1

Chapter 1

An overview of the recent trends in the

coordination chemistry of the functionalized

polycarboxylic acid ligands.

2

INTRODUCTION

In recent years metal complexes with functionalized polycarboxylic acid

ligands viz. 2,6-dipicolinic acid (H2PDA), iminodiacetic acid (H2IDA), oxydiacetic

acid (H2ODA), nitrilotriacetic acid (H3NTA), ethylenetriaminetetraacetic acid

(H4EDTA) or diethylenetriaminepentaacetic acid (H5DTPA) (Fig. 1) have attracted

attention of inorganic and bioinorganic chemists [1-6]. The ligating characteristics of

these flexible functionalized polycarboxylic acid ligands constitute an important class

of polydentate [N,O,O] or [O,O,O] chelators resulting in metal complexes differing in

coordination numbers, conformations and 3-D architectures. Furthermore, in mixed

ligand metal carboxylate complexes, the polycarboxylate moieties in ternary

complexes containing α-diimine spacers also play an important role to construct

supramolecular networks via. extensive H-bonding and interactions of aromatic rings

[7-9]. The carboxylate moiety may adopt a range of different coordination modes

whether it binds the metal ion as anionic (COO)¯ or neutral unionized (COOH) form.

[10-19] (Fig. 2).

A large numbers of polymeric metal organic frameworks (MOFs) containing

carboxylate ligands have been prepared and well characterized [7-9]. The

dicarboxylic ligands with additional donor sites as for example pyridyl ‘N’ in

pyridine-2, 6-dicarboxylic acid and iminic ‘N’ in iminodiacetic acid and ethereal ‘O’

in oxydiacetic acid and their derivatives are of great interest to medicinal chemists.

H2PDA and its derivatives are present in many natural products, such as alkaloids,

vitamins and coenzymes and are found to display a wide variety of physiological

properties. Metal complexes of these ligands therefore, have been exploited as

interesting model systems [20-22].

3

HN

O

OHO

OH

NHO OH

OO

OO O

OH OHN

O

OH

O OH

N N

HO

OH

OH

HO

O

O

O

O NN

N

O

O

HO

OH

O

O

OH

OH

HO O

O

HO

(a) (b) (c) (d)

(e) (f)

Fig. 1. (a) H2IDA, (b) H2PDA, (c) H2ODA, (d) H3NTA, (e) H4EDTA, (f) H5DTPA.

CO O

M

CO O

M

CHO O

M

CHO O

M

CO O

M

O O

M M

O O

M

O OMMM

i ii iii iv

v vi vii viii

Fig. 2. Various coordination modes in metal–carboxylate complexes.

4

Pyridine-2,6-dicarboxylic acid (H2PDA), typically called as dipicolinic acid,

has an elaborately attractive coordination chemistry. It has a rigid 120° angle between

the central pyridine ring and two carboxylate groups, henceforth could potentially

provide various coordination motifs to form both discrete and consecutive metal

complexes under appropriate synthetic conditions [23]. The systematic studies

undertaken by several research groups for transition [24] as well as rare earth [25]

metal complexes based on pyridine dicarboxylic acids indicate versatile coordination

motifs for pyridine-2,6-dicarboxylic acid (Fig. 3). The presence of additional donor

centers in the pyridine-2,6-dicarboxylic acid frame as for example OH group in 4-

hydroxypyridine-2,6-dicarboxylic acid generates a unified coordination geometry of

H2PDA and hydroxyl group providing more coordination motifs than H2PDA [26]

itself.

Many transition metal ions with dicarboxylate ligands have been exploited as

possible drugs for many diseases [24,27]. The recent successes in the development of

metal based drugs incorporating suitable organic moieties suggest that modifications

of the metal ion chemistry by the organic ligands not only enhance the efficacy but

also decrease toxicity. Many vanadium complexes containing pyridine dicarboxylic

acid and its derivatives have been reported in literature [28]. Most of them are of

particular interest because a range of these compounds are comparable with insulin

like effects. These compounds include simple salts (sodium ortho− and meta−

vanadate, vanadyl sulphate [29] and a few organic vanadium compounds. The

complexes bis(pyrrolidine−N−carbodithioate)oxovanadium(IV) and bis(cystein

methyl ester)oxovanadium(IV) [30], have been propagated as an effective insulin

mimics (antidiabetic drugs). The most successful vanadium complexes in this regard

5

are considered to have reasonably good solublity in both organic and aqueous media

and compatible with the human metabolism. Recent efforts are focused on identifying

vanadium compounds with increased potency and decreased toxicity [31-35]. Most of

the compounds reported contain bidentate ligands and have a 1:2 metal-to-ligand

stoichiometry. The functionalized dicarboxylate ligands are desirable because of low

toxicity and amphophilic nature. There are reports that different classes of Vanadium

compounds [36,37] exhibit the insulin-enhancing properties. Many V-dipicolinate

complexes viz. NH4[VVO2(PDA)] (1), [VIVO(PDA)(H2O)2]·2H2O (2),

[VIII(PDA)(HPDA)H2O]·3H2O (3) or [VIII(PDA)(HPDA)]·3H2O (4) (Fig. 4) and even

the H2PDA ligand alone, have been shown to be effective in diabetes.

Fig. 3. Coordinating modes in PDA2–

6

Fig. 4.

