N-Nitrosamine-{cis-Re[CO]2}2+ cobalamin conjugates as mixed CO/NO-releasing molecules

Abstract

Mixed CO/NO-releasing molecules were prepared by conjugation of the 17-electron rhenium dicarbonyl cis-[Re(CO)₂Br₄]²⁻ complex to N-nitrosamine modified cyanocobalamin (B12) bio-vectors. The species were fully characterized by standard analytical techniques, including X-ray crystallography for cyanocobalamin-5′-O-pyrazine and (1) and its N-pyrazine nitrosylated derivative (1a). The N-nitrosamine B12 derivatives are able to liberate low NO doses in buffer solutions and appear to be “activated” towards NO release if in contact with cultured cells. Coordination of the cis-[Re(CO)₂Br₄]²⁻ complex on the axial cyanide of B12 allows for the combined loss of CO and NO from the conjugates. The mixed CO/NO-releasing molecules show cytoprotection in an ischemia–reperfusion model but no significant enhanced synergistic effects over the relative NORMs and CORMs building constituents.