Identification of Au-hydrides as key intermediates in the reduction of Au(iii) prodrugs to active Au(i) species under protic conditions.

ABSTRACT: Similar to Pt^IV prodrugs, Au^III anticancer complexes are believed to undergo intracellular reduction, thereby gaining their activity from the resulting Au^I species. Unlike for Pt^IV, the underlying mechanism of this process remains poorly understood for Au^III. To elucidate this mechanism, we investigated the reaction of [Au(ppy)Cl₂], a model Au^III complex (ppy: phenylpyridine), with two biologically relevant reductants: lipoic acid (lpa) and N-acetyl-l-cysteine-methyl ester (NAC-OMe). Our findings reveal that lpa transfers a hydride to the Au, while cysteine derivatives only bind to the metal. The Au-H complex, even visible in protic solvents by NMR spectroscopy, produced by lpa is essential for enabling a s

SUBMITTER: Ochs J 

PROVIDER: S-EPMC12777740 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature