts.268

Cu

NHN

NH

R

R

R

XX

n+

R = Me, Et, n-Pr, CH2-2-thienyl

and CH2-2-furanyl, X= Cl, n = 0

R= Et, X2 = (Br)0.8(Cl)1.2, n = 0

R = Et, X = (H2O), n = 2

Fig.45.

Majority of 6-coordinated octahedral Cu(II) complexes involve elongated

tetragonal distortion resulting from having the odd electron in the dx2-y

2

orbital after splitting the eg degenerate orbital to two non-degenerate

orbitals dx2-y

2 and dz2. The elongation is along one four-fold axis, so that

there is a planar array of tetragonal structure. In the extreme case of

this distortion, of course, the elongation leads to a square planar

coordination. There are also Cu(II) complexes with compressed

tetragonal octahedral structure. The compressed tetragonally distorted

octahedron results from having the odd electron in the dz2 orbital.108


Introduction []

A copper(II) complex of the bidentate ligand derived from

cinnamaldehyde and acetylacetone (3-cinnamalideneacetylacetone

{cinac}) has been synthesized and characterized by elemental analysis,

UV-Vis, IR, ESR and magnetic susceptibility measurements (Fig. 46).

Magnetic susceptibility measurements, ESR and electronic spectral data

indicate the presence of six coordinated Cu(II) ion. The d–d band at

13,850 cm–1 for [Cu(cinac)] is attributed to the dxz,dyz→dx2–y

2 electronic

transition. Observation of this d–d transition suggests a tetragonally

elongated octahedral geometry around Cu2+ in [Cu(cinac)].269

HC C

HCH

C

C

H3C

C

H3C

O

O

Cu

OH2

OAc

OAc

OH2

Fig.52. [Cu(cinac)]

A copper(II) complex of the amino acid L-tryptophan, of stoichiometry

Cu(Trp)2, was obtained from aqueous solution. Its structural

characteristics were deduced from the careful analysis of infrared,

Raman and electronic absorption spectra, complemented with magnetic

susceptibility measurements in the temperature range between 2 and

300 K. The metal center presents a distorted octahedral CuN2O4

environment with a trans arrangement of the amino acids in the

equatorial plane, involving the terminal amino and carboxylate groups.

The coordination sphere is complemented with two longer apical Cu-O

bonds involving ―free‖ O-carboxylato atoms of the neighboring complex

moieties.270

The copper(II) complex, [Cu(tdp)(ClO4)].0.5H2O, where H(tdp) is a

tetradentate ligand 2-[2-(2-hydroxyethylamino)-ethylamino)methyl]

phenol, and mixed ligand complexes [Cu(tdp)(diimine)]+ where diimine is

2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 3,4,7,8-tetramethyl-

1,10-phenanthroline (tmp), and dipyrido-[3,2-d:2',3'-f]-quinoxaline

(dpq), have been isolated and characterized by analytical and spectral

methods (Fig. 47). Complexes [Cu(tdp)(ClO4)].0.5H2O and


Introduction []

[Cu(tdp)(phen)]ClO4 have been structurally characterized, and their

coordination geometries around Cu(II) are described as distorted

octahedral.271

Cu

OH2

OClO3

OH

NH

O

N

Cu

N

O

N

NH

O

N

H

N N =

bpy

phen

tmp

dpq

OH

N HN

HO

H(tdp)

Fig.47. Possible Coordination Geometries of Simple and

Mixed Ligand Copper(II) Complexes of H(tdp)

The complex [Cu(terpy-NIT)2](ClO4)2 {where terpy-NIT = 2-[4'-(2,2':6',2''-

terpyridyl)-4,4,5,5-tetramethylimidazolinyl-3-oxide-1-oxyl)} has been

prepared (Fig. 48). The complex has been characterized by FAB-MS,

UV-VIS, FT-IR, EPR spectroscopies, elemental analysis, and

susceptibility measurements. It is found that the pyridyl fragments of

the free ligand are in an anti confirmation, however the complex is

obtained by the coordination of two terpyridines in a syn confirmation,

forming a distorted octahedron around the metal center.272

N

N N

N

N

N

Cu

=

N

N

O

O

where

2

2ClO4

Fig.48. [Cu(terpy-NIT)2](ClO4)2


Introduction []

