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

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