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

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 Cu I pairs, which are oxidized by molecular O 2 to afford the Cu II 2 (μ 2 -OH) 2 cofactor in the MOF-based artificial binuclear monooxygenase Ti 8 -Cu 2 . An artificial mononuclear Cu monooxygenase Ti 8 -Cu 1 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, Ti 8 -Cu 2 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. Ti 8 -Cu 2 showed a turnover frequency at least 17 times higher than that of Ti 8 -Cu 1 . Density functional theory calculations revealed O 2 activation as the rate-limiting step in the monooxygenation processes. Computational studies further showed that the Cu 2 sites in Ti 8 -Cu 2 cooperatively stabilized the Cu–O 2 adduct for O–O bond cleavage with 6.6 kcal/mol smaller free energy increase than that of the mononuclear Cu sites in Ti 8 -Cu 1, accounting for the significantly higher catalytic activity of Ti 8 -Cu 2 over Ti 8 -Cu 1 .