Two dinuclear oxidovanadium(V) complexes of N2O2 donor amine-bis(phenolate) ligands with bromo-peroxidase activities: Kinetic, catalytic and computational studies

Article abstract of DOI:10.1016/j.ica.2018.04.044

Two dinuclear oxidovanadium(V) complexes [LⁱV^VO(μ₂-O)V^VO(Lⁱ)] (i = 1, H₂L¹, complex 1 and i = 2 for H₂L², complex 2) of two ONNO donor amine-bis(phenolate) ligands have been synthesized and characterized by X-ray diffraction studies which exhibited distorted octahedral geometry around each V center. In MeCN the complexes exist as dimers as indicated by HRMS studies, however, in the presence of 2 or more equivalents of H⁺ the dimers turned into monomers, ([LⁱV^V = O]⁺ which exists in equilibrium with ([LⁱV^V = OH]²⁺ and evidenced from the shift in λ_max from 685 nm to 765 nm for complex 1 and 600 to 765 nm for complex 2. The complexes 1 and 2 efficiently catalyze the oxidative bromination of salicylaldehyde in the presence of H₂O₂ to produce 5-bromo-salicylaldehyde as the major product with TONs 405 and 450, respectively in the mixed solvent system (H₂O:MeOH:THF = 4:3:2, v/v). The kinetic analysis of the bromide ion oxidation reaction indicates a mechanism which is first order in peroxidovanadium complex and bromide ion and limiting first-order on [H⁺]. The evaluated k^Br and k^H values are (8.82 ± 0.35) and (65.0 ± 2.23) M^?1 s^?1 for complex 1 and (6.74 ± 0.19) and (61.87 ± 2.27) M^?1 s^?1 for complex 2, respectively. The K_a of protonated species ([LⁱV^V = OH]²⁺ are: K_a = (4.3 ± 0.40) × 10^?3 (pK_a = 2.37) and (4.7 ± 0.50) × 10^?3 (pK_a = 2.33) for complex 1 and 2 respectively. On the basis of the chemistry displayed by these model compounds, a mechanism of bromide oxidation and a tentative catalytic cycle have been framed which might be relevant to vanadium haloperoxidase enzymes and supported by DFT calculations.

Full text of DOI:10.1016/j.ica.2018.04.044

Inorganica Chimica Acta 480 (2018) 149–158
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Inorganica Chimica Acta
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Research paper
Two dinuclear oxidovanadium(V) complexes of N2O2 donor amine-bis
(phenolate) ligands with bromo-peroxidase activities: Kinetic, catalytic
and computational studies
Mainak Debnath a, Malay Dolai a, Kaberi Pal a, Arpan Dutta a, Hon Man Lee b, Mahammad Ali a,
⇑
a Department of Chemistry, Jadavpur University, 188, Raja Subodh Chandra Mullick Rd, Kolkata, West Bengal 700032, India
b Department of Chemistry, National Changhua University of Education, Changhua 50058, Taiwan
a r t i c l e i n f o
a b s t r a c t
Two dinuclear oxidovanadium(V) complexes [LiVVO(m2-O)VVO(Li)] (i = 1, H2L1, complex 1 and i = 2 for
H2L2, complex 2) of two ONNO donor amine-bis(phenolate) ligands have been synthesized and character-
ized by X-ray diffraction studies which exhibited distorted octahedral geometry around each V center. In
MeCN the complexes exist as dimers as indicated by HRMS studies, however, in the presence of 2 or more
Article history:
Received 29 November 2017
Received in revised form 26 March 2018
Accepted 22 April 2018
equivalents of H+ the dimers turned into monomers, ([LiVV = O]+ which exists in equilibrium with ([LiVV
=
OH]2+ and evidenced from the shift in kmax from 685 nm to 765 nm for complex 1 and 600 to 765 nm for
complex 2. The complexes 1 and 2 efficiently catalyze the oxidative bromination of salicylaldehyde in the
presence of H2O2 to produce 5-bromo-salicylaldehyde as the major product with TONs 405 and 450,
respectively in the mixed solvent system (H2O:MeOH:THF = 4:3:2, v/v). The kinetic analysis of the bro-
mide ion oxidation reaction indicates a mechanism which is first order in peroxidovanadium complex
and bromide ion and limiting first-order on [H+]. The evaluated kBr and kH values are (8.82 0.35) and
(65.0 2.23) Mꢀ1 sꢀ1 for complex 1 and (6.74 0.19) and (61.87 2.27) Mꢀ1 sꢀ1 for complex 2, respec-
tively. The Ka of protonated species ([LiVV = OH]2+ are: Ka = (4.3 0.40) ꢁ 10ꢀ3 (pKa = 2.37) and
(4.7 0.50) ꢁ 10ꢀ3 (pKa = 2.33) for complex 1 and 2 respectively. On the basis of the chemistry displayed
by these model compounds, a mechanism of bromide oxidation and a tentative catalytic cycle have been
framed which might be relevant to vanadium haloperoxidase enzymes and supported by DFT
calculations.
Keywords:
Oxido-bridged dinuclear vanadium(V)
complexes
Crystal structures
Bromoperoxidaes activities
Kinetic and catalytic studies.
DFT calculations
Ó 2018 Elsevier B.V. All rights reserved.
