Mechanistic Studies on the Reactions between Cobalamins and the Biological Signaling Molecule Nitroxyl (HNO)

• Published in: Meeting abstracts (Electrochemical Society) Vol. MA2021-01; no. 16; p. 752
• Main Authors: Brasch, Nicola E, Polaczek, Justyna, Cink, Ruth B, Subedi, Harishchandra, van Eldik, Rudi
• Format: Journal Article
• Language: English
• Published: The Electrochemical Society, Inc 30.05.2021
• ISSN: 2151-2043; 2151-2035
• DOI: 10.1149/MA2021-0116752mtgabs

The N-hydroxysulphonamide Piloty’s acid, PhSO 2 NHOH, was first reported in the scientific literature over a century ago. N-hydroxysulphonamides have recently attracted considerable attention, due to their propensity to spontaneously decompose to cleanly release nitroxyl (HNO) upon deprotonation of the parent molecule. Like its well-established cousin nitric oxide (NO), HNO is a biological signaling molecule with a rich redox chemistry. Furthermore therapeutics that generate HNO in vivo show considerable promise in treating cardiovascular disease including congestive heart failure, through mechanisms unique to HNO. HNO reacts primarily with metal centres and thiols (protein thiol residues and small molecular weight thiols) in biological systems. The cobalt-containing vitamin B 12 macrocycle is a cofactor for numerous enzymes in humans and bacteria. Detailed mechanistic studies on the reactions of Piloty’s acid with all three oxidation states of vitamin B 12 – Co(I), Co(II) and Co(III) – will be presented, and reveal a complex and rich coordination chemistry for this simple triatomic molecule.