Structural models of vanadate-dependent haloperoxidases, their reactivity, immobilization on polymer support and catalytic activities

Article abstract of DOI:10.1007/s12039-011-0114-3

The design of structural and functional models of enzymes vanadate-dependent haloperoxidases (VHPO) and the isolation and/or generation of species having {VO(H₂O)}, {VO₂}, {VO(OH)} and {VO(O ₂)} cores, proposed as intermediate(s) during catalytic action, in solution have been studied. Catalytic potential of these complexes have been tested for oxo-transfer as well as oxidative bromination and sulfide oxidation reactions. Some of the oxidovanadium(IV) and dioxidovanadium(V) complexes have been immobilized on polymer support in order to improve their recycle ability during catalytic activities and turn over number. The formulations of the polymer-anchored complexes are based on the respective neat complexes and conclusions drawn from the various characterization studies. These catalysts have successfully been used for all catalytic reactions mentioned above. These catalysts are stable and recyclable. Indian Academy of Sciences.

Full text of DOI:10.1007/s12039-011-0114-3

c
J. Chem. Sci. Vol. 123, No. 2, March 2011, pp. 215–228. ꢀ Indian Academy of Sciences.
Structural models of vanadate-dependent haloperoxidases, their
reactivity, immobilization on polymer support and catalytic activities
MANNAR R MAURYA∗
Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667, India
e-mail: rkmanfcy@iitr.ernet.in
Abstract. The design of structural and functional models of enzymes vanadate-dependent haloperoxidases
(VHPO) and the isolation and/or generation of species having {VO(H2O)}, {VO2}, {VO(OH)} and {VO(O2)}
cores, proposed as intermediate(s) during catalytic action, in solution have been studied. Catalytic potential
of these complexes have been tested for oxo-transfer as well as oxidative bromination and sulfide oxidation
reactions. Some of the oxidovanadium(IV) and dioxidovanadium(V) complexes have been immobilized on
polymer support in order to improve their recycle ability during catalytic activities and turn over number. The
formulations of the polymer-anchored complexes are based on the respective neat complexes and conclusions
drawn from the various characterization studies. These catalysts have successfully been used for all catalytic
reactions mentioned above. These catalysts are stable and recyclable.
Keywords. Vanadium complexes; haloperoxidases; structural models; functional models; catalysts.
1. Introduction
chain of the protein where vanadium is in a trigonal-
bipyramidal environment, with the imidazole-N and an
OH− in the axial positions.5–7
Discovery of vanadium(V) in the active site of
vanadate-dependent enzymes, vanadium haloperoxi-
dases1–3 isolated from various sea algae4 and terres-
trial fungi, has stimulated research on the coordina-
tion chemistry of vanadium. These enzymes catalyse
the oxidation of halides (X−), by peroxide as oxidant,
to hypohalous acid (HOX) which further halogenates
hydrocarbons non-enzymatically according to (1)
and (2).
Many vanadium complexes provide a suitable struc-
tural and/or functional model for these enzymes.8–10
Oxidations of aliphatic as well as aromatic sub-
strates11–14 including organic sulfides to sulfoxides,15,16
catalysed by vanadium complexes, have also been
achieved in excellent yield. Recently, we have directed
our investigations into the coordination chemistry of
vanadium in its higher oxidation states. Novel struc-
tural features and reactivity patterns of these complexes
present model character for VHPO. The catalytic poten-
tial of oxidovanadium(IV) and dioxidovanadium(V)
complexes as mimics for the catalytic activity of VHPO
and oxidation of other organic substrates have also been
studied.
Generally, these functional models are homogeneous
in nature and decompose during the catalytic action
and thus are not suitable for potential industrial appli-
cations. The stability and recycle ability of these com-
plexes have been improved by immobilizing them onto
polymer support. For the development of industrial pro-
cesses, such modifications to model complexes acting
as homogeneous catalysts would be very important and
this, in addition, would lead to operational flexibility of
the catalyst as well.
X− + H2O2 + H+ → HOX + H2O,
(1)
X− = Cl−, Br− and I−,
HOX + RH → RX + H2O,
(2)
RH = organic substrates, RX = halogenated products.
They also catalyse the oxidation of sulfide to sulfox-
ide, as
RSRꢁ + H2O2 → RS(O)Rꢁ + H2O.
The active centre of vanadate-dependent haloperox-
idases (VHPO) is constituted by vanadate(V) cova-
lently linked to the imidazole moiety of a histidine side-
(3)
∗For correspondence
215

216
Mannar R Maurya
2. Structural models of haloperoxidases
aerial oxidation. Reaction of 4 with H2O2 in methanol
resulted in the formation of oxidoperoxidovanadium(V)
Reaction of [VO(acac)2] and benzimidazole derived lig- complex [VVO(O2)(sal-aebmz)] (7).
ands Hsal-ambmz (I) or Hsal-aebmz (II) (scheme 1)
The existence of two sharp bands in the 888–
in dry, refluxing methanol gave the brown oxidovana- 958 cm−1 region in dioxidovanadium(V) complexes
dium(IV) complexes [VIVO(acac)(sal-ambmz)] (1) or suggested a cis–VO2 arrangement.10 The 51V NMR
[VIVO(acac)(sal-aebmz)] (2), respectively. Aerial oxi- spectral data of the complexes 3, 4 and 5 show one
dation of 1 and 2 in methanol, yielded the dioxi- strong resonance in the range δ = −540 and −568 ppm
dovanadium(V) complexes [VVO2(sal-ambmz)] (3) and due to a mixed O/N donor coordination.18 These com-
[VVO2(sal-aebmz)] (4), respectively. Further, 3 and 4 plexes can be considered as structural models of VHPO
were obtained from the reaction of the respective lig- as they attain a trigonal bipyramid geometry with
and with aerially oxidized solution of [VO(acac)2] in slight distortion towards the square pyramid, confirmed
methanol. Aerial oxidation of the filtrate obtained after by single crystal X-ray diffraction studies. The τ-
separating 1 resulted in the formation of [VVO2(acac- parameters amount to 0.61–0.71, and the bzm-N and O
ambmz)] (5) and the known complex [VIVO(sal-phen)] of the acac/sal moiety are in the axis.
(6). Apparently, the formations of these complexes pro-
A solution of potassium vanadate generated in
ceed through a complex reaction pattern as depicted in situ by dissolving V2O5 in aqueous KOH, reacts
scheme 1.17 The complex [VVO2(acac-ambmz)] (5) can with the potassium salts of H2sal-inh (III), H2sal-
also be prepared directly by reacting [VO(acac)2] with nah (IV) and H2sal-fah (V) (scheme 2) at pH ca.
2-aminomethylbenzimidazole (ambmz) followed by 7.5 to give the corresponding dioxidovanadium(V)
N
OH
N
NH
O
N
NH
[VO(acac)2]
O2
V
O
O
V
N
N
N
N
O
O
N
H
O
O
Hsal-ambmz (I)
3
Filtrate
O2
1
H2N
[VO(acac)2], O2
O
O
O
N
V
V
O
N
H
NH
+
O
N
N
N
ambmz
O
6
5
N
N
OH
O
NH
N
[
NH
VO(acac)2]
O
V
N
O2
O
V
N
N
O
O
O
N
H
O
4
Hsal-aebmz (II)
2
H2O2
NH
N
O
V
O
N
O
O
7
Scheme 1. Synthesis of vanadium complexes.17

