Structure and electronic properties of (+)-catechin: aqueous solvent effects

Abstract

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.

Exploratory conformational study of (+)-catechin. Modeling of the polarizability and electric dipole moment

“…The angles between the bonds that define rings C and E, and their respective lengths were quite similar for both conformers; although the C3-C2-C1′ angle differed approximately 4.0°between conformers, Z2 was considered as rotamer of Z1 [20][21][22]. It is worth mentioning that in gas phase similar results were obtained in our previous report on CTQ, as Z1-and Z2-type rotamers were also defined [15], which is found again in this extended study of the conformational space. Taking into account in this work the 107 structures, the average value for τ: C3-C2-C1′-C-6′ dihedral angle is 87.45°or −89.26°, and 176.23°or −7.00°for Z1-and Z2-type rotamers, respectively.…”

“…Relative weights so calculated do not differ appreciably from those obtained by considering the entire conformational space (107 conformers), being the reason of proposing this subspace as descriptive enough. On the other hand, the energy difference between the structures belonging to the a and b groups with *Conformers studied in a previous work [15] respect to those of c-type, and the tiny population of the latter, indicate the stabilizing influence of the intramolecular hydrogen bonding (HB) in the catechol ring, as previously shown [15].…”

“…In the present report the same notation is used as that defined in our previous work [15]. The possible arrangements of the OH groups of the catechol ring lead to the classification of the conformers into three groups, which are indicated with the a, b, c subscripts.…”

“…However, except for a breakthrough in this regard recently reported [15], in the literature there is neither an exploratory study of the conformational space of this compound nor advances in the analysis of how this account can affect the theoretical prediction of the value of different properties of the electronic distribution of the compound, which is a central aim of the present work.…”

“…In addition, we present the calculation of polarizabilities and electric dipole moments taking into account the whole conformational space described, analyzing the importance of considering it in the modeling of these properties, and also proposing to define a descriptive subspace of only 16 conformers. Results are interpreted in terms of the accumulated knowledge on (4α → 6″, 2α → O → 1″)-phenylflavans [20][21][22][23] and (+)-catechin in previous work [15], enriching the analysis of both types of structures.…”