title: 17 e- rhenium dicarbonyl CO-releasing molecules on a cobalamin scaffold for biological application.
abstract: 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 [Et(4)N](2)[Re(II)Br(4)(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 μM concentrations) of the resulting metal fragment after CO release is attributed to the oxidation of the metal and formation in solution of the ReO(4)(-) 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.
authors: Institute of Inorganic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland. fzobi@aci.uzh.ch
authors: Fabio
authors: F
authors: Zobi
authors: Olivier
authors: O
authors: Blacque
authors: Robert A
authors: RA
authors: Jacobs
authors: Marcus C
authors: MC
authors: Schaub
authors: Anna Yu
authors: AY
authors: Bogdanova
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002248:Carbon Monoxide / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D015195:Drug Design; D004355:Drug Stability; D008958:Models, Molecular; D015394:Molecular Structure; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D012211:Rhenium / Q000737:chemistry*; D014805:Vitamin B 12 / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D009942:Organometallic Compounds; D012211:Rhenium; D002248:Carbon Monoxide; D014805:Vitamin B 12