1. Introduction
halogenation of various organic substrates possibly via the reaction
of HOX, X2 or Xꢀ3 [12–14]. In the case of bromoperoxidase, the exis-
Structural and functional modeling of biological activities of
various vanadium containing enzymes have long been of interest
to chemists. The discovery of the presence of vanadium(V) in the
active site of vanadium dependent haloperoxidases (V-HalPO) [1]
and its importance in catalytic reactions [2–9] has stimulated the
research on coordination chemistry of vanadium. Haloperoxidases
are the enzymes that catalyze the oxidation of halides to the corre-
sponding hypohalous acids or to a related two-electron oxidized
halogenating intermediate such as OXꢀ, X3ꢀ and X+ in the presence
of H2O2 as oxidant which in the subsequent step reacts with suit-
able nucleophilic acceptors to form the corresponding halogenated
compounds [10–14]. Kinetic studies suggest the formation of per-
oxido-vanadium intermediate, which ultimately facilitates the
tence of peroxido as well as hypobromite-like vanadium interme-
diates in solution have been demonstrated [15,16]. Besides,
evidence for peroxide binding to the active center of bromoperox-
idase isolated from Ascophyllum nodosum has been presented by
´
Cãsny et al. [17].
To get a better understanding of the working mechanism of the
vanadium haloperoxidase enzyme and to determine the role of
vanadiumn, a variety of vanadium compounds have been studied
as functional models [12]. The first reported functional mimic of
V-BrPO is cis-dioxidovanadium(V) [V(O)2]+ in acidic aqueous solu-
tion [18,19]. cis-Dioxido-vanadium(V) catalyze the bromination of
1,3,5-trimethoxybenzene (TMB) and also the bromide-mediated
disproportionation of H2O2. In a first step, H2O2 is complexed to
give red oxidoperoxido [VO(O2)]+ and yellow oxidodiperoxido
[VO(O2)2]ꢀ complexes, the ratio between them depends on the
H2O2 concentration and the pH of the medium. In a second step
⇑
Corresponding author.
E-mail address: mali@chemistry.jdvu.ac.in (M. Ali).
https://doi.org/10.1016/j.ica.2018.04.044
0020-1693/Ó 2018 Elsevier B.V. All rights reserved.

150
M. Debnath et al. / Inorganica Chimica Acta 480 (2018) 149–158
Scheme 1. Bromination activity of the V-BrPO mimic cis -dioxidovanadium(V) [18]
these two species combine to give dioxidotriperoxido-divanadium
(V) [(VO)2(O2)3] compound, which is considered to be the actual
oxidant (Scheme 1).
Contrary to the natural haloperoxidases, cis-dioxidovanadium
(V) functions only at low pH (2 or less), because at lower acidity
the amount of monoperoxidovanadate is insufficient for dimerisa-
tion to form [(VO)2(O2)3].
2.2. Materials
Starting materials for the synthesis of the ligands (H2L1 and
H2L2) and their vanadium(V) complexes (1 and 2), namely, 2, 4-
di-tert-butylphenol (Aldrich), 2-aminoethylpyridine (Aldrich), N,
N0-dimethyl-ethylenediamine (Aldrich), formaldehyde (Merck
India), [VO(acac)2] (Lancestar India), are of reagent grade and used
as received. Substrates namely salicylaldehyde (Aldrich) used in
the catalytic reactions is of reagent grade and used as received.
30% H2O2 (Merck India), KBr (Merck India) and 70% of HClO4 were
used in the catalytic bromination reactions.
Another difference with the enzyme is its low catalytic rate
indicating the importance of the presence of protein environment
around the active site. A V-BrPO mimic that has been well studied
is the oxidovanadium(V) complex of hydroxyphenylsalicylide-
neamine [(HPS)VO(OEt)(EtOH)] [20]. The bromination reaction
becomes catalytic when acid is used in at least stoichiometric
quantities with respect to H2O2. Nevertheless, the exact nature of
this halogenating intermediate has not been determined as yet.
The structure of vanadium haloperoxidase contains the vana-
dium ion attached to the protein backbone via one histidine nitro-
gen donor atom, whilst the oxido moieties are strongly H-bonded
to arginine, lysine, histidine and serine amino acids [20] (Fig. 1).
In the view of the above observations, we have decided to
design and synthesize structural and functional models of the bio-
molecules, which has the potential ability to catalyze the bromina-
tion of organic substrate in order to get a better understanding of
the mechanism of such reactions. Meanwhile, we have been inter-
ested in vanadium chemistry of amine bis-phenolate ligands show-
ing interesting catalytic activities towards hydrocarbon oxidation
and epoxidation reactions [21–24]. We will reveal here the struc-
tures of two oxido-bridged dinuclear vanadium complexes of
N2O2 donor amine-bis(phenolate) ligands (Scheme 2) that showed
interesting bromoperoxidase activity towards the bromination of
salicyldehyde.
2.3. Synthesis of amine-bis(phenolate) ligand
The ligands (H2L1 and H2L2) have been synthesized according to
a reported method [25] and further characterized by CHN and 1H
NMR analyses.
H2L1: Yield 83%. Ana. Cal value for Molecular formula,
C
37H54N2O2 C, 79.52%; H, 9.74%; N, 5.01%; Found C,79.16%; H
9.52%; N, 5.15%.: 1H NMR (d, ppm) 1.28 (s, 36-H); 2.81 (t, 2-H);
3.10 (t, 2-H); 3.73 (s, 4-H); 6.87–7.22 (m, 6-ArH); 7.57 (t, 1-ArH);
8.688 (d, 1-ArH); 9.45 (b, –OH protons) (Fig. S1).
