Asymmetric catalytic sulfoxidation by a novel v IV 8 cluster catalyst in the presence of serum albumin: A simple and green oxidation system

Article abstract of DOI:10.1039/c6ra08153c

A novel VIV8 cluster formulated as [V₈O₁₂(OH)₄(CH₃O)₄(DAC)₄]·7CH₃OH (1) (DAC = 1,2-diaminocyclohexane) has been constructed successfully. Enantioselective oxidation of a series of alkyl aryl sulfides catalyzed by 1 is tested in an aqueous medium in the presence of serum albumin. The catalytic procedure is found to be simple and environmentally friendly. The influences of the parameters such as concentration of catalyst and oxidant, pH, and reaction time on the thioanisole as models are investigated. Under optimum conditions, 1 exhibits high conversion (up to 99%), excellent chemoselectivity (≥90% in all cases) and moderate enantioselectivity (up to 75% ee). After binding with serum albumin, the catalytic activity of 1 is promoted. The bovine serum albumin (BSA) and pig serum albumin (PSA) molecules have a more positive effect on the catalytic activity.

Full text of DOI:10.1039/c6ra08153c

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Asymmetric catalytic sulfoxidation by a novel
VI8V cluster catalyst in the presence of serum
Cite this: RSC Adv., 2016, 6, 44154
albumin: a simple and green oxidation system†
a
a
a
a
Jie Tang,ac Peng-Fei Yao, Xiao-Ling Xu, Hai-Ye Li, Fu-Ping Huang,
*
a
c
a
ab
*
Qing-Qing Nie, Mei-Yi Luo, Qing Yu and He-Dong Bian
A novel VI8V cluster formulated as [V8O12(OH)4(CH3O)4(DAC)4]$7CH3OH (1) (DAC ¼ 1,2-diaminocyclohexane) has
been constructed successfully. Enantioselective oxidation of a series of alkyl aryl sulfides catalyzed by 1 is tested in
an aqueous medium in the presence of serum albumin. The catalytic procedure is found to be simple and
environmentally friendly. The influences of the parameters such as concentration of catalyst and oxidant, pH,
and reaction time on the thioanisole as models are investigated. Under optimum conditions, 1 exhibits high
conversion (up to 99%), excellent chemoselectivity ($90% in all cases) and moderate enantioselectivity (up to
75% ee). After binding with serum albumin, the catalytic activity of 1 is promoted. The bovine serum albumin
(BSA) and pig serum albumin (PSA) molecules have a more positive effect on the catalytic activity.
Received 30th March 2016
Accepted 27th April 2016
DOI: 10.1039/c6ra08153c
www.rsc.org/advances
Serum albumins (SAs) are the major soluble protein constitu-
ents of the circulatory system and have many physiological func-
tions.32 They are generally robust, abundant, readily accessible,
Introduction
Polyoxometalates (POMs) stimulate many current research
activities in broad elds of science, such as catalysis,1–7
materials,8 medicine,9 magnetism,10–13 and photochemistry.14,15
This can be attributed to their favorable chemical and physical
properties, such as redox potentials,16–18 acidities,2 solubility in
various media,19 and impressive sensitivity to light and elec-
tricity.20 Notably, their thermal,8 hydrolytic,21 and oxidative
redox stabilities22 make them competitive candidates to rival
organometallic complexes and enzymes for deployment in
organic oxidation processes.23–25
The use of POMs for carrying out asymmetric catalysis26
remains a major challenge because most POM anions possess
high symmetry.18 To date, much effort has been devoted to
exploring the preparation of chiral POM-based systems,18 as
well as the enantioselectivity achievable with enantiopure POMs
for asymmetric transformations.27–30 Nevertheless, there are still
many shortcomings, such as low efficiency,27 instability,31 use of
toxic organic solvents,28 rapid racemization in solution,31 and
complicated synthetic steps to obtain POMs with chiral
structures.
inexpensive, and easy to handle.33,34 In addition, SAs have the
unique property of specic binding sites for hydrophobic organic
molecules,35 and as additives presenting a chiral environment36
may be capable of inducing enantioselectivity. For example,
Manfred T. Reetz and Ning Jiao carried out Diels–Alder reactions
in water with phthalocyanine–CuII complexes in the presence of
SAs, which afforded the products with up to 98% ee.37 In situ
generated dioxiranes have been used to oxidize a series of
prochiral suldes to the corresponding sulfoxides with up to 89%
ee in the presence of bovine serum albumin (BSA) as a chiral
auxiliary.38 However, to the best of our knowledge, few studies have
demonstrated the catalysis systems based on POMs with SAs as
chiral additives for obtaining enantiomerically pure products.
Chiral sulfoxides and their derivatives are an important class
of compounds that are extensively used as chiral synthetic
intermediates and auxiliaries for the preparation of biologically
active molecules, both in academia and in industry.39 Further-
more, compounds with sulfur chirality play a crucial role in
many biochemical processes40 and are widely exploited in the
pharmaceutical industry.41 The selective oxidation of organic
suldes to sulfoxides without any over-oxidation to sulfones,42–44
as well as devising environmentally benign catalytic oxidations,
are still key challenges in the synthesis of enantiopure
sulfoxides.
aState Key Laboratory for the Chemistry and Molecular Engineering of Medicinal
Resources, School of Chemistry and Pharmacy, Guangxi Normal University, Guilin,
541004, P. R. China. E-mail: huangfp2010@163.com
bSchool of Chemistry and Chemical Engineering, Guangxi University for Nationalities,
Key Laboratory of Chemistry and Engineering of Forest Products, Nanning, 530008, P.
