Abstract
Effective chemical catalysts can artificially control intracellular metabolism. However, in conventional catalytic chemistry, activity and cytotoxicity have a trade-off relationship; thus, driving catalysts in living cells remains challenging. To overcome this critical issue at the interface between catalytic chemistry and biology, we developed cell-driven allosteric catalysts that exert catalytic activity at specific times. The synthesized allosteric redox catalysts up- and downregulated their foldase- and antioxidase-like activities in response to varying Ca(2+) concentrations, which is a key factor for maintenance of the redox status in cells. In the absence of Ca(2+) or at low Ca(2+) concentrations, the compounds were mostly inactive and hence did not affect cell viability. In contrast, under specific conditions with elevated cytosolic Ca(2+) concentrations, the activated compounds resisted the redox imbalance induced by the reactive oxygen species generated by Ca(2+)-stimulated mitochondria. Smart catalysts that crosstalk with biological phenomena may provide a platform for new prodrug development guidelines.