Contribuições da eletroquímica molecular para a química medicinal e para a análise de sondas fluorescentes

Abstract

Molecular electrochemistry is useful for characterizing redox reactions and deciphering reactional electron-transfer-associated mechanisms. Quinones represent a wide and diversified family of natural metabolites, along with synthetic ones. The interest in these substances has increased due to their contribution to vital biochemical processes and increasing prominence for their biological, pharmacological and technological activities. Despite several beneficial effects, quinones are also considered toxins. It is precisely this dual behavior (pro-oxidant versus antioxidant) that enlarge the interest of researchers, especially in medicinal chemistry. Fluorescent compounds are theoretically and technological attractive and have been widely used as sensors for in-vitro or in-vivo chemical analyses, as laser dyes, and for therapeutic applications. Their electrochemical properties, adjustable and structurally-dependent, are analytically, mechanistic and theoretically- relevant parameters, once the electron transfer processes (ET) drive the activation of these classes of compounds. Substitution at different positions affects the electronic environment around the BODIPY core, causing characteristic changes in oxidation and reduction potentials and other physicochemical properties. Both quinones and BODIPYS are promising bioactive molecules that may evolve as prototypes for drugs or probes. This work investigated the electrochemical behaviour, in electrochemical cells, of hybrid quinones and nitrosyl-BODIPYs, in an aprotic medium (ACN or DMF + TBAPF6 0.1 mol L-1 ) to obtain data on their redox mechanisms, electrogenerated intermediates, formation of reactive oxygen species, and interaction with biological macromolecules. The electrochemical techniques used were cyclic voltammetry and differential pulse voltammetry on vitreous carbon electrodes (d = 3 mm). The counter electrode was a platinum wire, and the reference electrode, Ag | AgCl, Cl− (saturated). We investigated fourteen acrylated quinones, and by the comparison among reduction/oxidation potentials and biological activities, it was noted that the most electrophilic (more positive reduction potentials) presented the highest trypanocidal activity (CI50/24 h, less than about 300 μM), except for one of them. An apparent correlation between the presence of an electron-withdrawing group, such as chlorine, with an easier reduction and a higher biological activity, appeared, together with an ideal range for the reduction potential. In the aprotic medium employed, all compounds, with first wave reduction potential values (Ep1c), around -0.5 V or more positive, were active. These compounds can be considered "highly oxidizing" in this biological context, with consequences on trypanocidal activity. Nitrosylated BODIPYs were investigated at α- (5-nitrosyl) and β- (6-nitrosyl). The location of the NO group on α or β strongly affects the electronic structures and redox behavior. Spectroelectrochemistry associated with computational studies (Conceptual Density analysis and Functional Theory (CDFT)) corroborate the voltammetric results and explains the unexpected reactivity differences. The nitrosyl group is the first to be reduced in 5-nitrosylBODIPY, while in the β-isomer, the nitrosyl group strongly facilitates the reduction of the BODIPY moiety. The results unveil that the understanding of the electrochemical mechanisms and the measurement of thermodynamic and kinetic parameters are useful as mimics of the invivo processes. This is a solid point for the planning and development of redox-based biologically active compounds.