Structural models of vanadate-dependent haloperoxidases, their reactivity, immobilization on polymer support 217
1.5
OH
N
OH
N
O
O
N
N
N
H
H
N
1.0
0.5
0.0
0.3
0.2
0.1
0.0
H2sal-nah (IV)
H2sal-inh (III)
OH
O
N
N
H
O
350
400
450
250
300
350
400
450
500
H2sal-fah (V)
Wavelength (nm)
Scheme 2. Ligands used for the synthesis of vanadium
complexes.
Figure 1. Titration of [VVO2(sal-aebmz)] (4) with 30%
H2O2 in MeOH. The spectra were recorded after successive
addition of 1-drop portions of H2O2 dissolved in MeOH to
10 mL of a ca. 1 × 10−4 M solution of 4.17
complexes, K[VVO2(sal-inh)]·H2O (8), K[VVO2(sal-
nah)]·H2O (9), and K[VVO2(sal-fah)]·H2O (10).19,20
Aqueous solutions of 9, and 10 further react with
HClO4 to yield the neutral complexes [VVO2(Hsal-
nah)] (11) and [VVO2(Hsal-fah)](12), respectively, in
which one of the nitrogens of the =N−N= group is
protonated as shown by (4). Such complexes have also
been reported by Plass et al.21
(a)
2.0
ꢀ
ꢁ
ꢀ
ꢁ
1.5
0.04
K VVO2L · H2O + HClO4 → VVO2 (HL)
+ KClO4 + H2O
0.03
(4)
0.02
1.0
(H2L = IV : 11; H2L = V : 12).
0.01
0.00
Slow crystallisation of these protonated complexes
from excess methanol causes the removal of the proton
from the NH group and conversion to the methoxido-
oxidovanadium(V) complexes 13 and 14, scheme 3.
The formation of complexes 13 and 14 from the cor-
responding neutral dioxidovanadium(V) complexes in
methanol is of interest in the context of vanadium com-
plexes used as oxo-transfer agents both in catalytic and
stoichiometric oxygenation reactions.22
400
450
500
0.5
0.0
250
300
350
400
450
500
Wavelength (nm)
(b)
2.0
1.5
1.0
0.5
0.0
Conversion of 4 into the peroxido complex 7 by the
treatment with H2O2 represents the formation of an
intermediate similar to that found in the catalytic cycle
0.2
0.1
0.0
O
V
O
V
350 400 450 500
O
O
OMe
O
O
MeOH
OMe
O
N
N
H
250
300
350
400
450
HN
N
Wavelength (nm)
R
R
R = 3-pyridyl (13)
R = 3-pyridyl (11)
2-furyl (12)
2-furyl (14)
Figure 2. Titration of [VVO2(sal-aebmz)] (4) with HCl in
MeOH. The spectra were recorded after successive addition
Scheme 3. Reaction of dioxidovanadium(V) complexes of 1-drop portions of HCl to 10 mL of ca. 10−4 M solution
with MeOH.22
of 4.17