H2L2: Yield 89%. Ana. Cal value for Molecular formula,
C
34H56N2O2 C, 74.12%; H, 9.05%; N, 7.86%; Found C,73.56%; H
9.01%; N, 7.25%. 1H NMR (d, ppm) 2.18 (s, 6-H); 2.25 (s, 12-H);
2.63 (s, 4-H); 3.65 (s, 4-H); 6.79 (s, 2-ArH); 7.20 (s, 2-ArH); 9.36
(s, –OH protons) (Fig. S2).
2.4. Preparation of complexes
2. Experimental
2.4.1. Synthesis of [{VO(L1)}2O] (1)
1.0 mmol (0.558 g) of the ligand H2L1 was dissolved in 20 ml
MeCN and was refluxed with 2 mmol (0.202 g) TEA for 10 min.
The solution was then cooled and a solution of [VO(acac)2]
(1 mmol, 0.265 g) in MeCN was added dropwise to it and refluxed
for 3 h. The resulting dark blue solution was filtered off after cool-
ing to room temperature and the filtrate was subjected to slow
evaporation at room temperature, whereupon dark blue block
shaped single crystals suitable for X-ray study were obtained
within 3 days.
2.1. Physical measurements
Perkin-Elmer 240 elemental analyzer was used for elemental
analyses while IR (Infrared) spectra were recorded from KBr pellets
on a Nicolet Magna IR 750 series-II FTIR spectrophotometer in the
range 400–4000 cmꢀ1. Agilent 8453 UV–Vis diode-array spec-
trophotometer was used to record the electronic spectra. Mass
spectra were recorded on an HRMS (model XEVO G2QTof) spec-
trometer. Electrochemical measurements were carried out using
a computer controlled AUTOLAB (Model: AutoLab 302) cyclic
voltammeter with platinum working electrode, platinum-wire
counter electrode and saturated calomel (SCE) reference electrode
in MeCN using tetrabutylammonium perchlorate as supporting
electrolyte.
[{VO(L1)}2O]: Yield 70%. Ana. Cal value for Molecular formula,
C
74H104N4O7V2 C, 70.34%; H, 8.30%; N, 4.43%; Found C, 70.12%; H,
8.19%; N, 4.36%. FTIR (KBr disc; cmꢀ1
) m(V = O) 934 and m(V-O-V)
757 (Fig. S3). 1H NMR (d, ppm) 1.19–1.44 (m, 72-H); 2.50 (s, 4-
H); 2.79 (s, 4-H); 3.22 (d, 4-H); 3.73 (s, 4-H); 6.01 (d, 2-ArH);
6.67–7.34 (m, 14-ArH) (Fig. S4).

M. Debnath et al. / Inorganica Chimica Acta 480 (2018) 149–158
151
Native site
Peroxo site
Fig. 1. The native and peroxidovanadium site in V-CPOs [20].
Scheme 2. Schematic presentation of preparation of the complexes 1 and 2 from ligands H2L1 and H2L2 respectively.
2.4.2. Synthesis of [{VO(L2)}2O] (2)
determined by direct methods using SHELXS-97 [26] and refined
anisotropically on F2 using the full-matrix least-squares procedure
of SHELXL-97 [27]. The data for publication were prepared by
SHELXL and PARST [28]. The crystal data collection and the proce-
dure for data refinement are listed in Table 1 for the two
complexes.
Complex 2 was synthesized following the same procedure as in
complex 1 taking H2L2 ligand instead of H2L1.
[{VO(L2)}2O]: Yield 70%. Ana. Cal value for Molecular formula,
C
44H60N4O7V2, C2H3N C, 61.40%; H, 7.06%; N, 7.78%; Found C,
61.29%; H, 6.95%; N, 7.62%. FTIR (KBr disc; cmꢀ1
(V@O) 939
and
(VAOAV) 776. 1H NMR (d, ppm) 2.20 (s, 8-H); 2.25 (s, 12-
)
m
m
H); 2.54–2.91 (m, 24-H); 3.09 (t, 4-H); 3.58 (d, 4-H); 6.18 (s, 2-
ArH); 6.60 (s, 2-ArH); 6.68 (s, 2-ArH); 6.89 (s, 2-ArH) (Fig. S5).
2.6. Experimental set up for catalytic bromination
In this method, a representative substrate, namely salicylalde-
hyde (20 mmol), was dissolved in mixed solvent (H2O:MeOH:
THF = 4:3:2) [29] and the resulting solution was taken in a 50 ml
capacity round bottom flask. To the above solution was then added
KBr (40 mmol) followed by 2 ml (67 mmol) of 30% H2O2.
An appropriate catalyst (say, complex 1) (0.05 g, 0.04 mmol)
and 70% HClO4 (0.10 ml) were added to it and the reaction was ini-
tiated with stirring. After 2 h of stirring at ambient temperature
0.1 ml of 70% HClO4 was further added and stirring was continued
for next 10 h. The separated white product was filtered, washed
with water followed by diethyl ether and dried in air. The crude
mass was dissolved in CH2Cl2 and insoluble material was separated
by filtration. After evaporation of the solvent to ca. 5 ml it was
loaded over column packed with silica gel. The fast moving band
on elution with CH2Cl2 was collected and evaporated to dryness
2.5. X-Ray crystallography
Intensity data of the complexes 1 and 2 were collected on a
smart CCD defractometer at 150(2) K in the
the range 2.75 < 2h < 27.50°. The intensities were corrected for Lor-
entz and polarization effects and for absorption using the -scan
method. The diffraction data for complex 2 were collected with a
KM4 CCD diffractometer with a four-circle area-detector (KUMA
Diffraction, Poland) equipped with an Oxford Cryostream Cooler
x
ꢀ2h scan mode in
w
(Oxford Cryosystems, UK). MoK
radiation (k = 0.71073 Å)
a
(monochromator Enhance, Oxford Diffraction, UK) was used in all
measurements. The cell parameters were refined from all strong
reflections. The data reductions were carried out using the CrysAlis
RED (Oxford Diffraction, UK) program. Both the structures were

152
M. Debnath et al. / Inorganica Chimica Acta 480 (2018) 149–158
Table 1
3. Results and discussion
Crystal data and structure refinement parameter of the complexes 1 and 2.
