Bioinspired Framework Catalysts: From Enzyme Immobilization to Biomimetic Catalysis

Abstract

Enzymatic catalysis has fueled considerable interest from chemists due to its high efficiency and selectivity. However, the structural complexity and vulnerability hamper the application potentials of enzymes. Driven by the practical demand for chemical conversion, there is a long-sought quest for bioinspired catalysts reproducing and even surpassing the functions of natural enzymes. As nanoporous materials with high surface areas and crystallinity, metal-organic frameworks (MOFs) represent an exquisite case of how natural enzymes and their active sites are integrated into porous solids, affording bioinspired heterogeneous catalysts with superior stability and customizable structures. In this review, we comprehensively summarize the advances of bioinspired MOFs for catalysis, discuss the design principle of various MOF-based catalysts, such as MOF-enzyme composites and MOFs embedded with active sites, and explore the utility of these catalysts in different reactions. The advantages of MOFs as enzyme mimetics are also highlighted, including confinement, templating effects, and functionality, in comparison with homogeneous supramolecular catalysts. A perspective is provided to discuss potential solutions addressing current challenges in MOF catalysis.

Figure 1

Overview of strategies to synthesize bioinspired MOF catalysts. (top) Enzymes are incorporated into MOFs to afford biocomposites. (bottom) Model compounds emulating enzyme’s active sites can be introduced into MOFs through guest encapsulation, metal node functionalization, and organic ligand functionalization.

Figure 2

Overview of strategies to prepare MOF–enzyme composites, including surface attachment, encapsulation, covalent linkage, and coprecipitation. Surface attachment directly anchors enzymes to MOFs’ surfaces via noncovalent interactions, including hydrophobic interactions, van der Waals forces, and electrostatic forces. Encapsulation indicates entirely absorbing the enzymes into the pores of MOFs and establishing interactions within the interior environment. Covalent linkage utilizes the functional groups on both MOFs and enzymes to form covalent bonding. Coprecipitation refers to mixing up enzymes and the reactants of MOFs in the homogeneous phase, embedding the enzymes in the instantaneously formed pores.

Figure 3

Schematic illustration of enzyme immobilization methods in MOFs. (a) PCN-222 as the supporter for immobilization of GOx by electrostatic interaction. Reproduced from ref (100). Copyright 2019 American Chemical Society. (b) The coordinative bond between the imidazole group from MO act as Lewis base and coordinatively unsaturated metal sites (CUS) acting as Lewis acid in immobilization. Reproduced from ref (106). Copyright 2017 American Chemical Society. (c) Enzyme encapsulation where formate dehydrogenase infiltrates into the pores of NU-1006. Reproduced with permission from ref (141). Copyright 2019 John Wiley and Sons. (d) Covalent linkage via N-hydroxysuccinimide to immobilize GOx on NH₂-MIL-53(Al). Reproduced with permission from ref (112). Copyright 2016 Royal Society of Chemistry. (e) Illustration showing coprecipitation and biomimetic mineralization via a one-pot synthesis to immobilize urease in ZIF-8. Reproduced with permission from ref (153). Copyright 2016 Royal Society of Chemistry.

Figure 4

Encapsulation of cutinase into the mesopores of NU-1000. Reproduced with permission from ref (125). Copyright 2016 Elsevier.

Figure 5

One-pot synthesis of BCL@MTV-ZIFs, in which the closed-lid/open-lid conformations of BCL were regulated via MTV-ZIFs. Reproduced with permission from ref (138). Copyright 2021 American Chemical Society.

Figure 6

Utilization of polypeptide to boost the stability of ZIFs toward acid treatment. Reproduced with permission from ref (130). Copyright 2021 John Wiley and Sons.

Figure 7

Hydrolysis reaction for chemical warfare agent degradation using enzyme OPAA encapsulated within NU-1003. Reproduced with permission from ref (125). Copyright 2016 Elsevier.

Figure 8

Glucose oxidase immobilized on 2D MOF to conduct an oxidation reaction. Oxygen is used as an oxidant to oxidize glucose to generate radicals to kill bacteria. Reproduced with permission from ref (178). Copyright 2019 American Chemical Society.

Figure 9

Catalase immobilized on MAF-7 and ZIF-90. The catalytic performances of catalase are presented to demonstrate residue H₂O₂ concentration decrease with a dependence on the time. Reproduced with permission from ref (50). Copyright 2019 American Chemical Society.

