title: 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 () 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.
authors.affiliation: Department of Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Santoro
authors.affiliation: Department of Chemistry, University of Fribourg, Chemin du Musée 9, CH-1700 Fribourg, Switzerland. fabio.zobi@unifr.ch.
authors.forename: Ruben
authors.initials: R
authors.lastname: Beltrami
authors.affiliation: Department of Chemistry, University of Fribourg, Chemin du Musée 9, CH-1700 Fribourg, Switzerland. fabio.zobi@unifr.ch.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Kottelat
authors.affiliation: Department of Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Blacque
authors.affiliation: Institute of Veterinary Physiology, University of Zürich, Winterthurerstrasse 260, CH-8057 Zürich, Switzerland.
authors.forename: Anna Yu
authors.initials: AY
authors.lastname: Bogdanova
authors.affiliation: Department of Chemistry, University of Fribourg, Chemin du Musée 9, CH-1700 Fribourg, Switzerland. fabio.zobi@unifr.ch.
authors.forename: Fabio
authors.initials: F
authors.lastname: Zobi
mesh_terms: D002248:Carbon Monoxide / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D009569:Nitric Oxide / Q000737:chemistry*; D009602:Nitrosamines / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D012211:Rhenium / Q000737:chemistry*; D014805:Vitamin B 12 / Q000737:chemistry*
chemical_list: D009602:Nitrosamines; D009942:Organometallic Compounds; D009569:Nitric Oxide; D012211:Rhenium; D002248:Carbon Monoxide; D014805:Vitamin B 12