Ternary complexes of oxygen-donor ligands (as primary ligands) and

heteroaromatic N-bases (as auxiliary ligands) have attracted much interest as they can

display exceptionally high stability [38]. The use of transition metal complexes of

iminodiacetic acid (H2IDA) and nitrilotriacetic acid (H3NTA) have been widely

adopted in biology, and are gaining uses specifically in biotechnology for the protein

purification. Organic ligands possessing multifunctional coordination sites such as N

and S have been shown to play crucial roles in the design and architecture of metal-

organized frameworks having interesting topologies [39, 40]. Furthermore ligands

with polyfunctional donor sites have been exploited for this purpose. N-

carbamoylmethyl-iminodiacetic acid [H2ADA = H2NCOCH2N(CH2COOH)2], which

is an amido (–CONH2) analogue of H2IDA, possesses three potential coordinating

groups, –N, –COOH and –CONH2 and has been exploited for this purpose. This

7

ligand can be partly or fully deprotonated (HADA– and ADA2–) and can perform a

wide range of coordination modes. However, the easily chelating effect of this

derivative (ADA2–) made it a limited ligand in coordination chemistry. Several papers

have appeared in recent years concerning the binary and ternary (mixed-ligand)

complexes of a variety of metal ions and ADA2– as primary ligand [41]. Most of the

complexes adopt mononuclear structures where ADA2– acts as a tridentate chelating

agent (Fig. 5). Carboxylates have been used extensively in the synthesis of di and

polynuclear metal complex [41]. Iminodiacetic acid (H2IDA) is one such ligand,

finding widespread synthetic applications. For example, using iminodiacetato–

copper(II) as a building block and polypyridine- type molecules as common cross-

linkers, several oligomeric complexes with aesthetically pleasing structural forms

have been reported in recent times [41]. The X-ray crystal structure analysis of a

dinuclear iminodiacetato–copper(II) complex,

[(H2O)2(IDA)Cu(PMZ)Cu(IDA)(OH2)2], (PMZ = N,N’-bis(pyridin-4-

ylmethylene)hydrazine ), where PMZ acts as a linear spacer was reported (Fig. 6).

Aromatic ring stacking interactions have also proved to be relevant intermolecular

forces for molecular recognition processes in chemistry and biology [42]. In this

broad context, a large variety of mixed-ligand metal complexes involving various

aromatic amino acetate ions or closely related derivatives and N-heterocycles as co-

ligands were investigated during the past 2-3 decades [41].

8

Fig. 5. Structure of [Ni(ADA)2]2–

Fig. 6.

9

Structural studies on many mixed−ligand compounds have revealed promising

informations not only on the metal ion surrounding but also on molecular recognition

phenomena involved in the crystal packing. copper(II) complexes having one IDA-

like chelating ligand and stoichiometric modes of N heterocycles such as imidazoles,

bipyridines, phenanthrolines and adenine have been reported [43-46]. Such complexes

have bio-inorganic interest because the copper(II)-IDA like chelate could stimulate a

protein-metal centre which would be able to display different recognition modes with

various N-heterocycles acting as “substrates” [43].

The crystal structure of the mixed-ligand complex had infinite multi-staked

chains with alternating benzyl-phen intra- and inter-molecular π–π interactions. The

salt also exhibited a large variety of inter-ligand π–π interactions [47]. The ternary

systems [Cu(II)/L/phen] where L is the substituted analogues of

nitrobenzyliminodiacetic acid (IDANBz) i.e. N-phenethyliminodiacetate(2-)(pheIDA)

or N-benzylaminoacetato-2-propionate(2-) (BAAP) instead of IDANBz as chelating

ligand are also reported [47].

On account of the tridentate chelating property of the iminodiacetate (IDA2–)

ligand and the flexibility of the Cu(II) coordination stereochemistry, extensive

research has been devoted to the structural investigations of a variety of the mixed-

ligand complexes of Cu(II), with IDA-like groups as primary ligands and N-

heterocyclic donors as auxillary ligands [44-47]. Such ternary complexes are useful

bioinorganic model compounds for mono- and dinuclear copper proteins. In this

context, the Cu(II) complex serves as a metal centre, while the tridentate H2IDA

ligand or its derivative acts as a protein-like moiety and the N-heterocyclic donors

play the role of substrate or inhibitor. All mixed-ligand complexes having 1:1:2 ratio

10

of Cu/IDA-like/N-heterocyclic donor results in complexes in which the primary

ligand adopts a fac-chelating conformation. In contrast, the complexes with an

equimolar Cu/IDA-like/N-heterocyclic donor ratio (1:1:1) adopt a distorted square-

pyramidal coordination (4+1 type), or more rarely in an elongated octahedral

coordination (4+2 or 4+1+1 type). In these complexes, the IDA-like ligand itself

adopts a mer-conformation binding as tridentate donor. Furthermore, the

stoichiometry and binding nature of the auxiliary ligand influence the coordination

geometry of IDA. It has been shown that 1,10-phenanthroline (phen) possesses a

stronger coordination ability (Figs. 7–9). In the mixed-ligand homo-bimetallic

complex [Cu(phen)2Cu(IDA)(phen)], IDA2– serves as a bridging ligand to link the two

different [Cu(phen)2]2+ and [Cu(phen)]2+ moieties via a carboxylate group. However,

the two Cu(II) centers exhibit totally different coordination geometries.

Fig. 7. The molecular structure of [Cu(phen)2Cu(IDA)(phen)] showing the atomic

labelling scheme. Thermal ellipsoids are drawn at 50% probability. H atoms, solvent molecules and counter ions have been omitted for clarity.

11

Fig. 8. The H-bonding network and octahedral coordination geometry around metal

atom in [Cu(phen)2Cu(IDA)(phen)].

Fig. 9. The π–π stacking interactions in [Cu(phen)2Cu(IDA)(phen)].

12

H-bonding and π–π interaction in mixed ligand complexes generally result in

the formation of a supramolecular framework. The supramolecular chemistry was first

introduced in the year 1978 [48,49] as the chemistry of molecular assemblies.

Supramolecular chemistry is the chemistry of intermolecular bonds comprising of

strong electrostatic interactions and often weak interactions such as hydrogen bonding

and Vander Waals forces, by mutual recognition. Molecules recognize each other

through a complex combination of geometrical and chemical factors and the

complementary relationship between interacting molecules is characteristic of

recognition process [50]. The characteristic properties of supramolecules are distinct

from the aggregate properties of their molecular constituents. The construction of a

supramolecular network from molecular components implies an accurate knowledge

of the chemical and geometrical properties of intermolecular interactions [51].

