Chemical Catalysis To Address Biological Questions and Therapeutic Challenges

Chemical catalysis that operates in biological systems without genetic manipulation is opening avenues to elucidate and manipulate the molecular networks of living organisms. In complex biological environments, catalysts must simultaneously deliver high activity under mild physiological conditions and stringent selectivity for their intended targets. Activity and selectivity have long been central challenges in traditional catalysis research performed in flasks; extending the reach of chemical catalysis to living systems not only revisits these issues but also propels the field into expanded conceptual territory. This Perspective focuses not on mere demonstrations of reactivity in biological contexts but on catalyst designs that directly target endogenous biomolecules─and on the biological insights these strategies enable. We highlight small-molecule catalysts, spanning photocatalysis and nonphotochemical catalysis, that are well-suited for biological applications owing to their design flexibility, synthetic tractability, and compatibility with cells and tissues. These examples reveal design principles for operation in biological environments: bioorthogonal light activation and long-wavelength excitation, targeting modalities that confer molecular precision, strategies for achieving reaction selectivity, and robustness to nucleophilic and reductive intracellular conditions. Taken together, chemical catalysis is evolving into a platform to interrogate and control the molecular logic of life, expanding biological understanding and therapeutic potential.