17 e- rhenium dicarbonyl CO-releasing molecules on a cobalamin scaffold for biological application

Cyanocobalamin (B-12) offers a biocompatible scaffold for CO-releasing 17-electron dicarbonyl complexes based on the cis-trans-[Re-II(CO)(2)Br-2](0) core. A Co-C N-Re conjugate is produced in a short time and high yield from the reaction of [Et4N](2)[(ReBr4)-Br-II(CO)(2)] (ReCORM-1) with B-12. The B-12-Re-II(CO)(2) derivatives show a number of features which make them pharmaceutically acceptable CO-releasing molecules (CORMs). These cobalamin conjugates are characterized by an improved stability in aqueous aerobic media over the metal complex alone, and afford effective therapeutic protection against ischemia-reperfusion injury in cultured cardiomyocytes. The non-toxicity (at mu M concentrations) of the resulting metal fragment after CO release is attributed to the oxidation of the metal and formation in solution of the ReO4- anion, which is among the least toxic of all of the rare inorganic compounds. Theoretical and experimental studies aimed at elucidating the aqueous chemistry of ReCORM-1 are also described.