Bio-inspired single-chain polymeric nanoparticles containing a chiral salen TiIV complex for highly enantioselective sulfoxidation in water

Article abstract of DOI:10.1039/c6gc02743a

A series of bio-inspired single-chain polymeric nanoparticles (SCPNs) containing a chiral salen Ti^IV complex in their hydrophobic cavity were constructed from the synthesized amphiphilic copolymers of poly(NIPAAm-co-IL/Ti(salen)) (NIPAAm, N-isopropylacrylamide; IL/Ti(salen), vinylimidazolium ionic liquid-modified chiral salen Ti^IV complex). These SCPNs behaved as enzyme-mimetic catalysts due to compartmentalization and site isolation, mediating enantioselective oxidation of various sulfides in water with excellent yields (90-99%) and enantioselectivities (ee, 88-99%). In particular, the ee values observed for electron-rich substrates (>95% ee) represented the best results so far in titanium-salen systems. Moreover, the catalysts could be easily recovered for steady reuse by thermo-controlled separation due to thermo-responsive properties. This work first constructed titanium-containing biomimetic SCNPs for biocatalysis of enantioselective sulfoxidation in water.

Full text of DOI:10.1039/c6gc02743a

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ARTICLE TYPE
Bio-inspired single-chain polymeric nanoparticles containing chiral
salen TiIV complex for highly enantioselective sulfoxidation in water
Yaoyao Zhang, Rong Tan,* Mengqiao Gao, Pengbo Hao and Donghong Yin
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
DOI: 10.1039/b000000x
A series of bioꢀinspired singleꢀchain polymeric nanoparticles (SCPNs) containing chiral salen TiIV complex in their hydrophobic
cavity were constructed from the synthesized amphiphilic copolymers of poly(NIPAAmꢀcoꢀIL/Ti(salen)) (NIPAAm, Nꢀ
isopropylacrylamide; IL/Ti(salen), vinylimidazolium ionic liquidꢀmodified chiral salen TiIV complex). These SCPNs behaved as enzymeꢀ
mimetic catalysts due to compartmentalization and site isolation, mediating enantioselective oxidation of various sulfides in water with
excellent yields (90–99%) and enantioselectivities (ee, 88–99%). Especially, the ee values observed for electronꢀrich substrates (>95%
ee) represented the best results so far in titaniumꢀsalen systems. Moreover, the catalysts could be easily recovered for steady reuse by
thermoꢀcontrolled separation due to the thermoꢀresponsive property. This work first constructed the titaniumꢀcontaining biomimetic
SCNPs for biocatalysis of enantioselective sulfoxidation in water.
construction of enzymeꢀlike comparment.3 The obtained SCPNs
often exhibit features that resemble natural enzymes. In particular,
Introduction
Asymmetric sulfoxidation catalyzed by chiral salen TiIV
waterꢀsoluble SCPNs, in which the active sites are located in the
hydrophobic core, have demonstrated enzymeꢀmimetic activity
and selectivity in aqueous catalysis.1d, 3b, 4 The fascinating SCPNs
approach encouraged us to design Ti(salen)ꢀcontaining waterꢀ
soluble SCPNs as enzymeꢀlike catalysts for efficient asymmetric
sulfoxidation in water. Since amphiphilic copolymers tended to
selfꢀfold into waterꢀsoluble SCPN in water via an intramolecular
hydrophobic interaction, as with proteins,4 we decided to prepare
a Ti(salen) containing amphiphilic copolymer precursor through
the copolymerization of hydrophobic Ti(salen) with hydrophilic
monomer. We envisioned that the Ti(salen) units should trigger
selfꢀfolding of the amphiphiles in water through intramolecular
hydrophobic interaction, forming the waterꢀsoluble SCPNs with a
complex is an importance transformation in organic synthesis,
since the obtained enantiopure sulfoxides are valuable chiral
intermediates for synthesis of fine chemicals.1 Although high
yields of chiral sulfoxides are often achieved in organic systems,
the transformation is inefficient in water due to poor waterꢀ
solubility of sulfides and catalyst. As we all know, in nature, most
chemical conversions are efficiently carried out in aqueous
environment with the use of enzymes. Although a few are
catalytic nucleic acid molecules, most enzymes are proteins,
which selfꢀfold into compartmentalized, threeꢀdimensional
structures with hydrophobic, catalytically active cores surrounded
by hydrophilic shells.2 The featured structure allows reactions to
occur inside the hydrophobic compartment efficiently, while the
hydrophilic shells remain compatible with aqueous environments.
Inspired by enzyme catalysis, we decided to develop an enzymeꢀ
mimetic chiral salen TiIV catalyst to realize effective asymmetric
sulfoxidation in water.
hydrophobic,
catalytically
active
interior.5
The
compartmentalized SCPNs enriched catalytic motifs and
substrates in confined hydrophobic interior, which hopefully not
only accelerated the aqueous asymmetric sulfoxidation, but also
improved the reaction selectivity. Moreover, multiple Ti(salen)
motifs confined in hydrophobic core may enforce a cooperative
reaction pathway favorable for asymmetric sulfoxidation,
resulting in further enhanced reaction rate and higher selectivity.6
However, the bulky polymer matrix inevitably increased local
steric hindrance around Ti(salen), which limited all complexes to
adopt their preferred conformation for cooperative catalysis.6b
This problem could be well solved by introducing a flexible IL
spacer between Ti(salen) unit and the polymer backbone. In
addition to ensuring the necessary conformational freedom of
Ti(salen), such an IL moiety with high polarity and ionic
character may also stabilize the formed metallosalen active
intermediates,7 thereby further enhancing the catalytic efficiency
of chiral salen TiIV catalyst. Unfortunately, waterꢀsoluble SCPNs
were difficult to be recovered from water for reuse. If the
Folding of a single linear polymer chain into a hydrophobicꢀ
cavityꢀcontaining SCPN, which is reminiscent of the folding of
proteins, has recently been realized as a feasible approach for the
* Key Laboratory of Chemical Biology and Traditional Chinese
Medicine Research (Ministry of Education); National & Local Joint
Engineering Laboratory for New Petroꢀchemical Materials and Fine
Utilization of Resources, Hunan Normal University, Changsha
410081 (P. R. China)
Fax:
+86ꢀ731ꢀ8872531;
Tel:
+86ꢀ731ꢀ8872576;
Eꢀmail:
yiyangtanrong@126.com
†Electronic Supplementary Information (ESI) available: Identity of
the catalysts, detailed NMR spectra and HPLC analysis for the chiral
sulfoxides. See DOI: 10.1039/b000000x/
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DOI: 10.1039/C6GC02743A
hydrophilic corona of SCPNs is thermoꢀsensitive, being able to
undergo hydrophilicꢀtoꢀhydrophobic switch at its lower critical
solution temperature (LCST), facile recovery of SCPNs can be
realized.
with the followed Ti(OiPr)4 treatment, gave vinylimidazolium ILꢀ
modified chiral salen TiIV complex (IL/Ti(salen)). The
IL/Ti(salen), featuring an vinyl group in one Nꢀalkyl chain of
imidazolium IL, was copolymerized with NIPAAm, providing
amphiphilic random copolymers of PNx(IS)y (where x and y
represented the repeated units number of NIPAAm and
IL/Ti(salen), respectively). The polymerization degree of
individual NIPAAm and IL/Ti(salen) blocks were determined in
1H NMR spectra by comparing the signals attributable to
individual blocks (NIPAAm at ca. 3.26 ppm assigned to CH3ꢀ
CHꢀCH3, and IL/Ti(salen) at ca. 6.05 ppm assigned to NꢀCHꢀ
CH2ꢀ of Nꢀvinyl in IL) with that of end methyl group (ꢀSHꢀCH2ꢀ
CH2ꢀCH3, at ca. 1.73 ppm) (see correspondingly 1H NMR spectra
in Section 1 of ESI).
Herein, amphiphilic random copolymers of poly(NIPAAmꢀcoꢀ
IL/Ti(salen)), in which multiple chiral salen TiIV complexes were
appended on linear polymeric backbone through IL linkers, were
synthesized by copolymerizing IL/Ti(salen) with NIPAAm via
catalytic chain transfer polymerization (CCTP) coupled with
ordinary radical polymerization technique.8 The resulted
copolymers were thermoꢀresponsive and underwent reversible
singleꢀchain selfꢀfolding in water. At reaction temperature (25
oC), they were amphiphilic and induced efficient asymmetric
sulfoxidation in water via selfꢀfolded hydrophobic compartment
around the catalytic sites, reminiscent of enzymatic catalysis.
Extremely high activity (conversion>99%), chemoꢀ (90–98%)
and enantioselectivity (88–99%) were observed over a wide range
of sulfides in water. After reaction, the catalysts turned to
hydrophobic upon heating, allowing for facilely recovery of
catalysts for steady reuse. More attractively, the activity
switching was repeatable even seven heating/cooling cycles.
N
N
N
N
N
O
N
N
N
Ti
Ti(OiPr)4
Cl
tꢀBu
O
tꢀBu
OH OH
tꢀBu tꢀBu
CH2Cl
OiPr
iPrO
Toluene, N2, 110 oC, 48 h
CH2Cl2, RT, 3 h
tꢀBu
tꢀBu
IL/Ti(salen)
CL1
H2
C
H
CH
C
CH CH2
S
CH2CH2 CH3
y
x
O
O
N
N
CH3
NH
CH2
CH
C
N
Cl
Water
25 o
CH3
CH
C
NIPAAM
C
H3
CH3
AIBN, nꢀpropanethiol,
MeOH, N2, 60 oC, 24 h
tꢀBu
O
N
Results and Discussion
iPrO
iPrO
Ti
N
O
tꢀBu
PNx(IS)y-based SCPNs
Preparation and Characterization of Catalysts
tꢀBu
Enzyme catalysis is a source of inspiration for chemists who
attempt to efficiently perform organic reaction in water.
