Studies towards Non-toxic, Water Soluble, Vasoactive Norbornene Organic Carbon Monoxide Releasing Molecules

Abstract

The optimisation of the aqueous solubility of organic carbon monoxide releasing molecules based on a norborn-2-en-7-one scaffold is reported. This culminated in the synthesis of oCOm-54 and oCOm-56 which contain water solubilising polyethylene oxide groups. Both compounds are highly water soluble and release CO at pH 7.4 with half-lives of 180 and 320 minutes respectively, to produce a reversible vasodilatory response in isolated, preconstricted tissue. Preliminary analysis indicates these oCOms are capable of forming micellar particles. Both oCOms exhibit significantly less cellular toxicity in AC16 human cardiomyocytes than earlier amine-containing oCOms.