A study has been performed to determine the factors that control carbon monoxide (CO) release from 3abromo-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.
Norbornenone (5b), obtained from the reaction of 2,5-dimethyl-3,4-diphenylcyclopentadienone dimer (3) with bromomaleic anhydride (4b), provides an excellent base-triggered source of carbon monoxide for palladium-catalysed carbonylation reactions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.