218
Mannar R Maurya
2+
NH
+
N
V
N
V
N
NH
HCl
HCl
NH
O
V
N
O
O
N
N
MeOH
MeOH
H
H
HO
O
O
O
O
O
Scheme 4. Reaction of [VVO2(sal-aebmz)] with HCl dissolved in MeOH.17
O
O
O
O
O
NH
NH
V
N
N
V
MeOH / O2
H2O2
O
N
O
N
16
15
Scheme 5. Oxidation of [VIVO(acac)(sal-his)] by aerial oxygen in MeOH.28
of VHPO.23 The stability of 7 is poor and decomposes of 4 in the electronic absorption spectra; figure 2. In
slowly at room temperature. However, freshly prepared the first set, the band at 405 nm shows a slight broad-
and dried sample shows three IR active vibrational ening with a decrease in intensity (inset in figure 2(a)),
modes associated with the peroxido moiety {V(O2)3+} while the intensity and band position of 313 nm band
at 878, 755 and 614 cm−1, and these are assigned to remains constant. With an increase in intensity, the
the O–O intra-stretch (ν1), the antisymmetric V(O2) band at 252 nm registers no change, the 273 nm band
stretch (ν3), and the symmetric V(O2) stretch (ν2), shifts to 276 nm, with increase in intensity, while the
respectively. The presence of these bands confirms the 281 nm band exhibits a gradual shift towards 280 nm
common η2-coordination of the peroxido group.24 In with decrease in intensity. The second set of spectral
addition, the complex exhibits an intense ν(V = O) pattern starts on addition of more HCl and are presented
stretch at 965 cm−1.25 The formation of the peroxido in figure 2(b). These spectral changes have been inter-
complex 7 has also been established in solution by the preted in terms of the formation of an oxidohydroxido
treatment of 4 with H2O2 and following the changes complex of composition [VVO(OH)(sal-aebmz)]2+ via
by electronic absorption spectroscopy. Thus, drop-wise [VVO2(sal-aebmzH)]+, scheme 4.
addition of aqueous 30% H2O2 dissolved in methanol
The solution acquired the original spectral pattern on
to 10 mL of a ca. 10−4 M solution of 4 resulted in spec- addition of a methanolic solution of KOH; the reaction
tral changes as presented in figure 1. The band appear- is thus reversible. This reversibility is an important
ing at 405 nm slowly broadens (see inset of figure 1), observation in the context of the active site structure and
while the band at 313 nm shifts to 321 nm along with the catalytic activity of vanadate-dependent haloper-
a decrease in intensity. Concomitantly, the bands at oxidases, for which a hydroxido-ligand at the vana-
273 and 281 nm split into three bands and appear at dium centre has been made plausible on the basis of
269, 276 and 279 nm along with a marginal decrease X-ray diffraction data.23,26 The generation of similar
in intensity. With considerable loss in intensity, the oxido-hydroxidovanadium complexes on acidification
212 nm band remains constant, while the 252 nm band of K[VVO2(sal-inh)]·H2O (8), K[VVO2(sal-nah)]·H2O
shifts marginally to 256 nm. The final spectrum is (9) and K[VVO2(sal-fah)]·H2O (10) has also been
similar to that recorded for the isolated peroxido demonstrated.
complex 7.
The oxidovanadium(IV) complex [VIVO(acac)(sal-
Model studies have also been carried out for pro- his)] (15) (where Hsal-his, VI = Schiff base derived
tonating and deprotonating the complex [VVO2(sal- from salicylaldehyde and histidine) has been reported
aebmz)] (4). At least two sets of spectral patterns were by Cornman et al.27 Aerial oxidation of 15 in the pres-
observed on addition of methanolic HCl to a solution ence of a few drops of aqueous 30% H2O2 results in the

Structural models of vanadate-dependent haloperoxidases, their reactivity, immobilization on polymer support 219
formation of dioxidovanadium(V) complex [VVO2(sal- to an oxidoperoxidovanadium(V), and the appearance
his)] (16), scheme 5.28 Solution of 15 in methanol is of a weak but new band at ca. 425 nm is probably due to
also sensitive towards the addition of H2O2, as mon- a LMCT band of the monoperoxido complex. The spec-
itored by electronic absorption spectroscopy, yielding tral changes during a similar titration of 16 in methanol
oxidoperoxido species; figure 3. Thus, the progressive with H2O2 (diluted in methanol) demonstrate the for-
addition of a dilute H2O2 solution in methanol to a solu- mation of same oxidoperoxidovanadium(V) species.
tion of 15 in methanol results first in flattening of the d–
Similarly, the reaction of [VO(acac)2] with an
d band appearing at 776 nm and finally disappears. The equimolar amount of Hsal-aepy (Hsal-aepy, VII =
532 nm band slowly broadens with increase in intensity Schiff base derived from salicylaldehyde and 2-
and finally disappears. The band at 382 nm gradually aminoethylpyridine or Hsal-dmen (Hsal-dmen, VIII =
shifts to 394. At the same time two new bands appear Schiff base derived from salicylaldehyde and N,N-
at 319 and 257 nm, while the intensity of the 265 nm dimethylethylenediamine) in solvent at room tem-
band also increases. The disappearance of d–d bands is perature yielded the oxidovanadium(IV) complexes
in accordance with the oxidation of the VIVO-complex [VIVO(acac)(sal-aepy)] (17) and [VIVO(acac)(sal-
dmen)] (19), respectively. Complexes [VVO2(sal-aepy)]
(18) and [VVO2(sal-dmen)] (20) were then obtained by
aerobic oxidation of 17 and 19, respectively, in solvent
in the presence of a small amount of H2O2, scheme 6.
Single crystal X-ray diffraction studies confirm the
mononuclear distorted octahedral structure for 1729
and 1930 while distorted square pyramidal for 20.30
(a)
1.5
1.0
0.5
0.0
3. Immobilization of model vanadium complexes
on polymer support
Immobilization of active metal complexes has evolved
as a promising strategy for combining the advantages of
homogeneous as well as heterogeneous catalysts, due
to their easy separation from the products by simple fil-
tration, and to meet the industrial demand of recycla-
bility for continuous operation.31,32 Catalytic potentials
of polymer-immobilized metal complexes in organic
transformations have been reviewed in detail by several
groups.33–37
Various methods have been followed, depending on
the nature of ligand, for immobilization of model vana-
dium complexes on polymer support. Reaction of imi-
dazolomethylpolystyrene (PS-im) with dioxidovana-
dium(V) complexes K[VVO2(sal-inh)]·H2O (8) and
K[VVO2(sal-fah)]·H2O (10) dissolve in DMF gave imi-
dazolomethylpolystyrene bound dioxidovanadium(V)
complexes, PS-K[VVO2(sal-inh)(im)] (21) and PS-
K[VVO2(sal-bhz)(im)] (22), respectively, scheme 7.38
The energy dispersive X-ray (EDX) analyses supported
the presence of 1.2% and 1.0% vanadium in 21 and 22,
respectively.
400
500
600
700
800
900
Wavelength (nm)
(b)
1.2
1.0
0.8
0.6
0.4
0.2
0.0
0.20
0.15
0.10
0.05
0.00
350 400 450 500
300
200
300
400
500
Wavelength (nm)
Figure 3. UV-Vis spectral changes observed during titra-
tion of [VIVO(acac)(sal-his)] (15) with H2O2. (a) The spec-
tra were recorded after successive additions of one drop por-
tions of H2O2 (6.6 × 10−4 mmol of 30% H2O2 dissolved in
10 mL of methanol) to 50 mL of ca. 10−3 M solution of 15
in methanol. (b) The equivalent titration, but with lower con-
centrations of a 15 solution (ca. 10−4 M); the inset shows an
enlargement of the 300–500 nm region.28
Immobilization of [VIVO(acac)(sal-his)] (15) to give
PS–[VIVO(acac)(sal-his)] (23) involved the reaction
of Hsal-his (VI) with chloromethylated polystyrene,
cross-linked with 5% divinylbenzene in DMF in the
presence of triethylamine followed by reaction of

