Estudo químico quântico do efeito da complexação na solubilidade do complexo de inclusão benznidazol-ciclodextrina

Abstract

In general, the computational chemistry can contribute significantly to the understanding of the effect of the solubility produced in the inclusion complexes between the drugs and the Cyclodextrins, as well as for the determination of physicochemical properties and properties of Cyclodextrins and their inclusion complexes. A theoretical analysis of the host-guest inclusion process involving the Benznidazole into the (α, β, γ-Cyclodextrin) was performed. Structure and stabilization energies were calculated, in both gas and aqueous phases, using Density Functional Theory level of theory, and semiempirical. The base set used in the ONION was 6-31G*. As results, a qualitative structure-property relationship could be established with structural features being relevant for inclusion complex stabilization: the hydrogen bonds established between guest and host molecules and the dispersion effect in the formation of the complexes in solvents. The ONIOM methodology used had aimed at evaluating the performance of the Benznidazole (BZN) geometries and energies at the level of the DFT (high level of theory) with Cyclodextrins (To lower levels of theory). Besides, analysis of theoretical IV, NBO, NMR and UV-vis proved to be effective procedures to correctly predict the mode of inclusion of the guest molecule (BZN) in the host (CD), using the appropriate density functional. In addition to an analysis made in Preadmet, without qualifying to use the term acronym ADME which means an expression used in the pharmacology for - absorption, distribution, metabolism and excretion and describes an arrangement of an essential organism. Analysis in NBO, natural bond orbital, requested for the theoretical calculation the assays of the calculated orbitals for maximum electron density and energy calculations in order to quantify the donor-receiver interactions between the host molecules (Cyclodextrins) and invited (BNZ) molecules. Using the aqueous process the influence of solvent in (PCM) on the stability of the BZN: CD complex increased in the order BZN: γ-CD > BZN: β-CD >BZN: α-CD when examined Gibbs free energy.