Haloperoxidase activity of oxovanadium(V) thiobisphenolates

Article abstract of DOI:10.1002/chem.201002890

By employing the 2,2′-thiobis(2,4-di-tert-butylphenolate) ligand (^SL^2-) a novel oxovanadium(V) complex, (PPh ₄)₂[^SLV(O)(μ-O)₂-O) ₂V(O)^SL] (1), was synthesised that exhibits haloperoxidase activity: on addition of H₂O₂ a sequence of successive peroxide formation and intramolecular thioether oxidation events (sulfoxide and sulfone) led to a mixture of five products, which were all identified unambiguously, partly through an independent synthesis and characterisation. It was shown that internal thioether oxidation proceeds through peroxide formation, but the sulfoxidation of external thioether functions requires further activation of the peroxide function by protons or alkyl cations. Consistently, the employment of tBuOOH instead of H₂O₂ led to a very active system for the catalytic sulfoxidation of thioethers.

Full text of DOI:10.1002/chem.201002890

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FULL PAPER
DOI: 10.1002/chem.201002890
Haloperoxidase Activity of OxovACHUNTGRNENUG anadium(V) Thiobisphenolates
C. Gunnar Werncke, Christian Limberg,* Christina Knispel, Ramona Metzinger, and
Beatrice Braun[a]
Dedicated to Professor Hansgeorg Schnçckel on the occasion of his 70th birthday
Abstract: By employing the 2,2’-thio-
bis(2,4-di-tert-butylphenolate) ligand
(SL2À) a novel oxovanadium(V) com-
plex, (PPh4)2A
[SLV(O)(m2-O)2V(O)SL]
(1), was synthesised that exhibits halo-
peroxidase activity: on addition of
H2O2 a sequence of successive peroxide
formation and intramolecular thioether
oxidation events (sulfoxide and sul-
fone) led to a mixture of five products,
which were all identified unambiguous-
ly, partly through an independent syn-
thesis and characterisation. It was
shown that internal thioether oxidation
proceeds through peroxide formation,
but the sulfoxidation of external thio-
ether functions requires further activa-
tion of the peroxide function by pro-
tons or alkyl cations. Consistently, the
employment of tBuOOH instead of
H2O2 led to a very active system for
the catalytic sulfoxidation of thioethers.
G
ACHTUNGTRENNUNG
Keywords: haloperoxidases · oxida-
tion · peroxides · thioethers · vana-
dium
Introduction
Oxovanadium(V) calixarene complexes have proved valua-
ble as polymerisation catalysts,[1] and they can also be uti-
lised as functional models for surface sites occurring on sup-
ported vanadium oxides:[2] they mimic the structure of these
sites and at the same time catalyse the oxidative dehydro-
genation of alcohols with O2.[2c–f] It was found, however, that
the addition of hydroperoxides to the oxovanadium(V) thia-
calixarene compound I[2e] (Scheme 1)—one of the most
active catalysts in combination with O2—leads to the partial
oxidation of the thioether units,[3] thereby hinting at haloper-
oxidase activity of such complexes. Vanadium-dependent
haloperoxidases (VHPO, Scheme 2) are enzymes responsi-
ble for the production of a variety of halogenated com-
pounds through the initial formation of hypohalous acids as
the halogenating agents, and at the same time they mediate
enantioselective sulfoxidations by hydrogen peroxide.
Therefore, a corresponding investigation was started by
employing a more simple ligand, which can be regarded as
the relevant section of the thiacalixarene ligand in I: 2,2’-
Scheme 1. The ligand SL2À as a simplified form of the thiacalixarene
ligand in I.
thioACHTUNGTRENNUNG
bis(2,4-di-tert-butylphenol) (SLH2; see Scheme 1).
[a] C. G. Werncke, Prof. Dr. C. Limberg, C. Knispel, R. Metzinger,
Dr. B. Braun
Institut fꢀr Anorganische Chemie
Humboldt-Universitꢁt zu Berlin
Brook-Taylor-Strasse 2, 12489 Berlin (Germany)
Fax : (+49)30-2093-6966
E-mail: christian.limberg@chemie.hu-berlin.de
Scheme 2. The active centres of vanadium-dependent haloperoxidases:
a) the resting state of native Ascophyllum nodosum bromoperoxidase,
b) the peroxo form of Curvularia inaequalis chloroperoxidase, and c) the
hydroperoxo intermediate proposed for the A. nodosum bromoperoxi-
dase.[4]
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002890.
