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