IX. BIOLOGICAL ROLE OF COPPER AND ITS COMPLEXES

Although known to be a normal constituent of human tissues for over

140 years, copper was only recognised as an essential nutrient as

recently as 1928. Much has since been learnt about the metabolism

and importance of copper in animal and human nutrition. Copper

exhibits considerable biochemical action either as an essential trace

metal or as a constituent of various exogenously administered

compounds in humans. In its former role it is bound to ceruloplasmin,

albumin, and other proteins, while in its latter it is bound to ligands of

various types forming complexes that interact with biomolecules, mainly

proteins and nucleic acids. The multifaceted role of copper in biological

systems is demonstrated by several studies. Copper is found in all

organs and tissues of the human body, in concentrations varying from a

few ppm to several hundred ppm; it is normally bound to proteins or to

organic compounds and is not found as free copper ions. It is not

surprising, in view of its capacity for storage, that high concentration of

copper is found in the liver. Other organs that have high concentrations

of copper are the brain, heart, stomach and various parts of the

intestine.

Total blood copper levels in healthy humans normally range from 1.1-

1.5 µg/ml, although these values can fluctuate with age, exercise and

health conditions. Copper found in erythrocytes is either associated

with superoxide dismutase or with a complex mixture of amino acids.273

The nature of the fundamental importance of copper is clearly revealed

when the enzymes that require copper are considered.

Current interest in Cu complexes is stemming from their potential use

as antimicrobial, antiviral, anti-inflammatory, antitumor agents,

enzyme inhibitors, or chemical nucleases. Cu is involved in both

enzymatic and non-enzymatic roles in animals. The nonenzymatic roles

include angiogenesis, neurohormone release, oxygen transport, and the

regulation of genetic expression.274 Copper enzymes are widely

distributed within the body; they perform several diverse functions

including transport of oxygen and electrons, catalysis in oxidation


Introduction []

reduction reactions and the protection of the cell against damaging

oxygen radicals.275 At least ten enzymes are known to be dependent

upon copper for their function, and whilst this may be a small number,

relative to zinc dependent enzymes, it is self evident that the impaired

function of any enzyme is likely to have deleterious effects.

Enzymes that contain copper play an important role in many biological

processes.276 Galactose oxidase, for example, is an enzyme containing

one copper(II) ion that catalyzes the oxidation of primary alcohols to the

corresponding aldehydes.277,278 Catecholase activity of model binuclear

copper(II) complexes with different structural features have received a

great deal of attention.279-284 Binuclear copper centers are commonly

found in metalloenzymes and play an important role in enzyme

activity.285 Hemocyanin, tyrosinase and catechol oxidase are all

classified as type 3 copper proteins and have magnetically coupled

binuclear copper(II) centers at their active sites. These metalloenzymes

perform functions such as dioxygen transport (hemocyanin), o-phenol

aromatic hydroxylations (tyrosinase) and catechol oxidation (catechol

oxidase). Cytochrome C oxidase is required by cells to produce the

energy needed to drive biochemical reactions. Dopamine B hydroxylase

is required in the conversion of dopamine to noradrenaline, a neural

hormone that plays a vital part in the transmission of nerve impulses.

Lysyl oxidase is required for the proper cross-linking of elastin and

collagen during the building, maintenance and repair of connective

tissue. Superoxide dismutase, which is being given an increasing

amount of attention, is required to prevent the accumulation of the

superoxide radicals which cause cellular damage; the enzyme

responsible is a copper/zinc metalloenzyme found in the cytosol of all

cells.

Copper is also required for a number of amine oxidases that are

responsible for the breakdown of amines that are no longer required.

The involvement of copper in these varied enzyme systems means that

disturbances to the copper metabolism have the potential for several

quite wide reaching effects; some are general through the provision of


Introduction []

energy, whilst others are more specific via disturbances to connective

tissue and the nervous system.

Copper proteins are known to be involved in a crucial role, such as

respiration, iron transport, oxidative stress protection, blood clotting

and pigmentation.263,286 Application of copper compounds in wood

protection, due to their fungicidal activity, is also known for a long

time.287 Although such protection is very commonly used, the mode of

copper action and its way of binding to wood are still not known

accurately.288,289

i. general introduction to...

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