Resonance structure contributions, flexibility, and frontier molecular orbitals (HOMO-LUMO) of pelargonidin, cyanidin, and delphinidin throughout the conformational space: application to antioxidant and antimutagenic activities.

This research refers to the study and understanding of the conformational space of the positive-charged anthocyanidin structures in relation with the known chemical reactivities and bioactivities of these compounds. Therefore, the planar (P) and nonplanar (Z) conformers of the three hydroxylated anthocyanidins pelargonidin, cyanidin, and delphinidin were analyzed throughout the conformational space at the B3LYP/6-311 ++ G** level of theory. The outcome displayed eleven new conformers for pelargonidin, fifty-four for cyanidin, and thirty-one for delphinidin. Positive-charged quinoidal structures showed a significant statistical weight in the conformational space, thus coexisting simultaneously with other resonance structures, such that under certain reaction conditions, the anthocyanidins behave as positive-charged quinoidal structures instead of oxonium salts. The calculations of the permanent dipole moment and the polarizability showed relationships with the quantity and arrangement of hydroxyls in the structure. In addition, theoretical calculations were used to analyze the frontier molecular orbitals (HOMO-LUMO) of the three anthocyanidins. The novel conception of this work lies in the fact that dipole moment, polarizability, and HOMO-LUMO values were related to the reactivity/bioactivity of these three anthocyanidins. HOMO-LUMO energy gaps were useful to explain the antioxidant activity, while the percent atom contributions to HOMO were appropriate to demonstrate the antimutagenic activity as enzyme inhibitors, as well as the steric and electrostatic requirements to form the pharmacophore. Delphinidin was the strongest antioxidant anthocyanidin, and pelargonidin the best anthocyanidin with antimutagenic activity.

Z-Isomers of (4α→6″, 2α→O→1″)-phenylflavan substituted with R'=R=OH. Conformational properties, electronic structure and aqueous solvent effects.

Procyanidins are highly hydroxylated polymers known as antioxidant compounds, thereby exhibiting beneficial effects. These compounds are protective agents against oxidative stress and the damage induced by free radicals in membranes and nucleic acids. This paper describes a study of the conformational space of (4α→6″, 2α→O→1″)-phenylflavan substituted with R'=R=OH as part of a larger study of similar structures with different substitutions. The relationships between aqueous solution-vacuum variations of some properties were studied, as well as the stabilization and reactivity of (4α→6″, 2α→O→1″)-phenylflavan substituted with R'=R=H, R'=H, R=OH, R'=R=OH, and (+)-catechin. The variations in geometric parameters and electronic properties due to conformational changes, as well as the effects of substituents and polar solvents, were evaluated and analyzed. Bader's theory of atoms in molecules was applied to characterize intramolecular interactions, along with a natural bond orbital analysis for each conformer described. The molecular electrostatic potential was rationalized by charge delocalization mechanisms and interatomic intramolecular interactions, relating them to the structural changes and topological properties of the electron charge density. Molecular polarizability and permanent electric dipole moment values were estimated. The results show the importance of a knowledge of the conformational space, and values for each conformer. Based on our previous results, we showed the existence of electron charge delocalization mechanisms acting cooperatively as "delocalization routes", showing interactions between different rings not even sharing the same plane. These "delocalization routes" were more effective for (4α→6″, 2α→O→1″)-phenylflavan substituted with R'=R=OH than for (+)-catechin, and are proposed as adding insight into the structure-antioxidant activity relationship of flavans.