R. China. E-mail: gxunchem@163.com
Herein, we report
[V8O12(OH)4(CH3O)4(DAC)4]$7CH3OH (1) (DAC
minocyclohexane) with a novel distorted shuriken-like topology
a
new VI8V cluster formulated as
1,2-dia-
¼
cGuilin Normal College, Guilin 541001, P. R. China
† Electronic supplementary information (ESI) available. CCDC 1439891. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c6ra08153c
containing two V4 buttery subunits arranged vertically. This
cluster has been used as
a homogeneous catalyst for
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vessel (25 mL), which was heated at 120 ꢀC fꢀor 3 days and then
cooled to room temperature at a rate of 10 C per hour. Black
block crystals of 1 were obtained and picked out, washed with
ethanol and dried in air. Yield: 37% (based on V(IV)). Anal. calc.
for C35H96N8O27V8: C, 28.62; H, 6.59; N, 7.63. Found: C, 28.57;
H, 6.64; N, 7.69. IR (KBr, cmꢁ1): 3748 w, 3425 s, 3296 s, 3244 s,
3142 m, 2936 s, 2863 m, 2820 w, 1642 s, 1602 m, 1451 m, 1399 w,
1384 w, 1359 w, 1304 w, 1236 w, 1202 w, 1132 m, 1040 s, 944 s,
754 s, 652 s, 563 m, 541 w, 508 w, 449 w, 422 w.
X-ray crystallographic determination
All reection data were collected on an Agilent Supernova
Scheme 1 Oxidation of sulfides catalyzed by 1 in the presence of SA.
˚
diffractometer (Mo, l ¼ 0.71073 A) at room temperature. A
semiempirical absorption correction by using the SADABS
program was applied, and the raw data frame integration was
performed with SAINT.47 The crystal structures were solved by
the direct method using the program SHELXS-97 (ref. 48) and
rened by the full-matrix least-squares method on F2 for all non-
hydrogen atoms using SHELXL-97 (ref. 49) with anisotropic
thermal parameters. All hydrogen atoms were located in
calculated positions and rened isotropically, except the
hydrogen atoms of water molecules were xed in a difference
Fourier map and rened isotropically. The details of the crystal
data were summarized in Table 1, and selected bond lengths
and angles for compounds 1 are listed in Table S1.†
asymmetric sulfoxidation reactions in water in the presence of
SAs (Scheme 1). Satisfactory chemoselectivities (>90%) for
sulfoxides were obtained in the presence of different SAs.
Compared to related chiral POM systems,31,45,46 this system has
the advantages of inexpensive chiral ligands, green reaction
media, and extremely simple working procedures. Conse-
quently, this VI8V cluster in conjunction with SAs represents
a promising type of POM catalytic system for diverse asym-
metric reactions, making it potentially useful in chemical and
biological synthesis.
Experimental section
Characterization of 1 in the absence of SA
Materials
A 33.3 mM solution of the 1 in 0.05 M phosphate-buffered saline
(PBS), pH 7.45, was prepared by mixing 100 mL of a 1 ꢂ 10ꢁ3
M
All reagents and solvents for synthesis and analysis were
commercially available. Bovine serum albumin (BSA) was
provided by Sigma-Aldrich, human serum albumin (HSA),
porcine serum albumin (PSA), rabbit serum albumin (RSA) and
sheep serum albumin (SSA) were obtained from Zhejiang,
China. All the suldes were purchased from Energy Chemical.
solution of the 1 and 2900 mL of 0.05 M PBS, pH 7.45. In parallel,
a 33.3 mM solution of SA-1 in 0.05 M PBS, pH 7.45, was obtained by
mixing 100 mL of a 1 ꢂ 10ꢁ3 M solution of 1 and 100 mL of a 1 ꢂ
10ꢁ3 M solution of SA (1.0 equiv.) in 2800 mL of 0.05 M PBS, pH
7.45. The UV/Vis spectra of these solutions were then recorded
between 250 and 500 nm.
Physical measurements
Table 1 Crystal data and structure refinement for 1
UV-Vis spectra were recorded on a Cary 100 UV-visible spectro-
photometer. The FT-IR spectra were recorded on a Perkin-Elmer
Spectrum One FT-IR spectrophotometer with a germanium
attenuated total reection (ATR) accessory, a DTGS KBr detector
and a KBr beam splitter ratio. Elemental analyses for C, H and N
were carried out on a model 2400 II, Perkin-Elmer elemental
analyzer. ESI-MS (electrospray ionization mass spectrum)
spectra were recorded on a Bruker HCT Electrospray Ionization
Mass Spectrometer. HPLC experiments were carried out using
Complex
1
C
Empirical formula
Formula weight (M)
Crystal system
Space group
35H96N8O27V8
1468.72
Triclinic
P1
14.1442 (11)
14.9100 (11)
16.0774 (13)
117.151 (8)
92.303 (6)
91.772 (6)
3009.9 (4)
2
1.621
1524
ꢀ
˚
a (A)
˚
b (A)
˚
c (A)
a (ꢀ)
b (ꢀ)
g (ꢀ)
1
UV2302II/P2302II high performance liquid chromatograph. H
3
and 13C NMR spectra were recorded on a Bruker NMR.
