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Table 2 DKR of rac-1-phenylethanol by CALB–SILLP and Nafion SAC–13 in cyclohexane at 40 uC under Mw heating for 60 mina
Yieldb. [%]
e.e.S [%]
e.e.P [%]
b
b
Entry
DKR catalytic mixture (mg)
1
2
3
4
CALB–SILLP-L(Cl)/NAFION 20/20
CALB–SILLP-L(Cl)/NAFION 20/40
CALB–SILLP-L(NTf2)/NAFION 20/100
CALB–SILLP-L(NTf2)/NAFION 20/200
64
70
81
72
92
85
37
20
99
99
94
95
a
rac-1-Phenylethanol (18.6 mL, 0.150 mmol), vinyl acetate (34.3 mL, 0.315 mmol, 2.1 equiv.), and 20 mg of the enzyme and a variable amount
b
of NAFION SAC-13 in cyclohexane (1.5 mL). Determined by GC.
we have reported that the heating effects of microwaves on
materials containing SILLPs are highly dependent of the loading
of IL-like units, the nature of the counterion and the polymer
architecture.9,13 Thus, tand parameter for SILLPs was significantly
higher than that observed for non-modified PS-DVD supports.9
Furthermore, for a given SILLP, this tand parameter increased by
6-fold when the NTf22 counterion was changed to Cl2. Hence, the
higher activity observed for CALB–SILLP-L can be related with the
fact that the supported IL-like-phase facilitates a more efficient
microwave energy absorption at the microenvironment of the
enzyme. In this way, these supported IL-like domains, where the
enzyme is located, are rapidly heated due to material–wave
interactions, leading to an enhancement of the enzyme activity
when compared with conventional heating. In the same context,
the enzyme activation by microwaves could be further enhanced
by changing the counteranion (NTf22 vs. Cl2). Indeed, the nature
of the counteranion determined the enzyme activity, being always
obtained the more active biocatalyst for the hydrophobic [NTf2].14
This fact could be related with a favoured transport of the
hydrophobic substrate towards the immobilized enzyme, resulting
in the excellent suitability of the CALB–SILLP-L derivatives.10c An
excessive absorption on microwave irradiation near to the enzyme
microenvironment might occur for CALB–SILLP-H cases, result-
ing, along with the above-mentioned effect of hydrophobic shell
formation around the enzyme, in enzyme deactivation.15
under conventional heating (71% e.e., (R)-ester),17 pushing towards
the excellences of the proposed approach.
The results reported here illustrate for the first time the
intrinsic effect of microwave irradiation on biocatalysis produced
by supported ionic liquid like phases. Furthermore, they indicate
that enzymes supported onto SILLPs could be used to regulate
biocatalytic rates by the appropriate selection of the structural
parameters of the polymeric SILLP such as resin morphology,
loading and nature of IL-like groups. Besides, the SILLPs can
contribute to the long-term stability of the corresponding
supported biocatalysts, which allows their prolonged use under
microwave irradiation. These results demonstrate that the SILLPs
are able to reproduce the behaviour observed for biocatalytic
processes under microwave activation assayed in bulk ILs.
However SILLPs lead to similar results using significantly fewer
amounts of IL equivalents and being supported in a polymeric
phase, which provides an easy mechanism for facilitating work-up
and reuse. Microwave-assisted multi-enzymatic and/or multi-
chemoenzymatic green chemical processes for synthesizing fine
chemicals are only a beginning, but the door to the development
of a sustainable chemical industry is open.
This work was partially supported by MINECO, Spain (Ref:
CTQ2011-28903), Generalitat Valenciana (PROMETEO 2012/020)
and SENECA Foundation, Spain (Ref: 08616/PI/08) grants.
Fig. 2 depicts residual activity profiles for the different catalysts
obtained during operating cycles under microwave heating. As can
be seen, the activity of both CALB–SILLP-L derivatives was
practically unchanged during reuse. The microenvironment
provided by the ILs-like units for these derivatives is able to
maintain the performance of the enzyme against deactivation by
superheating due to microwave irradiation. However, without the
presence of IL-fragments, or at high IL content (SILLP-H and
SILLP-R derivatives), the CALB–SILLPs derivatives showed a fast
deactivation under microwave irradiation. Hence, the adequate
design of the SILLP support not only contributes to enhance the
catalytic activity of the immobilised enzyme but also its stability.
The DKR of rac-1-phenylethanol catalyzed by the combined
action of Nafion–SAC13 and CALB–SILLP-L has been also carried
out in a one-pot system at different catalyst ratios under Mw
irradiation (see Table 2).16 The DKR process is achieved with good
yields for the corresponding R-ester (70–80%) at high enantios-
electivities (94–99% e.e.). These results are better than those
recently reported for lipase PS–CI and Nafion–SAC 13 mixtures
References
1 A. de la Hoz and A. Loupy, Microwaves in Organic Synthesis,
Wiley-VCH, Weinheim, 2012.
2 D. Yu, Z. Wang, P. Chen, L. Jin, Y. Cheng, J. Zhou and S. Cao, J.
Mol. Catal. B: Enzym., 2007, 48, 51–57.
3 (a) B. Rejasse, S. Lamare, M. D. Legoy and T. Besson, Org.
Biomol. Chem., 2004, 2, 1086–1089; (b) P. Bachu, J. S. Gibson,
J. Sperry and M. A. Brimble, Tetrahedron: Asymmetry, 2007, 18,
1618–1624; (c) G. D. Yadav and S. V. Pawar, Appl. Microbiol.
Biotechnol., 2012, 96, 69–79.
4 B. Rejasse, T. Besson, M.-D. Legoy and S. Lamare, Org. Biomol.
Chem., 2006, 4, 3703–3707.
5 P. Lozano and E. Garcıa-Verdugo, Ionic Liquids in
Biotransformations and Organocatalysis: Solvents and Beyond (Ed.
P. Dominguez de Maria), pp. 103–150, Wiley-VCH, 2012.
6 (a) J. Hoffmann, M. Nuchter, B. Ondruschka and
P. Wasserscheid, Green Chem., 2003, 5, 296–299; (b)
R. Martinez-Palou, J. Mex. Chem. Soc., 2007, 51, 252–264.
´
´
7 R. Martınez-Palou, Mol. Diversity, 2010, 14, 3–25.
8 (a) A. Loupy, L. Perreux, L. Marion, K. Burle and M. Moneuse,
Pure Appl. Chem., 2001, 73, 161–166; (b) K. Lundell, T. Kurki,
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