Abordagem teórica das interações dissacarídeo-protótipo de membrana fosfolipídica

Abstract

The main objective of this thesis was to study the interactions between a disaccharide molecule and a phospholipid membrane prototype, formed by a dimeric system composed of two phospholipid molecules. This study was carried out theoretically, using quantum methods to model the molecular systems of interest: a method based on the Density Functional Theory (B97-D/6-31G(d,p)) and a semi- empirical method (PM6). The disaccharides considered were trehalose, maltose and cellobiose. The phospholipid considered was dioctanoyl-phosphatidylcholine. The study of such interactions involved the construction of the phospholipid membrane prototype and the creation of a protocol for the approximation of the disaccharides to the prototype. Based on geometric criteria, two types of interactions were identified between all disaccharides and the phospholipid membrane prototype: interactions with phosphate groups and with trimethyl-ammonium groups. Infrared absorption spectra were obtained for the isolated phospholipid membrane prototype and for all interacting systems - four for trehalose, three for maltose and two for cellobiose, in order to compare the behavior of the signal corresponding to the asymmetric stretching of the phosphate group for dry phospholipid aggregates and phospholipid aggregates in the presence of different carbohydrates, indicated in the literature as differently affected by the presence of different carbohydrates. Using an equation that relates the value of the heteronuclear spin coupling constant 3JC1,H1' to the value of the dihedral angle defined by the sequence of atoms C1–O–C1'–H1', along the glycosidic bond of trehalose, the respective values of 3JC1,H1' were calculated for all four interacting systems obtained. From the calculation of the Boltzmann population for the interacting systems, an average value for the coupling constant was obtained, which was compared to the experimental result available in the literature. The values of disaccharide-prototype phospholipid membrane interaction energy did not show agreement with the behavior of the signal corresponding to the asymmetric stretching of the phosphate group, considering the lowest energy interacting systems, without zero point correction. This result was understood as a strong indication that interactions with trimethyl-ammonium groups also need to be considered in this evaluation. The average value obtained for the heteronuclear spin coupling constant, compared very well to the experimental value available in the literature, being an indication that the values of the glycosidic angles of trehalose present in the interacting systems theoretically obtained are compared to those assumed by the disaccharide in real interacting systems, so that the PM6 method, used to model the interacting systems, can be pointed out as a computational method capable of adequately describing the stabilizing effects of the trehalose glycosidic bond in this type of system.