This review summarizes recent developments in using bioorthogonal chemistry in prodrug design for the delivery of traditional small molecule- and gasotransmitter-based therapeutics.

Hydrogen sulfide (H2S) is recognized as one of three gasotransmitters together with nitric oxide (NO) and carbon monoxide (CO). As a signaling molecule, H2S plays an important role in physiology and shows great potential in pharmaceutical applications. Along this line, there is a need for the development of H2S prodrugs for various reasons. In this review, we summarize different H2S prodrugs, their chemical properties, and some of their potential therapeutic applications.

Metal-free CO prodrugs with a biological trigger and tunable release rate are described herein for the first time.