Mechanistic Studies of Carbon Monoxide Release from Norborn-2-en-7-one CORMs

Abstract

A study has been performed to determine the factors that control carbon monoxide (CO) release from 3a-bromo-norborn-2-en-7-one-based organic CO-releasing molecules (oCOms). Such molecules have recently become of interest for the therapeutic potential of targeted delivery of the gasotransmitter CO, however the mechanism controlling the release of CO has not been comprehensively studied. Elucidation of this mechanism would enable tuning of the rate of CO release to specific therapeutic needs, such as acute vs chronic administration. By the synthesis and evaluation of substituted oCOms, CO release has been shown to be controlled by a rate-determining E1cB(irr)-type elimination of HBr followed by rapid chelotropic decomposition to give CO and a substituted phthalimide byproduct. Based on this result we report the successful rational design and synthesis of water-soluble oCOms with targeted half-lives intermediate to those reported previously.