Although supramolecular chemistry is still novel, it has drawn a great deal of attention

for further investigations. Since Supramolecular chemistry is a highly

interdisciplinary field of science covering the chemical, physical, and biological

features of the chemical species of greater complexity than molecules themselves

[52]. Coordination chemistry of metal-carboxylate species is an attractive subject

from the bioinorganic standpoint because the carboxylate group of glutamate and

aspartate works as a supporting ligand for the metal centers in various metallo-

proteins. The carboxylate group is also suggested to play an important role for

structural holding and proton transfer via a hydrogen bonding interaction in proteins.

Reports on metallo-proteins reveal the variety of the coordination mode of the

carboxylate ligands and the formation of the hydrogen-bonding interaction with the

other functions [53]. Dinuclear carboxylate-bridged complex is the most attractive

synthetic target because the carboxylate bridged bimetallic core is the common

13

structural motif of the various proteins [54]. The pH of the reaction medium plays an

important role [55] in deciding the formation of the carboxylate bridged complexes as

mononuclear or polynuclear unit. By adjusting a suitable pH, one can obtain desired

product under certain conditions [56,57].

Besides the functionalized dicarboxylic acid ligands, the

diethylenetriaminepantaacetic acid (H5DTPA), a higher homologue of polycarboxylic

acids is also an important polydentate ligand. The ligand appears to have eight

coordination sites comprising of three amino nitrogen donors and five carboxyl

groups, capable to bind metal ions. However, the dianion, [H3DTPA]2– forms stable

solid complexes with first row transition metal ions acquires flexible coordination

geometry where the ligand invariably involves lower than the available octa-

coordination sites [57]. This behaviour is comparable to that the lower homologous

like H4EDTA. Albeit, it has been reported that the resulting complexes have a less

number of water molecules binding (including two that present in the hydration

sphere) compared to that observed for the complexes of lower polycarboxylic acids

analogues H4EDTA [58]. This is consistent with higher stabilities (or formation

constant) of the H5DTPA compared to corresponding ethylenediamine tetraacetic

acetate (H4EDTA) complexes. The most marked reduction in water binding on

replacing EDTA by DTPA occurs with Fe3+ and Mn2+. Furthermore, there is a change

in overall stereochemistry from a seven- to a predominantly six- co-ordinate structure

for Fe3+. Other H5DTPA complexes adopt octahedral symmetry as do all the

derivatives of H5DTPA especially the diethylenetriaminepentamethyl phosphonate

(DTPMP) analogues [58]. Complexes of DTPMP with Co2+, Ni2+ and a lesser extent,

Cu2+ have lower hydration numbers than the corresponding ethylenediaminetetram-

ethylphosphonate (EDTMP) counterparts, due to possibility of simultaneous binding

14

of three nitrogen donors in DTPMP. The [Fe3+−(DTPMP)] complex has one bound

water similar to [Fe3+−(EDTMP)], but the manganese (II) complex of DTPMP is

more hydrated than the corresponding EDTMP complex [58].

Radioactive labeling has been an indispensable tool in the investigation of

biological activities that requires high sensitivity and specificity. In recent years, the

use of fluorescence of lanthanide chelates (e.g., europium and terbium) has been

gaining favour as a viable alternative to the radioactivity. This is based on the facts

that lanthanide fluorescence has high sensitivity and its fluorescence is more specific

than that of conventional fluorescent probes [59,60]. The higher specificity and

sensitivity result from the fact that the fluorescence emission of these lanthanide ions

is narrow banded with a long Stokes shift and a very long fluorescence decay time

[61]. The latter two characteristics allow detection of lanthanide fluorescence in the

presence of background fluorescence derived from biological samples and common

plastic ware, especially if the time-resolved fluorescence measurement is made.

The obvious advantage of lanthanide is that there is no need for special

handling, including the waste disposal, such as that required for radioactive materials.

However, the major disadvantage of lanthanide labeling is the requirement for

incorporating a chelating agent, a structure much larger than radioisotopes, which

may affect the property of the compound labeled. For this reason it is prudent to aim

for minimum level of incorporation of a chelater (ideally <1 mol/mol on the average)

into biological macromolecules, such as proteins.

Diethylenetriaminepentaacetic acid (H5DTPA) and related

polyaminocarboxylic acids and their derivatives are proven chelaters of lanthanide

ions. Simple polyaminocarboxylate-lanthanide chelates are not fluorescent. To

15

potentiate the fluorescence of lanthanide for measurement, two strategies are

generally used. One way is to incorporate a suitable aromatic group close to the

chelater which will deliver the captured light to lanthanide so as to make it

fluorescent. The second way is to use dissociation-enhanced lanthanide fluorescence

immunoassay (DELFIA) technique, in which at the final stage of fluorescence

measurement the lanthanide is displaced from the polyaminocarboxylate chelate and

transferred into a micellar chelating environment, which will make it highly

fluorescent. The former method is required when a lanthanide is used for certain

experiments, e.g., fluorescence resonance energy transfer (FRET), for which a

number of synthetic compounds based on H5DTPA and related

polyaminocarboxylates have been reported [62-65 ]. The second method requires an

extra enhancement step, but the incorporation of H5DTPA group into proteins is as

simple as reacting them directly with commercially available HDTPA dianhydride

[66]. The shortcomings of reacting directly with the dianhydride are (1) difficulty in

controlling the extent of H5DTPA incorporation; (2) possibility of conjugation via

both anhydride groups, which will cause undesirable cross-linking and incorporation

of a lanthanide chelate that is unstable in the acidic pHs; and (3) possible change in

protein stability due to neutralization of the amino group utilized in conjugation. A

monofunctional reagent, p-isothiocyanatobenzyl DTPA, is available commercially

(Wallac, Gaithersburg, MD). However, this reagent introduces an aromatic group as

well as neutralizes the positive charge of the amino group when it reacts with

proteins. Both of these facts may introduce undesirable characteristics to the protein

modified [67].

