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.

In the search for new antioxidants, flavan structures called our attention, as substructures of many important natural compounds, including catechins (flavan-3-ols), simple and dimeric proanthocyanidins, and condensed tannins. In this work the conformational space of the Z-isomers of (4α→6´´, 2α→O→1´´)-phenylflavans substituted with R = H, OH and OCH(3) was scanned in aqueous solution, simulating the solvent by the polarizable continuum model (PCM). Geometry optimizations were performed at B3LYP/6-31 G level. Electronic distributions were analyzed at a better calculation level, thus improving the basis set (6-311++G). A topological study based on Bader´s theory (atoms in molecules) and natural bond orbital (NBO) framework was performed. Furthermore, molecular electrostatic potential maps (MEPs) were obtained and thoroughly analyzed. The stereochemistry was discussed, and the effect of the solvent was addressed. Moreover, intrinsic properties were identified, focusing on factors that may be related to their antioxidant properties. Hyperconjugative and inductive effects were described. The coordinated NBO/AIM analysis allowed us to rationalize the changes of MEPs in a polar solvent. To investigate the molecular and structural properties of these compounds in biological media, the polarizabilities and dipolar moments were predicted which were further used to enlighten stability and reactivity properties. All conformers were taken into account. Relevant stereoelectronic aspects were described for understanding the stabilization and antioxidant function of these structures.

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A computational kinetics study of the antioxidant activity of tryptamine toward HO and HOO radicals in water at 298 K has been carried out. Density functional methods have been employed for the quantum chemical calculations, and the conventional transition state theory was used for rate constant evaluation. Different mechanisms have been considered: radical adduct formation (RAF), single electron transfer (SET), and hydrogen atom transfer (HAT). For the reaction of tryptamine with the hydroxyl radical, nearly all channels are diffusion-controlled, and the overall rate constant is very high, 6.29 × 10 M s. The RAF mechanism has a branching ratio of 55%, followed by the HAT mechanism (31%), whereas the SET mechanism accounts just for 13% of the products. The less hindered carbon atom neighboring to the nitrogen of the indole ring seems to be the preferred site for the RAF mechanism, with a branching ratio of 16%. The overall rate constant for the reaction of tryptamine with the HOO radical is 3.71 × 10 M s, suggesting that it could be a competitive process with other reactions of hydroperoxyl radicals in biological environments. For this reaction only the HAT mechanism seems viable. Furthermore, only two centers may contribute to the HAT mechanism, the nitrogen atom of the indole ring and a carbon atom of the aminoethyl chain, the former accounting for more than 91% of the total products. Our results suggest that tryptamine could have a noticeable scavenging activity toward radicals, and that this activity is mainly related to the nitrogen atom of the indole ring, thus showing the relevance of their behavior in the study of aminoindoles.

We report a study of the structure of (+)-catechin, which belongs to the family of the flavan-3-ols-one of the five most widely distributed phenolic groups. The biological activities and pharmaceutical utility of these compounds are related to antioxidant activity due to their ability to scavenge free radicals. A breakthrough in the study of the conformational space of this compound, so far absent in the literature, is presented herein. A detailed analysis of the electronic distribution, charge delocalization effects, and stereoelectronic effects is presented following application of the theory of atoms in molecules (AIM) and natural bond orbital analysis. The stability order, and the effects of electron delocalization in the structures were analyzed in depth. The molecular electrostatic potential (MEP) was also obtained, assessing changes in the electronic distribution in aqueous solution, the effects of the solvent on the intrinsic electronic properties, and molecular geometry. The effect of the aqueous solvent on MEP was also quantified, and rationalized by charge delocalization mechanisms, relating them to structural changes and topological properties of the electronic charge density. To further analyze the effects of the aqueous solvent, as well as investigating the molecular and structural properties of these compounds in a biological environment, the polarizabilities for all conformers characterized were also calculated. All results were interpreted on the basis of our accumulated knowledge on (4α→6", 2α→O→1")-phenylflavans in previous reports, thus enriching and deepening the analysis of both types of structure.