Mesoporous Core-Shell Nanostructures Bridging Metal and Biocatalyst for Highly Efficient Cascade Reactions

Article abstract of DOI:10.1021/acscatal.9b04877

Mesoporous core-shell structured nanocatalysts with a PdPt bimetallic core and enzyme-immobilized polydopamine (PDA) shell were designed, in which the PDA shell worked as a barrier to position the bimetallic core and enzyme in separated locations. The accessible mesoporous structures of both the core and shell significantly facilitate mass transfer and catalyst utilization, improving the synergistic catalytic abilities in cascade reactions. The obtained bifunctional nanocatalysts enabled efficient two-step one-pot cascade reactions of different types: dynamic kinetic resolution of primary amines in organic solvent with high yield and enantioselectivity (up to 99% yield and 98% ee) and degradation of organophosphate nerve agent in aqueous solution with high rate constant and turnover frequency number values (0.8 min^-1 and 20 min^-1, respectively).

Full text of DOI:10.1021/acscatal.9b04877

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Letter
Mesoporous Core-Shell Nanostructures Bridging Metal
and Biocatalyst for Highly Efficient Cascade Reactions
Shiqi Gao, Zihan Wang, Li Ma, Yunting Liu, Jing Gao, and Yanjun Jiang
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b04877 • Publication Date (Web): 27 Dec 2019
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Mesoporous Core-Shell Nanostructures Bridging Metal and Biocatalyst
for Highly Efficient Cascade Reactions
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Shiqi Gao,† Zihan Wang,† Li Ma,† Yunting Liu,*,† Jing Gao*,† and Yanjun Jiang,*,†,‡
†
School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300130, China
‡
National Local Joint Engineering Laboratory for Energy Conservation of Chemical Process Integration and Resources, Tianjin
300130, China
KEYWORDS: core-shell nanostructures, mesoporous metals, enzyme, dynamic kinetic resolution, cascade degradation
ABSTRACT: Mesoporous core-shell structured nanocatalysts with PdPt bimetallic core and enzyme-immobilized polydopamine (PDA) shell
were designed, in which the PDA shell worked as a barrier to position the bimetallic core and enzyme in separated locations. The accessible
mesoporous structures of both the core and shell significantly improve mass transfer and catalyst utilization, improving the synergistic
catalytic abilities in cascade reactions. The obtained bifunctional nanocatalysts enabled efficient two-step one-pot cascade reactions of
different types: dynamic kinetic resolution of primary amines in organic solvent with high yield and enantioselectivity (up to 99% yield and
98% ee) and degradation of organophosphate nerve agent in aqueous solution with high rate constant and turnover frequency number values
(0.8 min-1 and 20 min-1, respectively).
Chemocatalysis and biocatalysis are usually considered two
complementary fields, each with its distinct advantages and
limitations.1 The combination of chemo- and bio-catalysts in one-
pot acquires synergistic catalytic abilities for cascade reactions that
cannot be achieved by either separately, which can reduce the
purification steps, suppress the side reactions and improve the
overall synthetic efficiency.2 Metal nanoparticles (MNPs), as
typical representative of chemocatalysts, have become an important
class of heterogeneous catalysts for various chemical reactions, such
as cyclization, reduction, C-C coupling, hydrogenation, and
racemization.3 However, the integration of metal and enzyme is still
in its infancy due to incompatibility and mutual inactivation.4 In an
efficient metal/enzymatic one-pot cascade process, metal catalyst
should not only exhibit high stability and catalytic activity, but also
be compatible with enzyme.5
in heterogeneous catalysis. MMs show more excellent catalytic
abilities than irregular MNPs thanks to their highly accessible
surfaces and abundant active sites.9 Apart from that, MMs exhibit
improved stability and durability for their relatively large particle
size compared with ultrafine MNPs (<3 nm).10 Therefore, from the
viewpoint of the balance between the stability and catalytic activity,
MMs are superior candidates of robust metal catalysts, and thus
have received unremitting attention.11 However, the application of
MMs in organic synthesis has not been reported, let alone their
integration with enzymes for cascade reactions.