Compartmentalization and site isolation are the typical
characteristics responsible for high efficiency demonstrated by
enzymes in natural systems.9 Waterꢀsoluble SCPNs with
hydrophobic interior are structurally regarded as artificial mimics
of enzymes, since they often generate compartments that express
enzymeꢀmimetic functions.3 Especially, if catalytically active
sites were confined in their hydrophobic compartments, it would
endow the SCPNs with enzymeꢀmimetic activity and selectivity
in aqueous catalysis. With these points in mind, we decided to
shield active Ti(salen) in waterꢀsoluble SCPNs compartment to
fabricate a enzymeꢀmimetic chiral salen TiIV catalyst for aqueous
asymmetric sulfoxidation. Given that waterꢀsoluble SCPNs are
often prepared from amphiphilic copolymers possessing pendant
groups that trigger a selfꢀfolding of the polymer,10 a range of
amphiphilic poly(NIPAAmꢀcoꢀIL/Ti(salen)) (PNx(IS)y) with
various amount of hydrophobic Ti(salen) pendants was decided to
prepare for this fabrication. We envisioned that the Ti(salen)
pendants should trigger selfꢀfolding of the amphiphilic
copolymers in water via intramolecular hydrophobic interaction,5
forming waterꢀsoluble SCPNs with hydrophobic Ti(salen) interior.
Thermoꢀresponsive PNIPAAM, which can undergo hydrophilicꢀ
toꢀhydrophobic transformation at its LCST, was incorporated in
the copolymer, to allow thermoꢀcontrolled switch of copolymers
between selfꢀfolding and precipitation. This switchable behavior
should not only lead to an efficient asymmetric sulfoxidation in
water as a result of the “biomimetic catalysis”, but also allow the
precipitation of catalyst for facile recovery.
PNx(IS)y (x= 60, y= 2; x= 68, y= 4;
x= 66, y= 6; x= 64, y= 8)
Scheme 1 Schematic representation of synthesis and selfꢀfolding of
PNx(IS)y.
For comparison, an ILꢀfree counterpart of PN68S4 was also
prepared according to a similar procedure, as shown in Scheme 2.
During the process, (R,R)ꢀNꢀ(3,5ꢀdiꢀtertꢀbutylsalicylidene)ꢀN’ꢀ[3ꢀ
tertꢀbutylꢀ5ꢀvinyl]ꢀ1,2ꢀcyclohexanediamine (CL2)12 was treated
with Ti(OiPr)4 in dichloromethane, giving a chiral salen TiIV
complex featuring a vinyl group at the 5ꢀposition. The Ti(salen)
motif was used instead of IL/Ti(salen) to copolymerize with
NIPAAm. Polymerization degrees of the individual NIPAAm and
1
Ti(salen) blocks were also determined in H NMR spectrum by
comparing the signals attributable to individual blocks (NIPAAm
at ca. 3.19 ppm assigned to CH3ꢀCHꢀCH3 and Ti(salen) at ca.
3.41 ppm assigned to ꢀCHꢀCH2ꢀPhꢀ) with that of end methyl
group (ꢀSHꢀCH2ꢀCH2ꢀCH3 at ca. 1.72 ppm) (see Fig. S5 in
Section 1 of ESI).
N
N
O
N
N
Ti
Ti(OiPr)4
tꢀBu
O
tꢀBu
OH OH
OiPr
iPrO
CH2Cl2, RT, 3 h
tꢀBu
tꢀBu
tꢀBu
CL2
tꢀBu
Ti(salen)
H2
C
H2
C
H
C
O
C
CH3
H
CH
S
CH2CH2 CH3
4
68
O
CH2
CH
N
C
CH3
NH
CH
NIPAAM
tꢀBu
iPrO
N
O
O
AIBN, nꢀpropanethiol, MeOH, N2, 60 oC, 24 h
Ti
H3
C
iPrO
tꢀBu
CH3
N
tꢀBu
The synthesis of PNx(IS)y was illustrated in Scheme 1. Nꢀ
alkylation of vinylimidazole with the benzyl chloride group in
(R,R)ꢀNꢀ(3,5ꢀdiꢀtertꢀbutylsalicylidene)ꢀN’ꢀ(3ꢀtertꢀbutylꢀ5ꢀchloroꢀ
methylꢀsalicylidene)ꢀ1,2ꢀcyclohexanediamine (CL1),11 together
PN68S4
Scheme 2 Synthesis of PN68S4.
2
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Characterization of Samples
FT-IR
The successful copolymerization of IL/Ti(salen) moiety with
average particle size of ca. 3 nm in water at room temperature
(Fig. 2aꢀe). These diameter value was consistent with that
adopted a singleꢀchain folded conformation in solution.3b,16
Notably, introducing imidazolium IL didn’t significantly affect
their singleꢀchain folding behavior of PNx(IS)y, since PNx(IS)y–
based SCPNs gave similar morphology to the SCPNs based on
PN68S4 (Fig. 2aꢀd vs 2e). We could thus deduced that the selfꢀ
folding process of PNx(IS)y was only triggered by Ti(salen)
groups, independent of the IL linkers. Logically, the hydrophobic
Ti(salen) pendants avoided contacting water, inducing the selfꢀ
foding of single PNx(IS)y chain into SCPNs via intramolecular
hydrophobic interaction. High dispersion of the nanoparticulars in
water implied the waterꢀsolubility of the SCPNs due to
hydrophilic NIPAAm corona. Indeed, transparent solutions were
observed when PNx(IS)y were dissolved in water at room
temperature (Fig. 2aꢀe), whereas, the transparent aqueous solution
NIPAAm was verified by FTꢀIR. Fig. 1 showed the FTꢀIR spectra
of typical PN68(IS)4, as well as PN68S4 and neat complex for
comparison. Obviously, neat complex exhibited characteristic
band at 1623 cmꢀ1 assigned to the stretching vibration modes of
C=N,13 as well as the bands at 805 and 709 cm−1 associated with
TiꢀO bond (Fig. 1a).14 While, these bands in PN68(IS)4 shifted
from 1623, 805 and 709 cmꢀ1 to 1626, 811 and 715 cmꢀ1,
respectively, compared with those in neat complex (Fig. 1b vs.
1a). The red shift was mainly due to the electronꢀdeficient effect
of imidazolium cation at 5ꢀposition of salen ligand.15 The
observation provided indirect proof for suspending Ti(salen) units
on linear polymer backbone through an imidazoliumꢀbased IL
spacer. A new characteristic band at 622 cmꢀ1 associated with
stretching of imidazole ring7a further confirmed the presence of
imidazoliumꢀbased IL linkers in PN68(IS)4 (Fig. 1b). Apart from
the characteristic signal associated with Ti(salen) and IL
moieties, additional bands at around 3441, 3064 and 1643 cmꢀ1
were also obvious in the FTꢀIR spectrum of PN68(IS)4. They were
assigned to the characteristic stretching vibration of NꢀH of
CONH, CH of CH2ꢀCH, and C=O of CONH in NIPAAm moiety,
respectively. The observation confirmed successful incorporation
of NIPAAm in PN68(IS)4. It was the thermoꢀresponsive NIPAAm
block that ensured selfꢀfolding of copolymers in water, and also
endowed the obtained SCPNs with thermoꢀresponsive switches.
As expected, PN68S4 exhibited simialr FTꢀIR spectrum to
PN68(IS)4, except for the disappearance of characteristic band
associated with imidazole ring (Fig. 1c vs. 1a). The difference
was related with the absence of imidazoliumꢀbased IL linker in
the PN68S4. It was expected that the featured IL moiety would
make PN68(IS)4 more efficient and stable in the asymmetric
sulfoxidation in water.
o
turned turbid when the local temperature was heated to 35 C, as
shown by the typical PN68(IS)4 (Fig. 2b’ vs. 2b). The principal
explanation might be that the NIPAAm conora switched from
hydrophilic to hydrophobic at the higher temperature,17 resulting
in a hydrophobic state of the SCPNs. Indded, PN68(IS)4–based
SCPNs tended to gather together in water under the condition
(Fig. 2b’). The thermoꢀsensitivity of PNx(IS)y–based SCPNs in
water made it possible that PNx(IS)y could be facilely recovered
from the aqueous system by simple thermoꢀcontrolled separation.
a
805
709
1623
Fig. 2 TEM micrograph of selfꢀfolded PN60(IS)2 (a), PN68(IS)4 (b),
PN66(IS)6 (c), PN68(IS)8 (d), and PN68S4 (e) in water at room temperature,
and selfꢀfolded PN68(IS)4 in water at 35 oC (b’) stained with
phosphotungstic acid.
b
3064
3441
b'
811
715
1643
1643
622
Cryo-TEM
1626
c
CryoꢀTEM was a powerful characterization technique to
observe the aqueous nanoparticles, thanks to the high contrast of
the nanoparticles’ hard core in vitrified water. The selfꢀfolding
behavior of typical PN68(IS)8 and PN68S4 in water was further
explored by CryoꢀTEM, as shown in Fig. 3. Obviously, the
copolymers could be directly observed as black dots by cryoꢀ
TEM. They almost uniformly showed nanoparticles of ca. 4 nm
diameter, without any intermolecular aggregation. The observed
dots probably indicated the hydrophobic cores of the coreꢀshellꢀ
like structures, due to the low contrast of the swollen hydrophilic
shell in water. These results further demonstrated that the
amphiphilic copolymers with and without IL moiety formed
805
709
4000
3500
3000
2500
2000
1500
1000
500
Wavenumbers (cmꢀ1)
Fig. 1 FTꢀIR spectra of neat complex (a), fresh PN68(IS)4 (b), recovered
PN68(IS)4 after the 7th reuse (b’) and PN68S4 (c).
TEM
The selfꢀfolding behavior of PNx(IS)y and PN64(IS)8) in water
was confirmed by TEM, as shown in Fig. 2. Obviously, the
amphiphiles folded into uniform spherical nanoparticulars with
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singleꢀchain nanoparticles in water (Fig. 3a vs 3b), and that there
is no intermolecular aggregation. The collapse was proposed to
be the result of the folding through intramolecular hydrophobic
interaction of Ti(salen) pendant groups within the hydrophobic
compartment.