220
Mannar R Maurya
O
O
O
O
O
V
V
OH
O
O
N
N
CH3CN
N
MeOH
N
N
N
H2O2, O2
VO(acac)2
17
18
Hsal-aepy (VII)
O
O
O
O
V
OH
N
N
V
O
O
N
N
MeOH
H2O2, O2
MeOH
VO(acac)2
O
N
N
20
19
Hsal-dmen (VIII)
Scheme 6. Scheme for the synthesis of oxidovanadium(IV) and dioxidovana-
dium(V) complexes.29,30
O
V
K
H2O
O
O
+
N
N
O
N
PS-im
R
N
DMF
K
N
N
V
O
O
R = 4-pyridyl (21)
= phenyl (22)
O
O
N
R
N
Scheme 7. Ball (
•
) represents the polystyrene matrix.38
NH
N
OH
OH
N
N
(C2H5)3N
DMF
+
Cl
N
N
PS-Hsal-his
Hsal-his (VI)
VO(acac)2
O
O
O
N
N
N
V
V
O
N
O
O2
O
O
N
N
MeOH
24
23
Scheme 8. Scheme for the synthesis of polymer-supported complexes.28

Structural models of vanadate-dependent haloperoxidases, their reactivity, immobilization on polymer support 221
(a)
(b)
(c)
(d)
g
2.5
2.4
2.3
2.2
2.1
2
1.9
1.8
1.7
1.6
1.5
Figure 4. 1st derivative EPR spectra of PS–[VIVO(acac)(sal–his)] (23):
(a) solid at room Temperature, (b) in contact with DMF at 77 K; and
[VOIV(acac)(sal–his)] (15): (c) in MeOH at 77 K, (d) in DMF at 77 K.28
Table 1. Spin Hamiltonian parameters obtained for [VOIV(acac)(sal–his)] (15) and PS-[VOIV(acac)(sal–his)] (23).28
Complex
Solvent
g
||
A
g
⊥
A
||
⊥
(×104 cm−1
)
(×104 cm−1
)
PS–[VIVO(acac)(sal-his)] (23)
[VIVO(acac)(sal-his)] (15)
Solid
DMF
MeOH
DMF
1.949
1.952
1.953
1.954
163.8
164.8
161.5
161.5
1.980
1.980
1.981
1.980
58.6
57.5
56.0
55.7
(a)
(b)
(c)
(d)
(e)
(f)
g
2.5
2.4
2.3
2.2
2.1
2
1.9
1.8
1.7
1.6
Figure 5. Treatment of compound [VOIV(acac)(sal-his)] (15) with 30%
H2O2 followed by the addition of methyl phenyl sulfide; (a) in MeOH; (b) 0.5
equiv. H2O2; (c) 2.0 equiv. H2O2; (d) 1.0 equiv. methyl phenyl sulfoxide; (e)
2.0 equiv. methyl phenyl sulfoxide; (f) 2.0 equiv. methyl phenyl sulfoxide (after
20 h) at 77 K.

222
Mannar R Maurya
O
O
HO
O
C
C
OH
OH
N
N
DMF, (Et)3N
+
N
N
Cl
CH3COOC2H5
PS-Hfsal-aepy
VO(acac)2
Hfsal-aepy (IX)
O
O
O
O
O
O
O
O
O
C
C
V
V
O
O
O2
N
N
N
N
25
26
Scheme 9. Scheme for the synthesis of polymer-supported complexes.29
Table 2. Spin Hamiltonian parameters obtained for [VIVO(acac)(sal-aepy)] (17) and PS-[VIVO(acac)(sal-aepy)] (25).29
Complex
Solvent
g
||
A
A
g
⊥
||
⊥
(×104 cm−1
)
(×104 cm−1
)
PS-[VIVO(acac)(fsal-aepy)] (25)
[VIVO(acac)(sal-aepy)] (17)
Solid
1.945
1.946
1.953
1.952
167.6
168.8
163.5
163.5
59.3
58.4
57.8
Ax 58.6,
Ay 57.1
1.979
1.980
1.981
gx 1.982,
gy 1.981
DMSO
DMSO
MeOH
VO(acac)2 in DMF with the obtained polymer sup- oxidation of PS-[VIVO(acac)(fsal-aepy)] in MeOH.
ported ligand. Aerial oxidation of 23 in methanol gave Hamoltonian parameters obtained for neat as well as
the dioxidovanadium(V) complex PS–[VVO2(sal-his)] polystyrene-supported complexes (table 2) are very
(24), scheme 8.28
similar to those reported above in table 1.29
The EPR spectra of PS–[VIVO(acac)(sal-his)] (23)
and [VIVO(acac)(sal-his)] (15) are shown in figure 4.
The spectrum of 23 is characteristic of magnetically
dilute VIVO-complex and the well-resolved EPR hyper-
fine features indicate that the vanadium(IV) centers are
well-dispersed in the polymer matrix. Comparison of
the spectra of 23 and 15 indicates that the coordination
environment are the same in both complexes and the
binding modes of these are also same in DMF solution,
as well as in the solid state, table 1 (figure 5).
A very similar procedure, as mentioned above
was applied in isolating complex PS-[VIVO(acac)(fsal-
aepy)] (25). Here, carboxylic group on salicylalde-
hyde of Hfsal-aepy (IX) reacted with chloromethy-
lated polystyrene to give polymer-supported ligand
as shown in scheme 9. Its dioxidovanadium(V) ana-
logue PS-[VVO2(fsal-aepy)] (26) was prepared by aerial
OMe
V
O
O
O
O
O
C
C
O
OH
DMF/MeOH
VO(acac)2
N
N
O
N
27
N
PS-Hfsal-dmen
H2O2, O2 MeOH
O
O
O
C
V
O
N
N
28
Scheme 10. Formation of PS-[VIVO(OMe)(fsal-dmen)]
(27) and PS-[VVO2(fsal-dmen)] (28).30

