THEORETICAL-STUDIES ON THE RELATIVE STABILITY OF NEUTRAL AND PROTONATED N,N'-DIARYLGUANIDINES IN AQUEOUS-SOLUTION USING CONTINUUM SOLVENT MODELS

The conformational properties in vacuo and in solution of neutral and protonated N,N'-diphenylguanidines have been studied making use of ab initio SCF and MP2 calculations in vacuo and continuum solvent free en ergy calculations in solution on the STO-3G and 4-31G optimized geomet ries obtained in vacuo. For the N,N'-diarylguanidine series with conde nsed rings (di-1-naphthyl, di-1-anthracenyl, and di-9-anthracenyl deri vatives) the calculations have been carried out on the relevant partia l charges located at the molecular mechanical geometries derived from the AMBER force field in MacroModel. The STO-3G solvation free energy is considerably less favorable than the 4-31G one for the diphenylguan idines, but only about 2 kcal/mol less favorable for the diphenylguani dinium rotamers, which an the whole show a better agreement between th e two basis sets. The STO-3G basis set predicts the syn-anti (SA) stru cture to be the most stable in solution for neutral diphenylguanidines , whereas the 4-31G basis set favors the AS rotamer. Extended basis se t calculations on N-phenylguanidine favor the anti structure as well. The MP2/4-3 1G//4-3 1G correlation corrections applied in solution pro duce a solvent effect lower than at the SCF level, and only the salvat ion free energies of AA and AA+ are reduced with respect to that of AS . The cavitation free energy is nearly independent of the basis set. T he salvation free energy obtained from the partial charge description of the diphenyl derivatives is analogous to that produced by the STO-3 G basis set for the neutral rotamers, while it is about 10 kcal/mol mo re favorable than the corresponding STO-3G values for the protonated c onformers. The free energy ab initio and electrostatic results are in fair qualitative agreement with those obtained with the GB/SA method. The stacking of the aromatic rings is followed by unfavorable electros tatic and favorable van der Waals interactions. The hydration of these rings is slightly favored by the GB/SA method in a nonstacked and rat her separated form.