Notably, the negative Cotton effect at 243 nm increased upon
heating the solution from 10 to around 70 oC, and then decreased
gradually (Fig. 5). It almost disappeared at 80 °C. This indicated
that the selfꢀfolding behaviors of PNx(IS)y was related to the local
temperature. In fact, the solution finally turned turbid due to the
lower critical solution temperature (LCST) of the copolymers
above 80 °C. Full reversibility without hysteresis was observed
upon slow cooling (Fig. 5). These results indicated that the
polymers folded and unfolded reversibly by controlling the
temperature due to the temperatureꢀdependent waterꢀsolubility of
NIPAAm units.
5
30
B
B
PN68(IS)
PN68(IS)
4
4
heating
cooling
PN60(IS)
PN60(IS)
2
2
heating
cooling
20
0
10
Fig. 3 CryoꢀTEM images of PN68(IS)4 (a) and PN68S4 (b).
ꢀ5
0
ꢀ10
ꢀ20
ꢀ30
ꢀ40
ꢀ10
ꢀ15
ꢀ20
Circular Dichroism (CD)
The selfꢀfolding process of PNx(IS)y in water was probed in
more detail by temperatureꢀdependent Circular Dichroism (CD)
spectroscopy, because of the chirality of structureꢀforming motif
of Ti(salen) moiety. The PNx(IS)y were investigated at 10 oC
10 20 30 40 50 60 70 80
Temperatrue (oC)
10 20 30 40 50 60 70 80
Temperatrue (oC)
5
5
0
PN64(IS)
PN64(IS)
8
8
heating
cooling
B
B
PN66(IS)
PN66(IS)
6
6
heating
cooling
0
ꢀ5
o
ꢀ5
intervals between 10 to 80 C (Fig. 4). As expected, CD spectra
ꢀ10
ꢀ15
ꢀ20
ꢀ10
ꢀ15
ꢀ20
of all PNx(IS)y showed negative Cotton effects at ca. 243 nm,
which indicated that the copolymers formed aggregates with a
preferred leftꢀhanded (M) helical sense (Fig. 4). Notably, the
maximum intensity of the CD effect was significantly higher in
PN68(IS)4 (−38 mdeg) than that in PN60(IS)2 (−18 mdeg),
suggesting that the increased Ti(salen) units in copolymers
enhanced the singleꢀchain folding. It demonstrated that the
Ti(salen) pendants induced the selfꢀfolding of single PNx(IS)y
chain into SCPNs via intramolecular hydrophobic interaction.
While, more number of Ti(salen) units per polymer chain lowered
the intensity of Cotton effect by comparing the CD spectra of
PN66(IS)6 (−23 mdeg) and PN64(IS)8 (−21 mdeg) with that of
PN68(IS)4 (−38 mdeg). It should be probably due to the too dense
packing of bulky Ti(salen) units upon selfꢀfolding. Both
observations indicated that the local Ti(salen) concentration was
responsible for the magnitude of the Cotton effect and that the
selfꢀassembly occured within a single chain.
10 20 30 40 50 60 70 80
Temperatrue (oC)
10 20 30 40 50 60 70 80
Temperatrue (oC)
Fig. 5 Temperatureꢀdependent CD heatingꢀcooling curves of PNx(IS)y
monitored at λ = 243 nm in water at temperatures range from 10 to 80 oC
(heating rate= 1 oC /min; cooling rate= ꢀ1 oC/min), (PNx(IS)y
concentration = 0.5 g/L)
Particle Size Distribution Analysis
Dynamic light scattering (DLS) was used to further determine
the hydrodynamic diameter and size distribution of selfꢀfolded
PNx(IS)y at room temperature (Fig. 6). The hydrodynamic
diameter analysis by DLS gave monomodal symmetrical
distributions with low polydispersity index (PDI) for PN60(IS)2,
PN68(IS)4, PN66(IS)6, and PN64(IS)8 (0.395, 0.267, 0.315, and
0.206, respectively). It indicated the homogeneous distribution,
spherical morphology, and uniform sizes of corresponding
SCPNs (Fig. 3).18 Although similar morphology, the size of
SCPNs gradually decreased with increasing the content of
hydrophilic Ti(salen) block in copolymer. The hydrodynamic
diameter of PN60(IS)2, PN68(IS)4, PN66(IS)6, and PN64(IS)8 was
ca. 15.8, 11.9, 8.8, and 6.5 nm, respectively. Reduced sizes were
mainly due to the enhanced intramolecular hydrophobic
interaction arisen from increased Ti(salen) pendants, which
resulted in the more contracted conformation of SCPNs.19
Notably, although the nanostructures were both in hydrated state,
the sizes for SCPNs determined by DLS were larger than from
CryoꢀTEM, as typical by as shown by the typical PN68(IS)4. It
was probably due to the low contrast of the swollen hydrophilic
shell in vitrified water in CryoꢀTEM images.
20
20
A
PN68(IS)4
A
PN60(IS)2
10
0
15
10
5
10 o
20 o
30 o
40 o
50 o
60 o
70 o
80 o
C
C
C
C
C
C
C
C
10 o
20 o
30 o
40 o
50 o
60 o
70 o
80 o
C
C
C
C
C
C
C
C
ꢀ10
ꢀ20
ꢀ30
ꢀ40
0
ꢀ5
ꢀ10
ꢀ15
ꢀ20
220
240
260
280
300
220
240
260
280
300
Wavelength(nm)
Wavelength(nm)
10
5
10
5
PN66(IS)6
PN64(IS)8
A
A
0
0
10 o
C
10 o
20 o
30 o
40 o
50 o
60 o
70 o
80 o
C
C
C
C
C
C
C
C
ꢀ5
ꢀ5
20 o
30 o
40 o
50 o
60 o
70 o
80 o
C
C
C
C
C
C
C
ꢀ10
ꢀ15
ꢀ20
ꢀ10
ꢀ15
ꢀ20
220
240
260
280
300
220
240
260
280
300
Wavelength(nm)
Wavelength(nm)
Fig. 4 CD spectra of PNx(IS)y in water from 10 to 80 oC with 10 K
intervals (PNx(IS)y concentration = 0.5 g/L).
4
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40
35
30
25
20
15
10
5
backbone, was prepared as control catalyst to investigate the
effect of IL spacer. As expected, although it had similar
compartmental structure, PN68S4 was less active and selective
than ILꢀtagged PN68(IS)4 (Table 1, entry 5 vs. 2). A conversion of
89% of sulfide with only 92% chemoselectivity and 95% ee was
obtained over PN68S4 under identical conditions (Table 1, entry
5). Logically, the flexible IL linker that placed the chiral
complexes away from the polymer backbone ensured preferred
conformation of Ti(salen) in PN68(IS)4. This was crucial for the
effective cooperative catalysis as otherwise selectivity will be
lost.6b In addition to the conformational freedom, the IL-tagged
11.9
15.8
PN60(IS)2, PDI = 0.395
PN68(IS)4, PDI = 0.267
PN66(IS)6, PDI = 0.315
PN64(IS)8, PDI = 0.206
8.8
6.5
PN68(IS)4
also
benefited
from the
local
catalyst
0
microenvironment created by the IL spacer, since the IL moiety
was encapsulated in SCPNs compartment along with Ti(salen)
units. The unique solvent power of encapsulated IL made PN68S4ꢀ
based SCPNs more compatible with organic sulfides and aq.
H2O2,22 increasing the concentrations of reactants in
compartmentalized SCPNs. Furthermore, the polarity and ionic
property of RTILs played positive effect on stabilizing the active
metallosalen intermediate in the asymmetric sulfoxidation.7
Indeed, midway addition of 1ꢀmethylꢀ3ꢀbuthylimidazolium
chlorine IL (equivalent to the IL amount in PN68(IS)4) into the
PN68S4ꢀmediated sulfoxidation system increased the conversion
(from 89 to 93%) and selectivity (93% of chemoselectivity and
96% of ee value) (Table 1, entry 6 vs. 5). While, the reactivity
was still lower than that obtained over PN68(IS)4 (Table 1, entry 6
vs. 2). It was reasonable that, unlike the IL in PN68(IS)4, the small
amount of IL added in PN68S4 system was hard to be entirely
encapsulated in the hydrophobic domain along with Ti(salen)
motif. The results supported our hypothesis that PN68(IS)4ꢀ
mediated sulfoxidations took place within the hydrophobic
compartment of SCPNs.
The advantage of SCPNs approach over PN68(IS)4, along with
the remarkable activity and selectivity, was also noticeable for
other aryl methyl sulfides, such as methyl pꢀbromophenyl sulfide,
methyl pꢀmethoxyphenyl sulfide, methyl pꢀnitrophenyl sulfide,
and methyl oꢀmethoxyphenyl sulfide. All the aryl methyl sulfides
get quantitatively oxidized to the corresponding sulfoxides with
excellent chemoꢀ (90ꢀ98%) and enantioselectivity (88ꢀ99%)
within 90 min in water with the employment of PN68(IS)4 (Table
1, entries 2, 9, 14, 18, and 23). The enantioselectivity was even
higher than that obtained over our reported micelleꢀbound chiral
salen TiIV catalyst (ee value, 74ꢀ95%),6c although the micelleꢀ
bound system also provided a confined reaction environment.
Higher chiral induction for PN68(IS)4 should benefit from the
positive effect of imidazolium IL moiety confined in SCPNs, as
well as more stable structure of the selfꢀfolded SCPNs than
previous micelleꢀbound system which was dynamic in nature.23
Notably, almost quantitative chiral induction to (R)ꢀsulfide
(>99%) was observed for the methyl pꢀbromophenyl sulfide and
methyl oꢀmethoxyphenyl sulfide over PN68(IS)4 (Table 1, entries
9 and 23). The chemoselectivity was also unusually high with
regard to the literature results.1
1
10
100
1000
Particle size(d/nm)
Fig. 6 Size distribution of selfꢀfolded PNx(IS)y in water at a concentration
of 0.5 mg/mL at room temperature.