˚
V/(A
)
Z
Dc (g cmꢁ3
F(000)
)
Syntheses of complex 1
q range for data collection (ꢀ)
Reections collected/unique
Goodness-of-t on F2
3.4–26.4
[V8O12(OH)4(CH3O)4(DAC)4]$7CH3OH (1). A mixture con-
taining 1,2-diaminocyclohexane (57 mg, 0.5 mmol), V2O5
(91 mg, 0.5 mmol), methanol (10 mL), water (5 mL) and trie-
thylamine (0.5 mL) was sealed in a Teon-lined stainless steel
25 154/12 271 [R(int) ¼ 0.032]
1.046
Final R indices [I > 2s(I)]
R indices (all data)
R1 ¼ 0.0604, uR2 ¼ 0.1433
R1 ¼ 0.0753, uR2 ¼ 0.1554
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experimental and computer-simulated patterns of the corre-
sponding complexes are shown in Fig. S2.† Although the
experimental patterns have a few unindexed diffraction lines
and some are slightly broadened in comparison with those
simulated from the single crystal models, it can still be
considered favorably that the bulk synthesized materials and
the as-grown crystals are homogeneous for 1.
General procedure for oxidation of suldes
The SA (2.7 mmol, 176 mg) was mixed for 10 min at room
temperature with 1 (2.7 mmol, 0.4 mg) through a simple
mechanical stirring in 2 mL 50 mM PB (phosphate buffer)
solution. 0.27 mmol sulde was added to the reaction mixture
and the stirring was continued for 5 hours. The oxidant
(1.5 equiv.) was then added to the solution in one portion and
the reaction mixture stirred for another 10 h at room temper-
ature. Then, the solution was quenched with sodium sulte
solution and extracted with dichloromethane (2 mL ꢂ 5).
Finally, the combined organic solutions were dried over by
anhydrous sodium sulfate, ltered, and evaporated under
vacuum. The same procedure was followed with complex 1
alone or without 1. A sample of the crude reaction mixture re-
dissolved in a minimum amount of isopropanol before being
analyzed by HPLC with Chiralcel OB-H (4.6F mm ꢂ 250 mm)
column (Daicel Chemical Industries, Tokyo) at room tempera-
ture. Further purication was achieved by chromatography on
silica gel then was taken for the NMR analysis. The enantio-
meric excess (ee) and chemoselectivity were calculated using the
formulas: ee% ¼ [peak area (S ꢁ R)/(S + R)] ꢂ 100%;
chemoselectivity% ¼ [peak area SO/(SO + SO2)] ꢂ 100%,
SO ¼ sulfoxide, SO2 ¼ sulfone. Conversions were based on
sulde substrate; yields were referred to isolated product aer
column chromatography and were based on substrate; the
absolute congurations of the sulfoxides were assigned by
comparison of HPLC elution orders reported in the
literature.50,51
Results and discussion
Description of the crystal structures
[V8O12(OH)4(CH3O)4(DAC)4]$7CH3OH (1). X-ray structural
analysis shows that compound 1 crystallizes in space group of
ꢀ
P1 (Table 1). The asymmetric unit contains a [V8O12(OH)4(CH3-
O)4(DAC)4] unit (Fig. 1e) as well as seven lattice methanol
molecules. And the [V8O12(OH)4(CH3O)4(DAC)4] unit consists of
eight V(IV) ions, four 1,2-diaminocyclohexane ligands, four m2-
OHꢁ anions, four m2-CH3Oꢁ anions, four m3-O2ꢁ anions, four m2-
O2ꢁ anions, and eight terminal O2ꢁ anions (Fig. 1e and f). Four
external V(IV) ions (V1, V2, V5 and V8) of the V8 octamer are six-
coordinate with a distorted octahedral [VN2O4] geometry
formed by the coordination of four O atoms (one terminal O2ꢁ
anion, one m2-OHꢁ anion, one m3-O2ꢁ anion, and one m2-CH3Oꢁ
anion), and two N atoms from a DAC ligand. The distorted
quartet cone coordination sphere of the internal V4 is [VO5], in
which two m3-O2ꢁ anions, one m2-OHꢁ anion and one m2-CH3Oꢁ
anion lie in the equatorial plane and one terminal O2ꢁ anion
locate in the axial position. The arrangement of eight vanadium
atoms supported by four m2-OHꢁ anions, four m2-CH3Oꢁ anions,
and four m3-O2ꢁ anions displays a distorted shuriken topology
XRPD results
To conrm whether the crystal structures are truly representa- which can be described as consisting of ve edge-sharing dis-
tive of the bulk materials, X-ray powder diffraction (XRPD) torted V4 tetrahedron (Fig. 1b) with the adjacent V/V distance
˚
experiments had also been carried out for 1. The XRPD range of 2.9012 (4)–3.1951 (5) A. To the best of our knowledge,
Fig. 1 (a) The simple structural anatomy of the V8 unit; (b) the V8 skeleton with shuriken topology which can be described as consisting of five
edge-sharing distorted V4 tetrahedron; (c) the two V4 butterfly subunits with vertical arrangement; (d) the arrangement of eight vanadium atoms
supported by four m2-OHꢁ anions, four m2-CH3Oꢁ anions, and four m3-O2ꢁ anions, and the distribution of the eight terminal O2ꢁ anions; (e)
a view of the V8 cluster; (f) the V8 cluster with polyhedron mode; (g) the space-filling plot of the V8 cluster, and it's the size.
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very rare of metallic skeletons with this topology have been
observed in the polynuclear metal complexes.52–54
From another perspective, 1 could also view as an unusual
linked-buttery structure (Fig. 1a and c). In the V4 buttery
subunit, the four V centers are connected by two m3-O2ꢁ anions
and two m2-CH3Oꢁ anions (Fig. 1d). Different with the Mn8
octamers with linked-buttery structure reported by Christou
et al.,55,56 the two V4 buttery subunits which are connect each
other by four m2-OHꢁ anions (Fig. S1d†) arrange vertically.