Figure 10

FateDH immobilized in ZIF-8 carrying out carbon sequestration under light. Reproduced with permission from ref (188). Copyright 2021 Elsevier.

Figure 11

Two enzymes, namely Gox and HRP, immobilized in a MOF that together perform the oxidation of glucose and electron transport to water. Meanwhile, 3,3′,5,5′-tetramethylbenzidine (TMB) is oxidized to oxTMB. Reproduced with permission from ref (197). Copyright 2015 Royal Society of Chemistry.

Figure 12

Building block design of MOFs emulating the enzymatic active sites. Model compounds are integrated into MOFs as metal clusters and organic ligands to reproduce functions of enzymes. Two representative metal clusters are Zr₆ cluster emulating phosphotriesterase and Zn cluster emulating carbonic anhydrase. Active sites, such as urea, diiron, and porphyrin, can be embedded onto the organic linkers.

Figure 13

Representative MOFs with open metal sites. (a) MOF-74 containing one-dimensional channels and M₂O₂ (CO₂)₂ metal-oxo chains. (b) HKUST-1 based on Cu₂ (CO₂)₄ paddle-wheel clusters. (c) MIL-100 and MIL-101 consisting of M₃O (CO₂)₆ clusters.

Figure 14

Pentapeptide cleavage using a multivariate MOF with enzyme-like structural complexity. Reproduced with permission from ref (282). Copyright 2016 American Chemical Society.

Figure 15

Long-range ordered arrangement of the urea/squaramide groups in frameworks helps to avoid the self-quenching of the active sites due to the oligomer formation for free urea/squaramide-based small molecules.

Figure 16

Structures and design principles for reported linkers used for constructing urea-based MOFs. The reported urea-based ligands consist of carboxylate groups or pyridyl groups. Urea groups can be incorporated into the backbone and substituent of the ligands, affording ligands with varied connectivities and configurations.

Figure 17

Enhanced catalytic activity of urea-based MOFs with the addition of Lewis acid. Reproduced with permission from ref (318). Copyright 2016 American Chemical Society.

Figure 18

Summary of nucleophilic substitution reactions catalyzed by urea- and/or squaramide-based MOFs.

Figure 19

Summary of reported linkers used for constructing squaramide-based MOFs.

Figure 20

Synthesis of multivariate squaramide-based UiO-67 and its catalytic activity toward Friedel–Crafts reaction. Reproduced with permission from ref (66). Copyright 2015 American Chemical Society.

Figure 21

Representative MOFs based on Zr₆ clusters and organic linkers with varied connectivities, including ditopic, tritopic, tetratopic, hexatopic linkers, and their mixtures.

Figure 22

Structural illustrations of phosphotriesterase’s active site and a Zr₆-based MOF named UiO-66. Reproduced with permission from ref (63). Copyright 2014 John Wiley and Sons.

Figure 23

High-throughput screening of Zr₆-based MOFs for DMNP degradation, in which the catalytic activity at pH 8 and 10 were compared. Reproduced with permission from ref (410). Copyright 2018 Royal Society of Chemistry.

Figure 24

Hydrolysis of nerve agent simulators containing phosphonate linkages, which is catalyzed by phosphotriesterase inspired MOFs with Zr₆O₄ (OH₄) clusters.

Figure 25

Fabrication of SILK@UiO-66@LiO^tBu for CWA degradation. Reproduced with permission from ref (424). Copyright 2015 John Wiley and Sons.

Figure 26

Ligand design of dehydrogenase-mimicking MOFs. (a) Active sites of formate dehydrogenase (FDH). (b) Crystal structure of a dehydrogenase-mimicking MOF as an electrochemical glucose sensor. Reproduced with permission from ref (218). Copyright 2020 American Chemical Society.

Figure 27

Preparation of MOF-derived carbon with neighboring Fe and Ni single-atoms, which was applied in CO₂ electroreduction. Reproduced with permission from ref (470). Copyright 2021 American Chemical Society.

Figure 28

Structural illustrations and CO₂ capture mechanism of carbonic anhydrase. Reproduced with permission from ref (472). Copyright 2018 Springer Nature.

Figure 29

Two triazolate-based MOFs as mimics of carbonic anhydrase. (a) Active site of carbonic anhydrase. (b) Structures of CFA-1 and MFU-4l with exposed Zn sites. Reproduced with permission from ref (476). Copyright 2020 Royal Society of Chemistry.

