"Análise conformacional de dimeros de ciclodextrinas: importantes reatores moleculares"

Abstract

Cyclodextrins are important cyclic oligosaccharides obtained from enzymatic degradation of starch, constituted by basic units of a-D-glucopyranose. The cyclodextrins have been used largely as molecular reactors acting through several ways in the kinetic and thermodynamic control of chemical processes. Calculations at semi-empirical (PM3), Hartree-Fock (HF/6-3 I G(d)) and DFT (B3LYP/6-31G(d)) involving a β-cyclodextrin dimer (β-CD2ur) linked by a urea group ((N,N'-Bis(6A-deoxi-β-cyclodextrin-6A-il)urea), was carried out aiming to identify the most favorable conformations. Three conformations were obtained, named Cl, C2 and C3, with energies showing, at the three levels of theory, the conformational stability increasing from C3 to Cl. In the next step, the inclusion of reactive species, leading to indigo and indirubin formation inside de cavity of the two most stable dimers, C1 and C2, was studied by means of semi-empirical (PM3) and hybrid method ONIOM (HF/6-31G(d,p):PM3). The results indicate that for reactants, the inclusion toward the wider cavity is most favorable for dimers C 1 and C2. The inclusion complex of the intermediate was found to be more stable in the form C2, supporting the experimental purpose. The indirubin product is more stabilized when inside the cavity of Cl dimer. The results show that exist a good agreement with experimental evidences reported in the literature about the indirubin formation inside the cavity and the decreasing in the formation of indigo, evidencing molecular aspects of the cyclodextrin templating effect. Solvation studies also were carried out to these dimers and to the basic unit in the composition of the cyclodextrin cone, the a-D-glucopyranose. The results were in good agreement with the available data for β-cyclodextrin, with the presence of seven water molecules inside each cavity. The solute-solvent hydrogen bonds were also analyzed and the results found in good agreement with those reported for a-cyclodextrin and β-cyclodextrin