DOI: 10.1002/chem.201405252
Communication
&
Biochemistry
Lipase-Supported Metal–Organic Framework Bioreactor Catalyzes
Warfarin Synthesis
Wan-Ling Liu, Ni-Shin Yang, Ya-Ting Chen, Stephen Lirio, Cheng-You Wu, Chia-Her Lin,* and
Hsi-Ya Huang*[a]
materials that consist of metal or metal oxide corners connect-
Abstract: A green and sustainable strategy synthesizes
clinical medicine warfarin anticoagulant by using lipase-
ed by organic linkers.[16] These highly ordered crystalline ma-
terials show unique properties, such as high-surface area (up
supported metal–organic framework (MOF) bioreactors
to thousands m2 gÀ1), porosity, and tunable pore sizes[17,18] and
(see scheme). These findings may be beneficial for future
have attracted considerable attention in applications for gas
studies in the industrial production of chemical, pharma-
storage,[19] heterogeneous catalysis,[20] sensors,[21] chroma-
ceutical, and agrochemical precursors.
tographic separation,[22] drug delivery,[23] and so on.
In recent years, research has become active towards MOFs
biocatalytic applications by using these materials as immo-
bilized carriers.[24–30] In contrast to mesoporous silicate mater-
Biocatalysis uses natural catalysts such as enzymes to facilitate
chemical transformations including organic synthesis.[1] The
ials, owing to its high surface area, MOFs are capable of carry-
use of enzymes for biocatalytic reactions can provide numer-
ous advantages including chemo-, regio-, and stereospecificity
even under mild reaction conditions.[2,3] However, drawbacks,
such as poor long-term stability under the conditioning pro-
cess as well as the difficulties in recovering and recycling,
often hinder its application.[4,5] To improve the mentioned
shortcomings, enzyme immobilization on solid supports has
been adapted as an effective alternative that enhances the
enzyme functions and activities and results in an improvement
in reusability, catalytic efficiency, and stability under drastic
catalytic conditions.[6,7] For a decade, various solid supports, in-
cluding nanoparticles,[8] polymers,[9,10] and mesoporous silica
materials,[11,12] have been developed as enzyme immobilizing
bioreactors. Among them, mesoporous silicate materials pro-
vided a high surface area with adequate pore size to retain
and accommodate enzyme biomolecules as host materials.[13]
Conversely, reviews on mesoporous silicate bioreactors have
reported that they suffer from leaching during the reaction
process due to the lack of specific interactions with enzyme
molecules.[14] To achieve a strong interaction for enzyme immo-
bilization, the support must be functionalized with a variety of
functional groups; however, the outcome might result in de-
creasing the enzyme activity.[15] Thus, to maintain the enzyme
activity, new immobilizers with improved effectiveness are
needed upon functionalization.
ing sufficient organic functional moieties without post-synthet-
ic modification; thus, these kind of porous materials can ex-
hibit superior enzymatic catalysis with stable recyclability for
immobilization supports. Several strategies including covalent
bonding,[24,28] encapsulation,[25] and physical adsorption[26,27,29,30]
were employed to immobilize biomolecules into the MOFs.
Among them, physical adsorption, without any chemical modi-
fication, is the most convenient way; however, a mesoporous
MOF or a chemical modification in the enzyme macromolecule
is needed. To the best of our knowledge, no microporous
MOFs combined with simple physical adsorption have been
used in the immobilization of an enzyme.
Herein, we explore the porcine pancreatic lipase (PPL)—one
of the most widely used enzymes in the biotransformation re-
action for chemical and pharmaceutical industries—as a test
enzyme[31,32] to evaluate the potential of microporous MOFs as
solid supports. Several microporous MOFs (UiO-66(Zr), UiO-66-
NH2(Zr), and MIL-53(Al) and carbonized MIL-53(Al); Table 1 and
Table S3 in the Suppoting Information) were employed to
adsorb PPL with particle sizes ranging from 150–200 nm. The
UiO-66(Zr) was synthesized using ZrCl4 and 1,4-benzenedicar-
boxylic acid (H2BDC), whereas UiO-66-NH2 was constructed by
using ZrCl4 and 2-amino-1,4-benzenedicarboxylic acid (H2BDC-
NH2). Meanwhile, the other types of MOF such as MIL-53(Al)
were produced by using Al(NO3)3·9H2O and H2BDC, whereas
the carbonized MIL-53(Al) was formed by MIL-53(Al) and was
heated up to 8008C (details of these MOFs are shown in the
Supporting Information). The PPL has a dimension of about
4.6ꢀ2.6ꢀ1.1 nm; thus, the diffusion and accessibility of this
large molecule can be limited in the microporous MOFs ma-
terials. The adsorption of PPL was carried out by using a freshly
synthesized MOFs solid and was immersed in a PPL solution of
methanol and DMSO followed by mixing using a vortex for 1 h
(Scheme 1, step 1), and subsequently centrifuged (6000 rpm,
5 mins) to give a PPL@MOF powder (Supporting Information).
Metal-organic frameworks (MOFs)—also known as porous
coordination polymers—are a new class of crystalline porous
[a] Dr. W.-L. Liu, N.-S. Yang, Y.-T. Chen, S. Lirio, C.-Y. Wu, Prof. C.-H. Lin,
Prof. H.-Y. Huang
Chung Yuan Christian University
200, Chung-Pei Rd., Chung-Li, 320 (Taiwan)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201405252.
Chem. Eur. J. 2014, 20, 1 – 6
1
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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