Catalytic Performances
As expected, the enzymeꢀmimetic SCPNs were capable of
significantly accelerating asymmetric sulfoxidation in water with
excellent selectivity, especially, rendering the reaction highly
enantioselective, as shown in Table 1. Only 0.5 mol% loading of
catalysts were sufficient to give excellent conversion (85ꢀ99%) of
methyl phenyl sulfide with remarkable chemo (89ꢀ95%) and
enantioselectivity (95ꢀ98%) in 60 min (Table 1, entries 1ꢀ4). In
contrast, traditional chiral ((R,R)ꢀsalen)TiIV(OiPr)2 complex (neat
complex, neatꢀC)14 gave 48% of conversion with disappointing
selectivity (65% of chemoselectivity and 76% of ee value) under
identical conditions (Table 1, entry 7). The discrepancy in
catalytic efficiency demonstrated the advantage of biocatalysis
approach. Apart from shielding catalytic sites from surrounding
aqueous environment, the compartmentalized SCPNs effectively
concentrated the substrates within catalytic core, enhancing
reaction rates and selectivity for the aqueous sulfoxidation.20 In
addition, multiple Ti(salen) catalytic sites confined in the
hydrophobic core may enforce an intramolecular, cooperative
reaction pathway resulting in enhanced reaction rates and higher
selectivities.6 Furthermore, excess aqueous H2O2 would be
excluded from the hydrophobic reaction space, which thus
minimized the undesired overꢀoxidation of sulfoxide to sulfone
and maximized the selectivity to chiral sulfoxide. Notably,
PN68(IS)4 showed the highest catalytic efficiency in the aqueous
asymmetric sulfoxidation of methyl phenyl sulfide, giving almost
quantitative yield (95%) of (R)ꢀsulfoxide with up to 98% ee value
(Table 1, entry 2). Less number of Ti(salen) units per polymer
chain (PN60(IS)2) was undesirable for this transformation due to
lower local concentration of Ti(salen) units in compartmentalized
SCPNs (Table 1, entry 1). While, PN66(IS)6 and PN64(IS)8 with
more number of Ti(salen) units per polymer chain were also
detrimental to the catalysis, since too dense packing of Ti(salen)
units confined in SCPNs should restrict all Ti(salen) to adopt
their preferred conformation for cooperative catalysis (Table 1,
entries 3 and 4).21
In addition to the fascinating “confined catalysis”, the higher
efficiency of PNx(IS)y should also relate to the flexible IL linker.
An ILꢀfree analog of PN68S4, in which multiple chiral salen TiIV
complexes were appended directly on the linear polymer
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Table 1 Results of asymmetric sulfoxidation of methyl aryl sulfides over
the nꢀhexyl phenyl sulfide was almost quantitatively converted to
(R)ꢀnꢀhexyl phenyl sulfoxide within 50 min (99%
chemoselectivity and 99% ee value) (Table 2, entry 4). The
enhanced catalytic efficiency should arise from the increased
hydrophobicity of sulfides with the increase of alkyl chains
length. The results indicated that the hydrophobicity of the
reactants was driving force of asymmetric sulfoxidation using
PN68(IS)4. Logically, the more hydrophobic the sulfide, the better
is the diffusion of sulfide into the hydrophobic core of the SCPNs
where the catalytic active centers are located.
different chiral salen TiIV catalysts in water a
T
(min)
Conv. b Sel. b
ee c
(%)
Substrate
Entry Catalyst
(%)
(%)
60
60
60
60
60
60
60
60
80
60
60
60
60
65
60
60
60
45
45
45
45
60
90
60
60
60
85
89
95
98
97
97
95
96
76
>99
>99
98
98
81
94
95
90
92
45
88
84
85
56
99
99
99
98
67
1
PN60(IS)2
PN68(IS)4
PN66(IS)6
PN64(IS)8
PN68S4
99
96
93
89
93
48
88
99
75
80
59
96
99
91
94
62
99
85
89
51
78
99
70
72
40
95
93
93
92
93
65
94
92
90
92
78
95
94
87
90
81
98
96
97
87
90
90
87
88
75
2
3
S
4
5
d
6
PN68S4
Table 2 Results of asymmetric sulfoxidation of alkyl phenyl sulfides over
PN68(IS)4 in water a
7
neatꢀC
PN68(IS)4
PN68(IS)4
PN68S4
Conv. c
(%)
Sel. c
(%)
ee d
(%)
Substrate b
8
T
(min)
Entry
9
S
S
1
60
60
>99
>99
95
97
98
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
Br
d
S
PN68S4
2
>99
neatꢀC
PN68(IS)4
PN68(IS)4
PN68S4
S
3
4
55
50
>99
>99
>99
>99
>99
>99
S
S
H3CO
a
PN68(IS)4 (0.5 mol% of substrate, based on titanium content), substrate (1.0
d
PN68S4
mmol), H2O2 (1.2 mmol, added within 15 min), deionized water (1 mL), 25 oC.
b The alkyl phenyl sulfides were synthesized according to reference [24], and
identified by NMR available in the Supporting Information. c Determined by
GC. d Determined by HPLC (Daicel chiralpak AD column).
neatꢀC
PN68(IS)4
PN68S4
S
O2
N
d
PN68S4
Kinetics was used to further investigate the advantages of
SCPNs approach in aqueous catalysis, as well as the positive
effect of IL moiety on catalytic performance. The corresponding
kinetic curves and rate curves were shown in Fig. 7. Obviously,
PN68(IS)4 showed gradient increase in conversion of sulfide in
corresponding kinetic curves, when asymmetric sulfoxidation
was performed in water (Fig. 7Aꢀa). The corresponding observed
rate constant (kobs) initially rose rapidly due to the dramatically
increasing concentration of substrate in hydrophobic
compartments, went through a maximum, and then drastically
decreased due to a dilution effect (Fig. 7Bꢀa).25 The featured
kinetics demonstrated confined catalysis of asymmetric
sulfoxidation in water over compartment. To further evaluate the
importance of compartmentalization, we carried out the reaction
with PN68(IS)4 in dichloromethane, a solvent in which PN68(IS)4
could also be well dissolved. As expected, at the same catalyst
concentration, PN68(IS)4 was far less efficient than in water (Fig.
7d vs. 7a). In fact, selfꢀfolding of PN68(IS)4 into SCPNs didn’t
occur when reaction was performed in dichloromethane.
Amphiphilic PN68(IS)4 just located at the interface between
dichloromethane and water (aqueous H2O2) in the biphasic
system, behaving as a common phaseꢀtransfer catalyst, rather
than a concentrator. Lower local concentration of substrates and
catalytic species in the biphasic system was insufficient for
efficient catalysis. The results were consistent with our
hypothesis that high local concentration of catalytic species was
crucial for this system to be active, and this was only achieved in
the folded state and in the presence of structured hydrophobic
compartments. For this reason, it was not surprising that
traditional neat complex gave the lowest kobs in water due to poor
solubility of catalyst and sulfides in water (Fig. 7e). These results
neatꢀC
PN68(IS)4
PN68(IS)4
PN68S4
S
OCH3
d
PN68S4
neatꢀC
a
Catalyst (0.5 mol% of substrate, based on titanium content), substrate (1.0
mmol), H2O2 (1.2 mmol, added within 15 min), deionized water (1 mL), 25 oC.
d
b Determined by GC. c Determined by HPLC (Daicel chiralpak AD column).
PN68S4 (0.5 mol% of substrate, based on titanium content), 1ꢀmethylꢀ3ꢀ
buthylimidazolium chlorine (0.001 g, equivalent to the amount of IL in
PN68(IS)4), substrate (1.0 mmol), H2O2 (1.2 mmol, added in 15 min), water (1
mL), 25 oC.
To further confine the universality of PN68(IS)4, a batch of
alkyl phenyl sulfides with various length of the alkyl chain (C1,
C2, C4, and C6) was synthesized and subjected to the
sulfoxidation conditions. As expected, all the alkyl phenyl
sulfides also get quantitatively oxidized to the corresponding
sulfoxides in water with excellent selectivity with the
employment of PN68(IS)4 (Table 2). Interestingly, we noticed that
increasing the length of alkyl chain in sulfides led to the
enhanced reaction rate and improved selectivity (in terms of
chemoꢀ and enantioselectivity). The asymmetric sulfoxidation of
methyl phenyl sulfide was complete in 60 min, giving 95%
chemoselectivity and 98% ee value (Table 2, entry 1). As the
number of carbon atoms of alkyl chain increased from 1 to 2, 4
and further to 6, the catalytic efficiency and selectivity increased
accordingly (Table 2, entries 2, 3, and 4 vs. entry 1)). In particular,
6
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confirm that PN68(IS)4 created
a
more favourable
by FTꢀIR spectra of the fresh and recovered typical PN68(IS)4
(Fig. 1b vs. 1b’). It suggested the perfect stability of PNx(IS)y in
aqueous asymmetric sulfoxidation. Oxidative decomposition of
chiral salen TiIV complex, a main reason for deactivation of the
catalyst in H2O2ꢀbased oxidation,27 did not occur during the
reaction. The excellent stability of catalysts should arise from the
shielding of chiral salen TiIV complex in a hydrophobic pocket,
which protected Ti(salen) complex from oxidative decomposition
by excluding excess H2O2 from the complex. Furthermore,
imidazolium IL moiety incorporated in the hydrophobic pocket
also played a positive effect on stabling the complex.7
microenvironment for sulfoxidation in water than in organic
solvent. Moreover, despite also SCPNs catalysis, the kobs over
PN68S4 was always lower than that over PN68(IS)4 in the aqueous
sulfoxidation (Fig. 7b vs. 7a), and simple addition of IL into the
PN68S4 system accelerated the reaction (Fig. 7c vs. 7b). The
observations did agree with the active role of imidazoliumꢀbased
IL in the overall reaction mechanism. Furthermore, we noticed
that the SCPNsꢀbased sulfoxidation started after 35ꢀ40 min (Fig.