Figure 30

CO₂ chemisorption on the Zn–OH site through intercluster hydrogen bonding interactions. Reproduced with permission from ref (221). Copyright 2018 American Chemical Society.

Figure 31

Subunits and cofactors of Mo nitrogenase. Reproduced with permission from ref (489). Copyright 1994 American Chemical Society.

Figure 32

Brief summary of catalysis reaction conducted by alternative nitrogenases. Reproduced with permission from ref (523). Copyright 2020 American Chemical Society.

Figure 33

Structural illustration of a MOF V₂Cl_2.8 (btdd) with accessible V site to bond nitrogen.

Figure 34

Synthesis of [Fe₄S₄]-based redox-active coordination polymers. Reproduced with permission from ref (228). Copyright 2019 American Chemical Society.

Figure 35

Illustration of hydrogenases and hydrogenase-mimicking ligands. (a) Active sites of [NiFe]–H₂ases and [FeFe]–H₂ases. (b) Ligand design of [FeFe]–H₂ase-mimicking MOFs. Reproduced with permission from ref (561). Copyright 2014 American Chemical Society.

Figure 36

Three strategies to synthesize [FeFe]–H₂ase-mimicking MOF. (a) Introducing [FeFe] ligand through ligand exchange to afford a multivariate MOF enabling photochemical hydrogen production. Reproduced with permission from ref (230). Copyright 2013 American Chemical Society. (b) Installing [FeFe] model compounds to accessible metal sites in a porphyrin MOF. Reproduced with permission from ref (232). Copyright 2014 Royal Society of Chemistry. (c) Integrating redox-active ligands and [FeFe]–H₂ase active sites into a defective MOF through linker installation to mimic the electron transport chain. Reproduced with permission from ref (235). Copyright 2021 American Chemical Society.

Figure 37

Structural illustration of (a) Heme-b and (b) TPP. (c) Decomposition of Fe(TPP) SPh to produce μ-oxo-bridged dimers.

Figure 38

Crystal structure of PCN-222(Fe) with a csq network topology, enabling oxidizing pyrogallol by hydrogen peroxide. Reproduced with permission from ref (64). Copyright 2012 John Wiley and Sons.

Figure 39

Crystal structure and building blocks of PCN-600 for catalytic oxidation. Reproduced with permission from ref (65). Copyright 2014 American Chemical Society.

Figure 40

Preparation of mixed-metal-salen MOFs through postsynthetic linker exchange. The salen-based MOFs enable conducting multiple asymmetric catalysis efficiently. Reproduced with permission from ref (630). Copyright 2018 American Chemical Society.

Figure 41

Constructing chiral MOF@MOF composites from M-salen ligands for asymmetric epoxidation/ring-opening reactions. Reproduced with permission from ref (631). Copyright 2019 Royal Society of Chemistry.

Figure 42

Illustration of bimetallic MOF-919 (Fe–Cu) mimicking bifunctional oxidase–peroxidase catalytic activity. Reproduced with permission from ref (640). Copyright 2022 Royal Society of Chemistry.

Figure 43

Comparison between enzymatic catalysis, supramolecular catalysis, and framework catalysis.

Figure 44

Polymerization within MOFs with different channel sizes resulting in diverse products. Reproduced with permission from ref (645). Copyright 2007 John Wiley and Sons.

Figure 45

Fixation and [2+2+2] cyclotrimerization of substituted pyridines bearing unsaturated functional groups within MIL-88B (Fe). The locations of pyridine monomers are confirmed by SCXRD. Reproduced with permission from ref (647). Copyright 2015 Springer Nature.

Figure 46

(top) Illustration of the azide sites and the site-selective click reaction of a dialkyne within a Mn-based MOF. Bottom: The click reaction products of dialkynes with varied chain length. The site-selective click reaction involves the immobilization of azides and regeneration via alkylation with MeBr. Reproduced with permission from ref (648). Copyright 2018 American Chemical Society.

Figure 47

Quantitative hydrogenolysis to generate catalytic Ru@MOF-5 composites. Reproduced with permission from ref (651). Copyright 2005 John Wiley and Sons.

