Organoiridium Complexes Enhance Cellular Defense Against Reactive Aldehydes Species

Abstract

AbstractAlthough reactive aldehyde species (RASP) are associated with the pathogenesis of many major diseases, there are currently no clinically approved treatments for RASP overload. Conventional aldehyde detox agents are stoichiometric reactants that get consumed upon reacting with their biological targets, which limits their therapeutic efficiency. To achieve longer‐lasting detoxification effects, small‐molecule intracellular metal catalysts (SIMCats) were used to protect cells by converting RASP into non‐toxic alcohols. It was shown that SIMCats were significantly more effective in lowering cell death from the treatment with 4‐hydroxynon‐2‐enal than aldehyde scavengers over a 72 h period. Studies revealed that SIMCats reduced the aldehyde accumulation in cells exposed to the known RASP inducer arsenic trioxide. This work demonstrates that SIMCats offer unique benefits over stochiometric agents, potentially providing new ways to combat diseases with greater selectivity and efficiency than existing approaches.