Theoretical study of Z isomers of A-type dimeric proanthocyanidins substituted with R=H, OH and OCH3: stability and reactivity properties

Abstract

The stereochemistry of A-type dimeric proanthocyanidins was studied, focusing on the factors that determine it, and the changes that occur with R = OCH₃, R' = H, and R = OH, R' = H as substituents, starting with the study of the conformational space of each species. Using molecular dynamics at a semiempirical level, and complementing with functional density calculations, two conformers of lowest energy were characterized for R = H, eight conformers for R = OH, and three conformers for R = OCH₃. Electronic distributions were analyzed at a higher calculation level, thus improving the basis set. Intramolecular interactions were examined and characterized by the theory of atoms in molecules (AIM). Detailed natural bond orbitals (NBO) analysis allowed the description of subtle stereoelectronic aspects of fundamental importance for understanding the stabilization and antioxidant function of these structures. The study was enriched by a deep analysis of maps of molecular electrostatic potential (MEP). The coordinated analysis of MEP, together with the NBO and AIM results, allowed us to rationalize novel distribution aspects of the potential created in the space around a molecule.

Structural and electronic properties of Z isomers of (4α→6´´,2α→O→1´´)-phenylflavans substituted with R = H, OH and OCH3 calculated in aqueous solution with PCM solvation model

“…The average values of the H-O-3´´-C-3´´-C-4´´and H-O-5´´-C-5´´-C-4´´di-hedral angles were about 180°(anti) or near 0°(syn). The characteristics of the conformers obtained in aqueous phase were similar to those obtained in gas phase [10]. The Z1 rotamers were the most stable in aqueous phase as in gas phase, showing the following stability order, CT>CC>TC> TT ( Table 1).…”

“…The lowest-energy conformers were further optimized in gas phase [9,10] by the density functional theory (DFT), as implemented by the Gaussian 03 package [12]. Geometry optimizations were performed using the Becke three-parameter hybrid functional combined with Lee-Yang-Parr correlation functional [13], giving rise to the well-known B3LYP method.…”

“…As in gas phase [10], the average value of bond ellipticity (ε) in each ring increased in the order of B<A<D. In terms of the orbital model of electronic structure, the ellipticity is a measure of the extend of π-character up to the limit of a "double bond" for which ε reaches a maximum [22]. Therefore our results can be rationalized through an enhanced ability of ring D to act on electrophilic aromatic substitution reactions due to the increased availability of π-electrons also in aqueous phase.…”

“…To our knowledge there are no crystallographic reported data of the A-type proanthocyanidins, and there has been no previous study on A-type proanthocyanidins using high-level ab initio calculations, except for a few theoretical studies on their electronic, structural, and energetic properties, which we have earlier reported, where the conformational space of unsubstituted and substituted 4-phenylflavans was scanned in gas phase [9,10]. In addition, intramolecular bonding interactions were thoroughly described and related to their stability and reactivity.…”

“…In addition, intramolecular bonding interactions were thoroughly described and related to their stability and reactivity. The stereochemistry of the molecules and the analysis of the effect of substitution on the behavior of the electron distribution were also studied in our laboratories [10].…”