Chem. Eur. J. 2011, 17, 2931 – 2938
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Results and Discussion
can be assigned to the complex anion. Each vanadium
centre is additionally coordinated by the 2,2’-thiobis(2,4-di-
tert-butylphenolate) ligand in a facial manner. Accordingly,
both vanadium atoms have distorted octahedral coordina-
tion geometries as in I, with the terminal oxo ligands and
the sulfur atoms positioned trans to each other. The vanadi-
um atom V1 is situated 0.3504(6) ꢃ above the mean plane
defined by O1, O2, O5 and O6. The V1=O3 bond in 1
(1.607(3) ꢃ) is slightly longer than the V=O bonds in I, the
Synthesis, structure and properties of (PPh4)2ACHTNURTGENNUG CAHTUNGTREN(NGUN m2-
[SLV(O)
S
O)2V(O)SL] (1): Thiobisphenolates, like L2À, have been em-
ployed as ligands in transition-metal chemistry before, also
in their S-oxidised forms.[5] In combination with vanadium,
so far the focus was on the exploration of the general coor-
dination properties[6,7] and the synthesis of potential ethyl-
ene polymerisation catalysts.[8] We started our investigation
by following the procedure for the preparation of I:[2e] A so-
lution of LH2 in acetonitrile was treated with PPh
V S distance of which (2.9445(11) ꢃ) in turn is longer than
À
S
À
[VO2Cl2]
the V1 S2 distance in 1 (2.8224(12) ꢃ). The deviation of the
in the presence of NEt3 with the expectation of obtaining an
O3, V1 and S1 atom arrangement from a linear geometry
[SLV(O)(m2-O)2V(O)SL] (1;
U
(166.45(11)8) is similar to that found in I. The bridging V O
À
analogue of I. Indeed, (PPh4)2A
see Scheme 3) could be isolated subsequently in the form of
dark violet crystals, which were investigated by X-ray dif-
fraction. The molecular structure of its dianion is shown in
Figure 1.
single bond lengths vary only between 1.831(3) and
1.842(3) ꢃ, so that the V2O2 core, in contrast to that of I, is
nearly symmetric. Accordingly, the distances of the pheno-
late oxygen atoms to the vanadium centres are also quite
similar, ranging from 1.948(3) to 1.965(3) ꢃ.
Surprisingly, a 51V NMR spectrum recorded for a 2.5 mm
solution of crystalline 1 dissolved in [D3]acetonitrile showed
two resonances at d=À488 and À502 ppm in the ratio of
1:2.6. The two species involved can also be discerned by
proton NMR spectroscopy. Both the chemical shift of the
minor species and its ratio to the major species proved to be
strongly dependent on the solvent used (d=À472 ppm in
CD2Cl2, shift of the ratio to 1:3.5). The ratio of the two sig-
nals also varied with temperature: on warming of a 2.5 mm
sample in acetonitrile to 758C the ratio increased to 1:19.
Moreover, it was observed that with increasing concentra-
tion the intensity of the minor species increased. These find-
ings point to a dimer/monomer equilibrium according to
Scheme 3, which is shifted to the right with increasing tem-
perature and decreasing concentration. Given the dimer/mo-
nomer equilibrium shown in Scheme 3, the equilibrium con-
stant (Keq) was determined to be 0.05 LmolÀ1 (acetonitrile,
ambient temperature). Consequently, under the conditions
chosen below for reactivity studies, both species are present
in solution with the monomer 1m being the major one. From
here on, the notations 1m and 1D are used if the monomer or
the dimer is specifically addressed. If no distinction is neces-
sary or possible and mainly the constitution matters, simply
“1” is used; the same applies for all other compounds dis-
cussed hereafter.
Scheme 3. Dimer/monomer equilibrium of compound 1.
