February 2011, Volume 2, No.

1
International Journal of Chemical and Environmental Engineering

Stability and Molecular Structure of Some

Vanadium Complexes Effective in Biological
Systems: a Quantum Mechanical Study
R. Hakimelahi a
a
Department of Chemistry, Islamic Azad university,Jahrom branch,Iran.
*
Corresponding Author Email: hakimelahi@jia.ac.ir

Abstract
Some important vanadium(V), vanadium(III) and vanadyl complexes with bidentate, tridentate and four-dentate ligands in different
coordination modes which are effective in several biological systems, especially as insulin mimetic agents are investigated. Due to
importance of adequate thermodynamic stability for Vanadium compounds as insulin enhancing agents, the stability of these
complexes are calculated . Quantum mechanical methods are used and the results show that vanadyl complexes which have
phenolate, alcoholate, carboxylate especially when these donors join to a Schiff base donor, constitute the most stable complexes, it is
clear that a four-dentate ligand with these donors is much more effective in stability. Deprotonated amide group with phenolate or
carboxylate form very stable vanadyl complexes but amine or thiolate groups without any interference of Schiff base, phenolate,
alcoholate or carboxylate donors, form less stable vanadyl complexes.

Keywords: Vanadium complexes; Biological systems; Quantum mechanic; Stabilization energy; Geometry optimization.

1. Introduction 1, and [VO(O2)2(L-L')]n-, n=1, 2 or 3). Coordinating

Vanadium is an important nutrient for most higher
animals and is known to be essential for certain
organisms, including tunicates, some fungi and bacteria
[1]. Although its essentiality for human life has not yet
been clearly established, it does generate significant
physiological responses; for example, vanadate inhibits a
number of enzymes, such as ion transport ATP-ases,
phosphotyrosine phosphatase, etc. [2]. Vanadium
coordination chemistry and biochemistry have attracted
increasing interest during the last few years[3].Vanadium,
participates in enzymatic reactions such as halogenation
of a variety of organic substrates by haloperoxidases[4]
and nitrogen fixation by vanadium nitrogeneses[5].
Oxovanadium(IV) complexes have been shown to
catalyze a variety of reactions such as the oxidation of
alcohols and the conversion of sulphide to sulphur oxides
and sulfones[6]. Vanadium compounds show interesting
biochemical and pharmacological properties [7]. Intensive
studies carried out over the last two decades[8] showed
that vanadium is one of the most important supplements
for oral diabetes therapy [9,10].
Three general classes of vanadium-containing
compounds are of interest for their utility as insulin-
mimetic agents: (1) inorganic vanadium, both anionic
(vanadate, [VO4]3-) and cationic (vanadyl, VO2+), (2)
coordination complexes, mostly of the general type
VOL2, and (3) peroxovanadium complexes (mono- and
di-peroxovanadates, [VO(O2)(H2O)2(L-L')]n-, n = 0 or
ligands have specifically been chosen or designed to
improve substantially the absorption, tissue uptake, and
intracellular mobility of vanadium, thereby reducing the
dose required for optimal insulin enhancement. Inorganic
vanadium salts are poorly absorbed from the digestive
system, thus high oral doses are required. Therefore,
various vanadium ions – organic ligands complexes were
tested in order to obtain more potent medicines than
inorganic vanadium salts [11,12]. For vanadium to be
useful as an orally available insulin mimetic agent(IMA)
it must be able to cross biological membranes, both for
the initial absorption process and for intracellular uptake
for vanadium in a complex the metallocomplex must have
no positive or negative charge, and a fair degree of
resistance to hydrolysis. A high synthetic yield and
known non–toxic metabolic products are advantageous.
The lipophilicity of the complex must be balanced with its
hydrophilicity. Moreover, the metal–ligand complex
should possess adequate thermodynamic stability[13].
several types of vanadyl complexes with different
coordination modes such as VO(O4), VO(N4), VO(S4),
VO(O2N2), VO(S2N2 ) and VO(O2S2) have been
developed [14]. The aim of the present study is try to
recognition of coordination modes effect on the
vanadium complexes stability via ab initio calculations,
HF(Hartree-Fock calculations) and DFT(a quantum
mechanics calculation level).
 2. Material and Methods: providing active sites capable of binding other
Quantum mechanical calculations have been molecules[20].
established for years as proper tools for the determination
O
of the chemical compounds structures. In this work, O
various structures of vanadium complexes were N V
O
examined. Single point energy calculations were
N
performed for input geometries of the complexes. Two
different levels of theory were used : Hartree-Fock(HF) N
and Density Functional Theory(DFT) with B3LYP(Beck's
Three Parameter Hybrid Functional Using the LYP 2
correlation Functional)[15] methods using the associated Complex 3 is similar to complex 2, as well as the
LANL2DZ[16,17] for vanadium element and 6-31G* for calculated energy. Schiff base complexes of vanadium
all other atoms in the ligands. The overall trend in the (VIII, VIV, VV) use as catalyst. In another research, we
DFT energies is similar to the HF results, with a small synthesized a schiff base vanadyl complex from reaction
variation in the energy values among the exchange of bis (acetylacetonate) oxovanadium(IV) and D-
correlation functional used. So stabilization energies for penicillamine(β,β- dimethyl cysteine) [21]. It has( N2O2)
different vanadium complexes with assorted coordination coordination mode with imine nitrogen and after
modes were dedicated. optimization, it prefers trans geometry, Calculation of
Calculations were executed using the GAUSSIAN98 stabilization energy shows that complex 4 is more stable
quantum mechanical package[18]. Furthermore, the than 1,2 and 3.
results of calculations were showed the extent of the O O
interaction between vanadium ion and all other donors
V O
which were useful for justification of the competition N
between different groups in a ligand to coordinate to N
vanadium ion. H
H