7aꢀc). The delayed reaction should be probably due to that the
compartmentalized structure of SCPNs somewhat hindered the
permeation of substrates into hydrophobic interior.26 The
observations provided further evidence for the confined catalysis
80
70
60
50
40
30
20
10
PN68(IS)4
PN60(IS)2
70
60
50
40
30
20
10
in SCPNs compartment.
100
a
b
B
A
a
12
10
8
c
b
c
80
60
40
20
0
0
2
4
6
8
10
12
0
2
4
6
8
10
12
Cycles
Cycles
90
80
70
60
50
40
30
20
10
90
80
70
60
50
40
30
20
10
PN64(IS)8
PN66(IS)6
d
6
e
4
2
d
e
0
2
4
6
8
10
12
0
2
4
6
8
10
12
0
Cycles
Cycles
0
10 20 30 40 50 60 70 80
Reaction time (min)
0
10 20 30 40 50 60 70 80
Reaction time (min)
Fig. 8 Optical transmittance at 450 nm of PNx(IS)y solution observed
upon several cycles under heating at 80 oC and then cooling to 15 oC
Fig. 7 Fitted kinetic curves (A) and rate curves (B) of asymmetric
sulfoxidation of methyl phenyl sulfide over PN68(IS)4 (a), PN68S4 together
with 1ꢀmethylꢀ3ꢀbuthylimidazolium (b), PN68S4 (c), and neat complex (e)
in water, and over PN68(IS)4 in dichloromethane (d).
100
80
60
40
20
0
Aside from exhibiting enzymeꢀmimetic activity and selectivity,
PNx(IS)y exhibited the reversibility of thermal driven waterꢀ
solubility switching. Waterꢀsolubility switching process was
determined by monitoring the optical transmittance of PNx(IS)y
solution at 450 nm using UVꢀvis spectrophotometry (Fig. 8).
C
D
B
A
o
Clear solutions of the PNx(IS)y in water were observed at 15 C.
Conv.
Sel.
ee
Conv.
Sel.
ee
Conv.
Sel.
ee
Conv.
Sel.
ee
After being heated to 80 oC, the transmittance decreased
dramatically, which was corresponding to the waterꢀsolubility
switch from amphiphilic to hydrophobic. By continuous cooling
to 15 oC, the solutions reverted to the initial clear state.
Significantly, the reversible transition between turbidity and
clarity could repeat several times, indicating the good thermal
responsiveness of the supramolecular assembly. The salient
features allowed for facile recovery of PNx(IS)y from the aqueous
phase by thermoꢀcontrolled separation.
0
1
2
3
4
5
6
7
8 0
1
2
3
4
5
6
7
8 0
1
2
3
4
5
6
7
8 0
1
2
3
4
5 6 7 8
Run times
Run times
Run times
Run times
Fig. 9 Reuse of PN60(IS)2 (A), PN68(IS)4 (B), PN66(IS)6 (C) and PN64(IS)8
(D) in asymmetric sulfoxiation of methyl phenyl sulfide in water.
Conclusions
A novel series of enzymeꢀinspired SCPNs which contained
chiral salen TiIV complex in the hydrophobic core was
constructed for asymmetric sulfoxidation in water. The SCPNs
demonstrated enzymeꢀmimetic activity and selectivity for a wide
range of methyl aryl sulfides in water due to the
compartmentalization and the effective shielding of active sites
from the aqueous environment. In particular, the
enantioselectivity observed for electronꢀrich substrates
represented the best results so far in titaniumꢀsalen systems. More
interestingly, the catalysts could be facilely recovered from the
aqueous system for efficient reuse by adjusting local temperature.
Fig. 9 gave the reusability of PNx(IS)y in asymmetric oxidation
of methyl phenyl sulfide in water. To our delight, the catalysts
could be reused up to seven times without significant loss in
activity and selectivity. Leaching tests of catalysts revealed
negligible leaching loss of titanium species (less than 0.1 ppm by
ICP) to reaction medium during the oxidation. Chemical analysis
of the recovered catalysts gave titanium content (0.449, 0.503,
0.521, and 0.562 mmol/g for recovered PN60(IS)2, PN68(IS)4,
PN66(IS)6, and PN64(IS)8, respectively) almost identical to that of
the corresponding fresh one. Furthermore, no significant change
of catalysts took place even after reuse for seven times, as shown
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The high activity and selectivity, as well as outstanding
reusability, made the enzymeꢀinspired SCPNs highly promising
for biocatalysis of various organic reactions in water.
Furthermore, the SCPNs approach also inspired researchers to
perfect the design and synthesis of other enzyme mimics and to
tailor their functionality for a much wider range of applications.
solutions for measurements were prepared for concentrations of 0.5 mg.
mLꢀ1 followed by filtering through a 0.45 lm disposable polyamide
membrane to free it from dust particles. The content of titanium contents
in the samples was determined by inductively coupled plasma mass
spectrometry (ICPꢀMS) on a NexION 300X analyzer (PerkinꢀElmer
Corp.). Optical rotation of samples was measured in dichloromethane on
a WZZꢀ2A Automatic Polarimeter. The surface tension of an aqueous
solution of catalyst was measured as a function of catalyst concentration
on a Krüss K12 tensiometer using the Wilhelmy plate method at 25 °C.
The surface tension vs. catalyst concentration plot gives information on
the critical micelle concentration (CMC). HPLC analyses were performed
on a TECHCOMP L2000 or JASCO 2089 liquid chromatograph using the
Daicel chiralpak AD column.
Experimental Section
Materials and Reagents
N,NꢀAzobis(isobutyronitrile) (AIBN), NIPAAm, nꢀpropanethiol, and
L(+)ꢀtartaric acid were purchased from Acros. Tetraꢀisopropyl titanate,
vinylimidazole and aryl methyl sulfides were obtained by J&K. 2ꢀtertꢀ
Butyl phenol was purchased from Alfa Aesar. Other commercially
available chemicals were laboratory grade reagents from local suppliers.
All solvents were purified by standard procedures. AIBN was
recrystallized from methanol. NIPAAm was purified by recrystallization
from nꢀhexane and dried in vacuo.
Preparation of Catalysts
Synthesis of IL/Ti(salen): The asymmetric chiral salen ligand (CL1,
3.2 mmol, 1.725 g) was mixed with vinyl imidazole (3 mmol, 0.28 g) in
dry toluene (15 mL). The mixture was refluxed for 48 h under nitrogen
protection, and then concentrated in vacuo. The residue was dissolved in
dichloromethane, and followed by treatment with Ti(OiPr)4 (3.2 mmol,
0.91 g) for 3 h at room temperature. After removal of solvent, the crude
product was treated with water (100 mL), filtered, and washed with water
and nꢀhexane. The crude product was dissolved in CH2Cl2 and filtered to
remove any traces of TiO2. The filtrate was concentrated in vacuum and
further dried in vacum at 40 oC overnight, giving yellow powder of
IL/Ti(salen). IL/Ti(salen): FTꢀIR (KBr): γmax/cmꢀ1 3437, 3310, 3073, 2973,
2933, 2882, 1653, 1540, 1458, 1384, 1365, 1263, 1172, 1130, 1051, 986,
922, 881, 838, 626, 518 cmꢀ1. 1H NMR (500 MHz, CD3Cl3): δ 8.11~
7.65(s, 2 H, CH=N ), 7.18~7.59 (m, 4 H, ArH), 6.05 (m, 1 H, Nꢀ
CH=CH2) 4.15 (s, 1H, C=NCH), 3.87(m, 1 H, C=NCH), 3.56 (m, 4 H, Nꢀ
Methods
FTꢀIR spectra were obtained as potassium bromide pellets with a
resolution of 4 cmꢀ1 and 32 scans in the range 400– 4000 cmꢀ1 using an
AVATAR 370 Thermo Nicolet spectrophotometer. NMR of samples was
recorded at a BRUKER AVANCE ꢀ500 spectrometer with TMS as an
internal standard. TEM images were obtained on a Microscope Tecnai
F20 at an accelerating voltage of 200 kV. Samples were prepared by
depositing aqueous solution (0.5 mg. mLꢀ1) onto a carbonꢀcoated copper
grid, followed by removal of excess solution by blotting the grid with
filter paper. The samples were dried for 72 h at room temperature in a
desiccator. After that, the samples were negatively stained by
phosphotungstic acid and dried for another 72 h before examination.
CryoꢀTEM measurements were performed on a FEI Technai 20, type
Sphera. The Technai 20 is equipped with a LaB6 filament operating at
200 kV and the images were recorded using a 1k x 1k Gatan CCD camera.
The sample vitrification procedure was carried out using an automated
vitrification robot (FEI Vitrobot™ Mark III). CryoTEM grids, R2/2
Quantifoil Jena grids, were purchased from Quantifoil Micro Tools
GmbH. The grids underwent a surface plasma treatment using a
Cressington 208 carbon coater operating at 5 mA for 40 s, prior to the
vitrification procedure that was carried out within the environmental
chamber of the VitrobotTM at room temperature (1 mg/mL polymer
solution in H2O, 3 ꢁL aliquots, 3 s blotting time, ꢀ2 mm blotting offset,
100 % relative humidity). The vitrified specimens were stored under
liquid nitrogen. Molecular weight and molecularꢀweight distribution of
the synthesized copolymers was obtained by gel permeation
chromatography (GPC). Analyses were performed on an Alltech
Instrument (Alltech, America) using THF as the solvent eluting at a flow
of 1 mL min−1 through a Jordi GPC 10 000 A column (300 mm × 7.8 mm)
equipped with an Alltech ELSD 800 detector. The system was calibrated
with standard polystyrenes. The detection temperature is 40 °C and
column temperature is 30 °C. CD measurements were performed on a
MOSꢀ500 spectropolarimeter where the sensitivity, time constant and
scan rate were chosen appropriately (sensitivity: standard; response: 2 s;
band width: 1 nm; data pitch: 0.1 nm; scanning speed: 20 nm/min).
