Ligand Effect on Modulating the Catalase-like Activity and Stability of Gold Nanoclusters for Urate Oxidase-Mediated Uric Acid Degradation through a Self-Cascade Reaction

Systematic research on the ligand effects of atomically precise metal nanoclusters toward enzyme-mimicking activity remains elusive. Herein, a series of Au 25 (SR) 18 nanoclusters capped with six types of thiolate ligands (varying in aliphatic chain length, backbone type, and functional groups) were employed as model catalysts for catalase-like (CAT-like) activity. Moderately increasing the chain length of carboxyl-terminated aliphatic thiolate ligands enhanced CAT-like activity. Au 25 (MHA) 18 (MHA = 6-mercaptohexanoic acid) exhibited satisfactory structural stability and superior CAT-like activity against external environmental variations, with an elevated electron density of Au accounting for its enhanced activity. Urate oxidase (UOx) and Au 25 (MHA) 18 were coencapsulated in zeolitic imidazolate framework-8 (ZIF-8) to construct a self-cascade system. This composite degrades uric acid (UA) via UOx, while generated hydrogen peroxide (H 2 O 2 ) is converted to oxygen (O 2 ) by Au 25 (MHA) 18, replenishing O 2 for UA degradation. Due to the cascade system and the protective effect of ZIF-8, UOx-Au 25 (MHA) 18 @ZIF-8 degraded 2.6 times as much UA as free UOx and inhibited UA crystallization. Moreover, the composite exhibits rapid, acid-responsive cargo release yet remains functional under neutral and weakly alkaline conditions. The ligand-engineering approach and self-cascade design provide a foundation for the molecular-level modulation of enzymatic activity in biomedicine.