Direct Copper(III) Formation from O<sub>2</sub> and Copper(I) with Histamine Ligation J. Brannon Gary Cooper Citek Timothy A. Brown Richard N. Zare Erik C. Wasinger T. Daniel P. Stack 10.1021/jacs.6b05538.s001 https://acs.figshare.com/articles/journal_contribution/Direct_Copper_III_Formation_from_O_sub_2_sub_and_Copper_I_with_Histamine_Ligation/3503960 Histamine chelation of copper­(I) by a terminal histidine residue in copper hydroxylating enzymes activates dioxygen to form unknown oxidants, generally assumed as copper­(II) species. The direct formation of copper­(III)-containing products from the oxygenation of histamine-ligated copper­(I) complexes is demonstrated here, indicating that copper­(III) is a viable oxidation state in such products from both kinetic and thermodynamic perspectives. At low temperatures, both trinuclear Cu­(II)<sub>2</sub>Cu­(III)­O<sub>2</sub> and dinuclear Cu­(III)<sub>2</sub>O<sub>2</sub> predominate, with the distribution dependent on the histamine ligand structure and oxygenation conditions. Kinetics studies suggest the bifurcation point to these two products is an unobserved peroxide-level dimer intermediate. The hydrogen atom reactivity difference between the trinuclear and binuclear complexes at parity of histamine ligand is striking. This behavior is best attributed to the accessibility of the bridging oxide ligands to exogenous substrates rather than a difference in oxidizing abilities of the clusters. 2016-07-28 12:48:34 copper hydroxylating enzymes activates dioxygen exogenous substrates oxygenation conditions oxidation state oxidizing abilities histamine ligand O 2 oxide ligands Histamine Ligation Histamine chelation terminal histidine residue bifurcation point Kinetics studies hydrogen atom reactivity difference histamine ligand structure Cu