16

The H5DTPA complexes of copper prepared in acidic media apparently

decomposed in-vivo with the radiometal being trapped in the liver [68,69]. That was

the reason why they were not used for in-vivo studies by direct injection into blood

stream, while their in vitro use as cell radio labeling tracer were proposed as an

alternative option. Meanwhile, there have been reports in the literature concerning the

preparation and use of 64Cu-DTPA for cisternography in the early 1980’s [70].

However, at that time the positron emission tomography (PET) was not yet developed

for regular clinical studies. The idea of incorporation of a (PET) radioisotope into a

suitable chelate used in cisternographic and blood cell labeling, i.e. H5DTPA led to

emphasis on the use of one of the chelate complex [CuDTPA] (Fig. 10) as a

suitable, non−conventional PET tracers.[71]. This important utility of the transition

metal−DTPA complexes has attracted attention of the coordination chemist to design

and develop the synthesis of novel binary as well as ternary complexes incorporating

H5DTPA as main ligating moiety incorporating suitable π−donor as auxillary or

supporting chelator (or spacers).

Fig.10. Scheme of Cu−DTPA complex

17

Carboxylic acid anhydrides are common acylating agents for the modification

of proteins at the amino group of lysine residues and at the hydroxyl group of tyrosine

residues [72,73] .There are two reported anhydride methods for conjugation of

H5DTPA to proteins: (a) the H5DTPA carboxycarbonic mixed anhydride method [74-

80], and (b) the cyclic DTPA anhydride method [81-83]. The former, however,

requires extreme caution because the DTPA carboxycarbonic mixed anhydride is

thermally unstable and hydrolyzes very rapidly. On the other hand, cyclic DTPA

anhydride is sufficiently stable to be isolated for identification. Hnatowich and

coworkers. [81] reported a successful conjugation of DTPA to human serum albumin

(18.8 mg/ml, 2.81×10−4 M) using cDTPAA as an acylating agents.

Gadolinium complexes of linear poly(aminocarboxylate) ligands are of

considerable interest as contrast agents in magnetic resonance

imaging (MRI) [84,85]. The octachelating ligands,

diethylenetriaminepentaacetic acid (H5DTPA), di(methylcarbamoylmethyl)

diethylenetriaminetriacetate (H3DMPTTA), 10-(2-hydroxypropyl)-1,4,7,10-

tetraazacyclododecane-1,4,7-triacetic acid (H3HDPDOTRA) and 1,4,7,10-

tetraazacyclododecanetetraacetic acid (H4DOTA) are effective MRI contrast agents

when complexed with the trivalent gadolinium ion [86]. These gadolinium chelates

possess sufficient paramagnetism and high stability. In order to obtain high contrast

for lesion, administration of high doses of contrast agent is sometimes required,

especially for non-ionic gadolinium complexes which may be used as low-osmolality

contrast agents for MRI [87] The toxic effect of uncomplexed Gd3+ and free pro-

ligand arising from dissociation of the metal complex is one of the major concerns in

MRI [88-94]. The acute toxicity of gadolinium complexes of the

18

poly(aminocarboxylates) correlates well with the selectivity of the later for Gd3+. The

release of Gd3+ is related to the stability constants of the gadolinium complexes

[95,96]. Three important bis(amide) derivatives of H5DTPA, i.e. bis(isopropylamide),

bis(tert-butylamide) and the bis(benzylamide) are reported. Their protonation

constants, thermodynamic stability constants of complexes with Gd3+, Cu2+, Zn2+ and

Ca2+ and their selectivity for Gd3+ over endogenously available metal ions are already

discussed in literature [97] . The Gd(III) ion, with a 4f7 electronic configuration has a

S = 7/2 ground state, it is particularly attractive as an imaging agent. However, the

free gadolinium metal ion, which is similar in size to free Ca2+ binding capablility to

calcium binding sites [84,99], is toxic and so must be sequestered in a metal complex

[84,100]. The first such agent in wide use has been [Gd(DTPA)]2−[101], but the

negative charge of this complex adversely affects tissue distribution for many

applications. Additionality, the high osmolity of formations containing this complex

make administration by painful injection [84, 98].

The aqueous 1HNMR spectra of [Ln(DTPA)]2−(Ln = La, Pr, Eu, and Lu)

complexes have been studied in some detail, [102-105] although later reports came to

different assingements for the structures and exchange mechanisms. Neutral

complexes of Gd(III) with DTPA derivatives have been shown to have properties

somewhat different from the parent ionic complex. Preliminary studies of the

bis(amide) ligands, which have effective symmetry for the ligand, showed highly

complex spectra due to rapidly interconverting [106,107]. The constraint of tethering,

the two amide groups together substantially diminishes both the number of isomers

and the pathways for interconversion. Hence, macrocyclic bis(amide) complexes

[108] were prepared (Fig.11, 12) to demonstrate this behaviour (Scheme 1).

19

Scheme 1. Synthetic procedure for the preparation of DTPA–dien.

The crystal structures of the La(III) and Eu(III) complexes (Fig 11 and 12) are

reported in the literature [108].

Fig. 11. Crystal structure of [La(DTPA−dienH+)]2

20

Fig. 12. Crystal structure of [Eu(DTPA−dienH+)]4

Schiff base ligands have played an integral and important role in the

development of coordination chemistry since the late 19th century. The studies of the

metal complexes of these ligands have attracted attention due to their facile syntheses,

wide applications and the accessibility of diverse structural modifications [109,110].