Immobilization of enzyme on solid supports can effectively
improve the activity and stability of enzyme, which has drawn much
attention from both the industry and academia.12 The integration
of metal and enzyme on a same defined matrix can reduce diffusion
distance of intermediates between the two active centers,13 and the
spatial separation of them provides an effective and straightforward
avenue to circumvent the incompatibility problems, although it is
highly challenging to realize. For example, Yang and coworkers
fabricated a hierarchical mesoporous silica nanocatalyst where
MNPs and enzyme immobilized on different domains, which
showed excellent activity and selectivity in cascade reaction.13
Wang and coworkers recently realized the cooperative cascade
catalysis by immobilizing MNPs and enzyme into different
locations of metal-organic framework.14 However, from an
application point of view, the current synthesis protocols require
multistep operation, large amounts of toxic organic solvents and
reducing reagents, which are uneconomical and ungreen.
The properties of MNPs strongly depend on their size, shape
and distribution. Typically, the smaller the size and the larger the
surface area of MNPs, the higher the catalytic activity.6 Until now,
several elegant methods have been developed to synthesize highly
dispersed MNPs with controlled size and shape, including
immobilizing MNPs onto high-surface-area supports7 and
protecting MNPs using surface capping agents.8 However, major
challenges remain. In the former case, defects like nanoparticles
coalescence, continuous leaching and irregular distribution are
often encountered in catalysts synthesis. While in the latter case,
extensive stabilizing reagents may increase diffusion limitation of
reactants to metal active sites, resulting in a decrease in catalytic
activity. Remarkably, recent researches have revealed that
mesoporous metals (MMs) have distinct and numerous advantages
Thus, in this work, we report a facile two-step process for
preparing mesoporous core-shell structured nanoreactor that
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spatially positioned MMs and enzyme in separated locations for
pH values influence the reduction capacity of DA, the nucleation
and growing rate of nanoparticles, which could change the size and
porosity of PdPt@PDA. Nanoparticles with smaller size (~10 nm)
could be obtained by reducing the acidity of the reaction system,
but their porosity was poor (Figure S4).
cascade reactions. In this protocol, the core-shell nanostructures
(PdPt@PDA) with bimetallic core and polydopamine (PDA) shell
were synthesized via simple oxidative polymerization of the
dopamine (DA) by metal ion in aqueous solution through a one-
pot approach, in which the elegant mesoporous structures were
formed simultaneously by a surfactant-directed hydrothermal
reaction. Subsequently, the metal-enzyme bifunctional catalysts
(PdPt@PDA@Enzyme) were obtained easily by immobilizing the
enzymes on outer surface of PDA shell through bioadhesion-
inspired strategy. This strategy exhibited the following advantages:
(1) the process was carried out in aqueous medium without using
any exogenous reducing reagents, which is environmentally
friendly; (2) MMs as active sites can strike the balance between the
catalytic activity and stability; (3) the accessible mesoporous
structures of both the core and shell significantly improve mass
transfer and catalyst utilization.
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Figure 1. a) SEM image of the PdPt@PDA; b) TEM image of the
PdPt@PDA; c) HAADF–STEM image of PdPt@PDA; d-f) Elemental
mappings of the PdPt@PDA.
The morphology of mesoporous PdPt@PDA nanospheres was
analyzed using SEM and TEM. Highly magnified SEM of the
PdPt@PDA showed a monodisperse nanostructure with obvious
well-defined cylindrically opened mesoporous channels,
approximately 58 nm in diameter (Figure 1a). TEM image clearly
revealed that the particles are core-shell structured nanospheres
(Figure 1b). The bimetallic PdPt core is wrapped in PDA shell with
a thickness of about 15 nm, which can be further proved by
HAADF-STEM image (Figure 1c). The elemental mappings
illustrated that N distributed over the shell, but Pd and Pt mainly
located in the inner part of the particles (Figures 1d-f). Notably, Pd
element was mainly concentrated in the interior of the PdPt core,
which was due to that Pd complex was more preferentially reduced
in the present system, although the reduction potential of the Pt
precursor is higher than that of the Pd precursor. From the results
of ICP and EDX analysis (Figure S5), the PdPt@PDA had very
high (∼59 wt %) metal loading, and the Pt/Pd ratio was about
1.3:1, which was obviously smaller than the Pt/Pd precursor ratio
of 3:1. These results confirmed the Pd precursor’s faster reduction
rate. Similar phenomenon have been reported in the co-deposition
of Pd and Pt.16 It is difficult to explained the metal species’
reduction by their standard reduction potential in the case that
additives and multiple metal precursors exist, due to their
coordination effect and complicated reduction kinetics.17 From the
results of nitrogen sorption isotherms and the corresponding pore
size distribution curve of PdPt@PDA (Figure S6), the mesopore
sizes of PdPt bimetallic core and PDA shell were determined to be
about 3 and 8 nm, respectively, which confirmed the mesoporous
structure of the material.
