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Published on: September 25, 2017
N-Nitrosamine-{cis-Re[CO]2}(2+) cobalamin conjugates as mixed CO/NO-releasing molecules
Giuseppe Santoro1, Ruben Beltrami2, Emmanuel Kottelat2
1Department of Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
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 () and its N-pyrazine nitrosylated derivative (). 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.
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