Complex 1 (CCDC
1454101)
Complex 2 (CCDC
853756)
3.1. Syntheses
Tetradentate H2Li (i = 1 or 2) ligands were synthesized by sim-
ple Mannich condensation of 2-amino-ethylpyridine with 2,4-
ditertiarybutylphenol and N,N0-dimethyl-ethylenediamine with
2,4-dimethylphenol in the presence of formaldehyde in MeOH.
Straight forward reactions between equimolar amounts of each
of the ligands and [VO(acac)2] and two equivalents of TEA in MeCN
separately under reflux afford complexes 1 and 2.
Formula
Formula Weight
Crystal System
Space group
C
74H104N4O7V2
C44H60N4O7V2, C2H3N
899.89
Monoclinic
P 21/c
10.573(5)
16.368(5)
25.925(5)
90
95.188(5)
90
1263.49
Triclinic
P-1 (No. 2)
10.5200(9)
15.7749(13)
22.8117(19)
79.824(1)
85.973(2)
75.321(1)
3603.2(5)
2
a
b [Å]
c
a
b[°]
c
V [Å3]
4468(3)
4
1.338
3.2. Structural descriptions of [{VO(L1)}2O] (1) and [{VO(L2)}2O] (2)
Z
D(calc) [g/cm3]
1.165
l
(MoK ) [/mm]
0.312
1356
0.474
1904.0
The molecular structures of complexes 1 and 2 are depicted in
Fig. 2 and Fig. 3 respectively. Some selected bond distances and
bond angles are summarized in Table 2 and Table S1, respectively
for complexes 1 and 2.
a
F(0 0 0)
Crystal Size [mm]
Temperature (K)
Radiation [Å]
h Min-Max [°]
Dataset
0.20 ꢁ 0.20 ꢁ 0.25
0.04 ꢁ 0.04 ꢁ 0.06
150
150
0.71073
0.71073
2.30, 26.0
ꢀ13: 13; ꢀ20: 20;
ꢀ31: 31
Complex 1 crystallizes in the triclinic system of space group P-1
while complex 2 crystallizes in the monoclinic system with space
group P21/c. In Complex 1 the asymmetric unit contains two
crystallographically independent dinuclear units A and B which
are isostructural but slightly different with respect to their respec-
tive bond distances and bond angles and are bridged by O6 and O2
respectively. In complex 2 the two vanadium centers are bridged
by O2. It is interesting to note that in both asymmetric unit A
and B of complex 1, co-linear oxido atom exactly bisects the two
metal centres (V1-O6 = 1.792 Å and V2-O2 = 1.7945 and lie in the
expected region [34] but this is closely missed in complex 2
(O2-V2 = 1.796 Å and O2-V1 = 1.782 Å). In complex 1 the relative
disposition of the two V@O groups are exactly trans, with
O5 = V1. . .V1#1 = O5#1 torsion angle of 180°, whereas, in
complex 2, the relative disposition of the two V@O groups is some-
what twisted with O3 = V1. . .O1 = V2 torsion angle of 133.33°.
The two vanadium centres in asymmetric units A and B of com-
plex 1 are in distorted octahedral geometry with O7-V1-O8 and
O4-V2-O1 bond angles of 161.38° and 163.82°, respectively indi-
cating a significant deviation from the ideal value of 180°. Simi-
larly, in complex 2, O5-V1-O6 (163.14°) and O7-V2-O8 (161.7°)
angles are also significantly deviated from 1800. In asymmetric
unit A of complex 1 the axial positions are held by donor atoms like
N2 and O5 (terminal). The basal coordinates are taken up by donor
atoms like N1, O7, O8 and O6 (bridging). In complex 2 the axial
2.2, 28.7
ꢀ14: 14; ꢀ21: 21;
ꢀ30: 30
Tot., Uniq. Data, R(int)
Observed data [I greater than
52901, 18724, 0.140 23769,8721,0.160
6690
5281
2.0r(I)]
Nref, Npar
R, wR2, S
18724, 787
0.0905, 0.2935, 1.03 0.1017,0.2716,1.047
8721, 542
to give 5-bromo-salicylaldehyde. We have performed the several
sets of such reaction for varying time (3h, 6 h, 9 h and 12 h) and
products were isolated and quantified in each case. Then the calcu-
lated yield (%) are tabulated in Table 3.
2.7. DFT calculations
The ground state optimized structures of free complex 2 and its
probable catalytic intermediates formed during oxidative bromi-
nation of salicylaldehyde have been carried out using DFT [30]
method in a Gaussian 09 W software package [31]. Becke’s hybrid
function [32] along with the Lee-Yang-Parr (LYP) correlation func-
tion [33] were used throughout the study. The geometry of all the
structures were fully optimized without any symmetry con-
straints. LanL2dz basis set under B3LYP was used for all the atoms
during the optimization of ground state geometries.
