title: Effect of Ascorbate on the Cyanide-Scavenging Capability of Cobalt(III) meso-Tetra(4-N-methylpyridyl)porphine Pentaiodide: Deactivation by Reduction?
abstract: The Co(III)-containing water-soluble metalloporphyrin cobalt(III) meso-tetra(4-N-methylpyridyl)porphine pentaiodide (Co(III)TMPyP) is a potential cyanide-scavenging agent. The rate of reduction of Co(III)TMPyP by ascorbate is facile enough that conversion to the Co(II)-containing Co(II)TMPyP should occur within minutes at prevailing in vivo levels of the reductant. It follows that any cyanide-decorporating capability of the metalloporphyrin should depend more on the cyanide-binding characteristics of Co(II)TMPyP than those of the administered form, Co(III)TMPyP. Addition of cyanide to buffered aqueous solutions of Co(II)TMPyP (pH 7.4, 25-37 °C) results in quite rapid (k2 = ∼10(3) M(-1) s(-1)) binding/substitution of cyanide anion in the two available axial positions with high affinity (K'β = 10(10) to 10(11)). Electron paramagnetic resonance spectroscopic measurements and cyclic voltammetry indicate that cyanide induces oxidation to the Co(III)-containing dicyano species. The constraints that these observations put on plausible mechanisms for the reaction of Co(II)TMPyP with cyanide are discussed. Experiments in which Co(III)TMPyP and cyanide were added to freshly drawn mouse blood showed the same sequence of reactions (metalloporphyrin reduction → cyanide binding/substitution → reoxidation) to occur. Therefore, in cyanide-scavenging applications with this metalloporphyrin, we should be taking advantage of both the improved rate of ligand substitution at Co(II) compared to that at Co(III) and the increased affinity of Co(III) for anionic ligands compared to that of Co(II). Finally, using an established sublethal mouse model for cyanide intoxication, Co(III)TMPyP, administered either 5 min before (prophylaxis) or 1 min after the toxicant, is shown to have very significant antidotal capability. Possible explanations for the results of a previous contradictory study, which failed to find any prophylactic effect of Co(III)TMPyP toward cyanide intoxication, are considered.
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, The University of Pittsburgh , 100 Technology Drive, Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Oscar S
authors.initials: OS
authors.lastname: Benz
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, The University of Pittsburgh , 100 Technology Drive, Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, The University of Pittsburgh , 100 Technology Drive, Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Cronican
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, The University of Pittsburgh , 100 Technology Drive, Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Jim
authors.initials: J
authors.lastname: Peterson
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, The University of Pittsburgh , 100 Technology Drive, Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Linda L
authors.initials: LL
authors.lastname: Pearce
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry*; D001665:Binding Sites; D003035:Cobalt / Q000097:blood / Q000737:chemistry*; D003486:Cyanides / Q000737:chemistry*; D055664:Electrochemical Techniques; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000737:chemistry*; D007700:Kinetics; D008297:Male; D008665:Metalloporphyrins / Q000097:blood / Q000737:chemistry*; D051379:Mice; D009942:Organometallic Compounds / Q000097:blood / Q000737:chemistry*; D010084:Oxidation-Reduction
chemical_list: D003486:Cyanides; D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D009942:Organometallic Compounds; C512795:cobalt(III)meso-tetrakis(N-methylpyridinium-4-yl)porphyrin; D003035:Cobalt; D001205:Ascorbic Acid