title: Thermal stability of the prototypical Mn porphyrin-based superoxide dismutase mimic and potent oxidative-stress redox modulator Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin chloride, MnTE-2-PyP(5+).
abstract: Cationic Mn porphyrins are among the most potent catalytic antioxidants and/or cellular redox modulators. Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin chloride (MnTE-2-PyPCl(5)) is the Mn porphyrin most studied in vivo and has successfully rescued animal models of a variety of oxidative stress-related diseases. The stability of an authentic MnTE-2-PyPCl(5) sample was investigated hereon by thermogravimetric, derivative thermogravimetric, and differential thermal analyses (TG/DTG/DTA), under dynamic air, followed by studies at selected temperatures to evaluate the decomposition path and appropriate conditions for storage and handling of these materials. All residues were analyzed by thin-layer chromatography (TLC) and UV-vis spectroscopy. Three thermal processes were observed by TG/DTG. The first event (endothermic) corresponded to dehydration, and did not alter the MnTE-2-PyPCl(5) moiety. The second event (endothermic) corresponded to the loss of EtCl (dealkylation), which was characterized by gas chromatography-mass spectrometry. The residue at 279°C had UV-vis and TLC data consistent with those of the authentic, completely dealkylated analog, MnT-2-PyPCl. The final, multi-step event corresponded to the loss of the remaining organic matter to yield Mn(3)O(4) which was characterized by IR spectroscopy. Isothermal treatment at 188°C under static air for 3h yielded a mixture of partially dealkylated MnPs and traces of the free-base, dealkylated ligand, H(2)T-2-PyP, which reveals that dealkylation is accompanied by thermal demetallation under static air conditions. Dealkylation was not observed if the sample was heated as a solid or in aqueous solution up to ∼100°C. Whereas moderate heating changes sample composition by loss of H(2)O, the dehydrated sample is indistinguishable from the original sample upon dissolution in water, which indicates that catalytic activity (on Mn basis) remains unaltered. Evidently, dealkylation at high temperature compromises sample activity.
authors.affiliation: Departamento de Química, CCEN, Universidade Federal da Paraíba, João Pessoa PB 58051-900, Brazil.
authors.forename: Victor H A
authors.initials: VH
authors.lastname: Pinto
authors.forename: Dayse
authors.initials: D
authors.lastname: Carvalhoda-Silva
authors.forename: Jonas L M S
authors.initials: JL
authors.lastname: Santos
authors.forename: Tin
authors.initials: T
authors.lastname: Weitner
authors.forename: Maria Gardênnia
authors.initials: MG
authors.lastname: Fonseca
authors.forename: Maria Irene
authors.initials: MI
authors.lastname: Yoshida
authors.forename: Ynara M
authors.initials: YM
authors.lastname: Idemori
authors.forename: Ines
authors.initials: I
authors.lastname: Batinić-Haberle
authors.forename: Júlio S
authors.initials: JS
authors.lastname: Rebouças
mesh_terms: D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D040761:Biomimetic Materials / Q000737:chemistry* / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D004055:Differential Thermal Analysis; D004355:Drug Stability; D006358:Hot Temperature; D008665:Metalloporphyrins / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D013056:Spectrophotometry, Ultraviolet; D013482:Superoxide Dismutase / Q000737:chemistry*; D013818:Thermogravimetry; D044366:Transition Temperature
chemical_list: D000975:Antioxidants; D008665:Metalloporphyrins; C431023:manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin; D013482:Superoxide Dismutase