Scheme 1. Systematic illustration and formation mechanism of
PdPt@PDA@Enzyme
In the synthesis process of PdPt@PDA (Scheme 1), Pd and Pt
precursors and Pluronic F127 were dissolved in deionized water,
and then DA solution was added in batches under vigorous stirring
at 70 °C. In this process, DA has sufficient reduction power to
reduce metal ions to MNPs, and self-polymerized to form PDA
shell that coated on the surface of metal core simultaneously. By
optimizing the amount of DA, it was found that its concentration
had an effect on the nucleation and growing rate. Highly dispersed
mesoporous nanospheres could be obtained only at the appropriate
concentration (25 mM). Reducing the concentration (15 mM) led
to the size of nanospheres varied greatly, while increasing the
concentration (35 mM) caused the coalescence of nanocomposites
(Figure S1). Furthermore, surfactant plays an important role in the
synthesis process. Specifically, F127 not only prevents the
agglomeration of the particles, but also serves as a pore-directing
agent. In fact, only aggregated particles without mesopores were
formed in the absence of F127 (Figure S2). To understand the
formation mechanism, the influence of precursor molar ratio of Pd
and Pt was also explored. It was found that Pt precursor could affect
the formation of the bimetallic mesoporous structure under this
condition, and the optimal Pt/Pd precursor ratio was determined
to be 3:1. Reducing the amount of Pt precursor, the mesopores in
particles disappeared gradually, giving rise to a smoother surface
(Figures S3a-c). The phenomenon is similar to the results observed
by Wang’s group,15 which could be attributed to that the faster
reduction rate of Pd precursor in the specific system hindered the
formation of F127 micelles. And just because of this, Pd@PDA
particles without obvious mesoporous structure were obtained
when only Pd precursor was added (Figure S3d). In addition, the
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eV and 336.3, 341.5 eV, corresponding to Pd0 and Pd2+ states,
respectively (Figure 2e). Similarly, in the Pt4f XPS spectrum, the
two peaks at 71.4 and 74.7 eV were corresponded to Pt0 state, while
the peaks at 72.0 and 76.2 eV were corresponded to Pt2+ state
(Figure 2f).21
Table 1. DKR of Primary Aminesa
O
R
H2 (0.1 atm)
O
Na2CO3 (2.0 equiv)
PdPt@PDA@CALB (0.1 equiv)
O
NH2
R
HN
9
+
O
O
O
Ar
Toluene, 70 o
C
Ar
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2a-f
3
1a-f
O
O
O
O
O
HN
HN
HN
Me
MeO
2a
99%, 98% ee
2b
2c
92%, 97% ee
93%, 98% ee
O
O
O
O
O
HN
NH
HN
O
MeO
2e
2f
2d
85%, 94% ee
99%, 98% ee
92%, 98% ee
a Reaction conditions: dry toluene (2.0 mL), 0.1 atm of hydrogen gas, 1
(0.3 mmol), 3 (0.6 mmol), PdPt@PDA@CALB (10 mg), Na2CO3 (30
mg); Isolated yield; The values of ee were determined by GC and
pentadecane as internal standard.
Figure 2. a) Wide-angle XRD patterns of the PdPt@PDA; b) XPS
spectra of the PdPt@PDA; c) The C1s spectrum of PdPt@PDA; d)
The N1s spectrum of PdPt@PDA; e) The Pd3d spectrum of
PdPt@PDA; f) The Pt4f spectrum of PdPt@PDA.