Structural models of vanadate-dependent haloperoxidases, their reactivity, immobilization on polymer support 223
O
S
OH
OH
OH
O
O
R
Br
[VO2L]-
KBr/H2O2/HClO4
S
S
O
H2O2
O
O
R
+
R
+
Catalyst
Br
Br
R = CH3: Methyl phenyl sulfide
R = C6H5: Diphenyl sulfide
Scheme 11. Oxidative bromination of salicylaldehyde.
Scheme 12. Oxidation products of sulfides.17
Ligand PS-Hfsal-dmen on reaction with VO(acac)2
gave PS-[VIVO(OMe)(fsal-dmen)] (27) which on
oxidation gave the expected VVO2-complex, PS-
[VVO2(fsal-dmen)] (28), scheme 10. The presence of
MeO− in PS-[VIVO(OMe)(fsal-dmen)] was confirmed
by GC-MS on keeping it in DMSO for ca. 15 h and
detecting MeOH in liquid part of the mixture.30
which ultimately oxidise bromide, possibly via a
hydroperoxido intermediate. The oxidised bromine
−
species (Br2, Br3 and/or HOBr) then brominates the
substrate.4,7,8
Maximum conversion of salicylaldehyde (ca. 51%)
was achieved with 4 mmol of HClO4, 2 mmol of sub-
strate, 15 mmol of H2O2, 0.020 g (ca. 0.05 mmol) of cat-
alyst and 0.476 g (4 mmol) of KBr. GC and GC-MS
analysis of the crude products obtained under optimised
conditions gave 85.8% 5-bromosalicylaldehyde, 9.0%
3,5-dibromosalicylaldehyde and 5.2% of other, uniden-
4. Catalytic activity
4.1 Oxidative bromination of salicylaldehyde
The model vanadium complexes have been used tified, products. Polymer-supported complexes PS-
as functional models successfully. Thus, K[VO2(sal- K[VO2(sal-inh)(im)] (21) and PS-K[VO2(sal-bhz)(im)]
inh)]·H2O (8) and K[VO2(sal-fah)]·H2O (10) catalyse (22) gave better conversion.38 They are more selective
the oxidative bromination, by H2O2, of salicylaldehyde also towards the formation of 5-bromosalicylaldehyde,
to afford 5-bromo and 3,5-dibromosalicylaldehyde, table 3. These catalysts demonstrate their practical
scheme 11. During this process vanadium reacts with applications as they have relatively high turn over fre-
one or two equivalents of H2O2, forming monoperox- quency and not much loss in the catalytic activities on
ido {VO(O2)+} or bis(peroxido) {VO(O2)−} species, recycling.
Table 3. Conversion and selectivity data for salicylaldehyde after 2 h of contact time.38
Catalyst
% Conv.
TOF (h−1 e
)
% Selectivity
5-Brsal
Other
8
10
53.8
50.5
85.2
81.4
78.6
77.8
77.1
81.7
78.7
76.1
75.5
75.0
60.2
61.8
775
-
-
-
-
87.3
85.3
90.4
90.0
87.0
86.8
87.0
89.6
87.6
86.4
86.0
86.0
12.7
14.7
9.6
10.0
13
13.2
13.0
10.4
12.4
13.6
14.0
14.0
21
21a
21b
21c
21d
22
800
22a
22b
22c
22d
-
-
-
-
aFirst cycle of used catalyst
bSecond cycle of used catalyst
cThird cycle of used catalyst
dForth cycle of used catalyst
eTOF values in moles of product per mole of catalyst

