On the characterization of host-guest complexes: surface tension, calorimetry, and molecular dynamics of...

Three host-guest systems have been characterized using surface tension (sigma), calorimetry, and molecular dynamics simulations (MD). The hosts were three native cyclodextrins (CD) and the guest the non-ionic carbohydrate surfactant octyl-beta-d-glucopyranoside. It is shown that, for any host-guest system, a rough screening of the most probable complex stoichiometries can be obtained in a model free form, using only calorimetric data. The sigma data were analyzed using a model that includes a newly proposed adsorption isotherm. The equilibrium constants for several stoichiometries were simultaneously obtained through fitting the sigma data. For alpha- and beta-CD, the predominant species is 1:1 and to a lesser extent 2:1, disregarding the existence of the 1:2. For gamma-CD, the 1:2 species dominates, the other two being also present. In an attempt to confirm these results, 10 ns MD simulations for each CD were performed using seven different starting conformations. The MD stable conformations agree with the results found from the experimental data. In one case, the spontaneous dissociation-formation of a complex was observed. Analysis of the trajectories indicates that hydrophobic interactions are primarily responsible for the formation and stability of the inclusion complexes. For the 2:1 species, intermolecular H-bonds between CD molecules result in a tight packed structure where their original truncated cone shape is lost in favor of a cylindrical geometry. Together, the results clearly demonstrate that the often used assumption of considering only a 1:1 species is inappropriate.