Figure 1. Structure of 1·2MeCN within the crystal. All hydrogen atoms,
the Ph4P+ cations and co-crystallised acetonitrile solvent molecules are
À
À
omitted. Selected bond lengths [ꢃ] and angles [8]: O1 V1 1.831(3), O2
À
À
À
À
V1 1.840(3), O3 V1 1.607(3), O5 V1 1.965(3), O6 V1 1.948(3), S1 V1
À
À
À
2.8224(12), V1 (O1, O2, O5, O6) 0.351(1), O1 V2 1.842(3), O2 V2
1.838(3), O4 V2 1.617(3), O7 V2 1.947(3), O8 V2 1.959(3), S2 V2
Reactions of 1 with hydroperoxides: The investigation con-
cerning the redox chemistry of 1 was started with H2O2 as
the oxidant, which demonstrably does not oxidise SLH2
under ambient conditions in the absence of vanadium. A so-
lution of 1 in acetonitrile was treated with H2O2 (1 equiv;
0.1m solution in acetonitrile, dried with MgSO4) and after
removal of all volatiles a 51V NMR spectrum of the product
dissolved in [D3]acetonitrile revealed an almost complete
conversion of 1 to several products (see Figure 2). Besides a
small signal at d=À501 ppm belonging to the starting mate-
rial, two further signals at d=À511 and À521 ppm could be
detected; these signals are due to single and double oxida-
tion of the thioether function of the monomeric form of 1,
À
À
À
À
À
À
2.8297(12), V2 (O1, O2, O7, O8) 0.339(1), V1 V2 2.7782(7); O1-V1-O2
81.93(12), O1-V1-O3 103.93(14), O2-V1-O3 105.32(14), O3-V1-O5
97.02(14), O3-V1-O6 96.74(13), O3-V1-S1 166.45(11), O1-V2-O4
104.22(14), O2-V2-O4 103.55(14), O4-V2-O7 96.39(14), O4-V2-O8
97.38(14), O4-V2-S2 166.65(11), V1-O1-V2 98.28(14), V1-O2-V2
98.10(15).
The two V=O groups are linked by two bridging oxo li-
gands in a way that positions the terminal oxo ligands in an
anti fashion, and—ignoring small variations of the bond
lengths and angles—an approximate Cs symmetry with a
mirror plane running through these oxovanadium(V) groups
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Oxovanadium(V) Thiobisphenolates
FULL PAPER
Again the signal with the highest intensity should belong to
the product with the lowest degree of oxygenation (i.e., that
at d=À448 ppm). A separate, small signal at d=À308 ppm
could not be assigned unambiguously.
Consistently, the addition of 4 equiv of H2O2 decreased
the intensity of all signals assigned to products with a lower
O content in favour of the signals assigned to the products
with the highest O content, 3m and 6m, respectively. Further-
more, new resonances appeared at around d=À600 ppm,
which originated from polyoxovanadates (in this case
4À [9]
V12O32
)
and thus indicated a significant amount of de-
composition under these highly hydrolytic conditions (note
that H2O is formed in the course of the oxygenations with
H2O2). The treatment of 1 with H2O2 at À308C gave no dif-
ferent results.
Figure 2. 51V NMR spectra after the treatment of a solution of 1 in
[D3]acetonitrile with varying amounts of H2O2.
Employing tBuOOH instead of H2O2 led to a much more
simple conversion. The addition of 1.2 equiv to a solution of
1 in acetonitrile resulted in an almost exclusive formation of
2m, which can be further oxidised by 1.2 equiv of tBuOOH
to give 3m besides polyoxovanadates as decomposition prod-
ucts (see Figure S1 in the Supporting Information).