ESI-MS solution analysis
Mass spectroscopy is a powerful tool for probing the properties
of inorganic clusters in solution as well as investigating the
supramolecular self-assemblies of inorganic coordination
architectures, as reported by Cronin and co-workers.57–59 In our
work, the electrospray mass spectrometric experiment of 1 was
taken to explore their solution stability in water.
Fig. 3 UV/Vis spectra of 1 (33.3 mM) in the absence and presence of
SAs (33.3 mM).
The ESI mass spectrum of 1 is shown in Fig. 2. The main ion
peak observed at a weight of 1246 which is isotopically resolved
and agree with the theoretical distributions (see Fig. 1, inset)
results from obtaining a proton of the [V8O12(OH)4(CH3O)4(DAC)4]
unit to form [V8O12(OH)4(CH3O)4(DAC)4 + H]+. These results
support the opinion that the VI8V cluster of 1 remains stable in
solution.60–62
(PhSMe) catalyzed by 1 was carried out in the presence of BSA
(1 : BSA molar ratio 1 : 1) employing the environmentally
benign oxidant H2O2 (ref. 64) (1.5 equiv.) (PhSMe and BSA were
chosen for these preliminary studies as a well-known model
substrate63 and serum albumin, respectively). Control reactions
without 1 or BSA were performed under the same conditions. As
shown in Fig. 4, the best result was obtained for 1 in the pres-
ence of BSA. Satisfactory yield (93%) and chemoselectivity (98%)
were obtained, albeit only with 10% ee. To rule out possible
catalysis by BSA alone, the reaction was repeated in the absence
of 1. Under otherwise identical conditions, inferior catalytic
activity (30% yield and 87% chemoselectivity) was observed. A
control experiment without BSA afforded the sulfoxide with
52% chemoselectivity in 51% yield, but the major product was
essentially racemic (ee < 1%). Thus, comparison of the results of
these reactions clearly demonstrates that the catalysis was
mainly due to complex 1, and that the enantiomeric excess was
determined by the protein.65–67
Binding of complex 1 with the serum albumin
UV/Vis spectra (Fig. 3) of 33.3 mM solutions of the 1 were recorded
in 50 mM PBS buffer, pH 7.45, in the absence and presence of
equimolar SAs (BSA, HSA, RSA, PSA, SSA) in order to examine the
extremely simple noncovalent binding.38 Comparing the spectrum
of the 1 with those recorded in the presence of SAs (Fig. 3), it can be
seen that PSA and BSA caused bathochromic shis of 10 nm (from
254 to 264 nm) and 6 nm (from 254 to 260 nm), respectively,
accompanied by strong increases in intensity. It is thus clear that
stronger association complexes of the 1 were formed with PSA and
BSA. On the contrary, in the presence of SSA, the spectrum of the 1
was largely unchanged, suggesting weaker binding.37
Disappointingly, unsatisfactory enantioselectivity was ob-
tained with H2O2. Therefore, sulfoxidation reactions were
evaluated with other oxidants. Among these oxidants, sodium
Asymmetric sulfoxidation
Taking the aspect of green chemistry into account, a prelimi- hypochlorite (NaClO) and sodium periodate (NaIO4) gave lower
nary investigation on the oxidation of methyl phenyl sulde yields and product selectivities, and the ee values obtained were
only 15% and 3%, respectively (Fig. 5). However, tert-butyl
hydroperoxide (TBHP) effectively oxidized PhSMe affording
a yield (92%) comparable to that with H2O2, but with somewhat
higher selectivity (97%) and ee (20%). Interestingly, the opposite
major enantiomer was produced (R-congured sulfoxide with
H2O2; S-congured sulfoxide with TBHP). Thus, the nature of
the oxidizing agent determines the enantiomeric excess of the
reaction product in some cases.
The reaction conditions for the oxidation of PhSMe were
further optimized by studying four different parameters,
namely the catalyst concentration, the oxidant concentration,
reaction time, and pH. Our results showed that the sulfoxide
yield and selectivity were strongly affected by the catalyst
concentration (Fig. 6). PhSMe was obtained in excellent yield
Fig. 2 The ESI mass spectrum of 1 in the scale of m/z ¼ 400–3000;
insert: the black spectra is the experimentally collected for low reso-
lution, and the red spectra is the predicted isotopic envelopes.
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Fig. 4 Controlled experiments for oxidation of PhSMe at room temperature for 10 h.
Fig. 5 Screening of oxidants for oxidation of PhSMe catalyzed by 1 in PB (pH 5.1) at room temperature after 10 h. The mol ratios of
oxidant : PhSMe : BSA : 1 (2.7 mmol) were 150 : 100 : 1 : 1.
with high selectivity and the maximum enantioselectivity using
The effects of the TBHP concentration on the catalytic
0.5 mol% 1 within 10 h. At higher catalyst concentration, the activity and enantioselectivity were studied by employing
yield and selectivity of the sulfoxide were much lower and the various TBHP/PhSMe molar ratios in the presence of 0.5 mol% 1
enantioselectivity decreased to 9%.
(Table 2). Increase of this ratio signicantly increased the
conversion and sulfoxide yield, which were maximized at
1.5 equiv. of TBHP. It is noteworthy that at a TBHP : PhSMe
molar ratio of 2.5 : 1 (entry 4), signicant decreases in both
selectivity (78%) and yield (76%) were observed. Compared with
the results at a 2 : 1 molar ratio, the conversion was almost the
same and the ee was slightly higher. These experimental results
clearly indicated that the reaction occurred with over-oxida-
tion,68,69 that is, a kinetic resolution process70–72 was operative in
the presence of excess oxidant.
