Steric control of copper nuclearity in sulfur ligated oxidase mimics alters catechol and phenoxazinone oxidation

Abstract

Abstract Control over copper nuclearity is a key issue in bioinspired oxidation chemistry, yet its mechanistic consequences in sulfur-donor environments remain insufficiently understood. Here, remote tert-butyl substitution on a flexible dithioether-dithiolate ligand scaffold switches the preferred copper(II) assembly from binuclear [CuS 4 ] 2 to mononuclear [CutBuS 4 ], enabling a direct assessment of nuclearity effects within a common sulfur-ligated framework. Combined spectroscopic, electrochemical, stopped-flow kinetic, and DFT studies show that this steric perturbation modifies complex stability, productive substrate binding, and the extent to which catalytic turnover benefits from metal-metal cooperativity. In the aerobic oxidation of 3,5-di-tert-butylcatechol, both complexes follow a two-step sequence of rapid reversible substrate binding and slower oxidation, and both reach similar maximum turnover frequencies under saturating conditions, ca. 1700–1750 h − 1 . The binuclear [CuS 4 ] 2 nevertheless shows stronger productive substrate binding, with K M values of 3.4 vs. 5.0 mM for the mononuclear $$\:\left[CutBu{S}_{4}\right]$$ , respectively. In contrast, oxidation of o-aminophenol to aminophenoxazinone is strongly nuclearity-dependent, with [CuS 4 ] 2 displaying substantially higher activity than $$\:\left[CutBu{S}_{4}\right]$$ (2772 vs. 684 h − 1 ), consistent with a decisive role for dicopper cooperativity in oxidative coupling. Detection of H 2 O 2 and the lack of 4-nitrocatechol oxidation support an oxidase-type pathway in which catalytic competence depends on substrate reducing power and access to productive oxygen-dependent redox chemistry.