SO2
that is, they arise from PPh
G
SOLVO2] (2m) and PPh
G
LVO2]
(3m; see Scheme 4). It is reasonable to assign the signal with
the highest integral at d=À511 ppm to 2m since the stoichi-
ometry should favour monooxygenation, and this resonance
is located closest to that of 1m (monooxygenation should
have a smaller electronic effect than dioxygenation). Some-
what remote from this group of signals, a second group of
Selective synthesis of the oxidation products 2, 3 and 6: To
further confirm the signal assignments in the 51 V NMR
spectra some of the oxidation products were synthesised by
alternative routes starting from the oxidised ligand precur-
SO2
sors SOLH2 and
LH2. SOLH2
can be prepared from SLH2 by
oxidation with 3-chloroperoxy-
benzoic acid (1 equiv) at 08C,
while the synthesis of SO LH2 re-
2
quires more forcing conditions
(30% H2O2, 40 equiv, glacial
acetic acid, 1008C).[10] The sub-
sequent preparation of 2 (PPh4-
ACTHNGUTRNENUG[
SOLVO2]) followed the proce-
dure described for 1: SOLH2 was
dissolved in acetonitrile and
treated with PPh4ACHTUNTRGNEU[GN VO2Cl2] in
the presence of NEt3. Workup
led to pure 2, and cooling of a
saturated dark violet solution of
2 in acetonitrile (that according
to Figure 2 mainly contains 2m)
led to red crystals. X-ray dif-
fraction revealed that 2 crystal-
lises as the dimer (PPh4)2-
Scheme 4. Products resulting from the oxygenation of 1m.
ACTHUNGTRENNUG[ ACTHUNGTRENNUNG
SOLV(O)(m2-O)2V(O)SOL] (2D).
The molecular structure of the
dianion is shown in Figure 3. It is very similar to that of 1D,
from which it can be derived formally by replacing the thio-
ether function by a sulfoxide unit. In contrast to 1D, there
does not seem to be a coordinative interaction between the
vanadium atom and the sulfur atom in 2D, since the distance
(3.2437(5) ꢃ) is longer than the sum of the van der Waals
radii of vanadium (1.34 ꢃ) and sulfur (1.85 ꢃ). The oxygen
atom of the sulfoxide bridge points away from the vanadium
three signals (d=À416, À428 and À448 ppm) can be found.
This shift difference indicates an electronic change for the V
centre of 1m that is larger than the one caused by oxidation
of the thioether unit and thus points to the introduction of
peroxo functions. Combination of
a
corresponding
(O2)V=O+ unit with L2À, SOL2À and
would yield fur-
ther products, PPh4A 4ACTHUNGTRENNU[G
[SLVO(O2)] (4m), PPh SOLVO(O2)] (5m)
S
SO2 2À
L
N
SO2
and PPh
N
LVO(O2)] (6m) corresponding to these signals.
Chem. Eur. J. 2011, 17, 2931 – 2938
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C. Limberg et al.
Figure 3. Structure of 2D·2CD3CN within the crystal. All hydrogen atoms,
Figure 4. Structure of 3D·4MeCN within the crystal. All hydrogen atoms,
the Ph4P+ cations and co-crystallised acetonitrile solvent molecules are
the Ph4P+ cations and co-crystallised acetonitrile solvent molecules are
À
omitted. Selected bond lengths [ꢃ] and angles [8]: O1 V1 1.8537(11),
À
À
omitted. Selected bond lengths [ꢃ] and angles [8]: O1 V1 1.951(3), O2
À
À
À
O1’-V1 1.8125(11), O2 V1 1.9241(11), O4 V1 1.9386(11), O5 V1
À
À
À
À
V1 1.869(2), O2’ V1 1.797(2), O3 V1 1.591(3), O4 V1 1.952(2), O5 V1
À
À
1.6007(11), V1 V1’ 2.7684(6), V1 (O1, O1’, O2, O4) 0.461(1); O1-V1-
O1’ 81.94(5), O1-V1-O5 196.80(5), O1’-V1-O5 105.44(6), O2-V1-O5
103.22(5), O4-V1-O5 101.45(5), V1-O1-V1’ 98.06(5).
À
À
2.527(3), V1 V1’ 2.7517(12), V1 (O1, O2, O2’, O4) 0.364(1); O1-V1-O3
98.15(13), O2-V1-O3 105.12(12), O2’-V1-O3 103.32(16), O3-V1-O4
97.90(12), O3-V1-O5 171.86(12), V1-O2-V1’ 97.3(12).