Next, complex 1 was used to catalyze the oxidation of PhSMe
in the presence of BSA under the above optimized reaction
conditions over a period of 22 h. From the reaction time prole
of the oxidation of PhSMe (Fig. 7), it can be seen that the
conversion increased steadily up to
8 h and attained
a maximum value of 99%. Notably, chemoselectivity (98–99%)
and enantioselectivity (35–36%) remained nearly constant
throughout the course of the reaction, conrming that the ob-
tained enantioselectivity was completely induced during the
Fig. 6 Effect of the concentration of 1 on the oxidation of PMS using
TBHP in PB (pH 5.1) at room temperature after 10 h. The mol ratios of
TBHP : PhSMe (2.7 mmol) were 150 : 100.
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Table 2 Effect of varying TBHP amount on oxidation of PhSMe
catalyzed by 1a
TBHP
(mmol)
Conversion
(%)
Yield
(%)
Chemoelectivity
(%)
ee
(%)
Entry
1
2
3
4
0.27
0.41
0.54
0.689
73
98
96
97
69
97
93
76
95
99
97
78
31
35
34
38
a
All reactions were carried out in PB buffer (2 mL, pH 5.1) at room
temperature for 10 h. The mol ratios of PhSMe : BSA : 1 (1.35 mmol)
were 100 : 0.5 : 0.5.
Fig. 8 Effect of pH values on the oxidation of PhSMe using TBHP at
room temperature after 8 h. The mol ratios of TBHP : PhSMe : BSA: 1
(1.35 mmol) were 150 : 100 : 0.5 : 0.5.
sulde oxidation process and was not due to a concomitant
kinetic resolution.73
Under the above optimized reaction conditions, the oxida-
tion of PhSMe was performed at different pH values (Fig. 8). The
oxidation of PhSMe in PBS (pH 4.7) gave a signicantly higher
enantioselectivity (up to 57% ee) compared to the other
reactions (3–33% ee), albeit with a lower yield. Increasing or
decreasing the pH from 4.7 signicantly reduced the conver-
sion, yield, and, enantioselectivity, possibly because complex 1
became less stable.74
We then tested the catalytic activity of complex 1 in the
presence of BSA and other commercially available serum albu-
mins, HSA, PSA, RSA, and SSA, in reactions of a series of alkyl
aryl sulfoxides (1–10). The results, which are summarized in
Table 3, showed that chemoselectivity was almost unaffected by
the albumin source or the substrate (>90% sulfoxide selectivity
in each case). However, in terms of conversion and yield, PSA,
RSA, and SSA led to poor results, whereas BSA and HSA per-
formed relatively well (typically >90% conversion/yield).
Furthermore, the albumin source had a highly signicant
effect on the ee values, with those for all of the substrates
averaging 45.1%, 24.3%, 42%, 7.8%, and 3.8% for 1 in the
presence of BSA, HSA, PSA, RSA, and SSA, respectively. The
experimental results and spectral studies discussed above
clearly indicate that the enantioselectivity was associated with
the binding strength between 1 and SA. The high enantiose-
lectivities induced by the PSA-1 and BSA-1 systems indicate that
1 was strongly anchored to the protein. However, in the cases of
HSA, RSA, and SSA, this effect was very small, leading to lower ee
values (typically <10% ee with SSA), implying weaker binding.
Thus, it seems that increasing the interaction of the metal
complex with the protein leads to better enantioselectivities.75
Compared with the other proteins, RSA provided the opposite
major enantiomer in many cases. For example, opposite results
in terms of the conguration were obtained for 2-Cl-, 3-Cl- and
4-Cl-phenyl methyl sulde (substrates 2, 3 and 5) with RSA; 3-Br-
phenyl methyl sulde (substrate 4) with PSA; vinyl phenyl sulf-
oxide (substrate 9) with SSA.
Irrespective of electron-withdrawing and/or electron-
donating groups and their position on the aromatic ring
(entries 2–8), good conversions (88–99%) and yields (81–99%)
were obtained. Nevertheless, the data suggested that electron-
donating groups had a more pronounced effect on the enan-
tioselectivity of the product. The average ee values obtained for
electron-decient 4-Cl- and 4-Br-phenyl methyl suldes
(substrates 5 and 6) were 23% and 28%, respectively. In
comparison, electron-rich 4-Me-phenyl methyl sulde and 4-
OMe-phenyl sulde (substrates 7 and 8) gave average ee values
of 30% and 41%, respectively. Sulfoxidations of sterically bulky
substrates, such as vinyl phenyl sulfoxide and methyl benzyl
sulfoxide (substrates 9 and 10), were successfully achieved with
high chemoselectivities. However, lower enantioselectivities
were observed in the oxidation of these sterically bulky
substrates to the corresponding sulfoxides, possibly due to the
increased steric demand.76 Signicantly, the oxidation-sensitive
C]C double bond was not sacriced under the mild oxidation
conditions, producing the requisite sulfoxide in high yield
(>85%). Notably, the results indicate that the steric effect had
a stronger inuence on the conguration. For example, except
for vinyl phenyl sulfoxide and methyl benzyl sulfoxide, the
products were obtained in the R form in the presence of BSA or
HSA. In particular, for vinyl phenyl sulfoxide, the opposite
conguration was obtained compared to the reactions of other
Fig. 7 Effect of the reaction time on the oxidation of PhSMe using
TBHP in PB (pH 5.1) at room temperature. The mol ratios of
TBHP : PhSMe : BSA : 1 (1.35 mmol) were 150 : 100 : 0.5 : 0.5.