224
Mannar R Maurya
4.2 Oxidation of sulfides (thioethers) and other
sulphur compounds
H
O
V O
Vanadate-dependent haloperoxidases catalyse the oxi-
dation, by H2O2, of sulfides (thioethers) to sulfox-
ides and further to sulfones.7,8,39 We have tested the
catalytic potential of complexes [VVO2(sal-ambmz)]
(3), [VVO2(sal-aebmz)] (4), [VVO2(acac-aebmz)] (5),
[VIVO(acac)(sal-his)] (15) and [VVO2(sal-his)] (16)
to mimic the sulfide-peroxidase activity of the
enzyme.17,28 Methyl phenyl sulfide and diphenyl
sulfide have electron-rich sulfur atoms which on elec-
trophilic oxidation give monosulfoxide, and upon fur-
ther oxidation disulfoxide, scheme 12. Catalysts PS–
[VIVO)(acac)(sal-his] (23) and PS–[VVO2(sal-his)] (24)
have also been tested for the oxidation of two sul-
fides. Table 4 compares the conversion of sulfides, TOF
and product selectivity data under optimized condi-
tions. As shown in table, conversions of both sulfides
using neat complexes are very good, but always lower
than their polymer-bound analogues. The selectivity of
the formation of the corresponding monosulfoxide is
also lower with neat complexes. Blank reaction tak-
ing methyl phenyl sulfide (1.24 g, 10 mmol), aqueous
30% H2O2 (1.71 g, 15 mmol) and acetonitrile (15 mL)
resulted in 15.2% conversion with sulfoxide: sulfone
selectivity of 68 : 32. Blank reaction for diphenyl sul-
fide under above reaction conditions gave only 5.5%
conversion with sulfoxide: sulfone selectivity of 57 : 43.
Step-wise addition of 2 equiv. H2O2 (0.5, 1, 1.5 and
2 equiv.) to a methanolic solution of [VIVO(acac)(sal-
his)] causes the decrease in the intensity of the EPR
spectrum, and after the addition of the 2 equiv. of H2O2
H2O
O
H
H2O2
O
O
O
V
N
O
O
V
H2O2
O
O
H2O2
O
N
H
O
O
O
V
V
V
H2O
H
O
S
S
+
H
Ph
CH3
Ph
CH3
Scheme 13. Reaction mechanism of oxidation of methyl
phenyl sulfide as a model substrate for sulfoxidations.
the EPR intensity becomes ca. 1/5th of that of the initial
solution. The 51V NMR of these solutions confirmed the
presence of vanadium(V) species. Subsequent addition
of 2 equiv. methyl phenyl sulfide originated spectrum
with the same values of g and A parameters, the EPR
signal increasing to ∼ 50% of the initial solution, indi-
cating the reversibility of the redox process occurring
during the catalytic reaction.
Successive additions of 30% H2O2, the relative inten-
sity of the δ = −547 ppm resonance due to [VVO2(sal-
his)] decreases, and after the addition of 1.5 equiv of
H2O2, a peak at δ = −579 ppm, appeared due to the for-
mation of [VVO(O)2(sal-his)] (29). However, restora-
tion of original signal upon addition of methyl phenyl
sulfide to the above solution confirms the reversibility
of the reaction. Original spectrum can also be obtained
Table 4. Conversion of sulfides, TOF and product selectivity data.28
Substrate
Catalyst
Conv.
(%)
TOF (h−1
)
% Selectivity
Sulfoxide
Sulfone
Methyl phenyl sulfidea
15
16
23
24
72.1
84.8
79.5
93.8
83.3
96.4
91.2
62.9
61.0
64.8
63.7
37.1
39.0
35.2
36.3
113.8
Diphenyl sulfideb
15
16
23
24
60.3
70.7
67.4
83.4
19.8
30.2
28.7
37.5
68.9
67.8
73.1
71.8
31.1
32.2
26.9
28.2
aReaction conditions for polymer-anchored complexes: methyl phenyl sulfide (10 mmol), catalyst
(0.025 g), H2O2 (1.71 g, 15 mmol) and CH3CN (15 mL). Neat complexes use same mole concentration
as used for the polymer-anchored complexes.
bReaction conditions for polymer-anchored complexes: diphenyl sulfide (10 mmol), catalyst (0.045 g),
H2O2 (3.42 g, 30 mmol) and acetonitrile (15 mL). Neat complexes use same mole concentration as used
for the polymer-anchored complexes.

Structural models of vanadate-dependent haloperoxidases, their reactivity, immobilization on polymer support 225
Table 5. Desulfurization of organosulfur compounds and reaction products.30
Catalysta
Sulfur-containing
compound
Sulfur content (in ppm)
Sulfur removal
(%)
Initial amount
After
desulfurization
19
19
19
19
27
27
27
27
20
20
20
20
28
28
28
28
Thiophene
500
500
500
500
500
500
500
500
500
500
500
500
500
500
500
500
148.5
144.5
141.5
140.5
65.5
63
60.5
57.5
113
109.5
111.5
108
9.5
70.3
71.1
71.7
71.9
86.9
87.4
87.9
88.5
77.4
78.1
77.7
78.4
98.1
98.3
98.4
98.8
Benzothiophene
Dibenzothiophene
2-Methylthiophene
Thiophene
Benzothiophene
Dibenzothiophene
2-Methylthiophene
Thiophene
Benzothiophene
Dibenzothiophene
2-Methylthiophene
Thiophene
Benzothiophene
Dibenzothiophene
2-Methylthiophene
8.5
8
6
aReaction conditions: Organosulfur compound (500 ppm) in heptane, 30% H2O2 (oxidant:substrate
molar ratio of 3 : 1) at 60◦C.
upon standing the solution having 29 for longer time. summarizes the percentage conversion of styrene, the
The peroxido-complexes being stable and detectable, turn over rates, and the selectivities for the various
it is likely that hydroperoxidovanadium(V) complexes reaction products under optimized reaction conditions.
also form as aqueous H2O2 is being added and the
With H2O2, these catalysts are more selective towards
pH decreases, enhancing the electrophilicity of the benzaldehyde (74–90%), than styrene oxide (5.5–11%),
peroxido intermediate. The peroxide thus activated is an expected product. The conversion of styrene is
subjected to a nucleophilic attack by the sulfide as though low with TBHP, the selectivity of the forma-
shown in scheme 13.40,41
tion of styrene oxide is much better than in the case of
The removal of sulfur compounds from petroleum H2O2. Due to the strong oxidizing nature of H2O2, the
products has attracted attention of researchers to ful- styrene oxide formed in the first step by epoxidation is
fill the demand of environment friendly fuels. The mainly converted into benzaldehyde via the intermedi-
oxidation of model organosulfur compounds with sul- ate hydroperoxistyrene. Benzaldehyde formation may
fur concentrations of 500 ppm was tested in heptane
using catalysts PS-[VIVO(OMe)(fsal-dmen)] (27) and
O
O
PS-[VVO2(fsal-dmen)] (28) in the presence of 30%
H2O2. The results are summarized in table 5. It is clear
from the table that polystyrene-supported catalysts are
significantly more effective in oxidizing organic sulfur
than their corresponding neat complexes. In addition,
the supported catalysts have advantages of being more
easily recovered from the reaction mixture.30
O
HO
Cat.
H2O2
Styrene
Styrene oxide
(so)
Benzaldehyde
(bza)
Benzoic acid
(bzaa)
OH
HO
4.3 Oxidation of styrene
Complexes [VO2(sal-ambmz)] (3), [VO2(sal-aebmz)]
(4) and [VO2(acac-aebmz)] (5), also catalyse the oxi-
dation of styrene and the major oxidation products
obtained are styrene oxide, benzaldehyde, benzoic acid
and 1-phenylethane-1,2-diol, scheme 14.17 Table 6
1-phenylethane-1,2-diol
(phed)
Scheme 14. Various oxidation products of styrene.

