Silicon mimics of unstable Carbon

Abstract

Silicon–carbon bonds are unknown in nature, yet the search for bioactive organosilanes has a rich and successful history. Substitution of silicon for a stable quaternary carbon in biologically active molecules often leads to bioactive organosilanes. An alternative approach is the substitution of silicon for an unstable carbon, such as a hydrated carbonyl. The proclivity of carbon to favor a carbonyl over a 1,1-diol is reversed for silicon. Tetrahedral, hydrated carbonyls are ubiquitous intermediates in the reactivity of carbonyl compounds including many enzymatic reactions, and hydrolase enzymes are critical mediators of a broad range of biological processes. Proteases, one group of hydrolase enzymes, can be potently inhibited by silanediol-based peptide mimics when the silanediol substitutes for the hydrated carbonyl of amide bond hydrolysis. This chapter outlines the key parameters for bioactive organosilanes, the evolution of the silanediols as protease inhibitors, the supporting chemistry, and the current status.