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 O₂ to afford the Cu^II₂(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.