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

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, h...

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Bibliographic Details
Published inAsian journal of organic chemistry Vol. 11; no. 10
Main Authors Bell, Nathan T., Payne, China M., Sammut, Ivan A., Larsen, David S.
Format Journal Article
LanguageEnglish
Published WEINHEIM Wiley 01.10.2022
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
Prodrugs
INJURY
STRUCTURAL-CHARACTERIZATION
REPERFUSION
CARDIOPULMONARY BYPASS
DAMAGE
MOLECULES
CHEMICAL STRATEGY
Reaction mechanism
Drug design
Carbon monoxide
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CO-RELEASE
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Summary: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.
ISSN:2193-5807
2193-5815
DOI:10.1002/ajoc.202200350