226
Mannar R Maurya
Table 6. Percentage conversion of styrene and selectivity for various oxidation products
after 6 h of reaction time.17
Catalyst
Oxidant
Conv. (%)
TOF (h−1
)
Product selectivitya
so
bza
bzaa
phed
3
4
5
3
4
5
H2O2
H2O2
H2O2
TBHP
TBHP
TBHP
51
55
59
20
31
35
8.5
7.6
6.6
2.6
4.3
5.1
5.5
11
10
47
43
37
90
74
82
52
50
53
0.5
9
5
1
5
4
6
3
-
2
2
8
aso = styrene oxide, bza = benzaldehyde, bzaa = benzoic acid and phed = 1-phenylethane-
1,2-diol.
[VIVO(acac)(fsal-aepy)] (25) and PS-[VVO2(fsal-aepy)]
H
O
(26) gave the corresponding enamines, scheme 17. The
Markovnikov and anti-Markovnikov products were
separated by column liquid chromatography and con-
firmed by 1H NMR spectroscopy. Table 7 presents data
on hydroamination, turn over frequency (TOF) of the
catalyst, and selectivity of the Markovnikov and anti-
Markovnikov products obtained under optimsed con-
ditions.29 The yield of the anti-Markovnikov products
are, in general, higher than those of the Markovnikov
products. This is possibly due to the steric hindrance
imposed by the amine, which decreases the formation
of the Markovnikov products.
The catalytic activity of the neat complexes
[VIVO(acac)(sal-aepy)] (17) and [VVO2(sal-aepy)] (18)
were also tested for the hydroamination of styrene,
table 7. It is clear from the table that the neat complexes
exhibit slightly lower conversion than the anchored ana-
logue for all reactions. The improvement in the cat-
alytic activity of the anchored complex may be due
to uniform distribution of metal centers on the poly-
mer matrix, and/or an increased availability of styrene
molecules which may adsorb on the polymer, close to
the catalyst. The recyclability of the polymer anchored
complexes 25 and 26 was checked up to two additional
cycles after washing the catalysts with acetonitrile and
drying after every use. No appreciable loss in the activ-
ities (see table 7), indicates that actual structures of
the metal complexes remain unchanged, and that the
catalysts remain equally active.
O
O OH
OOH
H
CH2
O
O
H2O +
+
Scheme 15. Proposed mechanism.
also be facilitated by direct oxidative cleavage of the
styrene side chain double bond via a radical mecha-
nism, scheme 15.42 Water present in H2O2 is probably
responsible for the hydrolysis of styrene oxide to form
1-phenylethane-1,2-diol to some extent. Formation of
other products, e.g., benzoic acid through oxidation of
benzaldehyde is extremely slow.
4.4 Hydroamination of styrene and vinyl pyridine
Transition metal catalysed hydroamination (scheme 16)
of olefins has attracted much attention in the past
decades due to the ubiquity of the amine functionality in
natural products, biological systems, pharmaceuticals
and fine chemicals.43–46
Hydroamination of styrene and vinyl pyridine
catalysed by polymer-anchored complexes, PS-
R
R
Catalyst
NR'2
+ 2HNR2
2 R
+
NR'2
H
anti-Markovnikov
product
Markovnikov
product
Scheme 16. Hydroamination of olefins producing the Markovnikov-
or anti-Markovnikov-type product.

Structural models of vanadate-dependent haloperoxidases, their reactivity, immobilization on polymer support 227
NH2
C2H5
C2H5
C2H5
C2H5
N
C2H5
C2H5
H
HN
HN
N
N
HN
+
H
+
(d)
(c)
(a)
(b)
NH2
C2H5
N
C2H5
C2H5
C2H5
C2H5
C2H5
H
HN
HN
+
H
+
HN
N
N
N
N
N
(h)
(g)
(e)
(f)
Scheme 17. (a) N-(1-phenylethyl)aniline, (b) N-phenethylaniline, (c) N,N-diethyl-
1-phenylethanamine, (d) N,N-diethyl-2-phenylethanamine, (e) N-(1-(pyridin-3-yl)ethyl)aniline,
(f) N-(2-(pyridin-3-yl)ethyl)aniline, (g) N,N-diethyl-1-(pyridin-4-yl)ethanamine, (h) N,N-
diethyl-2-(pyridin-4-yl)ethanamine.29
Table 7. Conversion (%) and type of reaction products obtained using neat and anchored catalysts.29
Catalyst Olefin
Amine
% Conv.
TOF
% Selectivity
(h−1
)
Markov. product Anti-Markov. product
25
Styrene
Aniline
66
65
64
48
47
45
82
82
81
60
60
59
76
75
74
60
58
58
92
92
91
71
70
69
53
31
69
46
66
42
88
64
47
-
-
34
-
-
59
-
-
43
-
-
65
-
-
50
-
-
77
-
-
59
-
-
22
22
21
27
26
26
18
17
16
12
11
10
14
14
13
29
28
27
19
18
18
23
23
22
33
35
30
24
26
34
32
25
78
78
79
73
74
74
82
83
84
88
89
90
86
86
87
71
72
73
81
82
82
77
77
78
67
65
70
76
74
66
68
75
25a
25b
25
Diethylamine
25a
25b
25
Vinylpyridine Aniline
25a
25b
25
Diethylamine
25a
25b
26
Styrene
Aniline
26a
26b
26
Diethylamine
26a
26b
26
Vinylpyridine Aniline
26a
26b
26
Diethylamine
26a
26b
17
Styrene
Aniline
Diethylamine
Vinylpyridine Aniline
Diethylamine
Aniline
Diethylamine
Vinylpyridine Aniline
Diethylamine
21
12
27
36
22
13
27
20
17
17
17
18
18
18
18
Styrene
aFirst cycle of used catalyst
bSecond cycle of used catalyst