Fig. 2. Molecular view of complex 1; H atoms are omitted for clarity.

M. Debnath et al. / Inorganica Chimica Acta 480 (2018) 149–158
153
Å, V1-N4 = 2.284 Å and V2-N2 = 2.274 Å for complex 2) reveal the
weakening of V–N bonds.
3.3. Electrochemical study
The electrochemical behavior of complex 2 (Fig. 4) was studied
by cyclic voltammetry in the range +1.00 to ꢀ1.00 V at a scan rate
100 mVsꢀ1 in Acetonitrile at platinum electrode versus SCE using
tetrabutyl-ammonium perchlorate (TBAPC) as supporting elec-
trolyte. The complex 1 and 2 remain as dinuclear entities as evi-
denced from HRMS spectra (Figs. S6a and S6b). The two anodic
peaks at -0.042 and 0.417 V correspond (peak to peak separation
value is 0.459 V) to V(IV)-V(IV) ? V(V)-V(IV) and V(V)-V(IV) ?
V(V)-V(V) oxidations while the cathodic peaks at 0.348 (not well
resolved) and ꢀ0.141 V (peak to peak separation value is 0.489
V) correspond to V(V)-V(V) ? V(IV)-V(V) and V(IV)-V(V) ? V(IV)-
V(IV) reductions. The E = 0.382 V corresponds to V(IV)-V(V) ꢀ
½
V(V)-V(V) process and E = ꢀ0.091 V corresponds to V(IV)-V(IV)
½
ꢀ V(IV)-V(V) process. The 1st redox couple (V(IV)-V(V)/V(V)-V
(V) appears to be quasi-reversible, whereas the other couple V
(IV)-V(IV)/V(V)-V(IV) is found to be irreversible. Controlled coulo-
metric experiment shows that the wave is one electron transfer
process. As the phenolate ligand as well as methoxy group could
not be reduced in this potential range [36], we assign them as
metal centered reduction potentials for the VO3+/VO2+ couple. No
reproducible CV for complex 1 was obtained.
3.4. Electronic spectra
Fig. 3. Molecular view of complex 2; H atoms are omitted for clarity.
Absorption spectra of complex 1 shows one pꢀe1ak at 685 nm
(e
/ Mꢀ1cmꢀ1 = 3040) and a hump at 565 nm (
e
e
/M cmꢀ1 = 2640)
/Mꢀ1cmꢀ1 = 3080)
whereas complex 2 shows a peak at 600 nm (
Table 2
which may be attributed to the ligand (Phenoxido) to metal [V
(V)] charge transfer (LMCT) bands (Fig. S7).
Selected bond distances of complex 1 and 2.
Complex 1
Complex 2
V1-O3
3.5. Oxidative bromination of salicylaldehyde
N1-V1
2.329(5)
1.611(4)
N2-V1
N3-V2
N4-V2
O1-V2
O2-V2
O3-V2
O4-V2
O5-V1
O6-V1
O7-V1
O8-V1
2.387(4)
2.320(5)
2.392(4)
1.844(4)
1.7945(10)
1.603(3)
1.845(4)
1.604(3)
1.7918(8)
1.840(3)
1.851(3)
V1-O2
V1-O5
V1-O6
V1-N4
V1-N3
V2-O1
V2-O2
V2-O7
V2-O8
V2-N2
V2-N1
1.783(5)
1.861(4)
1.873(5)
2.284(5)
2.399(5)
1.597(4)
1.795(5)
1.875(5)
1.881(5)
2.273(6)
2.367(5)
Vanadium(V) complexes were found to catalyze the oxidative
bromination of organic substrates in the presence of H2O2 and
bromide ion [37,38] where vanadium centers were claimed to be
coordinated by
1 or 2 equivalents of H2O2, forming oxido-
monoperoxido, [VO(O2)]+ and oxido-diperoxido, [VO(O2)2]- species
which ultimately gave rise to the actual oxidant [(VO)2(O2)3]
positions are also taken up by N3 and O3 (terminal) for V1 and N1
and O1 (terminal) for V2 centre. The equatorial positions are occu-
pied by donor atoms N4, O5, O6. O2 (bridging) for V1 while N2, O7,
O8 and O2 (bridging) atoms for V2 centre.
In the asymmetric unit A of complex 1, the central metal atom is
shifted towards the terminal oxygen atom (O5) by 0.184 Å from
the equatorial plane defined by N1, O7, O6 and O8. In case of com-
plex 2 the V1 atom is shifted from the equatorial plane towards the
terminal oxygen O3 by 0.257 Å whereas the V2 center is shifted by
0.263 Å.
The distances between the terminal oxygen atom and central
metal atoms in both the complexes fall in the comparable range
(V1-O5 = 1.603 Å for complex 1A and V1-O3 = 1.611 and V2-O1 =
1.597 Å for complex 2) with other structurally characterized
oxido-vanadium complexes [35]. In both the complexes, the signif-
icant longer distances between the axial and equatorial nitrogen
atom from the central vanadium atom (V1—N2 = 2.387 Å and
V1—N1 = 2.329 Å for complex 1; V1-N3 = 2.399 Å, V2-N1 = 2.367
Fig. 4. CV of complex 2 in MeCN solvent at 25 °C, [C] = 1.0 mM; [TBAPC] = 0.10 M,
scan rate = 100 mVsꢀ1.

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M. Debnath et al. / Inorganica Chimica Acta 480 (2018) 149–158
Scheme 3. Schematic presentation of the formation different intermediates of complex 2 in the presence of HClO4 and H2O2.