Corresponding temperatureꢀdependent measurements were performed
i
CH=CH2 and ꢀNꢀCH2ꢀNꢀ), 2.36~2.65 (m, 2 H, CH3ꢀCHꢀCH3 in PrOꢀ),
1.46 (m, 8 H, cyclohexylꢀH), 1.23~1.37 (m, 27 H, Hꢀ in tꢀbutyl), 1.31(m,
12 H, CH3ꢀCHꢀCH3 in iPrOꢀ).
Preparation of PNx(IS)y: Monomers of NIPAAm and IL/Ti(salen)
with various molar feed (9.0 mmol of NIPAAm and 0.3 mmol of
IL/Ti(salen) for PN60(IS)2, 9.0 mmol of NIPAAm and 0.5 mmol of
IL/Ti(salen) for PN68(IS)4, 9.0 mmol of NIPAAm and 0.8 mmol of
IL/Ti(salen) for PN66(IS)6, 8.8 mmol of NIPAAm and 1.0 mmol of
IL/Ti(salen) for PN64(IS)8) were dissolved in dry methanol (20 mL) in
Schlenk tube. nꢀPropanethiol (chain transfer reagent, 1 mmol, 0.076 g)
and AIBN (radical initiator, 0.5 mmol, 0.082 g) were then added into the
solutions. The reaction mixtures were degassed by bubbling with nitrogen
gas at room temperature for 30 min. Polymerizations were carried out at
60 oC for 24 h under nitrogen gas atmosphere. After being cooled to room
temperature, the mixtures were concentrated under vacuum. Crude
products were purified by dialysis in THF. PNx(IS)y were precipitated in
diethyl ether as yellow powders (where x and y represented the repeated
units number of NIPAAm and IL/Ti(salen), respectively; the number was
determined by 1H NMR spectra of corresponding copolymers, see Section
S1 in ESI). Different molar feed ratio of 9.0/0.3, 9.0/0.5, 9.0/0.8, and
8.8/1.0 resulted in the copolymers of PN60(IS)2, PN68(IS)4, PN66(IS)6, and
PN64(IS)8, respectively.
PN60(IS)2: FTꢀIR (KBr): γmax/cmꢀ1 3436, 3313, 3075, 2971, 2942,
2891, 1653, 1542, 1457, 1386, 1368, 1263, 1170, 1131, 1054, 927, 880,
1
836, 806, 709, 624, 519 cmꢀ1. H NMR (500 MHz, CDCl3): δ 6.24~6.89
with
a
PFDꢀ425S/15 Peltierꢀtype temperature controller with
a
(m, 60 H, HCꢀNHꢀC=O), 6.08 (m, 2 H, NꢀCHꢀCH2ꢀ of Nꢀvinyl), 4.18 (m,
2 H, C=NCH), 3.99 (m, 60 H, ꢀCHꢀCH2 in NIPAAm), 3.88 (m, 2 H,
C=NCH), 3.67 (m, 8 H, ꢀCHꢀCH2ꢀ of Nꢀvinyl in IL and ꢀNꢀCH2ꢀNꢀ), 3.45
(m, 60 H, CH3ꢀCHꢀCH3 in NIPAAm), 3.06 (m, 12 H, ꢀNꢀCH2ꢀCH2ꢀNꢀ
o
temperature range of 10–80 C and adjustable temperature slope, in all
cases temperature slope of 1 oC /min was used. DLS was performed using
a ZS90 Laser Particle Size Analyzer (Malvern, UK). The sample
8
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DOI: 10.1039/C6GC02743A
and ꢀNꢀCH2ꢀPhꢀ), 2.84 (m, 2 H, SHꢀCH2ꢀCH2ꢀCH3), 2.64~2.73 (m, 4 H,
copolymerize with NIPAAm in the presence of AIBN and nꢀpropanethiol,
giving the amphiphilic PN68S4 (where the repeated number of NIPAAm
units is 64, and the repeated number of Ti(salen) units is 8, as determined
i
CH3ꢀCHꢀCH3 of PrOꢀ in Ti(salen)), 2.38 (m, 2 H, SHꢀCH2ꢀCH2ꢀCH3),
1.86~2.12 (m, 120 H, ꢀCH2ꢀCHꢀ in NIPAAm), 1.71(s, 3 H, SHꢀCH2ꢀCH2ꢀ
CH3), 1.43 (16 H, cyclohexylꢀH), 1.13~1.33 (54 H, Hꢀ in tꢀbutyl),
1.09~1.16 (m, 384 H, CH3ꢀCHꢀCH3 in iPrOꢀ and NIPAAm). GPC (THF):
Mn = 8990, Mw = 12840, PDI = 1.43. α25D = ꢀ16.0 (C = 0.005 g/mL,
CH2Cl2), titanium content: 0.452 mmol.gꢀ1.
1
by H NMR spectrum of the copolymer, see Section S1 in ESI). FTꢀIR
(KBr): γmax/cmꢀ1 3435, 3304, 3077, 2965, 2924, 2868, 1664, 1539, 1457,
1380, 1369, 1268, 1174, 1125, 1050, 967, 926, 880, 835, 806, 708, 679,
1
507 cmꢀ1. H NMR (500 MHz, CDCl3): δ 8.31~7.78 (m, 8 H, CH=N),
PN68(IS)4: FTꢀIR (KBr): γmax/cmꢀ1 3436, 3302, 3064, 2967, 2923,
2867, 1645, 1541, 1454, 1382, 1365, 1265, 1175, 1128, 1053, 920, 882,
834, 809, 709, 635, 624, 509 cmꢀ1. 1H NMR (500 MHz, CD3Cl3): δ
8.15~7.68 (m, 8 H, CH=N), 7.14~7.64 (m, 16 H, ArH), 6.24~6.89 (m, 68
H, HCꢀNHꢀC=O), 6.05 (m, 4 H, NꢀCHꢀCH2ꢀ of Nꢀvinyl), 4.14 (m, 4 H,
C=NCH), 3.99 (m, 68 H, ꢀCHꢀCH2ꢀ in NIPAAm), 3.85(m, 4 H, C=NCH),
3.58 (m, 16 H, ꢀCHꢀCH2ꢀ of Nꢀvinyl in IL and ꢀNꢀCH2ꢀNꢀ), 3.26 (m, 68
H, CH3ꢀCHꢀCH3 in NIPAAm), 2.90 (m, 24 H, ꢀNꢀCH2ꢀCH2ꢀNꢀ and ꢀNꢀ
CH2ꢀPhꢀ), 2.78(m, 2 H, SHꢀCH2ꢀCH2ꢀCH3), 2.34~2.68 (m, 8 H, CH3ꢀCHꢀ
7.11~7.72 (m, 16 H, ArH), 6.06~6.78 (s, 68 H, HCꢀNHꢀC=O), 4.76 (s, 4
H, C=NCH), 4.09 (s, 68 H, ꢀCHꢀCH2ꢀ in NIPAAm), 3.48 (s, 4 H,
C=NCH), 3.41 (m, 8 H, ꢀCHꢀCH2ꢀPhꢀ in Ti(salen)), 3.19 (m, 68 H, CH3ꢀ
CHꢀCH3 in NIPAAm), 2.91 (s, 2 H, SHꢀCH2ꢀCH2ꢀCH3), 2.72~2.84 (s, 8
H, CH3ꢀCHꢀCH3 of iPrOꢀ in Ti(salen)), 2.63 (m, 2 H, SHꢀCH2ꢀCH2ꢀCH3),
1.73~2.11 (s, 136 H,ꢀCHꢀCH2ꢀ in NIPAAm), 1.72 (s, 3 H, SHꢀCH2ꢀCH2ꢀ
CH3), 1.59~1.67 (s, 32 H, cyclohexylꢀH), 1.37~1.51 (108 H, Hꢀ in tꢀ
i
butyl), 1.07~1.32 (456 H, CH3ꢀCHꢀCH3 in PrOꢀ and NIPAAm). GPC
(THF): Mn = 10830, Mw = 13270, PDI = 1.50. α25D = ꢀ12.6 (C=0.005
i
CH3 of PrOꢀ in Ti(salen)), 2.10 (m, 2 H, SHꢀCH2ꢀCH2ꢀCH3), 1.78~1.98
g/mL, CH2Cl2), titanium content: 0.586 mmol.gꢀ1.
(m, 136 H, ꢀCHꢀCH2 in NIPAAm), 1.73 (s, 3 H, SHꢀCH2ꢀCH2ꢀCH3), 1.47
(m, 32 H, cyclohexylꢀH), 1.21~1.38 (m, 108 H, Hꢀ in tꢀbutyl), 1.06~1.15
General procedure for asymmetric oxidation of sulfides to
sulfoxides
i
(m, 456 H, CH3ꢀCHꢀCH3 in PrOꢀ and NIPAAm). GPC (THF): Mn =
10953, Mw = 11830, PDI = 1.08. α25D = ꢀ14.2 (C = 0.005 g/mL, CH2Cl2),
titanium content: 0.508 mmol.gꢀ1.
