LAUSR

Until recently, both homogeneous and enzymatic catalysis have by-and-large grown independently, ultimately allowing scientists to address complementary synthetic challenges. Combining computation with detailed structural and mechanistic insights has led to the design and optimization of homogeneous catalysts that bear a well-defined second coordination sphere and proceed via reaction mechanisms that resemble those of highly sophisticated metalloenzymes. The progress in aqueous coordination chemistry has also been beneficial for biocatalysis. This has led to the realization that metalloproteins may be repurposed and ultimately evolved to catalyze new-to-nature reactions, thus greatly expanding the reaction repertoire available to enzymes. This virtual issue of ACS Central Science provides a timely snapshot of the lively field of bioinspired catalysis. Fourteen articles have been selected to highlight the stateof-the-art in this broad field. Current challenges in bioinspired catalysis, which relies on both homogeneous catalysts and enzymes, include (i) engineering second coordination sphere interactions to place substrates and solvent in catalytically competent poses; (ii) exploiting selective substrate channels to ensure the timely delivery of reagents to a highly reactive catalytic intermediate; (iii) relying on redox mediators to facilitate challenging reactions; (iv) deciphering the subtle catalytic details that lead to chiral amplification and autocatalysis; and (v) combining the versatility of non-natural cofactors with the power of directed evolution. Some of the essential features of metalloenzymes that are collected in this virtual issue are depicted in Scheme 1. Brief introductions for each of the 14 articles in this virtual issue are presented below. These sections are arranged according to the grand challenge that they set out to address: the emergence of homochirality, engineering second coordination sphere interactions, C−H activation, substrate engineering, and finally, artificial and repurposed metalloenzymes.