228
Mannar R Maurya
16. Volcho K P and Salakhutdinov N F 2009 Russian Chem.
5. Conclusions
Rev. 78 457
17. Maurya M R, Kumar A, Ebel M and Rehder D 2006
Inorg. Chem. 5924
18. Rehder D, Weidemann C, Duch A and Priebsch W 1988
Inorg. Chem. 27 584
19. Maurya M R, Agarwal S, Bader C and Rehder D 2005
Eur. J. Inorg. Chem. 147
20. Maurya M R, Agarwal S, Abid M, Azam A, Bader C,
Ebel M and Rehder D 2006 Dalton Trans. 937
21. Plass W, Pohlmann A and Yozgatli H K 2000 J. Inorg.
Biochem. 80 181
22. Hirao T 1997 Chem. Rev. 97 2707
23. Messerschmidt A, Prade L and Wever R 1997 Biol.
Chem. 378 309
24. Westland A D, Haque F and Bouchard J-M 1980 Inorg.
Chem. 19 2255
25. Casný M and Rehder D 2004 Dalton Trans. 839
26. Macedo-Ribeiro S, Hemrika W, Renirie R, Wever R and
Messerschmidt A 1999 J. Biol. Inorg. Chem. 4 209
27. Cornman C R, Kampf J, Lah M S and Pecoraro V L 1992
Inorg. Chem. 31 2035
28. Maurya M R, Arya A, Kumar A and Costa Pessoa J 2009
Dalton Trans. 2185
29. Maurya M R, Arya A, Kumar U, Kumar A, Avecilla F
and Costa Pessoa J 2009 Dalton Trans. 9555
30. Maurya M R, Arya A, Kumar A, Kuznetsov M L,
Avecilla F and Costa Pessoa J 2010 Inorg. Chem. 49
6586
31. Meunier B 1992 Chem. Rev. 92 1411
32. Sherrington D C 1998 Supported reagents and catalyst
in chemistry (eds) Hodnett B K, Keybett A P, Clark J H
and Smith K (Cambridge: Royal Society of Chemistry)
p. 220
33. Canali L and Sherrington D C 1999 Chem. Soc. Rev.
28 85
Structural models of vanadate-dependent haloperoxi-
dases (VHPO), where vanadium(V) is covalently linked
to the imidazole-N, benzimidazole-N, pyridine-N or
hydrazide-N, are presented. These model complexes
exhibit interesting oxidative bromination and sulfox-
idases activities, thus behaving as functional mod-
els as well. Immobilisation of these model complexes
on chloromethylated polystyrene cross-linked with 5%
divinylbenzene enhances the catalytic turn over num-
bers of these complexes along with their recyclable
properties. These neat as well as polymer-supported
complexes are also good catalysts for other organic
transformations.
Acknowledgements
Financial assistances from the Department of Science
and Technology (DST), New Delhi 110016 and Coun-
cil of Scientific and Industrial Research (CSIR), New
Delhi 110012 are gratefully acknowledged.
References
1. Weyand M, Hecht H J, Kiess M, Liaud M F, Vilter H and
Schomburg D 1999 J. Mol. Biol. 293 595
2. Carter-Franklin J N, Parrish J D, Tchirret-Guth R A,
Little R D and Butler A 2003 J. Am. Chem. Soc. 125
3688
34. de Miguel Y R 2000 J. Chem. Soc. Perkin Tans. I 4213
35. Leadbeater N E and Marco M 2002 Chem. Rev. 102
3217
36. Punniyamurthy T and Rout L 2008 Coord. Chem. Rev.
252 134
37. Gupta K C, Sutar A K and Lin C-C 2009 Coord. Chem.
Rev. 1926
38. Maurya M R, Kumar M and Sikarwar S 2008 Catal.
Commun. 10 187
39. Rehder D, Santoni G, Licini G M, Schulzke C and Meier
B 2003 Coord. Chem. Rev. 237 53
40. Zampella G, Fantucci P, Pecorao V L and De Gioia L
2005 J. Am. Chem. Soc. 127 953
3. Rehder D, Santoni G, Licini G M, Schulzke C and Meier
B 2003 Coord. Chem. Rev. 237 53
4. Butler A 1999 Coord. Chem. Rev. 187 17
5. Messershmidt A and Wever R 1996 Proc. Natl. Acad.
Sci. USA 93 392
6. Isupov M I, Dalby A R, Brindley A, Izumi Y, Tanabe T,
Murshudov G N and Littlechild J A 2000 J. Mol. Biol.
299 1035
7. Butler A, Clague M J and Meister G E 1994 Chem. Rev.
94 625
8. Butler A 1999 Bioinorganic catalysis 2nd edn (eds) J
Reedijk and E Boiwman (New York: Marcel Dekker)
ch. 5
9. Rehder D 1999 Coord. Chem. Rev. 182 297
10. Maurya M R 2003 Coord. Chem. Rev. 237 163
11. Maurya M R, Kumar A, Manikandan P and Chand S
2004 Appl. Catal. A Gen. 277 45
12. Maurya M R, Agarwal S, Bader C, Ebel M and Rehder
D 2005 Dalton Trans. 537
13. Maurya M R, Sikarwar S and Manikandan P 2006 Appl.
41. Smith T S II and Pecoraro V L 2002 Inorg. Chem. 41
6754
42. Hulea V and Dumitriu E 2004 Appl. Catal. A: Gen. 277
99
43. Johnson J S and Bergman R G 2001 J. Am. Chem. Soc.
123 2923
44. Li Y and Marks T J 1996 J. Am. Chem. Soc. 118
9295
Catal. A: Gen. 315 74
14. Maurya M R, Kumar U and Manikandan P 2007 Eur. J.
Inorg. Chem. 2303
45. Beller M, Trauthwein H, Eichberger M, Breindl C and
Müller T E 1999 Eur. J. Inorg. Chem. 1121
15. Ashikhmina E V, Rubtsova S A, Dvornikova I A and 46. Nobis M and Driessen-Holscher B 2001 Angew. Chem.,
Kuchin A V 2009 Russian J. Org. Chem. 45 1509
Int. Ed. 40 3983