Novel cytoprotective and catalytic properties of ruthenium(ii) arene complexes in metabolic redox dysregulation

Abstract

Ruthenium coordination complexes offer unique opportunities for regulating redox processes due to their tunable electronic structures and catalytic versatility. In this work, four structurally defined Ru(ii)–arene complexes incorporating saccharinate as a monodentate ligand and 1,10-phenanthroline or its o-vanillin-functionalized derivative as bidentate chelators were synthesized and fully characterized by spectroscopic techniques and single-crystal X-ray diffraction. The complexes display good stability under physiological and mildly acidic conditions, moderate albumin binding, and favourable lipophilicity, indicating potential compatibility with biological environments. Functional studies revealed strong antioxidant properties, including concentration-dependent DPPH radical scavenging, hydroxyl radical neutralization, and efficient hydrogen peroxide decomposition through catalase-like activity via a non-Fenton pathway. The complexes also exhibit peroxidase-mimetic catalytic behaviour across a broad pH range. Molecular docking and enzymatic studies demonstrate inhibitory interactions with xanthine oxidase, a key enzyme responsible for the generation of reactive oxygen species in metabolic disorders. Cellular assays further confirm the cytoprotective behaviour of the complexes, which mitigate H2O2-induced oxidative stress in HeLa cells and preserve mitochondrial membrane potential, particularly with complex C4. In addition, the peroxidase-like catalytic activity enables sensitive detection of glutathione in biological matrices with limits of detection in the sub-micromolar range. Collectively, these findings establish Ru(ii)–arene complexes as multifunctional redox-active systems that combine catalytic activity, antioxidant capacity, and cytoprotective properties, highlighting their potential as artificial enzyme mimics for regulating oxidative stress in biological systems. This journal is © The Royal Society of Chemistry, 2026.