UREA - POTENTIAL FUNCTIONS, LOG-P, AND FREE-ENERGY OF HYDRATION

Intermolecular potential functions have been developed for urea. Ab in itio 6-31G(d) calculations were performed on urea-water complexes to o btain interaction energies and hydrogen-bond lengths that were used in developing the partial charges for the OPLS model. An important test was made by computing through Monte Carlo simulations the difference i n chloroform/water partition coefficients for urea and acetamide, Delt a log P. The accord between the computed result from statistical pertu rbation theory for TIP4P water and OPLS chloroform (2.0 +/- 0.1) and t he experimental value (1.9) is excellent. The computed absolute free e nergy of hydration of acetamide (-9.5 +/- 0.4 kcal/mol) also matches t he experimental data at 25 degrees C (-9.68 kcal/mol). These facts pro vide confidence in the computed value of 13.6 +/- 0.4 kcal/mol for the absolute free energy of hydration of urea, an experimentally unavaila ble result. The water structure around urea and acetamide was also cha racterized; the average numbers of solute-water hydrogen bonds are 5 f or urea and 3-4 for acetamide.