Catalytic copolymer (0.5 mol% substrate, based on the titanium content
in catalyst) and sulfides (1.0 mmol) were added to H2O (1 mL) under
o
PN66(IS)6: FTꢀIR (KBr): γmax/cmꢀ1 3441, 3309, 3061, 2974, 2927,
2864, 1651, 1530, 1453, 1382, 1363, 1266, 1176, 1123, 1051, 920, 883,
836, 805, 708, 625, 504 cmꢀ1. 1H NMR (500 MHz, CD3Cl3): δ
8.13~7.72(m, 12 H, CH=N), 7.18~7.69 (m, 24 H, ArH), 6.21~6.92 (m, 66
H, HCꢀNHꢀC=O), 6.16 (m, 6 H, NꢀCHꢀCH2ꢀ of Nꢀvinyl), 4.04 (m, 6 H,
C=NCH), 3.97 (m, 66 H, ꢀCHꢀCH2ꢀ in NIPAAm), 3.81(m, 6 H, C=NCH),
3.56 (m, 24 H, ꢀCHꢀCH2ꢀ of Nꢀvinyl in IL and ꢀNꢀCH2ꢀNꢀ),3.23 (m, 66 H,
CH3ꢀCHꢀCH3 in NIPAAm), 3.09 (m, 36 H, ꢀNꢀCH2ꢀCH2ꢀNꢀ and ꢀNꢀCH2ꢀ
Phꢀ), 2.75(m, 2 H, SHꢀCH2ꢀCH2ꢀCH3), 2.41~2.61 (m, 12 H, CH3ꢀCHꢀCH3
stirring at 25 C. H2O2 (30 wt%, 1.2 mmol) was then dropwise added
within 15 min. The resulting mixture was stirred at room temperature
until the reaction was judged to be complete based on GC analysis. Then,
the reaction mixture was heated to 80 °C. Catalyst was precipitated out
from the reaction system, washed with nꢀhexane (3×5 mL), dried in a
vacuum. The supernatants separated from reaction system were extracted
with dichloromethane thrice. Combined organic phase was concentrated
in vacuum. Further purification of the residue by chromatography on
silica gel (petroleum ether/ethyl acetate, 1.5/1) afforded pure sulfoxides.
The pure sulfoxides have been identified by 1H and 13C NMR spectra. The
conversion and chemoselectivity of chiral sulfoxide were measured by a
6890N gas chromatograph (Agilent Co.) equipped with a capillary
column (HP19091GꢀB213, 30 m × 0.32 mm × 0.25 ꢁm) and a FID
detector. Ee values of corresponding chiral sulfoxides were determined by
HPLC analysis using the Daicel chiralpak AD columns. Detailed NMR
and HPLC analysis for produced sulfoxides were available in Section S2
of ESI.
i
of PrOꢀ in Ti(salen)), 2.23 (m, 2 H, SHꢀCH2ꢀCH2ꢀCH3), 1.76~1.82 (m,
132 H, ꢀCHꢀCH2 in NIPAAm), 1.75 (s, 3 H, SHꢀCH2ꢀCH2ꢀCH3), 1.41(m,
48 H, cyclohexylꢀH ), 1.22~1.31(m, 162 H, Hꢀ in tꢀbutyl), 1.01~1.12 (m,
i
469 H, CH3ꢀCHꢀCH3 in PrOꢀ and NIPAAm). GPC (THF): Mn = 12160,
Mw = 13620, PDI = 1.12. α25D = ꢀ16.8 (C = 0.005 g/mL, CH2Cl2), titanium
content: 0.525 mmol. gꢀ1.
PN64(IS)8: FTꢀIR (KBr): γmax/cmꢀ1 3435, 3302, 3066, 2974, 2924, 2860,
1655, 1535, 1455, 1380, 1365, 1264, 1174, 1125, 1054, 924, 882, 839,
1
806, 709, 634, 625, 507 cmꢀ1. H NMR (500 MHz, CD3Cl3): δ 8.11~7.62
Methyl phenyl sulfoxide: Chemoselectivity: 95% determined by GC,
nitrogen was used as the carrier gas with a flow of 30 mL.min−1, injector
temperature and detector temperature were 250 oC, the column
(m, 16 H, CH=N), 7.13~7.67 (m, 32 H, ArH), 6.24~6.87 (m, 64 H, HCꢀ
NHꢀC=O), 6.22 (m, 8 H, NꢀCHꢀCH2ꢀ of Nꢀvinyl), 4.46 (m, 8 H, C=NCH),
4.05 (m, 64 H, ꢀCHꢀCH2ꢀ in NIPAAm), 3.78 (m, 8 H, C=NCH), 3.58 (m,
32 H, ꢀCHꢀCH2ꢀ of Nꢀvinyl in IL and ꢀNꢀCH2ꢀNꢀ), 3.18 (m, 64 H, CH3ꢀ
CHꢀCH3 in NIPAAm), 2.86 (m, 48 H, ꢀNꢀCH2ꢀCH2ꢀNꢀ and ꢀNꢀCH2ꢀPhꢀ),
2.75(m, 2 H, SHꢀCH2ꢀCH2ꢀCH3), 2.45~2.63 (m, 16 H, CH3ꢀCHꢀCH3 of
iPrOꢀ in Ti(salen)), 2.12 (m, 2 H, SHꢀCH2ꢀCH2ꢀCH3), 1.75~1.87 (m, 128
H, ꢀCHꢀCH2ꢀ in NIPAAm), 1.73(s, 3 H, SHꢀCH2ꢀCH2ꢀCH3), 1.41 (m, 64
H, cyclohexylꢀH ), 1.22~1.31 (m, 216 H, Hꢀ in tꢀbutyl), 1.01~1.12 (m,
o
o
temperature was programmed from 80 to 180 C with 6 C·min−1, tmethyl
= 6.9 min; ee value: 98% determined by HPLC (iꢀPrOH/n-
phenyl sulfoxide
hexane = 1: 9 (v/v)); flow rate = 1.0 mL.min−1; 25 °C; λ = 254 nm; major
enantiomer tR = 18.7 min, minor enantiomer tS = 21.2 min; 1H NMR
(CDCl3, 500 MHz): δ (ppm): 2.55ꢀ2.57 (s, 3 H, Me), 7.27ꢀ7.38 (m, 3 H,
ArH), 7.39ꢀ7.51 (m, 2 H, ArH).13C NMR (CDCl3, 125 MHz): δ (ppm):
43.9 (SCH3), 123.5, 129.3, 130.9, 145.6(ArC).
i
Methyl p-bromophenyl sulfoxide: Chemoselectivity: 92% determined
by GC, nitrogen was used as the carrier gas with a flow of 30 mL.min−1,
480 H, CH3ꢀCHꢀCH3 in PrOꢀ and NIPAAm). GPC (THF): Mn = 13504,
Mw = 14970, PDI = 1.11. α25D = ꢀ18.0 (C=0.005 g/mL, CH2Cl2), titanium
content: 0.568 mmol.gꢀ1
o
injector temperature and detector temperature were 250 C, the column
temperature was 180 oC, tmethyl p-bromophenyl sulfoxide = 11.2 min; ee value: >99%
was determined by HPLC (iꢀPrOH/n-hexane = 5:5 (v/v)); flow rate = 1.0
mL min−1; 25 °C; λ = 254 nm; major enantiomer tR = 8.2 min and minor
enantiomer tS =10.0 min; 1H NMR (CDCl3, 500 MHz): δ (ppm): 3.15 (s, 3
H, SCH3), 7.74ꢀ7.76 (d, 2 H, ArH), 7.83ꢀ7.84 (d, 2 H, ArH).13C NMR
(CDCl3, 125 MHz): δ (ppm): 44.5 (SCH3), 125.3, 129.1, 132.8,
139.6(ArC).
Preparation of PN68S4: The ILꢀfree counterpart of PN68S4, in which
multiple chiral salen TiIV complexes were directly appended on linear
polymer backbone, was also prepared according to a similar procedure to
that of PNx(IS)y. The chiral salen ligand of (R,R)ꢀNꢀ(3,5ꢀdiꢀtertꢀ
butylsalicylidene)ꢀN’ꢀ[3ꢀtertꢀbutylꢀ5ꢀvinyl]ꢀ1,2ꢀcyclohexanediamine
(CL2) treated with Ti(OiPr)4 was used as the hydrophobic monomer to
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 9

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DOI: 10.1039/C6GC02743A
Methyl p-methoxyphenyl sulfoxide: Chemoselectivity: 94% determined
(CDCl3, 500 MHz): δ (ppm): 0.87ꢀ0.90 (s, 3 H, Me), 1.26ꢀ1.68 (m, 4 H,ꢀ
CH2ꢀ CH2ꢀ), 1.66ꢀ1.69 (m, 2 H, ꢀCH2ꢀ), 2.89ꢀ2.93 (m, 2 H, ꢀCH2ꢀ), 7.15ꢀ
7.16 (m, 1 H, ArH), 7.25ꢀ7.28 (m, 2 H, ArH), 7.31ꢀ7.32 (m, 2 H, ArH).
13C NMR (CDCl3, 125 MHz): δ (ppm): 14.04 (CH3), 22.55 (CH2), 28.54
(CH2), 31.38 (CH2), 33.60 (CH2), 58.21 (CH2), 125.62, 128.80, 128.85,
137.08 (ArC).
by GC, nitrogen was used as the carrier gas with a flow of 30 mL.min−1,
o
injector temperature and detector temperature were 250 C, the column
o
o
temperature was programmed from 80 to 180 C with 6 C·min−1, tmethyl p-
= 11.7 min; ee value: 95% determined by HPLC (iꢀ
methoxyphenyl sulfoxide
PrOH/n-hexane = 2:8 (v/v)); flow rate = 1.0 mL.min−1; 25 °C; λ = 254 nm;
1
major enantiomer tR = 8.9 min and minor enantiomer tS = 10.2 min; H
Sulfoxidation reaction for kinetic measurement
NMR (CDCl3, 500 MHz): δ (ppm): 3.07 (s, 3 H, SCH3), 3.95 (s, 3 H,
OCH3), 7.06ꢀ7.10 (d, 2 H, ArH), 7.84ꢀ7.91 (d, 2 H, ArH). 13C NMR
(CDCl3, 125 MHz): δ (ppm): 44.8 (SCH3), 55.8 (OCH3), 114.6, 129.6,
132.3, 163.7 (ArC).
Catalyst (0.5 mol% of substrate, based on titanium ion content in
copolymer) was stirred with methyl phenyl sulfide (1.0 mmol) in
o
deionized water (1 mL) at 25 C. H2O2 (30 wt%, 1.2 mmol) was then
added into the mixture in one portion. To determine the rate of
sulfoxidation, aliquots at an interval of 5 min were drawn from the
reaction mixture, filtrated through silica gel with ethyl acetate as an eluent
and analyzed by GC.