3. Results and Discussion: N

Vanadium complexes which are neutral, are more
common as a good insulin enhancing, but in this research, 3
certain negative complexes have been studied too; for Complex 4 is VOL2 that L is:
example complex1 has two negative charge, it has a four-
dentate ligand, coordination mode is (N2O2), it has a high CH3 CH3
O
stability because phenolate and deprotonated amide
groups have been linked to vanadyl ion. Complex 1 acts O C CH C N CH C OH
as a catalyst(vanadium halo peroxidase )[19]. Oxo and
dioxo-vanadium(V) complexes based on ligands with CH3 C CH3
oxygen and nitrogen donor atoms, contain the largest
number of compounds. Within this class, the Schiff base SH
compounds are the largest group. Complex 2 is a
dioxovanadium(V) with a tridentate ligand, it has been
distinguished that at least two or three oxygen donor is
necessary to get suitable stability as a catalyst[19]. This
complex is a Schiff base complex too, so is a very
stable complex.

2- 4
D-penicillamine(D-H2Pen) in a weak alkali pH
O
O
converts to HPen¯ and with vanadyl ion (VO2+) can form
VO(HPen)2, a complex with (N2O2) coordination mode
N O N
and trans geometry(complex 5), but its stability is less
V than Schiff base complexes; such as 4.
O O
1

Schiff base ligands are of particular interest, because

they provide coordination environments which efficiency
stabilize different oxidation states of vanadium, while still

77
 O
H H

NO N
H C
H
H H V
N O H H
H C C
C
H
H
C

C
C
H O N
HC
OC
S
V
O H
C H
H H
H
H O O
H
S
5
9
Two complxes of V(III) has been reported[22], one of A phenolate anion constitutes a more stable complex
them corresponds to a six-coordination VIII complex with than a β-diketone and related derivatives as bis(3-methyl-
the VIII center coordination to three carboxylate oxygen 2,4-pentanedionato)oxovanadium(IV) (complex 11), so
and three amine nitrogen atoms provided by three HCys¯ complex 10, bis(maltolato)oxovanadium(IV) , is more
chelating ligand, [VIII(HCys)3](complex6), the structurally stable than 11.
characterized [VIII(Cys)2]¯ (complex7) species shows that
the vanadium(III) atom is ligated to two tridentate Cys2-
O
ligands at the Namine, Sthiolato, Ocarboxylato atoms. O O
O
The calculations show that complex 6 is more stable V
than complex 7. A vanadyl complex with coordination O
O O
mode of (N4), bis(metforminato) oxovanadium (IV)
(complex8), is a stable Schiff base vanadyl 10
complex.Complex 9 is a vanadyl complex including a
O
four-dentate ligand, with(N2O2) O O
V
SH
O O
H2C O

NH2 O 11
O
III
Bis (histidinato)oxovanadium(IV) (complex 12) is a
O V N CH2
H2 very stable complex, it has (N2O2) coordination mode
H2N O SH with carboxylate oxygen and amine nitrogen groups.

O
H2 O O
HS CH2
N O N
HN N NH
6 V
O O N
H2
H2 H2
S N N S 12
III

H2C CH V CH CH2 Bis(pyridine-2-carboxylato)oxovanadium(IV) or

O O VO(pic)2 with (N2O2) coordination mode(complex 13) is
more stable than complex 14 and 15.
O O O
7 O
O N
V
coordination mode which has Schiff base and phenolate N O
O
groups, [N,N'–bis(salicylidene)ethane-1,2-diaminato], is a
very stable complex too. 13

O H O
N NH2 N N
O
N N V
N N N
N V H O
N N
H2N N 14
8 O
O O OH2
V
N OH2
COOH

15
78
 A variety of coordination spheres of vanadium(IV) sulphur coordination occurs with macromolecules in
and thio-ligands have been synthesized by simple biological systems , or even with small molecules such as
methods. For example, vanadyl bis(cysteinate methyl dimercaptosuccinic acid, which forms a complex with
ester)[23]. This complex (complex 16) has been found to (S4) coordination mode at high pH. In recent decade,
be a five coordinate vanadium(IV) complex, with a square detailed solution speciation and structural studies of
pyramidal geometry; its stability is compared with some numerous oxovanadium(IV) /oligopeptide systems
other complexes which have thio-ligands; such as and
complex 17,18,19. All of them are less stable than
complexes with coordination modes of (N2O2), (O4) and
Table 1. Relative stabilization energy of vanadium complexes
(N4). During geometry optimization, complex 16 prefers
(kcal mol-1)
trans configuration.
Complex Number Relative Energy (E× 104)
O O 18 0
O 7 -3.12
NH2 H2N
MeO OMe 17 -7.9
V 16 -12.7
S S 19 -13.8
15 -14.8
O
5 -17.7
H 14 -18.3
S