The chemistry of Schiff base ligands and their metal complexes have been widely

studied including the various aspects of bioinorganic chemistry [110]. Schiff bases

have been reported to show a variety of biological actions by virtue of the azomethine

linkage, which is responsible for various antibacterial, antifungal, herbicidal, clinical

and analytical activities [111-114]. The chemistry of metal complexes containing

salen–type Schiff base ligand derived from condensation of aldehydes and amines is

of enduring significance, since they have common features with metalloporphyrin

with respect to their electronic structure and catalytic activities that mimic enzymetic

21

oxidation [115]. Manganese plays an important role in several biological redox–active

systems, e.g. manganese superoxide dismutase [115], manganese catalase [116],

manganese peroxidase [117] manganese ribonucleotide reductase [118] and the

oxygen–evolving complex (OEC) [119,120]. In general manganese (II) complexes

with Schiff–bases are air–sensitive and easily oxidized to manganese (III) complexes

by molecular oxygen. The crystal structure consists of diverse binuclear clustering.

The hexa–coordinate coordinate geometry around each Mn atom is attained from

coordination of additional water molecules [120,121] in axial direction. The transition

metal Schiff base complexes with an N2O2 donor set have been extensively studied

[122-129]. The manganese complexes containing N, N΄–propane–1, 3–bis

(salicylideneaminate) derivatives are best documented [130-133]. The uses of

hydroxyl–rich Schiff base ligands to form dimeric manganese (III) complexes to

mimic the substructure of oxygen evolution centre (OEC) [134-136] are also known.

The water alkoxo bridge dimeric manganese complexes like

[(Mn2(Salpa)2(H2O)2Cl2]·DMF and [Mn2(Salpa)2(H2O)2(N3)3]·EtOH with coordinated

H2O are recently reported [137] according to the scheme (Fig. 14).

22

Fig.13. Formation of dimeric manganese complexes from Schiff base ligand L [L=1–

(salicyaldeneamino)–3–hydroxypropane and the derivatives].

23

The crystal structure of the dimer has been certained from single crystal

structure as shown in Fig. 14.

Fig. 14. Perspective view of [Mn2(Salpa)2(H2O)2Cl2]∙2DMF

The novel polynuclear complexes of paramagnetic metals have attracted

considerable current interest due to the potential of these spin clusters to act as single-

molecule magnets [138,139]. The single-molecule magnets need to have relatively

high spin ground states with uniaxial magnetic anisotropy. It is, therefore, expected

that multi-nuclear nickel (II) complexes can be a good candidate for the single-

molecule magnets [140]. Utilization of polydentate Schiff base ligands, which can

function in both bridging and chelating capacities, represents a promising route to the

synthesis of new spin clusters and single-molecule magnets. Ligands derived from

salicylidene-2-ethanolamine incorporated into a number of mono- and dinuclear

24

transition metal complexes are known to have a tetranuclear Fe(II) and Cu(II) clusters

with cubane type structures [141].

The structure of the [Ni2(Hsae)2(CH3COO)2(H2O)2] has been certained from

single crystal structure as shown in Fig. 15.

Fig.15. Molecular structure of [Ni2(Hsae)2(CH3COO)2(H2O)2]

25

REFERANCES

[1] L. Carlucci, G. Ciani, D.M. Proserpio, Coord. Chem. Rev., 246 (2003) 247.

[2] Y.W. Li, R.T. Yang, J. Am. Chem. Soc., 128 (2006) 726.

[3] A. C. Gozalez-Baro, E.E. Castellano, O.E. Piro, B.S. Parajon-Costa,

Polyhedron, 24 (2005) 49.

[4] B. Setlow, P. Setlow, Appl. Environ. Microbiol., 59 (1993) 640.

[5] J. J. Wang, X.H. Bu, Cryst. Growth Des., 6 (2006) 656.

[6] C. D. Wu, W.B. Lin, Chem. Commun., (2005) 3673.

[7] J. -G. Mao, L. Song, X.-Y. Huang, J.-S. Huang, Polyhedron, 16 (1997) 963,

and references cited therein.

[8] R. Baggio, M.T. Garland, Y. Moreno, O. Pena, M. Perec, E. Sposine, J. Chem.

Soc., Dalton Trans. (2000) 2061, and references cited therein.

[9] S. K. Ghosh, J. Ribas, P.K. Bharadwaj, Cryst. Eng. Commun., 6 (2004) 250,

and references cited therein.

[10] P. P. Quaglieri, H. Loiseleur, T. Germaine, Acta Cryst., B28 (1972) 2583.

[11] H. Gaw, W. R. Robinson, R. A. Walton, Inorg. Nucl. Chem. Lett., 7 (1971)

695.

[12] A. Chiesi Villa, C. Guastini, A. Musatti, M. Nardelli, Gazz. Chim. Ital. 102

(1972) 226.

[13] K. Hakansson, M. Lindahl, G. Svensson, Albertsson, J. Acta Chem. Scand. 47

(1993) 449.

[14] N. Okabe, N. Oya, Acta Cryst. (2000) 305.

[15] P. Laine, A. Gourdon, J. -P. Launay, J. -P. Tuchagues, , Inorg. Chem., 34

(1995) 5150.

26

[16] P. Laine, A. Gourdon, J. -P. Launay, Inorg. Chem., 34 (1995) 5138.

[17] M. Biagini-Cingi, A. Chiesi Villa, C. Guastini, M. Nardelli, Gazz. Chim. Ital.,

101 (1971) 825.

[18] M. Biagini-Cingi, A. Chiese Villa, C. Guastini, M. Nardelli, Gazz. Chim. Ital.

102 (1972) 1026.

[19] M.G.B. Drew, R.W. Matthews, R.A. Walton, J. Chem. Soc. A (1970) 1405.

[20] A.C. Gozalez-Baro, E.E. Castellano, O.E. Piro, B.S. Parajon-Costa,

Polyhedron, 24 (2005) 49.

[21] B. Setlow, P. Setlow, Appl. Environ. Microbiol., 59 (1993) 640.

[22] D.C. Crans, M. Yang, T. Jakusch, T. Kiss, Inorg. Chem., 39 (2000) 4409.

[23] B. Zhao, L. Yi, Y. Dai, X.Y. Chen, P. Cheng, D. Z Liao, S.P. Yan, Z.H.

Jiang., Inorg. Chem., 44 (2005) 911.

