The interaction between cytochrome c (Cyt) and potential vanadium drugs, formed by 1,2-dimethyl-3-hydroxy-4 (1H)-pyridinonate (dhp) and maltolate (ma), was studied by ElectroSpray Ionization-Mass Spectrometry (ESIMS). Since under physiological conditions redox processes are possible, the binding of the complexes in the oxidation state +IV and +V, [(VO)-O-IV(dhp)(2)], [(VO)-O-IV(ma)(2)], [(VO2)-O-V(dhp)(2)](-) and [(VO2)-O-V(ma)(2)](-), was examined. In all systems V-IV,V-V-L-Cyt adducts are observed, their formation depending on V oxidation state, ligand L and metal concentration. The larger stability of vanadium(IV) than vanadium(V) complexes favors the interaction of the moieties (VOL2)-O-IV and (VOL+)-O-IV with V-IV, while with V-V adducts with (VO2L)-O-V and (VO2+)-O-V fragments are observed. The analysis of the protein structure suggests that Glu4, Glu21, Asp50, Glu62, Glu66 and Glu104 are the most plausible candidates for monodentate coordination, while the couples (Asp2, Glu4), (Glu92, Asp93) and (His33, Glu104) for bidentate binding. The values of E-1/2 for [(VO)-O-IV(dhp)(2)] and [(VO)-O-IV(ma)(2)], measured by cyclic voltammetry (CV), 0.53 V and 0.60 V vs. standard hydrogen electrode, indicate that the oxidation of V-IV to V-V is possible. The presence of a protein can alter the redox behavior and stabilize one of the states, V-IV or V-V. Overall, the data reinforce the conclusion that, for V drugs, the biotransformation is fundamental to explain their biological action and the analysis should not be limited to the ligand exchange and hydrolysis but also include the redox processes, and that a mixture of V-IV and V(V )species, V-IV,V-V-L-Protein and VIV,V-Protein, could be responsible of the pharmacological effects.

Interaction of pharmacologically active pyrone and pyridinone vanadium(IV,V) complexes with cytochrome c / Ugone, Valeria; Pisanu, Federico; Garribba, Eugenio. - In: JOURNAL OF INORGANIC BIOCHEMISTRY. - ISSN 0162-0134. - 234:(2022), p. 111876. [10.1016/j.jinorgbio.2022.111876]

Interaction of pharmacologically active pyrone and pyridinone vanadium(IV,V) complexes with cytochrome c

Ugone, Valeria;Pisanu, Federico;Garribba, Eugenio
2022

Abstract

The interaction between cytochrome c (Cyt) and potential vanadium drugs, formed by 1,2-dimethyl-3-hydroxy-4 (1H)-pyridinonate (dhp) and maltolate (ma), was studied by ElectroSpray Ionization-Mass Spectrometry (ESIMS). Since under physiological conditions redox processes are possible, the binding of the complexes in the oxidation state +IV and +V, [(VO)-O-IV(dhp)(2)], [(VO)-O-IV(ma)(2)], [(VO2)-O-V(dhp)(2)](-) and [(VO2)-O-V(ma)(2)](-), was examined. In all systems V-IV,V-V-L-Cyt adducts are observed, their formation depending on V oxidation state, ligand L and metal concentration. The larger stability of vanadium(IV) than vanadium(V) complexes favors the interaction of the moieties (VOL2)-O-IV and (VOL+)-O-IV with V-IV, while with V-V adducts with (VO2L)-O-V and (VO2+)-O-V fragments are observed. The analysis of the protein structure suggests that Glu4, Glu21, Asp50, Glu62, Glu66 and Glu104 are the most plausible candidates for monodentate coordination, while the couples (Asp2, Glu4), (Glu92, Asp93) and (His33, Glu104) for bidentate binding. The values of E-1/2 for [(VO)-O-IV(dhp)(2)] and [(VO)-O-IV(ma)(2)], measured by cyclic voltammetry (CV), 0.53 V and 0.60 V vs. standard hydrogen electrode, indicate that the oxidation of V-IV to V-V is possible. The presence of a protein can alter the redox behavior and stabilize one of the states, V-IV or V-V. Overall, the data reinforce the conclusion that, for V drugs, the biotransformation is fundamental to explain their biological action and the analysis should not be limited to the ligand exchange and hydrolysis but also include the redox processes, and that a mixture of V-IV and V(V )species, V-IV,V-V-L-Protein and VIV,V-Protein, could be responsible of the pharmacological effects.
Interaction of pharmacologically active pyrone and pyridinone vanadium(IV,V) complexes with cytochrome c / Ugone, Valeria; Pisanu, Federico; Garribba, Eugenio. - In: JOURNAL OF INORGANIC BIOCHEMISTRY. - ISSN 0162-0134. - 234:(2022), p. 111876. [10.1016/j.jinorgbio.2022.111876]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/297929
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