MOLECULAR RECOGNITION IN NONAQUEOUS SOLVENTS .2. STRUCTURAL AND THERMODYNAMIC ANALYSIS OF CATIONIC SELECTIVITY OF 18-CROWN-6 IN METHANOL

Molecular dynamic simulations are used to predict the binding affinity in host-guest systems by the thermodynamic cycle-perturbation method. The relative free energy of solvation of Na+ and K+ in methanol (19.8 and 19.1 kcal mol-1) and the relative free energy of binding of Na+ and K+ to 18-crown-6 in methanol (-3.8 and-3.0 kcal mol-1) are calculated by thermodynamic integration and thermodynamic perturbation, respectively. These results are in reasonable agreement with the experimental values, 17.3 and-2.47 kcal mol-1, respectively. In addition, the contributions to the relative free energy from the internal energy and entropy are calculated. Finally, a detailed analysis is made of the structure and its fluctuations in this system to provide additional insight to the selectivity of binding. © 1990, American Chemical Society. All rights reserved.