[24] L. Yang, D.C. Crans, S.M. Miller, A. la Cour, O.P. Anderson, P.M.

Kaszynski, M.E. Godzala, L.D. Austin, G.R. Willsky, Inorg. Chem., 41

(2002) 4859.

[25] H.-H. Songa, Y.-J. Lia, Y. Songb, Z.-G. Hana, F. Yang, J. Solid State Chem.

181 (2008) 1017, and references cited therein.

[26] H.L. Gao, Yi. Long, B. Zhao, X.Q. Zhao, P. Cheng, D. Liao, S.P. Yan, Inorg.

Chem., 45 (2006) 5980.

[27] P. Buglyό, D.C. Crans, E.M. Nagy, R.L. Lindo, L. Yang, J.J. Smee, W. Jin,

L.-H. Chi, M.E. Godzala III, G.R. Willsky, Inorg. Chem., 44 (2005) 5416.

[28] D.C. Crans, L.Yang, T. Jakusch and T. Kiss, Inorg. Chem., 39 (2000) 4409.

[29] Y. Shechter, Diabetes, 39 (1990) 1.

[30] H. Sakurai, K. Tsuchiya, M. Nukatsuka, J. Kawada, S. Ishikawa, H. Yoshida,

M. Komatsu, J.Clin. Biochem. Nutr., 8 (1990) 193.

27

[31] H. Watanabe, M. Nakai, K. Komazawa, H. Sakurai, J. Med. Chem., 37 (1994)

876.

[32] H. Sakurai, K. Tsuchiya, M. Nukatsuka, J. Kawada, S. Ishikawa, H. Yoshida,

M. Komatsu, J. Clin. Biochem. Nutr., 8 (1990) 193.

[33] K. Kawabe, M. Tadokoro, Y. Kojima, Y. Fujisawa, H. Sakurai, Chem. Lett.,

(1998) 9.

[34] J. Li, G. Elberg,; D. C. Crans, Y. Shechter, Biochemistry, 35 (1996) 8314.

[35] J.H. McNeil, V.G.Yuen, H.R. Hoveyda, C. Orvig, J. Med. Chem. 35 (1992)

1489.

[36] D.C. Crans, J.J. Smee, E. Gaidamauskas, L. Yang, Chem. Rev., 104 (2004)

849.

[37] K.H. Thompson, B.D. Liboiron, Y. Sun, K.D.D. Bellman, I.A. Setyawati, B.O.

Patrick, V. Karunaratne, G. Rawji, J. Wheeler, K. Sutton, S. Bhanot, C.

Cassidy, J.H. McNeill, V.G.Yuen, C. Orvig, J. Biol. Inorg. Chem., 8 (2003)

66.

[38] H. Sigel, Inorg. Chem., 19 (1980) 1411.

[39] S.M. Humphrey, R.A. Mole, J.M. Rawson, P.T. Wood, Dalton Trans. (2004)

1670.

[40] R.H. Wang, D.Q. Yuan, F.L. Jiang, L. Han, S. Gao, M.C. Hong, Eur. J. Inorg.

Chem. (2006) 1649.

[41] E. Bugella-Altamirano, J.M. González-Pérez, A.G. Sicilia-Zafra, J. Niclós-

Gutiérrez, A. Castińeiras-Campos, Polyhedron, 19 (2000) 2463, and

references cited therein.

[42] C. Janiak, J. Chem. Soc., Dalton Trans. (2000) 3885, and references cited

therein.

28

[43] O. Yamauchi, A. Odani, M. Takani, J. Chem Soc., Dalton Trans. (2002) 3411.

[44] E. Bugella-Altamirano, D. Choquesillo-Lazarte, J. M. González-Pérez, M. J.

Sánchez-Moreno, R. Marín-Sánchez, J. D. Martín-Ramos, B. Covelo, R.

Carballo, A. Castińeiras, J. Niclós-Gutiérrez, Inorg. Chim. Acta, 339 (2002)

160.

[45] M. J. Sánchez-Moreno, D. Choquesillo-Lazarte, J. M. González-Pérez, R.

Carballo, A. Castińeiras, J. Niclós-Gutiérrez, Inorg. Chem.Commun., 5 (2002)

800.

[46] P. X. Rojas-González, A. Castińeiras, J. M. González-Pérez, D. Choquesillo-

Lazarte, J. Niclós-Gutiérrez, Inorg. Chem., 41 (2002) 6190.

[47] A. Castińeiras-Campos, J. D. Martín-Ramos, E. Bugella-Altamirano, J. M.

González-Pérez, D. Choquesillo-Lazarte, J. Niclós-Gutiérrez, X Italian-

Spanish Congress on Thermodynamics of Metal Complexes, Book of

Abstracts, S. Martinoal Cimino (Viterbo), Italy, C18 (1999).

[48] J.M. Lehn., Pure Appl. Chem., 50 (1978) 871.

[49] J.M. Lehn., Acc.Chem. Res., 11 (1978) 49.

[50] Y. Aoyama, M.R. Chira, G.R. Desiraju, J.P. Glusker, A.D. Hamilton, R.E.

Melendez, A. Nagina. Design of organic solids, (Eds.: Weber, E.), Springer,

Berlin, 1998.

[51] G.R. Desiraju, The crystal as a supramolecular Entity, Eds.: G. R. Desiraju,

Wiley, Chichester, Vol. 2, 1996.

[52] J. M. Lehn. Supramolecular Chemistry: concept and perspective; VCH:

Weinheim (Germany), 1995.

[53] R.H. Holm, P. Kennepohl, E.I. Solomon, Chem. Rev., 96 (1996) 2314.

[54] B.K. Wallar, J.D. Lipscomb, Chem. Rev., 96 (1996) 2625.

29

[55] P.M. Forster, N. Stock, A.K. Cheetham, Angew. Chem., Int. Ed., 44 (2005)

7608 (2005) 7608.

[56] P. Yang, M. Guo, Coord. Chem. Rev., 189 (1999) 185.

