CHEMICAL CHAMELEONS - HYDROGEN-BONDING WITH IMIDES AND LACTAMS IN CHLOROFORM

Monte Carlo statistical mechanics simulations have been used to elucidate the origin of the novel variations in complex formation observed for imides and lactams. The OPLS potential functions were employed in conjunction with statistical perturbation theory to calculate relative association constants for the dimerization of succinimide and butyrolactam as well as for their cross complex in chloroform. The solution environment significantly dampens the gas-phase preference for the hydrogen bonding with butyrolactam. Consistent with recent experimental results for related intramolecular associations, the symmetry-corrected K(a) ratios for lactam-lactam over imide-lactam and imide-lactam over imide-imide are both computed to be about 3, while the differences in optimal gas-phase interactions are nearly 2 kcal/mol. However, the remarkable observations of stronger association of imides rather than lactams with adenines also emerges from similar simulations for complexes of succinimide and butyrolactam with 9-methyladenine. The symmetry-corrected K(a) ratios favoring the imide are now ca. 2 and 6 for the Watson-Crick and Hoogsteen orientations. The origin of these variations is shown to arise in a straightforward way from secondary electrostatic interactions.