美国芝加哥大学Wenbin Lin团队报道了一种在MOFs中合理构建人工双核铜单加氧酶的策略。 相关研究成果于2021年1月7日出版的《美国化学会志》。

人工酶系统被广泛研究，以模拟其天然对应的结构和功能。然而，在这些人工体系中，结构模拟和催化活性之间仍然存在着很大的差距。

该文报道了一种从钛金属有机骨架（MOF）出发构建人工双核铜单加氧酶的新方法。MIL-125（Ti）（MIL=Matériaux de l'Institut Lavoisier）的二级结构单元（SBU）上的氢氧化物基团的去质子化允许SBUs与具有紧密间隔的CuI对金属化，这些CuI对被分子O2氧化以提供基于MOF的人工双核单加氧酶Ti8-Cu2中的CuI2（μ2-OH）2辅因子。

研究人员还制备了人工单核铜单加氧酶Ti8-Cu1进行比较。采用热重分析、电感耦合等离子体质谱、X射线吸收光谱、傅立叶变换红外光谱和紫外-可见光谱对MOF基单加氧酶进行了表征。在存在共沸物的情况下，Ti8-Cu2对一系列单加氧过程表现出优异的催化活性，包括环氧化、羟基化、Baeyer–Villiger氧化和硫氧化，转化率高达3450。Ti8-Cu2比Ti8-Cu1的转化率至少高17倍。

密度泛函理论计算表明，O2活化是单加氧反应的限速步骤。计算研究进一步表明，Ti8-Cu2中的Cu2位点协同稳定了用于O-O键断裂的Cu-O2加合物，自由能增加比Ti8-Cu1中的单核Cu位小6.6 kcal/mol，说明Ti8-Cu2比Ti8-Cu1具有更高的催化活性。

附：英文原文

Title: Rational Construction of an Artificial Binuclear Copper Monooxygenase in a Metal–Organic Framework

Author: Xuanyu Feng, Yang Song, Justin S. Chen, Ziwan Xu, Soren J. Dunn, Wenbin Lin

Issue&Volume: January 7, 2021

Abstract: Artificial enzymatic systems are extensively studied to mimic the structures and functions of their natural counterparts. However, there remains a significant gap between structural modeling and catalytic activity in these artificial systems. Herein we report a novel strategy for the construction of an artificial binuclear copper monooxygenase starting from a Ti metal–organic framework (MOF). The deprotonation of the hydroxide groups on the secondary building units (SBUs) of MIL-125(Ti) (MIL = Matériaux de l’Institut Lavoisier) allows for the metalation of the SBUs with closely spaced CuI pairs, which are oxidized by molecular O2 to afford the CuII2(μ2-OH)2 cofactor in the MOF-based artificial binuclear monooxygenase Ti8-Cu2. An artificial mononuclear Cu monooxygenase Ti8-Cu1 was also prepared for comparison. The MOF-based monooxygenases were characterized by a combination of thermogravimetric analysis, inductively coupled plasma–mass spectrometry, X-ray absorption spectroscopy, Fourier-transform infrared spectroscopy, and UV–vis spectroscopy. In the presence of coreductants, Ti8-Cu2 exhibited outstanding catalytic activity toward a wide range of monooxygenation processes, including epoxidation, hydroxylation, Baeyer–Villiger oxidation, and sulfoxidation, with turnover numbers of up to 3450. Ti8-Cu2 showed a turnover frequency at least 17 times higher than that of Ti8-Cu1. Density functional theory calculations revealed O2 activation as the rate-limiting step in the monooxygenation processes. Computational studies further showed that the Cu2 sites in Ti8-Cu2 cooperatively stabilized the Cu–O2 adduct for O–O bond cleavage with 6.6 kcal/mol smaller free energy increase than that of the mononuclear Cu sites in Ti8-Cu1, accounting for the significantly higher catalytic activity of Ti8-Cu2 over Ti8-Cu1.

DOI: 10.1021/jacs.0c11920

Source: https://pubs.acs.org/doi/10.1021/jacs.0c11920