Boronic acid with high oxidative stability and utility in biological contexts
Brian J. Graham, Ian W. Windsor, Brian Gold, Ronald T. Raines
Abstract
Significance Like thiols, boronic acids are unstable to oxidation in biological contexts, limiting their utility. We discovered that the rate-limiting step in the oxidation of a boronic acid can be slowed by the installation of a pendant carboxyl group that is a ligand to the boron atom. The ensuing boronic acid is 10,000-fold more resistant to oxidation. Experimental and computational analyses reveal that the orientational constraints and electronic effects imposed by the carboxyl group act as intended, slowing the rate-limiting step during oxidation. The new boronic acid retains the useful attributes of simple boronic acids such as forming reversible covalent bonds with saccharides and a protein and could be useful in chemical biology, medicinal chemistry, and allied fields.