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Table 3 Effects of albumin source, and substrate on asymmetric oxidation of aryl alkyl sulfidesa (conversions of $90%, chemoselectivities of
$90% and enantiomeric excesses (ee) of $50% are emphasized)
Complex 1: conversion (%), chemoselectivity (%), yield (%), ee (%) (conguration)
Substrate
BSA
HSA
PSA
RSA
SSA
71, 99, 70, 77, R
90, 98, 88, 35, R
75, 99, 74, 41, R
77, 99, 76, 5, R
82, 99, 81, 2, R
99, 100, 99, 23, R
98, 97, 95, 19, R
90, 100, 90, 3, R
95, 96, 91, 3, R
95, 95, 90, 36, R
90, 98, 88, 23, R
95, 95, 90, 6, S
90, 98, 88, 2, S
88, 92, 81, 1, R
95, 92, 87, 1, R
98, 98, 96, 75, R
94, 97, 91, 56, R
92, 97, 89, 62, S
92, 96, 88, 10, R
91, 98, 89, 9, R
97, 98, 95, 41, R
95, 100, 95, 57, R
96, 98, 94, 2, R
95, 99, 94, 60, R
94, 100, 94, 46, R
95, 100, 95, 9, S
94, 94, 88, 4, R
95, 97, 92, 3, R
97, 98, 95, 13, R
94, 100, 94, 21, R
99, 98, 97, 58, R
99, 98, 97, 64, R
99, 98, 97, 34, R
99, 98, 97, 67, R
99, 98, 97, 50, R
95, 98, 93, 68, R
95, 98, 93, 3, R
89, 98, 87, 2, R
99, 100, 99, 3, R
96, 98, 94, 4, R
91, 100, 91, 26, S
98, 96, 94, 11, S
97, 95, 92, 18, S
94, 98, 92, 4, S
95, 90, 85, 25, S
90, 96, 86, 9, R
95, 91, 86, 29, S
95, 99, 94, 8, R
87, 97, 85, 1, R
71, 99, 76, 1, R
a
Reactions were performed in 2 mL PB pH 4.7 at room temperature for 8 h. The ratios of TBHP: substrate: SA: 1 (2.7 mmol) were 150 : 100 : 0.5 : 0.5.
suldes in the presence of the same SA (except SSA). The and Molecular Engineering of Medicinal Resources, Ministry of
mechanistic details of this reaction are still under investigation. Education of China (CMEMR2011-20, CMEMR2013-A05).
Conclusions
References
In conclusion, a novel VI8V cluster has been successfully con-
1 N. Mizuno and M. Misono, Chem. Rev., 1998, 98, 199–217.
2 N. Mizuno and K. Kamatal, Coord. Chem. Rev., 2011, 255,
2358–2370.
structed based on 1,2-diaminocyclohexane. Using this
VI8V cluster as a homogeneous catalyst, we have devised an effi-
cient biomimetic procedure for the oxidation of suldes to
3 G. J. Hutchings, J. Mater. Chem., 2004, 14, 3385–3395.
sulfoxides in the presence of serum albumin in water at room
4 F. Cavani, N. Ballarini and A. Cericola, Catal. Today, 2007,
127, 113–131.
5 S. Takizawa, T. Katayama and H. Sasai, Chem. Commun.,
2008, 4113–4122.
6 A. G. J. Ligtenbarg, R. Hage and B. L. Feringa, Coord. Chem.
Rev., 2003, 237, 89–101.
7 C. Bolm, Coord. Chem. Rev., 2003, 237, 245–256.
8 J. T. Rhule, C. L. Hill and D. Judd, Chem. Rev., 1998, 98, 327–
temperature. This methodology is simple and environmentally
friendly. Its simplicity lies in the preparation of the catalyst
from easily available starting materials as well as a facile sul-
foxidation procedure by physical stirring at room temperature.
In addition to the above-mentioned advantages, the use of eco-
friendly reaction media and inexpensive chiral additives make it
cost-effective, environmentally benign, and thus compatible
with the goals of green sustainable chemistry.
358.
¨
9 J. Oble, B. Riade, A. Noel, M. Malacria, S. Thorimbert,
ˆ
B. Hasenknopf and E. Lacote, Org. Lett., 2011, 13, 5990–5993.
Acknowledgements
10 C. L. Wang, Z.-B. Zhang, J. Fu, Y. Xu and D.-R. Zhu, Chem.–
Eur. J., 2012, 18, 11909–11912.
We gratefully acknowledge the National Nature Science Foun-
dation of China (No. 21361003, 21461003 and 21101035), the 11 M. I. Khan, S. Cevik, D. Powell, S. Li and C. J. O'Connor,
Guangxi Natural Science Foundation (2014GXNSFBA118056), Inorg. Chem., 1998, 37, 81.
the Scientic Research Foundation for the Returned Overseas 12 A. Muller, F. Peters, M. T. Pope and D. Gatteschi, Chem. Rev.,
Chinese Scholars, State Education Ministry, the Talent's Small 1998, 98, 239–271.
Highland project of Guangxi Medicinal Industry (1201), New 13 M. J. Manos, A. J. Tasiopoulos, E. J. Tolis, N. Lalioti,
¨
Century Ten, Hundred, Thousand Talents Project in Guangxi,
IRT 1225 and the Foundation of Key Laboratory for Chemistry
J. D. Woollins, A. M. Z. Slawin, M. P. Sigalas and
T. A. Kabanos, Chem.–Eur. J., 2003, 9, 695–703.
44160 | RSC Adv., 2016, 6, 44154–44162
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
RSC Advances
14 L. Chen, F.-L. Jiang, Z.-Z. Lin, Y.-F. Zhou, C.-Y. Yue and 44 C. Mealli, A. Ienco, A. Poduska and R. Hoffmann, Angew.
M.-C. Hong, J. Am. Chem. Soc., 2005, 127, 8588–8589. Chem., Int. Ed., 2008, 47, 2864–2867.
