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-PyP5

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 73; pp. 29 - 34
• Main Authors: Pinto, Victor H.A., CarvalhoDa-Silva, Dayse, Santos, Jonas L.M.S., Weitner, Tin, Fonseca, Maria Gardênnia, Yoshida, Maria Irene, Idemori, Ynara M., Batinić-Haberle, Ines, Rebouças, Júlio S.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 25.01.2013; Elsevier
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Antioxidant; Biological and medical sciences; Dealkylation; Fundamental and applied biological sciences. Psychology; General pharmacology; Medical sciences; Pharmacology. Drug treatments; Porphyrin; SOD mimic; Thermal analysis; SOD mimic; Porphyrin; Dealkylation; MnT-2-PyPCl; SOD; MnTE-2-PyPCl5; Thermal analysis; H2T-2-PyP; Antioxidant; H2TE-2-PyPCl4; MnP; Oxidative stress; Enzyme; Manganese Complexes; Superoxide dismutase; Transition metal Complexes; Thermal stability; Chlorides; Metalloporphyrin; Oxidoreductases; Porphyrin derivatives
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2012.03.033

[Display omitted] ► MnTE-2-PyPCl5 is the Mn porphyrin-based therapeutics most studied in vivo. ► Heating sample under static atmosphere may lead to dealkylation and demetallation. ► Thermal events observed: dehydration, dealkylation, demetallation, and combustion. ► Dealkylation does not occur up to 100°C, preserving thus MnTE-2-PyP5+ activity. 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-PyPCl5) 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-PyPCl5 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-PyPCl5 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 Mn3O4 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, H2T-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 H2O, 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.