Substrate and Lewis Acid Coordination Promote O-O Bond Cleavage of an Unreactive L2CuII2(O22-) Species to Form L2CuIII2(O)2 Cores with Enhanced Oxidative Reactivity.

Copper-dependent metalloenzymes are widespread throughout metabolic pathways, coupling the reduction of O2 with the oxidation of organic substrates. Small-molecule synthetic analogs are useful platforms to generate L/Cu/O2 species that reproduce the structural, spectroscopic, and reactive properties of some copper-/O2-dependent enzymes. Landmark studies have shown that the conversion between dicopper(II)-peroxo species (L2CuII2(O22-) either side-on peroxo, SP, or end-on trans-peroxo, TP) and dicopper(III)-bis(μ-oxo) (L2CuIII2(O2-)2: O) can be controlled through ligand design, reaction conditions (temperature, solvent, and counteranion), or substrate coordination. We recently published ( J. Am. Chem. Soc. 2012 , 134 , 8513 , DOI: 10.1021/ja300674m ) the crystal structure of an unusual SP species [(MeAN)2CuII2(O22-)]2+ (SPMeAN, MeAN: N-methyl-N,N-bis[3-(dimethylamino)propyl]amine) that featured an elongated O-O bond but did not lead to O-O cleavage or reactivity toward external substrates. Herein, we report that SPMeAN can be activated to generate OMeAN and perform the oxidation of external substrates by two complementary strategies: (i) coordination of substituted sodium phenolates to form the substrate-bound OMeAN-RPhO- species that leads to ortho-hydroxylation in a tyrosinase-like fashion and (ii) addition of stoichiometric amounts (1 or 2 equiv) of Lewis acids (LA's) to form an unprecedented series of O-type species (OMeAN-LA) able to oxidize C-H and O-H bonds. Spectroscopic, computational, and mechanistic studies emphasize the unique plasticity of the SPMeAN core, which combines the assembly of exogenous reagents in the primary (phenolates) and secondary (Lewis acids association to the MeAN ligand) coordination spheres with O-O cleavage. These findings are reminiscent of the strategy followed by several metalloproteins and highlight the possible implication of O-type species in copper-/dioxygen-dependent enzymes such as tyrosinase (Ty) and particulate methane monooxygenase (pMMO).