15 S. S. Wang and G. Y. Yang, Chem. Rev., 2015, 115, 4893–4962. 45 C. Jahier, M. Coustou, M. Cantuel, N. D. McClenaghan,
¨
16 J. Forster, B. Rosner, M. M. Khusniyarov and C. Streb, Chem.
T. Buffeteau, D. Cavagnat, M. Carraro and S. Nlate, Eur. J.
Inorg. Chem., 2011, 5, 727–738.
Commun., 2011, 47, 3114.
17 S. Li, W. Sun, K. Wang, H.-Y. Ma, H.-J. Pang, H. Liu and 46 Y. Sasaki, Y. Deguchi, M. Morimoto, Y. Imai, M. Matsunaga,
J.-X. Zhang, Inorg. Chem., 2014, 53, 4541–4544.
18 D.-Y. Du, L.-K. Yan, Z.-M. Su, S.-L. Li, Y.-Q. Lan and
E. B. Wang, Coord. Chem. Rev., 2013, 257, 702–717.
19 C. L. Hill, J. Mol. Catal. A: Chem., 2007, 262, 1–242.
T. Sakane, J. Ichihara and S. Yamaguchi, Mater. Tech., 2009,
27, 191–195.
47 SAINT Soware Reference Manual, Bruker AXS, Madison, WI,
1998.
20 D. L. Long, E. Burkholder and L. Cronin, Chem. Soc. Rev., 48 G. M. Sheldrick, Phase Annealing in SHELX-90: Direct
2007, 36, 105–121.
21 R. Neumann, Prog. Inorg. Chem., 1998, 47, 317–370.
Methods for Larger Structures, Acta Crystallogr., Sect. A:
Found. Crystallogr., 1990, 46, 467–473.
22 N. Mizuno, K. Kamata and K. Yamaguchi, Surf. Nanomol. 49 G. M. Sheldrick, SHELXS-97, Program for X-ray Crystal
€
€
Catal., 2006, 463–491.
Structure Solution, University of Gottingen, Gottingen,
23 R. Neumann, Prog. Inorg. Chem., 1998, 47, 317–370.
Germany, 1997.
24 N. Mizuno, K. Yamaguchi and K. Kamata, Coord. Chem. Rev., 50 (a) M. I. Donnoli, S. Superchi and C. Rosini, J. Org. Chem.,
2005, 249, 1944–1956.
25 N. Mizuno, K. Kamata and K. Yamaguchi, Top. Catal., 2010,
53, 876–893.
26 S. K. Maiti, S. Dinda, S. Banerjee, A. K. Mukherjee and
R. Bhattacharyy, Eur. J. Inorg. Chem., 2008, 2038–2051.
27 S.-Z. Luo, S. J.-Y. Li, H. Xu, L. Zhang and J.-P. Cheng, Org.
Lett., 2007, 9, 3675–3678.
28 Q. Gao, S.-M. Lu, Y. Liu and C. Li, Tetrahedron Lett., 2011, 52,
3779–3781.
29 R. Ishimoto, K. Kamata, K. Suzuki, K. Yamaguchi and
N. Mizuno, Dalton Trans., 2015, 44, 10947–10951.
30 Q. Chen, C. Xin, L.-L. Lou, K. Yu, F. Ding and S.-X. Liu, J.
Inorg. Organomet. Polym., 2013, 23, 467–471.
31 Y.-Z. Wang, H.-L. Li, W. Qi, Y. Yang, Y. Yan, B. Li and
L.-X. Wu, J. Mater. Chem., 2012, 22, 9181–9188.
32 S. Colonna, S. Ban, R. Annunziata and L. Casella, J. Org.
Chem, 1986, 51(6), 891–895.
33 V. Oliveri and G. Vecchio, Eur. J. Med. Chem., 2011, 46, 961–
965.
34 Y.-J. Hu, Y. Ou-Yang, Y. Zhang and Y. Liu, Protein J., 2010, 29,
234–241.
1998, 63, 9392–9395; (b) J.-T. Sun, C.-J. Zhu, Z.-Y. Dai,
M.-H. Yang, Y. Pan and H.-W. Hu, J. Org. Chem., 2004, 69,
8500–8503; (c) K. Tanaka, K. Kubo, K. Iida, K. Otani,
T. Murase, D. Yanamoto and M. Shiro, Asian J. Org. Chem.,
2013, 2, 1055–1060; (d) H. Egami and T. Katsuki, J. Am.
Chem. Soc., 2007, 129, 8940–8941.
51 (a) P. Pitchen, E. Duiiach, M. N. Deshmukh and H. B. Kagan,
J. Am. Chem. Soc., 1984, 106, 8188–8193; (b) M. A. M. Capozzi,
C. Cardellicchio, F. Naso and P. Tortorella, J. Org. Chem.,
2000, 65, 2843–2846; (c) P. Pitchen, E. Duiiach,
M. N. Deshmukh and H. B. Kagan, J. Am. Chem. Soc., 1984,
106, 8188–8193; (d) O. G. Mancheno, J. Dallimore, A. Plant
and C. Bolm, Org. Lett., 2009, 11, 2429; (e) F. A. Davis,
R. T. Reddy, W. Han and P. J. Carroll, J. Am. Chem. Soc.,
1992, 114, 1428–1437; (f) J. H. Egami and T. Katsuki, J. Am.
Chem. Soc., 2007, 129, 8940–8941.
52 X.-N. Cheng, W. Xue, J.-B. Lin and X.-M. Chen, Chem.
Commun., 2010, 46, 246–248.