Figure 48

Overview of strategies to synthesizing hydrophobic MOFs or MOF-based composites. (a) Introducing hydrophobic modulator acid into the MOF. Reproduced with permission from ref (674). Copyright 2016 American Chemical Society. (b) Coating the MOF surface with poly(dimethylsiloxane) (PDMS). Reproduced with permission from ref (675). Copyright 2014 American Chemical Society. (c) Fabricating composites consisting of MOFs and highly fluorinated graphene (HFGO). Reproduced with permission from ref (679). Copyright 2016 John Wiley and Sons. (d) Functionalizing MOFs with aliphatic chains through covalent bonds. Reproduced with permission from ref (681). Copyright 2011 John Wiley and Sons.

Figure 49

Catalytic activity of a homochiral BINAP-MOF metalated with Rh and Ru. Reproduced with permission from ref (677). Copyright 2014 American Chemical Society.

Figure 50

Structural of Pd₁₂L₂₄ molecular assembly that enables increasing the gold concentration and improving catalytic efficiency. Reproduced with permission from ref (723). Copyright 2014 John Wiley and Sons.

Figure 51

Self-assembly of Co (II) phthalocyanine within the bio-MOF-1’s nanopores, involving metal cation exchange and cation-directed assembly. Reproduced with permission from ref (39). Copyright 2014 American Chemical Society.

Figure 52

MOF-templated stepwise synthesis of homo- (a) and heterobimetallic (b) supramolecular coordination compounds within the confined MOF channels. Step (i) indicates the incorporation of organic ligand with desired structural and coordination information. Step (ii) indicates postsynthetic metalation. Reproduced with permission from ref (732). Copyright 2019 American Chemical Society.

Figure 53

Installing sulfuric acid onto PCN-222 to generate a photoactive and acidic MOF, which can catalyze photocatalytic oxidation of dihydroartemisinic acid to artemisinin. Reproduced with permission from ref (733). Copyright 2019 American Chemical Society.

Figure 54

Construction of catalytic MOFs through postsynthetic linker installation. (a) PCN-700 features two types of missing-linker defects, which can accommodate carboxylate ligands with varied sizes. (b) Active sites were introducing to endow the MOF with catalytic activity. Reproduced with permission from ref (256). Copyright 2016 American Chemical Society.

Figure 55

Illustration of the pore environment in MUF-77 equipped with catalytic unit and modulator groups. The potential contacts between the aldo intermediate (orange) and the modulator groups (violet and red) are shown in the right. Reproduced with permission from ref (711). Copyright 2017 American Chemical Society.

Figure 56

Regio- and enantioselective hydroformylation of Rh-monophosphane complexes confined within cyclodextrins. Reproduced with permission from ref (746). Copyright 2014 John Wiley and Sons.

Figure 57

Regio- and enantioselective photodimerization confined within a cyclodextrin-based MOF. The substrates can form superstructures with cyclodextrin frameworks. Reproduced with permission from ref (749). Copyright 2021 American Chemical Society.

Figure 58

Endowing a gold nanocluster with water solubility and HRP-mimicking catalytic activity through bonding with CD-MOF-1. Reproduced with permission from ref (751). Copyright 2020 American Chemical Society.

Figure 59

Structural illustration of the calix[4]arene linker and the (4,6)-connected MOF. The two nonintersecting pores are depicted in the framework in red and orange. The N₂ sorption isotherm at 77 K is displayed. Reproduced with permission from ref (764). Copyright 2018 John Wiley and Sons.

Figure 60

Dynamic self-assembly of a guest/host/metal–cation complex. The transition metal promoted the selective photoreactions within the cucurbiturils. Reproduced with permission from ref (773). Copyright 2011 John Wiley and Sons.

Figure 61

Structural illustration of the SMOF-1 and WD-POM@SMOF-1. Carbon, nitrogen, oxygen, and hydrogen are represented in gray, blue, red, and white, respectively. Reproduced with permission from ref (781). Copyright 2016 Springer Nature.

Figure 62

Self-assembly of cavitands to form a capsule to store steroids. Reproduced with permission from ref (783). Copyright 2004 American Chemical Society.

Figure 63

Distinct regioselectivity of Diels–Alder reaction confined within cage-shaped and bowl-shaped self-assembled container molecules. Reproduced with permission from ref (786). Copyright 2006 the American Association for the Advancement of Science.

Figure 64

Structural illustration of the [Ga₄L₆]^12– cage and the catalytic mechanism for orthoformate hydrolysis. Reproduced with permission from ref (799). Copyright 2007 the American Association for the Advancement of Science.