Prediction of binding constants of alpha-cyclodextrin complexes.

Proceeding from a phenomenological theory of pairwise interactions (solvent-solvent, solvent-solute, and solute-solute), the binding constant K11 (in M-1) for 1:1 complex formation by alpha-cyclodextrin at a substrate binding site, at 25 degrees C in water, is given by log K11 = -1.74 - [Z] + 0.032(-delta A), where [Z] incorporates solvent-solute (solvation) and solute-solute interactions and delta A is the decrease in nonpolar surface area (in A2 molecule-1) on the substrate that is exposed to solvent when the binding site enters the cyclodextrin cavity. delta A is estimated from the structure of the binding site. Three levels of approximation are described for estimating [Z]. At the third (highest) level, the procedure when applied to 569 complex systems generated predicted values of log K11 that agreed within 0.30 unit of the experimental values in 58% of cases, and that agreed within 1.00 unit in 95% of cases.