H H
H N V
11 -19.3
H H
C O

C C
C
H 8 -20.4
C S C
H
O H
HN
H
13 -20.8
H
H C
O
9 -21.2
O

H
10 -23.4
H
C
6 -24.1
H
2 -29.2
3 -29.4
16 12 -34.8
O 1 -40.1
O S 4 -51.3
N Calculations executed at the B3LYP/LANL2DZ level
V
N a critical survey of the relevant literatures have
S O revealed that a number of factors influence the
17 oxovanadium(IV) binding properties of peptide
Complex 17 [bis(1-oxido-2- pyridinethiolato) molecules. The strength of the coordination has been
oxovanadium (IV)] and 18 [oxobis(pyrrolidine-N- found to be largely determined by the possibility of
carbodithioato) vanadium (IV)] have (S2O2) and ( S4) participation of the amide-N in metal ion binding. This is
coordination modes respectively. affected primarily by the nature of the anchoring donor,
according to the following sequence:
O phenolate-O¯ >/alcoholate-O¯> thiolate-
S S
N V N S¯>/carboxylate-COO¯ > /NH2. This sequence is finely
S S tuned by the presence of additional donors in the
18 molecule[25].
H3C O CH3 This work has been an attempt to determine the
S S
O N V N O stability of vanadium complexes. Table1 shows the
C H2C S S CH2 C relative energy of described complexes, the energy of the
O
O least stable one (complex18) has been assumed zero and
19 the others have been compared with it. Results of HF and
B3LYP computational methods, show similar
Complex 18 is less stable than 16 and 17 and 19. stabilization energies, so just B3LYP results have been
Complex 19 shows when thiolate anions are in a ligand, reported. The results show, nevertheless vanadyl ion gives
these donors have more tendency to coordinate to vanadyl priority to thiolate anion than carboxylate and amine
ion than carboxylate or amine groups. donors as it has been observed in complex 19 , but it does
According to Pearson’s HSAB (hard and soft acids and not mean thiolate donors constitute very stable
bases) rule [24], vanadium in oxidation states +/4 and +5 complexes. As the calculations show complex 12 is much
is considered a rather hard metal ion, which prefers more stable than 19. The computational calculations
coordination to O donors, and especially to negatively report condensation magnitude of all atoms to vanadium
charged O donors, such as carboxylate or phenolate. ion, in some complexes that N, O and S donors are seen
According to the hard-soft theory, its coordination to soft for example in 7 , thiolate anion has stronger interaction
sulphur donors is expected to be fairly weak, although than carboxylate anion and amine nitrogen. In 1 , a

79
 vanadyl complex as N2O2 coordination mode with amide
nitrogen and phenolate oxygen donors, nitrogen
interaction is as well as oxygen interaction to vanadyl
ion. 12 is a complex as type N2O2, with carboxylate
oxygen and amine nitrogen which oxygen interaction to
vanadyl is stronger than nitrogen. In 16, a vanadyl
complex with S2N2 coordination mode, thiolate
interaction is stronger than amine nitrogen but
stabilization energies show that 16 is more stable than 18
with (S4) coordination mode.
4. Conclusion:
In this work, the stabilization energy of various
vanadium complexes shows that not only the difference
between coordination modes affects the stability of the
complexes, but also the essence of donors is very
important. Complexs with N2O2 coordination mode might
have various navigate and stability due to nitrogen donor
can be an amine, imine, amide, imide type and so on, also
oxygen donor can be phenolate, alcoholate, carboxylate or
other type too. A number of factors influence the
oxovanadium(IV) binding properties to different ligands.
Vanadyl ion gives priority to thiolate anion than
carboxylate and amine donors although vanadyl ion is
considered a rather hard metal ion and seems that it
prefers coordination to O donors, and especially to
negatively charged O donors such as phenolate,
alcoholate and carboxylate but thiolate anion acts as
stronger anchoring donor and has stronger interaction to
vanadyl ion than carboxylate ion so in a competition
between amine nitrogen, carboxylate oxygen and thiolate
anion for coordination to a vanadyl ion, thiolate shows a
distinct preference and carboxylate oxygen has second
rank but it never means that a thiolate vanadyl complex
(S4 coordination mode) is very stable. The quantum
mechanical calculations show that vanadyl complexes which
have just thiolate donors or have only amine and thiolate groups
without any other donors such as carboxylate, alcoholate or
phenolate , form less stable complexes. In contrast vanadyl
complexes with phenolate, alcoholate or carboxylate especially
when a Schiff base donor is in the complex , constitute the most
stable complexes. Deprotonated amide group with phenolate or
carboxylate form very stable vanadyl complexes too.
ACKNOWLEDGMENT
The support of the science department of Jahrom azad
university is gratefully acknowledged.
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