O
H2 (0.1 atm)
PdPt@PDA@CALA (0.1 equiv)
NH2
Pr
NH
O
CO2Et
CO2Et
To identify the existence of PDA shell, FTIR analysis was
performed. The most significant peak is found at 3430 cm-1 (Figure
S7), which is related to the -NH2 or -OH stretching vibration. The
peaks at 2922 and 2852 cm−1 are attributed to the presence of -CH
and -CH2. The peak at 1627 cm−1 is assigned to C=C functional
groups. Furthermore, the observed band at 1380 and 1108 cm−1
can be assigned to the vibrations of C-N and C-O, respectively. All
the results confirmed the existence of PDA shell.
+
Bu2O, 50 oC, 24 h
Pr
O
CF3
1g
4
2g,
78%, 93% ee
Scheme 2. DKR of β-aminoester
We further functionalized the shell of PdPt@PDA by adhering
enzymes to the outer surface of PDA through covalent bonds to
obtain the metal-enzyme bifunctional nanocatalysts.22 In order to
demonstrate the advantages of combining mesoporous core-shell
structure and two complementary catalysts, the cascade catalytic
activities of the fabricated PdPt@PDA@Enzyme were carefully
studied. As a perfect alternative to the kinetic resolution (KR), the
dynamic kinetic resolution (DKR) can well overcome the former’s
drawback that can only achieve a maximum of 50% yield. In DKR
process, two supplementary steps occur: asymmetric
transformation in parallel with an in situ racemization, which
increase the theoretical yield up to 100%. Therefore, lipase B from
Candida Antarctica (CALB) was chosen as a biocatalyst and the
two-step (enzymatic kinetic resolution and metal catalytic
racemization) one-pot DKR of 1-phenylethylamine (1a) in organic
solvent was chosen as a model transformation to demonstrate the
power of the bifunctional nanocatalyst.
XRD and XPS were performed to estimate the crystalline
structure and elemental composition of PdPt@PDA. The five
distinct peaks (Figure 2a) centered at 2θ = 40.0°, 46.6°, 68.4°, and
82.4° are assigned to (111), (200), (220) and (311) crystalline
planes of the face-centered cubic (fcc) structures of Pd (JCPDS01-
1190) and Pt (JCPDS88-2335), respectively. However, it is
impossible to distinguish grain boundaries of Pt and Pd in the wide-
angle XRD patterns due to their small lattice mismatch ratio
(0.77%).18 The existence of C, N, O, Pd and Pt elements was
verified by XPS spectra (Figure 2b). Besides, the high-resolution
N1s spectrum contains only one signal at 399 eV, which is
originated from the amine NH groups (Figure 2c), indicating that
the indole structure of PDA formed.19 The C1s core-level spectrum
of PdPt@PDA can be curve-fit into five peaks at 284.6, 285.7,
286.5, 286.8 and 289.0 eV (Figure 2d), which are assigned to C−C,
C−N, C−OH, C=O and O−C=OH groups of indole structure,
respectively.20 These results illustrated the successful coating of
PDA on bimetallic core. XPS analysis for the Pd3d and Pt4f binding
energy was performed to understand the oxidation state of the
MNPs in PdPt@PDA. The high resolution Pd3d spectrum was
fitted with two sets of spin-orbit doublets with peaks at 335.1, 340.6
To find the optimal racemization and DKR conditions, different
parameters such as temperature, solvents, hydrogen pressure,
catalysts and bases were evaluated (Table S1, S2). To our delight, it
was found that PdPt@PDA@CALB exhibited high racemization
activity at the following conditions: 10 mol% of catalyst and
Na2CO3 as the base in dry toluene under 0.1 atm of H2 at 70 °C
(Table S1, Entry 9). The different loadings of CALB on
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PdPt@PDA, which were achieved by adjusting immobilized time
and the stability of the covalent immobilization. Moreover, the
morphology of the recycled nanocatalyst almost did not change
according to the SEM image (Figure S9) and there was no
significant decrease in activity after two weeks of storage in the
refrigerator, which revealed that the nanocatalyst was robust and
stable.
