A nonlinear group contribution method for predicting the free energies of inclusion complexation of organic molecules with alpha- and beta-cyclodextrins.

A group-contribution method was developed for calculating the binding constants or the free energies of complexation between native alpha- or beta-cyclodextrin (CD) and organic guest molecules. The nonlinear models for binary (1:1 stoichiometry) complexes of alpha- and beta-CDs were derived with squared correlation coefficients (r(2)) of 0.868 and 0.917 based on a database consisting of 102 and 218 diverse guest molecules, respectively. The parameters used in the models are first-order molecular connectivity index as a measure of molecular bulk and atom/group counts in the guest molecules. The models allow accurate estimations for the wide range of guests containing C, H, N, O, S, and/or all halogens by summing the contribution values of each defined group present in the chemical structure of the guest along with guest's molecular size factors (linear and square terms) and then the summation to a constant coefficient value. The predictive performance of the models was tested by extra set of 27 compounds which were not included in the original data set. The predicted values by the models are in good agreement with the experimentally determined data.