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

Abstract

Procyanidins are highly hydroxylated polymers

known as antioxidant compounds, thereby exhibiting benefi- cial 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 electron- ic 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 mo- lecular electrostatic potential was rationalized by charge delo- calization mechanisms and interatomic intramolecular interac- tions, relating them to the structural changes and topological

properties of the electron charge density. Molecular polariz- ability 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 coopera- tively as “delocalization routes”, showing interactions be- tween 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.