[20,39] to oxidize bromide ion most likely to HOBr and brominates
the substrates.
presence of HClO4 in mixed solvents (H2O:MeOH:THF = 4:3:2)
[29] at room temp.; cf. Scheme 3. The presence of acid was found
to be essential during the catalytic reaction to facilitate the bromi-
nation reaction, but an excess of HClO4 (ꢃ80 mmol) causes decom-
position of the catalysts as well as lowering of selectivity of the
reaction. In the absence of acid no catalysis were observed. Under
the reaction conditions, a maximum of ꢄ89% conversion was
achieved with both the complexes (Table 3).
In the absence of catalyst, the reaction mixture gave only 4%
conversion of salicylaldehyde to 5-bromosalicylaldehyde. Almost
comparable conversion of the substrate, TON as well as selectivity
were achieved for complexes 1 and 2.
Here also complexes 1 and 2 are found to catalyze the bromina-
tion of salicylaldehyde in the presence of H2O2 and bromide ion. In
acidic medium both the dinuclear complexes [LiOV(O)VOLi] turn
into mononuclear species [L2V = O]+ (See the HRMS data in Sup file,
Fig. S8) through the abstraction of bridging O atom by H+ eliminat-
ing one water molecule (Scheme 3) which may be in equilibrium
[LiV = O]+ + H+ ꢀ [LiV = OH]2+ and reacts with H2O2 to form
hydroxido-hydroperoxido species, [LiV(OH)(OOH)]+ and then
hydroxido-peroxidospecies [LiV(OH)(O2)] (Eq. (13), Scheme 3) as
the active intermediate for the catalytic oxidation of Brꢀ to Br+
and to brominate the substrate Scheme 4.
3.6. Kinetic and mechanistic studies
½LiOVðOÞOLiꢂ þ 2Hþ () 2½LiVðOÞꢂþ þ H2O
½LiVðOÞꢂþ þ Hþ () ½LiV ¼ OHꢂ2þ
ð1Þ
ð2Þ
ð3Þ
It was observed that complexes 1 and 2 ([LiOV(O)VOLi]) satis-
factorily catalyze the oxidative bromination of salicylaldehyde to
give 5-bromosalicylaldehyde in the presence of H2O2/KBr and
HClO4 in mixed solvents (H2O:MeOH:THF = 4:3:2) [29] at room
temp. However, all the kinetic studies have been carried out the
in MeCN by following the change in absorbance at 685 nm (kmax
for complex 1) and 765 nm. Addition of 2 or more equivalents of
HClO4 to an acetonitrile solution of the complex 1 produced
observable changes in the UV/visible spectra with a shift in kmax
from 685 nm to 765 nm for complex 1. Similarly kmax at 600 was
shifted to 765 nm for complex 2. The oxidation of Brꢀ to Br+ by
the reaction with [LiV(OH)(OOH)]+ is given in Eq. (4) (i = 1 or 2
½LiV ¼ OHꢂ2þ þ H2O2 () ½LiVðOHÞðOOHÞꢂþ þ Hþ
It is proposed that dioxidovanadium(V) [L2V(O)2]+ (Scheme 5,
see later), formed through the oxidation of Brꢀ to Br+ by
[L2V(OH)(O2)] which is again formed from [L2V(OH)(OOH)]+
(Scheme 3), satisfactorily catalyzes the oxidative bromination of
salicylaldehyde to give 5-bromosalicylaldehyde as major product
along with 3,5-dibromosalicylaldehyde and 2,3,5-tribromosalicy-
laldehyde as minor products (Fig. S9) using H2O2/KBr in the
Scheme 4. Catalytic reaction products.

M. Debnath et al. / Inorganica Chimica Acta 480 (2018) 149–158
155
Scheme 5. Proposed catalytic cycle for the oxidative bromination of salicylaldehyde catalyzed by complex 2.
Table 3
Catalytic parameters for the bromination of salicylaldehyde by KBr/H2O2 (KBr = 40 mmol, H2O2 = 2 ml i.e. 67 mmol) using complexes 1 and 2 as catalysts (0.04 mmol) in mixed
solvents H2O:MeOH:THF = 4:3:2 [29] at room temperature (25 °C) in presence of 0.2 ml HClO4.
Catalyst
Substrate (mmol)
Reaction time (hr)
Conversion (%)
% Yield
Selectivity
TONy
5-Br-sal (major)
3,5-di-Br-sal (minor)
Complex 1
20
3
6
9
12
12
37
66
89
10
33
58
74
2
4
8
15
83.3
89.1
87.8
83
445
440
Complex 2
20
3
6
9
12
12
40
67
88
9
3
9
15
18
75.0
77.5
77.6
79.5
31
52
70
y
TON is determined by the ratio of No. of moles of substrate converted to product and the number of moles of catalyst (0.04 mmol) used.
½LiVðOHÞðOOHÞꢂþ þ H2O2 þ OHꢀ ! ½LiVðOÞðO2Þꢂ þ O2 þ H2O
In the presence of sufficient equivalents of H2O2, substrate and
acid each of these complexes has been found to catalyze the bromi-
nation of salicylaldehyde giving multiple turnovers in hours at
room temperature.
ð7Þ
for complexes 1 and 2 respectively). The product observed by
UV/visible spectroscopy is primarily tribromide under the
experimental conditions used here but without substrate (RH). In
the presence of an organic substrate capable of electrophilic
aromatic substitution, reaction (5) leads to halogenations.