atom and is thus not oriented appropriately for an interac-
tion, though this could have been expected on the basis of
previous reports by Cornman et al.[7]
the O3, V1 and O5 atoms from a linear geometry
(171.86(12)8) is smaller than that found for the O-V-S unit
in 1D. Overall, both vanadium atoms exhibit a distorted oc-
tahedral coordination with the vanadium atom positioned
0.364(1) ꢃ above the mean plane defined by O1, O2, O2’
and O4. The 51V NMR spectrum revealed only a single
signal at d=À522 ppm even at higher concentrations and
temperatures, which hints at the exclusive presence of
Accordingly, both vanadium atoms show a distorted
square pyramidal coordination geometry. The missing sulfur
coordination, nonetheless, has hardly any influence on all
the other bond lengths and bond angles relative to 1D. The
vanadium atoms in 2D are situated somewhat higher
(0.461(1) ꢃ) above the mean plane defined by O1, O1’, O2
and O4 than those of 1D, which is probably due to the miss-
ing ligand trans to the terminal oxo ligand. The 51V NMR
spectrum of crystalline 2 dissolved in [D3]acetonitrile shows
only one signal at d=À511 ppm, even at higher concentra-
tions. Neither heating to 758C (in CD3CN) nor stepwise
cooling to À758C (in CD2Cl2) led to the appearance of a
second signal. With the background of the observations
made for compound 1, these findings point to the exclusive
presence of monomeric 2m in solution. The fact that the posi-
tion of the signal is closer to that of 1m than to the one of 1D
lends further support to this assignment. Finally, the chemi-
cal shift is in excellent agreement with that assigned to 2m in
Figure 2, which confirms the interpretation.
monoACHTNUGRTNEUNG
meric 3m in solution. Again, this signal matches the
one assigned to 3m in Figure 2. With respect to the occur-
rence of the polyoxovanadate signals in the 51V NMR spec-
trum of the system 1/4H2O2 (see above) it is noteworthy
that in the presence of traces of water 3 decomposes to give
free ligand and polyoxovanadates (mostly V12O324À).
Finally, we have succeeded in the independent synthesis
SO2
of the peroxide PPh
G
LVO(O2)] (6) by treating 3 with an
equivalent amount of H2O2, which led to an immediate
colour change from violet to red. After workup at À308C
red crystals could be obtained by diffusion of hexane into a
solution of 6 in CH2Cl2 at À308C, which were investigated
by X-ray diffraction. The molecular structure of the anion of
6m is shown in Figure 5.
Compound 3 was prepared analogously to the former
In contrast to compounds 1–3, compound 6 has a mono-
meric constitution in the solid state. If the side-on bound
peroxide ligand is regarded as occupying two coordination
sites, the coordination sphere of the vanadium centre can be
described as distorted octahedral, which is remarkable con-
sidering that usually a pentagonal pyramidal arrangement of
SO2
complexes: The ligand precursor
LH2 was suspended in
acetonitrile and treated with PPh4ACHNUTGTRENNG[NU VO2Cl2] in the presence
of NEt3. Workup and cooling of a saturated acetonitrile so-
lution gave red crystals, which were suitable for X-ray dif-
fraction measurements. Like 1 and 2, compound 3 also crys-
SO2
D
2
tallises as the dimer (PPh4)
[
LV(O)
(m2-O)2V(O)SO L] (3 )
the ligands is found for [L3V(O)ACTHGNUTERNNUG
(h2-O2)] complexes.[11] The
and the molecular structure of its dianion is similar to that
octahedral arrangement in 6m is the result of the facial bind-
of 1D (Figure 4).
ing of the
L
ligand by means of the two phenolate func-
SO2 2À
À
The V2O2 core is somewhat more asymmetric (d
(V1
tions and an oxygen atom of the sulfone linker, which is sit-
uated trans to the terminal oxo ligand O3. The peroxide
À
O2)=1.869(2) ꢃ and d
N
À
minal oxygen bonds are slightly shorter (1.591(3) ꢃ). The
function binds at the V centre with two almost identical V
SO2 2À
À
À
L
ligand binds in a facial fashion so that one of the
oxygen atoms of the sulfone bridge is situated trans to the
terminal V=O bond. The deviation of the arrangement of
O bond lengths at 1.829(3) ꢃ (V O1) and at 1.850(3) ꢃ (V
À
O2). The O–O distance of 1.471(4) ꢃ is rather long. O O
bond lengths of known vanadium complexes with side-on
2934
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Chem. Eur. J. 2011, 17, 2931 – 2938