(4 h, 8 h and 12 h), were screened and the obtained nanocatalysts
were assessed in DKR of 1a. When the immobilization time was 8 h
for CALB, the obtained PdPt@PDA@CALB showed best activity
and selectivity in the DKR reaction with 99% yield and 98%
enantiomeric excess (ee) (Table S2, Entry 2). From elemental
analyses, the loadings of CALB and PdPt on the optimal
PdPt@PDA@CALB were calculated to be 10.8 wt% and 46.2 wt%,
respectively. Shorting the immobilization time to 4 h, a significantly
slower DKR and only 80% of the amide was obtained (Table S2,
Entry 1). On the other hand, increasing the immobilization time to
12 h, the enantioselectivity of the product reduced to 91% ee
(Table S2, Entry 3). In addition, the “nonporous”
PdPt@PDA@CALB and Pd@PDA@CALB (prepared without
F127) counterparts were also tested in the optimal condition. The
yields of the reaction were lower than that of the mesoporous
catalyst even under a longer reaction time, although the
stereoselectivity did not decrease obviously (Table S2, Entries 4,
5). These results can be attributed to the abundant mesopores in
the catalysts, which can facilitate the mass transport of the
substrates and products. The smaller “nonporous”
PdPt@PDA@CALB showed higher efficiency (Table S2, Entry 9)
than the ones with larger size (Table S2, Entry 4) in the DKR
reaction, which revealed that the smaller the metal size, the higher
the catalytic activity. The DKR reaction catalyzed by PdPt@PDA
and Novozyme-435 with similar catalytic site concentrations under
the same condition was also conducted, and the yield of the
reaction reduced from 99% to 92% (Table S2, Entry 10), which
demonstrated the real advantage of the bifunctional catalyst. After
the optimized reaction protocol for the DKR was established, a
variety of primary amines with different substituted groups were
converted into the corresponding enantiomerically enriched
amides in high yield and enantioselectivity (Table 1, 2b-f). To
expand this method, another nanocatalyst PdPt@PDA@CALA
was fabricated by incorporating Candida antarctica lipase A
(CALA) with PdPt@PDA. The resultant catalyst showed good
activity for the one-pot DKR of β-amino ester (ethyl 3-amino-3-
phenylpropanoate, 1g) with 78% yield and 93% ee in the reported
condition.23 (Scheme 2, Supporting Information). From the results
of the DKR experiments, the obtained mesoporous catalysts
exhibited high catalytic activity and enantioselectivity, which were
comparable or even superior to the reported catalysts under
analogous conditions.13,24
OCH3
H3CO
P
S
9
O
OH
OH
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OPH
Pd-Pt
Hydrolysis
Hydrogenation
NO2
Parathion-methyl,
NO2
6
NH2
7
5
PdPt@PDA@OPH
Cascade Degradation
Scheme 3. Cascade Degradation of Parathion-methyl
Figure 3. Time-dependent absorption spectra of catalyzed
hydrogenation of parathion-methyl: a), b) in the presence of
PdPt@PDA@OPH.
To further extend the method and the practical application,
organophosphorus hydrolase (OPH) was used to fabricate
bifunctional catalyst PdPt@PDA@OPH with the aforementioned
experimental procedure for cascade degradation of
organophosphate nerve agent (parathion-methyl, 5) in aqueous
solution. This one-pot process involves enzymatic hydrolysis of 5
to 4-nitrophenol (6) and the subsequent metal catalytic
hydrogenation of 6 to 4-aminophenol (7), which was constantly
monitored by ultraviolet-visible spectroscopy (UV-Vis)
measurements (Scheme 3). The gradual increase and decrease of
characteristic peaks of 6 at 400 nm with time indicated its
formation and consumption, respectively. The hydrolysis reaction
was completed in 90 min in the presence of PdPt@PDA@OPH
(Figure 3a). For the catalytic hydrogenation of 6, the reaction rate
constant (k) and the turnover frequency number (TOF) for the
nanocatalyst were calculated. To our delight, the complete
hydrogenation only needed 5 min (n(Pd)/n(6) = 1/100) with
high k and TOF values (0.8 min-1 and 20 min-1, respectively)
(Figures 3b and S10). For comparison, the “nonporous”
PdPt@PDA@OPH counterpart gave a comparable result in the
first step, but it showed a lower catalytic performance with
complete conversion in 10 min in the second step (Figures S11),
which demonstrated that mesoporous PdPt@PDA@OPH
exhibited an enhanced cascade catalytic activity.
