Sci Rep. 2026 Jul 9;16(1):21432. doi: 10.1038/s41598-026-60865-4.

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 [CuS₄]₂ to mononuclear [CutBuS₄], 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 [CuS₄]₂ nevertheless shows stronger productive substrate binding, with K_M values of 3.4 vs. 5.0 mM for the mononuclear [Formula: see text], respectively. In contrast, oxidation of o-aminophenol to aminophenoxazinone is strongly nuclearity-dependent, with [CuS₄]₂ displaying substantially higher activity than [Formula: see text] (2772 vs. 684 h^{– 1}), consistent with a decisive role for dicopper cooperativity in oxidative coupling. Detection of H₂O₂ 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.

PMID:42426226 | DOI:10.1038/s41598-026-60865-4