Análise conformacional e estudo de interações intramoleculares em derivados do flavonol

Abstract

Flavonols are part of a particular group of secondary metabolites, the phenolic compounds. They appear along the whole plant as a complex mixture of different components and have been widely studied due to their potential benefits for the human health. The study of the intramolecular interactions and preferable conformations in flavonol derivatives is an important task to better understand their biological activities. The present work reports the study of these interactions, and is divided into two parts: the conformational analysis of 2'-haloflavonols and the study about the behavior of the 1JF,H(O) coupling constant as a function of the OH∙∙∙F intramolecular hydrogen bond. The conformational isomerism of 2'-haloflavonols is dependent on the rotation about the α (H-O-C-C(=O)) and β (C(X)-C-C-C(OH) torsional angles, and the conformer stabilities are dependent on the intramolecular interactions involved. In addition to hydrogen bond, other intramolecular non-bonding interactions are operating, such as the attractive X∙∙∙O interaction. These interactions involving halogens (X) as electron acceptors are less common than those involving oxygen and nitrogen. Conformational analysis of 2'-haloflavonols as prototype compounds was carried out using theoretical calculations, by using DFT methods together with NBO and QTAIM analyses. The C=O∙∙∙H-O intramolecular hydrogen bond was found to be the determining factor ruling the conformational isomerism of 2'-haloflavonols, but C-X∙∙∙O-C non-bonding interactions and secondary hydrogen bonds are also operating. The 1JF,H(O) coupling constant for 2'-fluoroflavonol describes the F∙∙∙H-O hydrogen bond very well. Therefore, this interaction was assumed to be the main transmission pathway for such a coupling, suggesting the use of 1JF,H(O) to study interactions like this for biomolecules similar to 2'-fluoroflavonol