The recyclability of PdPt@PDA@CALB was assessed by the
DKR reaction of 1a under the optimal conditions over five cycles
(Table S3, Figure S8). After each cycle, the solid catalyst and base
were recovered by centrifugation and used in a new cycle. The
enantioselectivity maintained a very high level (98% ee), while the
yield greatly decreased but still more than 75% after five cycles,
which was due to the increase of byproduct ethylbenzene (2a’). To
further understand the reason of the increase in 2a’, the metal
catalytic racemization and enzymatic KR were independently
assessed. After five cycles, the activity of metal was slightly reduced,
while the activity of enzyme was significantly decreased (Table S4
and S5). Therefore, it can be speculated that the inactivation of the
enzyme led to an increase in byproduct. It is delightful that no
significant metal leaching could be detected (PdPt <1.0 ppm) in
the reactions and no lipase was detected in the reaction eluate,
demonstrating the efficient protection of MNPs by the PDA shell
In conclusion, we fabricated mesoporous core-shell structured
metal-enzyme bifunctional nanocatalysts with PdPt bimetallic core
and enzyme-immobilized PDA shell. The mesoporous core-shell
nanostructures not only permitted spatial separation of the two
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Nitrone Synthesis: Platinum Nanoclusters in Amine-Functionalized Metal-
different catalytic disciplines, but also facilitated the mass transport
and enhanced catalyst utilization, improving the synergistic
catalytic abilities in cascade reactions. The protocol of integrating
mesoporous metals and enzymes at spatially distinct locations of
advanced materials with high compositional and structural
complexities holds great promise in fabrication of multifunctional
catalysts, as well as in other cascade catalysis systems. There is also
much room for future research and developing more metal-enzyme
nanocatalysts, especially by combining cheaper metals and the
enzymes that can catalyze other types of reactions.
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Nanocatalysis. Chem. Mater. 2014, 26, 72-83; (b) Lu, G.; Li, S.; Guo, Z.;
Farha, O. K.; Hauser, B. G.; Qi, X.; Wang, Y.; Wang, X.; Han, S.; Liu, X.;
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Organic Framework Material by Controlled Nanoparticle Encapsulation.
Nat. Chem. 2012, 4, 310-316; (c) Snelders, D.; Yan, N.; Gan, W.;
Laurenczy, G.; Dyson, P. J. Tuning the Chemoselectivity of Rh
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ACS Catal. 2012, 2, 201-207.
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Trimetallic Core–Shell Au@ PdAuCu Mesoporous Nanospheres for
Ethanol Electrooxidation. Green Chem. 2019, 21, 2043-2051; (b) Iqbal,
M.; Kim, Y.; Li, C.; Jiang, B.; Takei, T.; Lin,J.; Yuliarto, B.; Bando, Y.;
Henzie, J.; Yamauchi, Y. Tailored Design of Mesoporous PdCu
Nanospheres with Different Compositions Using Polymeric Micelles. ACS
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ASSOCIATED CONTENT
Supporting Information.
The Supporting Information is available free of charge on the ACS
Publications website at http://pubs.acs.org.
Materials and methods, optimization details, general catalytic
procedures, figures, tables, NMRs of compounds, GC of
compounds and references (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: ytliu@hebut.edu.cn;
*E-mail: jgao@hebut.edu.cn;
*E-mail: yanjunjiang@hebut.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank the National Natural Science Foundation of China
(21576068, 21878068 and 21901058), the Natural Science
Foundation of Hebei province (B2015202082, B2017202056 and
B2019202216), the Science and Technology Research Project of
Hebei Higher Education (ZD2019045).
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