Thermodynamics of the dimer formation of 2(I),3(I)-O-(o-xylylene)-per-O-Me-gamma-cyclodextrin: fluorescence, molecular mechanics and molecular dynamics.

The thermodynamics of the dimer formation of 2(I),3(I)-O-(o-xylylene)-per-O-Me-gamma-cyclodextrin (XmgammaCD) in aqueous solution was studied by fluorescence techniques, Molecular Mechanics and Molecular Dynamics. Lifetime averages <tau>, obtained from fluorescence decay profiles upon excitation of the xylylene appended group, were used as the property sensitive to the association process. The dimerization equilibrium constants (K(D)) were obtained from non-linear regression analysis of the plots of <tau> against [XmgammaCD] at several temperatures and they were compared with the values obtained for the counterparts Xmalpha- and XmbetaCDs. The van't Hoff plot allows us to obtain the DeltaH and DeltaS showing that the dimerization process was also entropically disfavoured. Molecular Mechanics as well as Molecular Dynamics calculations in the presence of water were also employed to study the conformational behaviour of isolated XmgammaCDs, the possible structure of the dimers formed and the driving forces involved in such association processes. Results indicate that those conformations where Xy moiety does not block the cavity entrance are favoured. Dimers are preferably formed by head-to-head CD approaching. However, the formation of stable head-to-tail is not dismissed.