½LiVðOHÞðOOHÞꢂþ þ Brꢀ ! ½LiVðO2Þꢂꢀ þ Brþ þ H2O
ð4Þ
The addition of 2 or more equivalents of HClO4 to an acetonitrile
solution of the complex 1 produced observable changes in the
UV/visible spectra with a shift in kmax from 685 nm to 765 nm
(Fig. 5a) (for complex 2, a shift in kmax occurs from 600 nm to
765 nm, see Fig. 5b) and may be attributed to the formation of
½LiVðOHÞðOOHÞꢂþ þ Brꢀ þ RH ! ½LiVðO2Þꢂꢀ þ RBr þ Hþ þ H2O ð5Þ
However, in the absence of an organic substrate, dioxygen gas
was generated upon the addition of an equivalent of hydrogen per-
oxide to a solution containing the oxidized halide species under
basic conditions. The halide-assisted disproportionation of hydro-
gen peroxide into water and dioxygen are given in Eqs. (6) and
(7). Here, the halogenation of the solvent or ligands has not been
detected.
[LiV-OH]2+
. In contrast, the addition of 10 equivalent of
tert-butyammonium bromide in the absence of acid produced no
observable change in the UV/visible spectra of these complexes.
The failure to oxidize Brꢀ by 1 in the absence of H+ clearly con-
firms acid catalyzed oxidation of Brꢀ. It was observed that the rate
of reaction increases with the increase in [H+]. Kinetics were
followed under pseudo-first-order conditions taking complex as a
minor component and monitoring the change in absorbance of
½LiVOðOÞOVLiꢂ þ 2Hþ þ 2H2O2 ! 2½LiVðOHÞðOOHÞꢂþ þ H2O
ð6Þ

156
M. Debnath et al. / Inorganica Chimica Acta 480 (2018) 149–158
Fig. 5. Shift in kmax of complex 1 and 2 with addition of HClO4 (blue line with 1 equiv acid, yellow with 2 equiv acid, magenta with 4 equiv acid, red with 6 equiv acid and
green with 10 equiv acid). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 6. (a) Time resolved spectra for the catalytic bromination of salicylaldehyde at [[L2(O)VOV(O)L2] (complex 2) = 1 ꢁ 10ꢀ4 M, [Substrate] = 2.5 ꢁ 10ꢀ3 M, [Brꢀ] = 1.25 ꢁ
10ꢀ3 M and [H2O2] = 1.25 ꢁ 10ꢀ3 M showing two clean isosbestic points at 560 and 650 nm; (b) corresponding kinetic trace at 600 nm.
the complex at either 685 nm (growth curve) or at 765 nm (decay
curve) for complex 1 but at both these wavelengths the rate con-
stants evaluated are to be almost identical. The dependence of
reaction rates on [Brꢀ] (1.0–10 mM) was carried out keeping [1]
= 1.0 ꢁ 10ꢀ4 M, [H+] = 1.25 ꢁ 10ꢀ3 M and temperature at 25 °C.
From the nature of kinetic traces it is obvious that the reaction
is first-order dependent on complex concentration (Figs. 6 and S10
for complex 1). The kinetic studies were carried out at fixed con-
centration of acid and bromide ion but varying the complex con-
centration. At each complex concentration we have deduced the
observed rate constant (kobs). Now a plot of log(kobs) vs. log[com-
plex] yielded a straight line with slope value 0.925 which clearly
manifests a first-order dependence of rate on complex concꢀe1ntra-
tion (Fig. S11). A linear least square fit to a plot of kobs (s ) vs.
[Brꢀ] yields slope = kBr = 8.82 0.35 and 6.74 0.19 Mꢀ1sꢀ1 for
complex 1 and 2 respectively (Fig. 7).
Analogously, the dependence of rate on [H+] was studied keep-
ing [Brꢀ] = 1.25 ꢁ 10ꢀ3 M and other conditions remaining the
same. A plot of k (=kobs/[Brꢀ]) vs. [H+] gives a non-linear curve of
decreasing slope (Fig. 8). Non-linear curve-fitting of experimental
Fig. 7. Variation of rate (kobs) with [Br-] in MeCN at [Complex] = 1 ꢁ 10ꢀ4 M, [Substrate] = 2.5 ꢁ 10ꢀ3 M, [H+] = 1.25 ꢁ 10ꢀ3 M and [H2O2] = 1.25 ꢁ 10ꢀ3 M for complex 1 (a)
and 2 (b).

M. Debnath et al. / Inorganica Chimica Acta 480 (2018) 149–158
157
Fig. 8. Variation of kobs/[Brꢀ] with [H+] in MeCN at [Complex] = 1 ꢁ 10ꢀ4 M, [Substrate] = 2.5 ꢁ 10ꢀ3 M, [Br-] = 1.25 ꢁ 10ꢀ3 M and [H2O2] = 1.25 ꢁ 10ꢀ3 M for complex 1 (a)
and 2 (b).
data to Eq. (11) gives Ka = (4.3 0.40) ꢁ 10ꢀ3 and (4.7 0.50) ꢁ
10ꢀ3 for complex 1 and 2 and kH = (65.0 2.23) and (61.87
2.27) Mꢀ1sꢀ1 for complex 1 and 2 respectively.
A plausible reaction sequence consistent with the experimental
observation may be framed as:
In case of mono-anionic species, 2d- the HOMO–LUMO energy
difference is 4.39 eV (Scheme 5), which indicates a more reactive
nature of it to form the starting species 2b+ in the catalytic cycle.