53 B. F. Abrahams, T. A. Hudson and R. Robson, J. Am. Chem.
Soc., 2004, 126, 8624–8625.
54 B. Moubaraki, K. S. Murray, T. A. Hudson and R. Robson,
Eur. J. Inorg. Chem., 2008, 4525–4529.
55 M. W. Wemple, H.-L. Tsai, W. E. Streib, D. N. Hendrickson
and G. Christou, J. Chem. Soc., Chem. Commun., 1994,
1031–1033.
35 S. Colonna, S. Ban and R. Annunziata, J. Org. Chem., 1986,
51, 891–895.
36 A. Pordea, M. Creus, J. Panek, C. Duboc, D. Mathis, M. Novic
and T. R. Ward, J. Am. Chem. Soc., 2008, 130, 8085–8088.
37 M. T. Reetz and N. Jiao, Angew. Chem., Int. Ed., 2006, 45, 56 M. W. Wemple, H.-L. Tsai, S. Wang, J. P. Claude, W. E. Streib,
2416–2419.
J. C. Huffman, D. N. Hendrickson and G. Christou, Inorg.
Chem., 1996, 35, 6437–6449.
38 A. Mahammed and Z. Gross, J. Am. Chem. Soc., 2005, 127,
2883–2887.
¨
57 G. J. T. Cooper, G. N. Newton, P. Kogerler, D.-L. Long,
39 A. Ghorbani-Choghamarani, Z. Darvishnejad and
M. Norouzi, Appl. Organomet. Chem., 2015, 29, 170–175.
L. Engelhardt, M. Luban and L. Cronin, Angew. Chem., Int.
Ed., 2007, 46, 1340–1344.
¨
40 M. Sutradhar, L. M. D. R. S. Martins, M. F. C. G. Silva and 58 G. N. Newton, G. J. T. Cooper, P. Kogerler, D.-L. Long and
A. J. L. Pombeiro, Coord. Chem. Rev., 2015, 301–302, 200–239. L. Cronin, J. Am. Chem. Soc., 2008, 130, 790–791.
41 K. A. Stingl, K. M. Weiß and S. B. Tsogoeva, Tetrahedron, 59 H. N. Miras, E. F. Wilsonw and L. Cronin, Chem. Commun.,
2012, 68, 8493–8501. 2009, 1297–1311, and references therein.
42 P. K. Khatri, S. L. Jain and B. Sain, Ind. Eng. Chem. Res., 2011, 60 S.-H. Zhang, Y. Song, H. Liang and M.-H. Zeng,
50, 701–704. CrystEngComm, 2009, 11, 865–872.
43 E. Muthuswamy and S. L. Brock, J. Am. Chem. Soc., 2010, 132, 61 B.-W. Li, Y.-L. Zhou, Q. Chen and M.-H. Zeng, Polyhedron,
15849–15851.
2010, 29, 148–153.
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 44154–44162 | 44161

View Article Online
RSC Advances
Paper
62 L.-Q. Wei, B.-W. Li, S. Hu and M.-H. Zeng, CrystEngComm, 70 H. Sroura, J. Jalkha, P. L. Mauxa, S. Chevancea, M. Kobeissib
2011, 13, 510–512.
and G. Simonneauxa, J. Mol. Catal. A: Chem., 2013, 370, 75–
63 P. K. Bera, D. Ghosh, S. H. R. Abdi, N. H. Khan, R. I. Kureshy
79.
and H. C. Bajaj, J. Mol. Catal. A: Chem., 2012, 361–362, 36–44. 71 J.-T. Sun, C.-J. Zhu, Z.-Y. Dai, M.-H. Yang, Y. Pan and
˜
64 S. M. G. Piresa, M. M. Q. Simoesa, I. C. M. S. Santosa,
S. L. H. Rebelob, M. M. Pereirac, M. G. P. M. S. Nevesa and 72 Z.-W. Yang, C.-F. Zhu, Z.-J. Li, Y. Liu, G.-H. Liu and Y. Cui,
J. A. S. Cavaleiroa, Appl. Catal., A, 2012, 439–440, 51–56. Chem. Commun., 2014, 50, 8775–8778.
65 A. Mahammed and Z. Gross, J. Am. Chem. Soc., 2005, 127, 73 M. I. Donnoli, S. Superchi and C. Rosini, J. Org. Chem., 1998,
2883–2887. 63, 9392–9395.
66 E. Wojaczynska and J. Wojaczynski, Chem. Rev., 2010, 110, 74 A. Rezaeifard, R. Haddad, M. Jafarpour and M. Hakimi, ACS
4303–4356. Sustainable Chem. Eng., 2014, 2, 942–950.
67 H. Egami and T. Katsuki, J. Am. Chem. Soc., 2007, 129, 8940– 75 E. S. Dagousset, A. Urvoas, K. Chelly, W. Ghattas,
H.-W. Hu, J. Org. Chem., 2004, 69, 7058–7065.
´
´
´
8941.
J.-D. Marechal, J.-P. Mahy and R. Ricoux, Dalton Trans.,
68 S. P. Das, J. J. Boruah, N. Sharma and N. S. Islam, J. Mol.
Catal. A: Chem., 2012, 356, 36–45.
69 A. Bayat, M. Shakourian-Fard and M. M. Hashemi, Catal.
Commun., 2014, 52, 16–21.
2014, 43, 8344–8354.
76 K. Tanaka, K. Kubo, K. Iida, K. Otani, T. Murase,
D. Yanamoto and M. Shiro, Asian J. Org. Chem., 2013, 2,
1055–1060.
44162 | RSC Adv., 2016, 6, 44154–44162
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