A Metastable Semiquinone Molecular Switch Modulated by Ascorbate/O2: A Study from a System Far‐From‐Equilibrium to Biological Assays in Mitochondria

Author:

Rodríguez‐Valdez Gabriela1,Martínez‐Cerda Marlen E.1,Mejía‐Reyes Jisell G.1,Tapia‐Juárez Melissa1,Olmos‐Orizaba Eridani1,Cortés‐Rojo Christian1ORCID,Cortés‐García Carlos J.1ORCID,Contreras‐Celedón Claudia A.1ORCID,Solorio‐Alvarado Cesar R.2ORCID,Chacón‐García Luis1ORCID

Affiliation:

1. Laboratorio de Diseño Molecular Instituto de Investigaciones Químico-Biológicas Universidad Michoacana de San Nicolás de Hidalgo Edificio B1, Ciudad Universitaria, Francisco J. Múgica S/N 58030 Morelia Mexico

2. División de Ciencias Naturales y Exactas Departamento de Química Universidad de Guanajuato Campus Guanajuato, Noria Alta S/N 36050 Guanajuato Mexico

Abstract

AbstractA molecular switch based on the metastable radical anion derived from a substituted heteroaryl quinone is described. Pyrrolyl quinone thiocyanate (PQ 9) showed an interaction with the fluoride anion that was visible to the naked eye and quantified by UV/vis and 1H and 13 C NMR. The metastable quinoid species formed by the interaction with F (“ON” state) showed a molecular switching effect autocontrolled by the presence of ascorbate (“OFF” state) and back to the “ON” state by an autooxidation process, measured by visible and UV/vis spectroscopy. Due to its out‐of‐equilibrium properties and the exchange of matter and energy, a dissipative structural behaviour is proposed. Considering its similarity to the mechanism of coenzyme Q in oxidative phosphophorylation, PQ 9 was evaluated on Saccharomyces cerevisiae mitochondrial function for inhibition of complexes II, III and IV, reactive oxygen species (ROS) production, catalase activity and lipid peroxidation. The results showed that PQ 9 inhibited complex III activity as well as the activity of all electron transport chain (ETC) complexes. In addition, PQ 9 reduced ROS production and catalase activity in yeast. The results suggest that PQ 9 may have potential applications as a new microbicidal compound by inducing ETC dysfunction.

Publisher

Wiley

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