Methyl p-nitrophenyl sulfoxide: Chemoselectivity: 98% determined by
GC, nitrogen was used as the carrier gas with a flow of 30 mL.min−1,
o
injector temperature and detector temperature were 250 C, the column
o
temperature was 180 C, tmethyl p-nitrophenyl sulfoxide = 8.6 min; ee value: 88%
determined by HPLC (iꢀPrOH/n-hexane = 3:7 (v/v)); flow rate = 1.0
mL.min−1; 25 °C; λ = 254 nm; major enantiomer tR = 11.5 min and minor
Acknowledgements
1
enantiomer tS =21.5 min; H NMR (CDCl3, 500 MHz): δ (ppm): 2.59 (s,
The work was supported by the National Natural Science
Foundation of China (21476069, 21676078), the Natural Science
Foundation of Hunan Province for Distinguished Young Scholar
(2016JJ1013), the Scientific Research Fund of Hunan Provincial
Education Department (13B072), and the Program for Excellent
Talents in Hunan Normal University (ET14103). The authors are
grateful to Prof. Linpeng Cheng and Bin Xu (Tsinghua University)
for their help with the characterization using CryoꢀTEM at
Tsinghua University Branch of the National Center for Protein
Sciences (Beijing).
3H, SCH3), 7.27ꢀ7.42 (d, 2H, ArH), 8.09ꢀ8.20 (d, 2H, ArH).13C NMR
(CDCl3, 125 MHz): δ (ppm): 43.8 (SCH3), 123.9, 124.9, 144.7, 148.8
(ArC).
Methyl o-methoxyphenyl sulfoxide: Chemoselectivity: 90% determined
by GC, nitrogen was used as the carrier gas with a flow of 30 mL.min−1,
o
injector temperature and detector temperature were 250 C, the column
temperature was 180 oC, tmethyl o-methoxyphenyl sulfoxide = 9.8 min; ee value: >99%
determined by HPLC (iꢀPrOH/n-hexane = 2:8 (v/v)); flow rate = 1.0
mL.min−1; 25 °C; λ = 254 nm; major enantiomer tR = 9.0 min and minor
enantiomer tS =10.3 min; 1H NMR (CDCl3, 500 MHz): δ (ppm): 2.68 (s, 3
H, SCH3), 3.78 (s, 3 H, OCH3), 6.79ꢀ7.90 (m, 4 H, ArH).13C NMR
(CDCl3, 125 MHz): δ (ppm): 13C NMR (CDCl3, 125 MHz): δ (ppm): 41.1
(SCH3), 55.7 (OCH3), 110.5, 121.5, 124.4, 132.0, 132.8, 154.7 (ArC).
Ethyl phenyl sulfoxide: Chemoselectivity: 97% determined by GC,
nitrogen was used as the carrier gas with a flow of 30 mL. min−1, injector
temperature and the detector temperature were 250 oC, the column
Notes and references
[1] a) T. Tanaka, B. Saito and T. Katsuki, Tetrahedron Lett., 2002, 43,
3259; b) B. Ferber and H. B. Kagan, Adv. Synth. Catal., 2007, 349, 493;
c) M. A. Fascione, S. J. Adshead, P. K. Mandal, C. A. Kilner, A. G.
Leach and W. B. Turnbull, Chem. Eur. J., 2012, 18, 2987; d) H. Srour,
P. L. Maux, S. Chevance and G. Simonneaux, Coord. Chem. Rev.,
2013, 257, 3030; e) W. Xuan, C. Ye, M. Zhang, Z. Chen and Y. Cui,
temperature was 180 oC, tethyl
= 2.5 min; ee value: >99%
phenyl sulfoxide
Chem. Sci., 2013, 4, 3154.
determined by HPLC (iꢀPrOH/ n-hexane = 1: 9 (v/ v)); flow rate = 1.0 mL.
min−1; 25 °C; λ = 254 nm; major enantiomer tR = 8.2 min. 1H NMR
(CDCl3, 500 MHz): δ (ppm): 1.18 (m, 3 H, Me), 2.90ꢀ2.98 (m, 2 H, ꢀCH2ꢀ
), 7.28ꢀ7.29 (m, 1 H, ArH), 7.33ꢀ7.49 (m, 2 H, ArH), 7.50ꢀ7.62 (m, 2 H,
ArH). 13C NMR (CDCl3, 125 MHz): δ (ppm): 5.90 (CH3), 50.23 (SCH2),
124.12, 128.76, 129.08, 145.87 (ArC).
[2] a) M. GarciaꢀViloca, J. Gao, M. Karplus and D. G. Truhlar, Science,
2004, 303, 186; b) A. Warshel, Angew. Chem. Int. Ed., 2014, 53, 10020.
[3] a) M. Ouchi, N. Badi, J. F. Lutz and M. Sawamoto, Nat. Chem., 2011,
3, 917; b) T. Terashima, T. Mes, T. F. A. De Greef, M. A. J. Gillissen,
P. Besenius, A. R. A. Palmans and E. W. Meijer, J. Am. Chem. Soc.,
2011, 133, 4742; c) N. Hosono, M. A. J. Gillissen, Y. Li, S. S. Sheiko,
A. R. A. Palmans and E. W. Meijer, J. Am. Chem. Soc., 2013, 135, 501;
d) Y. Liu, T. Pauloehrl, S. I. Presolski, L. Albertazzi, A. R. A. Palmans
and E. W. Meijer, J. Am. Chem. Soc., 2015, 137, 13096; e) M.
GonzalezꢀBurgos, A. LatorreꢀSanchez and J. A. Pomposo, Chem. Soc.
Rev., 2015, 44, 6122.
n-Butyl phenyl sulfoxide: Chemoselectivity: >99% determined by GC,
nitrogen was used as the carrier gas with a flow of 30 mL. min−1, injector
temperature and the detector temperature were 250 oC, the column
temperature was 180 oC, tn-butyl
= 2.9 min; ee value: >99%
phenyl sulfoxide
[4] a) N. Giuseppone and J. F. Lutz, Nature, 2011, 473, 40; b) M. A. J.
Gillissen, T. Terashima, E. W. Meijer, A. R. A. Palmans and I. K.
Voets, Macromolecules, 2013, 46, 4120; c) P. J. M. Stals, C. Cheng,
L. van Beek, A. C. Wauters, A. R. A. Palmans, S. Han and E. W.
determined by HPLC (iꢀPrOH/ n-hexane = 1: 9 (v/v)); flow rate = 1.0 mL.
min−1; 25 °C; λ = 254 nm; major enantiomer tR = 9.2 min. 1H NMR
(CDCl3, 500 MHz): δ (ppm): 0.90ꢀ0.93 (m, 3 H, Me), 1.41ꢀ1.48 (m, 2 H,ꢀ
CH2ꢀ), 1.60ꢀ1.67 (m, 2 H,ꢀCH2ꢀ), 2.90ꢀ2.93 (m, 2 H,ꢀCH2ꢀ), 7.15ꢀ7.16 (m,
1 H, ArH), 7.24ꢀ7.26 (m, 2 H, ArH), 7.28ꢀ7.31 (m, 2 H, ArH). 13C NMR
(CDCl3, 125 MHz): δ (ppm): 13.52 (CH3), 21.86 (CH2), 31.13 (CH2),
58.12 (CH2), 125.56, 128.72, 128.77, 136.91 (ArC).
Meijer, Chem. Sci., 2016, 7, 2011.
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Ed., 2009, 48, 48; b) D. M. Stevens, S. Tempelaar, A. P. Dove and E.
Harth, ACS Macro. Lett., 2012, 1, 915; c) A. SanchezꢀSanchez, D. A.
Fulton and J. A. Pomposo, Chem. Commun., 2014, 50, 1871; d) G. M.
ter Huurne, M. A. J. Gillissen, A. R. A. Palmans, I. K. Voets and E.W.
Meijer, Macromolecules, 2015, 48, 3949.
[6] a) Y. N. Belokon, M. North, V. I. Maleev, N. V. Voskoboev, M. A.
Moskalenko, A. S. Peregudov, A. V. Dmitriev, N. S. Ikonnikov and H.
B. Kagan, Angew. Chem. Int. Ed., 2004, 43, 4085; b) R. M. Haak, S. J.
Wezenberg and A. W. Kleij, Chem. Commun., 2010, 46, 2713; c) Y.
n-Hexyl phenyl sulfide: Chemoselectivity: >99% determined by GC,
nitrogen was used as the carrier gas with a flow of 30 mL.min−1, injector
temperature and the detector temperature were 250 oC, the column
temperature was 180 oC, tn-hexyl
= 4.3 min; ee value: >99%
phenyl sulfoxide
determined by HPLC (iꢀPrOH/ n-hexane = 1: 9 (v/v)); flow rate = 1.0 mL.
1
min−1; 25 °C; λ = 254 nm; major enantiomer tR = 17.5 min. H NMR
10 | Journal Name, [year], [vol], 00–00
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Page 11 of 12
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DOI: 10.1039/C6GC02743A
Zhang, R. Tan, G. Zhao, X. Luo, C. Xing and D. Yin, J. Catal., 2016,
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Green Chemistry
Page 12 of 12
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DOI: 10.1039/C6GC02743A
Graphical Abstract
Bio-inspired single-chain polymeric nanoparticles containing chiral
salen TiIV complex for highly enantioselective sulfoxidation in water
Yaoyao Zhang, Rong Tan, * Mengqiao Gao, Pengbo Hao and Donghong Yin
Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education);
National & Local Joint Engineering Laboratory for New Petro-chemical Materials and Fine Utilization
of Resources, Hunan Normal University, Changsha 410081 (P. R. China)
Bio-inspired SCPNs containing chiral salen TiIV complex in IL-mediated hydrophobic cavity exhibited
enzyme-mimetic activity and selectivity in aqueous enantioselective sulfoxidation.
* Corresponding authors. Fax: +86-731-8872531. Tel: +86-731-8872576
E-mail: yiyangtanrong@126.com