Characterization of the structure and reactivity of monocopper–oxygen complexes supported by β‐diketiminate and anilido‐imine ligands

Abstract

Copper–oxygen complexes supported by β-diketiminate and anilido-imine ligands have recently been reported (Aboelella et al., J Am Chem Soc 2004, 126, 16896; Reynolds et al., Inorg Chem 2005, 44, 6989) as potential biomimetic models for dopamine β-monooxygenase (DβM) and peptidylglycine α-hydroxylating monooxygenase (PHM). However, in contrast to the enzymatic systems, these complexes fail to exhibit CH hydroxylation activity (Reynolds et al., Chem Commun 2005, 2014). Quantum chemical characterization of the 1:1 Cu-O₂ model adducts and related species (Cu(III)-hydroperoxide, Cu(III)-oxo, and Cu(III)-hydroxide) indicates that the 1:1 Cu-O₂ adducts are unreactive toward substrates because of the weakness of the OH bond that would be formed upon hydrogen-atom abstraction. This in turn is ascribed to the 1:1 adducts having both low reduction potentials and basicities. Cu(III)-oxo species on the other hand, determined to be intermediate between Cu(III)-oxo and Cu(II)-oxyl in character, are shown to be far more reactive toward substrates. Based on these results, design strategies for new DβM and PHM biomimetic ligands are proposed: new ligands should be made less electron rich so as to favor end-on dioxygen coordination in the 1:1 Cu-O₂ adducts. Comparison of the relative reactivities of the various copper–oxygen complexes as hydroxylating agents provides support for a Cu(II)-superoxide species as the intermediate responsible for substrate hydroxylation in DβM and PHM, and suggests that a Cu(III)-oxo intermediate would be competent in this process as well. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006