[57] S. Chaberek, A.E. Martell ‘Organic sequesting Agents’ Wiley, New York, 1959.

[58] J. Oakes, J. Chem. Soc., Dalton Trans., (1984) 1133.

[59] E. Soini, H. Kojola, Clin. Chem., 29 (1983) 65.

[60] T. Takeuchi, T. Nishikawa, R. Matsukawa, Matsui, J. Anal. Chem., 67 (1995)

2655.

[61] E. Soini, T. Lovgren, Crit. Rev. Anal. Chem., 18 (1987) 105.

[62] M. Li, P. R .Selvin,. J. Am. Chem. Soc., 117 (1995) 8132.

[63] M. Li, P. R. Selvin,. Bioconjugate Chem., 8, (1997) 127.

[64] Heyduk, E., Heyduk, T. Anal. Biochem., 248, (1997) 216.

[65] Blomberg, K., Hurskainen, P., I. Hemmila, Clin Chem., 45, (1999) 855.

[66] N. Kawasaki, Y. C. Lee, Anal. Biochem., 250, (1997) 260.

[67] Y. C Lee, N. Kawasaki, R.T. Lee, N. Suzuki, Glycobiology, 8, (1998) 849.

[68] G.D. Robinson, Prog Nucl Med, 4, (1978) 80.

[69] G.D. Robinson, F.W. Zielinski, A.W. Lee Int J Appl Radiat Isot 31, 2, (1980)

111.

[70] B. Maziere, O. Stulzaft, J.M. Verret, D..Comar, A .Syrota Int J Appl Radiat

Isot., 34, 3, (1983) 595.

[71] A. R. Jalilian, P. Rowshanfarzad, M. Sabet, M. Kamalidehgen, 51, 2, (2006)

111.

[72] G.E. Means, R. E. Feeney, Chemical Modification of Proteins. San Francisco,

Holden-Day Inc., 1971, 68.

[73] D. E. Hoarge, D.E.Koshland, J Biol Chem 242, (1967) 2447.

30

[74] G.E. Krejcarek, K.L. Tucker, Biochem. Biophy. Res. Comm., 77, (1977) 581.

[75] S.J.Wagner, M. J. Welch, J Nucl. Med., 20, (1979) 428.

[76] B.A.Khaw, J. T. Fallon, H.W. Strauss, Science, 209, (1980) 295.

[77] B.A. Khaw, H.W. Strauss, A. Corvalho et al, J. Nucl. Med.,23, (1982)1011.

[78] D.A. Scgeinberg, M. Strand, O.A. Gansow, Science, 215, (1982)1511.

[79] C. H. Paik, P. R. Murphy, W.C. Eckelman.etal., J Nucl. Med. 23, (1982) 37.

[80] C.H. Paik, P.R. Murphy, W.C. Eckelman, et al, J. Nucl. Med., (1983) 932.

[81] D.J. Hnatowich, W.W. Layne, R.L. Childs, J. Appi Radiat. Isot 33, (1982)

327.

[82] W.W. Layne, D.J. Hnatowich, P.W. Doherty, et al. J. Nucl. Med. 23, (1982)

627.

[83] C.H. Paik, M.A. Ebbert, C.R. Lassman, et al. Hybridoma 2, (1983) 126, (abst).

[84] R. B. Lauffer, Chem. Rev., (1987) 87, 901.

[85] S. C. Quay, U.S. Pat., 4 687 (1987) 659.

[86] D. D. Dischino, E. J. Delaney, J. E. Emswiler, G. T. Gaughan, J. S. Prasad, S.

K. Srivastava and M. F. Tweedle, Inorg, Chem., 30(1991) 1265.

[87] C. A. Chang, Invest. Radiol. (1993), 28, S21.

[88] K. Kumar, M. F. Tweedle, Pure Appl. Chem., 65 (1992) 515.

[89] K. Kumar, C. A. Chang, M. F. Tweedle, Inorg. Chem.,32 (1993)587.

[90] K. Kumar, M. F. Tweedle, Inorg. Chem., 32 (1993) 4183.

[91] K. Kumar, C. A. Chang, L. C. Francesconi, D. D. Dischino, M. F. Malley, J.

Z. Gougoutas, M. F. Tweedle, Inorg. Chem, 33 (1994)3567.

[92] K. Kumar, M. F. Tweedle, M. F. Malley, J. Z. Gougoutas, Inorg. Chem., 34

(1995) 6472.

[93] C. Paul-Roth, K. N. Raymond, Inorg. Chem., 34 (1995) 1408.

31

[94] H.-J. Weinmann, W.-R. Press, H. Gries, Invest. Radiol., 25 (1990) S49.

[95] M. F. Tweedle, J. J. Hagan, K. Kumar, S. Mantha, C. A. Chang, Magn. Reson.

Imaging, 9 (1991) 409.

[96] W. P. Cacheris, S. C. Quay, S. M. Rocklage, Magn. Reson. Imaging 8 (1990)

467.

[97] Y.M. Wang, T.H.Cheng, G.C. Liu, R. S.Sheu, J.Chem. Soc., Dalton Trans.

(1997) 833.

[98] M.F. Tweedle, M. F. In Lanthanide Probes in Life, Chemical, and Earth

Sciences: Biinzli. J.-C. G. Choppin. G. R. Eds., Elsevier: Amsterdam (1989);

Chapter 5.

[99] G. R. Choppin,. In Lanthanide Probes in Life, Chemical, and Earth Sciences;

J.-C. G. Bunzli, G. R. Choppin, Eds.; Elsevier: Amsterdam, (1989); Chapter 1.

[100] W. P Cacheris.; S. C. Quay, S . M. Rocklage,. Magn. Reson. Imaging 8,

(1990) 467.

[101] H. Gries, D.Rosenberg, H-J.Weinmann, U.S. Patent 4,647,447.

[102] G. R. Choppin, P. A. Baisden, S. A. Khan, Inorg. Chem., 18 (1979)1330

[103] C. F. G. C.Geraldes, A. D.Sherry, J. Magn. Reson., , 66, (1986) 274.

