CONSISTENT VALENCE FORCE-FIELD PARAMETERIZATION OF BOND LENGTHS AND ANGLES WITH QUANTUM-CHEMICAL AB-INITIO METHODS APPLIED TO SOME HETEROCYCLIC DOPAMINE D-3-RECEPTOR AGONISTS

To secure a broad utilization of molecular mechanics in medicinal chem istry appropriate parameters (e.g., reference values and force constan ts) are required to describe correctly all possible atomic interaction s. For this purpose parameters for bond lengths and bond angles were d erived for some heterocyclic dopamine D-3-receptor agonists. Some new atom types were introduced and consistent valence force-field (CVFF) w as supplied with several bond-stretching and angle-bending force const ants as well as reference values. Representative fragments containing these missing parameters were minimized at the HF/6-31G level of theo ry using Gaussian-92. After frequency calculation, corresponding force constants were extracted from the Hessian matrix. The values were the n appropriately converted and scaled. Also, reference values were take n from quantum mechanically minimized structures, applying the same ba sis set. The transferability of the calculated force constants to CVFF was investigated using fragments with already known parameters. The q uality of the extended force field was checked in comparison with ''au tomatic parameters'' and ab initio-minimized structures. Finally, the evaluated procedure was applied successfully to related structures. (C ) 1998 John Wiley & Sons, Inc.