So, on the basis of DFT calculation, one can easily frame a catalytic
cycle (Scheme 5) which describes the driving force of the catalytic
efficiency of 2. In acidic medium complex 2 ([{VO(L2)}2O]) takes up
two protons to give [L2V = O]+ (2a+) and H2O. [L2V = O]+ (2a+) is in
Ka
VHþ () V þ Hþ
ð8Þ
protic equilibrium [LiV=O]+ + H+ ꢀ [LiV=OH]2+ (2a++
) and is
k
VH þ Brꢀ ! Products
ð9Þ
favoured by 420 kcal/mol energy. 2a++ in subsequent step reacts
with H2O2 to give [L2V(OH)(OOH]+ (2b+) which is favoured by
219.4 kcal/mol which then forms 2c which is favoured by 12.54
kcal/mol (Scheme 3). Now 2b+ forms 2d- through two transient
rate ¼ k½VHꢂ½Brꢀꢂ
k½Hþꢂ½Brꢀꢂ
ð10Þ
ꢀ
intermediates (2b+ and 2b+00) where oxidation of Br to Br+ takes
place which is favoured by 81.5 kcal/mol. 2b+ is one of the member
of catalytic cycle. Now the regeneration of 2b+ from 2d- is again
favoured by ꢄ 338.6 kcal/mol. So our proposed catalytic
Scheme seems to be well suited on the basis of energy considera-
tion obtained from DFT calculations (Table S2).
0
kobs
¼
ð11Þ
Ka þ ½Hþꢂ
The very high Ka is different from Ka value determined by Pec-
oraro et al., which corresponds to the protonation of peroxido oxy-
gen atom. In the present reaction this protonation occurs at V = O
oxygen atom which might be responsible for significantly higher
Ka values than that reported by Pecerarro et al. [5].
The existence of [L2V(OH)(OOH)]+ (2b+) species in catalytic
solution mixture was confirmed by HRMS studies which appears
at 456.0933 ([L2V(OH)(OOH)]+ + H+) (Fig. S13). Another intermedi-
ate [L2V(O2)]- (2d-) appears at 437.0948 when the complex treated
with H2O2 (Fig. S14).
In the presence of multiple equivalents of H2O2, bromide and H+
ions the vanadium complexes act as catalyst for the peroxidative
halogenation of salicylaldehyde. Under this catalytic conditions
(H2O2/KBr 500 equivalent each with respect to catalyst in mixed
solvents H2O:MeOH:THF = 4:3:2 in the presence of 2 or more
equivalents of HClO4 with respect to complex at room tempera-
ture) bromination of salicylaldehyde occurs within 12 h with
TON 405 and 450 for complexes 1 and 2, respectively. The catalytic
bromination of salicylaldehyde can be rationalized by adopting the
following reaction sequences:
4. Conclusion
Dinuclear oxidovanadium(V) complexes [L1VVO(m2-O)VO(L1)]
(1) and [L2VVO(m2-O)VO(L2)] (2) of ONNO donor amine-bis(pheno-
late) ligands (H2L1 and H2L2) have been synthesized and character-
ized by single crystal X-ray diffraction studies. The complexes 1
and 2 are efficient to catalyze the oxidative bromination of salicy-
laldehyde in the presence of H2O2 to produce 5-bromo salicylalde-
hyde as the major product with TONs more than 400. The kinetic
analysis of the bromide oxidation reaction indicates a mechanism
which is first order in protonated peroxidovanadium complex
and bromide ion and limiting first-order on [H+]. The Ka of proto-
nated oxido species are: Ka = (4.3 0.40) ꢁ 10ꢀ3 (pKa = 2.37) and
(4.7 0.50) ꢁ 10ꢀ3 (pKa = 2.33) respectively for complex 1 and 2.
On basis of the chemistry observed for these model compounds,
a mechanism of halide oxidation and a detailed catalytic cycle
are proposed for the vanadium haloperoxidase enzyme and sub-
stantiated by DFT calculations.
½LiVðOHÞðOOHÞꢂþ þ Brꢀ () ½LiVðOÞ2ꢂꢀ þ H2O þ Brþ
RH þ Brþ () RBr þ Hþ
ð12Þ
ð13Þ
½LiVðOÞ2ꢂꢀ þ H2O2 þ 2Hþ () ½LiVðOHÞðOOHÞꢂþ þ H2O
ð14Þ
ð15Þ
RH þ H2O2 þ Brꢀ þ Hþ ! RBr þ 2H2O
To gain some insight into the mechanism of catalytic process,
the ground state geometry of complex 2 and some probable cat-
alytic intermediates of 2 (2a+, 2b+, 2c and 2d-) formed during the
oxidative bromination of salicylaldehyde (Schemes 3 and 5) were
performed in the gas phase.
The HOMO–LUMO energy difference is 2.69 eV for the complex
2 which reduces to 2.43 eV for 2a+, 3.17 eV for 2b+ and ultimately
2.85 eV for 2c giving rise to a species produced by binding of 2 with
H2O2 in acidic medium. The other selected HOMO and LUMO plots
of 2 and other intermediates viz. 2a+, 2b+, 2c and 2d- are given into
the Figs. S12, S13 and S14.
Acknowledgement
M. Ali thanks to DST West Bengal (Ref. No. 809(Sanc/ST/P/
S&T/4G-9/2014) for financial support.

158
M. Debnath et al. / Inorganica Chimica Acta 480 (2018) 149–158
274 (1988) 477;
Appendix A. Supplementary material
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Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.ica.2018.04.044.
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