[104] B. G. Jenkins, R. B. Lauffer, Inorg. Chem., 27 (1988) 4703.

[105] S. Aime , M. Botta, Inorg. Chim. Acta., 177 (1990)101.

[106] (a) C. F. G. C. Geraldes, A. M. Urbano, M. C. Alpoim,; M. A. Hoefnagel, J.

A. Peters, J. Chem. Soc., Chem. Commun., 9 (1991) 656.

(b) C. F. G. C.Geraldes, A. M. Urbano,; M. A. Hoefnagel, J. A. Peters, Inorg.

Chem., 32, (1993) 2426.

[107] E. N. Rzkalla, G. R. Choppin, W. Cacheris, Inorg. Chem., 32, (1993)582.

[108] S. J. Franklin, K. N. Raymond, Inorg. Chem., 33, (1994) 5794.

32

[109] S. J. Coles, M.B. Hursthouse, D,G. Kelly, A.J. Toner, N.M.Walker, J.Chem.

Soc., Dalton Trans. (1988) 3489.

[110] S.Yamada, Coord. Chem. Rev. 537, (1999)109.

[111] A. A. Jarrahrahpour, M.Motamedifar, K.Pakshir, N.Hadi, M.Zarei, Molecules

9, (2004) 815.

[112] A. M. Mahindra, J. M. Fisher, Rabinovitz, Nature (London) 64 (1983) 303.

[113] P.R. Palet, B.T. Thaker, S. Zele,Indian J. Chem. 38 A (1999) 563.

[114] T.L.Yang, X.S.Tai, W., W. Qin, W.S. Liu, M.Y.Tan, Anal. Sci., 20 (2004)493.

[115] J.T. Groves, in : P. Ortez de Montellano(ED), Cytochrome P–450: Structures,

Mechanism and Biochemistry, Vol. 7, Plenum Press,New Yrk, (1986), P.1.

[116] W.C. Stalling, K. A. Pattridge, R.K. strong, M. L. Ludwig, J.Bio. Chem. 260

(1985) 16424.

[117] J. E. Halm, C.J. Bender, J.Am.Chem. Soc., 110, (1988) 7554.

[118] H. Wariishi, L. Akileswaran, M. H. Gold, Biochemistry, 27 (1988) 5365.

[119] A. Willing, H.Follman, G.Auling, Eur. J.Biochem.,70 (1998) 603.

[120] V.L. Pecoraro, Photochem. Photobiol.,48 (1988) 249.

[121] Wieghardt, K.Agnew. Chem, Int Ed. Engl, 22 (1989) 328.

[122] C. E. Dube, D.W. Wright, S.Pal, Jr. P. J. Bonitatebus, W. H. Armstrong, J.Am.

Chem. Soc., 120 (1998)3704.

[123] L. Stelzig, B.Donnadieu, J. P. Tuchagues, Angrew. Chem. Int. Ed. Engl., 36

(1997) 2221.

[124] L. Stelzig, A. Steiner, B. Chansou, J. P. Tuchagues, Chem. Commun. (1998)

771.

[125] O. Horner, M. F. Charlot, A.Boussac, E. Anxolabehere- Mallart,

L.Tchertanov, J. Guilhem, J. J. Gorered, Eur. J. Inorg. Chem. (1998) 721.

33

[126] M. Hirotsu, M. Kojima, Y. Yoshikawa, Bull. Chem. Soc. Jpn., 70 (1997) 649.

[127] S.Theil, R. Yerande, R. Chikate, F. Dahan, A. Bousseksou, S. Padhye and J. P.

Tuchagies, Inorg. Chem., 36 (1997) 6279.

[128] J.W. Gohdes, W. H. Armstrong, Inorg. Chem., 31 (1992) 368.

[129] E. Larson, M.S. Lah, X. Li, V.L. Pecoraro, Inorg. Chem., 31 (1992) 373.

[130] F.M. Ashmawy, C.W. McAuli, R.V. Parish, J. Tames, J.Chem. Soc., Chem.

Commun., 14 (1984).

[131] F.M. Ashmawy, C.W. McAuli, R.V. Parish, J. Tames, J. Chem. Soc., Dalton

Trans. (1985) 1391.

[132] N. Aurangzeb, C.E. Hulme, C.A. McAuli, R. G. Pritchard, J. Sanmartin and A.

Sousa, J. Chem. Soc., Chem. Commun., (1994) 1153.

[133] M. Watkinson, A. Whriting, C. A. McAulie, J.Chem,. Soc., Chem Commun.,

(1994) 2141.

[134] C. Zhang, J. Sun, X. Kong, C.Zhao, J. Chem. Crystallogr., 29 (1999) 203.

[135] M. Mikuriya, N. Torihara, H. Okawa, S.Kida, Bull. Chem. Soc. Jpn., 54

(1981) 1063.

[136] C. Zhang, Q. Zhou, Q.Meng, D. Xu, Y. Xu, Synth. React. Inorg. Met.-org.

Chem., 29 (1999) 865.

[137] C.G. Zhang,G. H. Tian, B. Liu, Trans. Met. Chem. 25 (2000) 377.

[138] P. Artus, C. Boskovic, J. Yoo, W. E. Streib, L. C. Brunel,. D. N.

Hendrickson, J. Christou, Inorg. Chem. 17, 40 (2001), 4199.

[139] S. M. J. Aubin, M. G. Wemple, D. M Adams, H. L Tsai, G. Christou, D. N.

Hendrickson. J. Am. Chem. Soc. 33, 18 (1996) 7746.

[140] N. Hoshino, T . Ito, M . Nihei, H. Oshio, Chem. Lett. 8, 31 (2002), 844.

34

[141] H. Liu, H. Wang, D. Niu, Z. Lu, J. Sun, Synth. and React. in Inorg., Met.-Org.

and Nano-Met. Chem., 35 (2005) 233.