Toward chemistry-based design of the simplest metalloenzyme-like catalyst that works efficiently in water.

Enzymes exhibit overwhelmingly superior catalysis compared with artificial catalysts. Current strategies to rival enzymatic catalysis require unmodified or minimally modified structures of active sites, gigantic molecular weight, and sometimes the use of harsh conditions such as extremely low temperatures in organic solvents. Herein, we describe a design of small molecules that act as the simplest metalloenzyme-like catalysts that can function in water, without mimicking enzyme structures. These artificial catalysts efficiently promoted enantioselective direct-type aldol reactions using aqueous formaldehyde. The reactions followed Michaelis-Menten kinetics, and heat-resistant asymmetric environments were constructed in water.