Banca de DEFESA: CINTHIA SANTOS SOARES

THEORETICAL APPROACH TO DISACCHARIDE- PHOSPHOLIPID MEMBRANE PROTOTYPE

Phospholipid membrane; Conformation of phospholipids; Disaccharide-membrane interaction.

The present thesis had as main objective to study the interactions between a disaccharide molecule and a phospholipid membrane prototype, formed by a dimer system composed of two phospholipid molecules. Such a study was carried out theoretically, using quantum methods for the modeling of molecular systems of interest: a method based on Density Functional Theory (B97-D/6-31G(d,p)) and a semi- empirical (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 disaccharides to the prototype and occurred through the calculation of the interaction energy when in the formation of the interacting systems (disaccharide-phospholipid membrane prototype). With 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. The Infrared absorption spectra for the membrane prototype phospholipid alone and for all interacting systems – four for the trehalose, three for maltose and two for cellobiose, in order to compare the behavior of the signal corresponding to the asymmetric stretching of the group phosphate for dry phospholipid aggregates and phospholipid aggregates in presence of different carbohydrates, indicated in the literature as differently affected by the presence of different carbohydrates. using an equation relating the value of the heteronuclear spin coupling constant with three 3 J C1,H1' bonds at the value of the dihedral angle defined by the sequence of C1–O–C1'–H1' atoms along the glycosidic bond of the trehalose, the respective values of 3 J C1,H1' were calculated for all four obtained interacting systems. From the Boltzmann population calculation for the interacting systems, an average value was obtained for the constant of coupling, which was compared to the experimental result available in literature. The energy values of disaccharide-prototype interaction of phospholipid membrane did not show agreement with the behavior of the signal corresponding to the asymmetric stretching of the phosphate group, this considering the lowest energy interacting systems, without zero point. This result was understood as a strong indication that interactions with trimethyl-ammonium groups also need to be considered in that assessment. The average value obtained for the coupling constant of heteronuclear spin, compared very well to the experimental value available in the literature, being an indication that the values of the glycosidic angles of the trehalose present in interacting systems theoretically obtained if to those assumed by the disaccharide in real interacting systems, in way that the PM6 method, used for modeling the systems interacting agents, can be pointed out as a computational method capable of adequately describe the stabilizing effects of the glycosidic bond of trehalose in this type of system.