PREDICTION OF BINDING CONSTANTS OF ALPHA-CYCLODEXTRIN COMPLEXES

Proceeding from a phenomenological theory of pairwise interactions (so lvent-solvent, solvent-solute, and solute-solute), the binding constan t K-11 (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 K-1 1 = -1.74 - [Z] + 0.032(-Delta A), where [Z] incorporates solvent-solu te (solvation) and solute-solute interactions and Delta A is the decre ase in nonpolar surface area (in Angstrom(2) molecule(-1)) on the subs trate that is exposed to solvent when the binding site enters the cycl odextrin cavity. Delta A is estimated from the structure of the bindin g site. Three levels of approximation are described for estimating [Z] . At the third (highest) level, the procedure when applied to 569 comp lex systems generated predicted values of log K-11 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.