Quantum/classical mechanical comparison of cation-pi interactions between tetramethylammonium and benzene

To consider whether existing molecular force fields can adequately reproduc e cation-pi interactions without adding special interaction terms, theoreti cal calculations with geometry optimization were performed on three configu rations of tetramethylammonium (TMA) interacting via one, two, or three N-m ethyl groups with a benzene ring, by use of density-functional theory (DFT) methods B3LYP/6-31G* and B3LYP/6-311G**; ab initio method MP2/6-31G*, and molecular mechanic methods EFF, Tinker's Amber and MM3. Only the first conf iguration was found to be stable from the DFT and MP2 results, and its geom etry was found to be highly flexible. ESP CHELPG charges estimated from the DFT and MP2 calculations were used to modify the atomic charges of the for ce fields employed in the molecular mechanics calculations to improve agree ment with the BSSE-corrected binding energies deduced from the DFT and MP2 results. After this modification, the molecular mechanics results were foun d to be in good agreement with those obtained by DFT and MP2, without a req uirement to add any additional terms to the force fields. This was confirme d by comparing the energy profiles of the complex as benzene was moved away from TMA in 0.2 Angstrom intervals, Hence it is possible to use existing f orce fields to represent cation-pi interactions by a simple adjustment of c ertain partial atomic charge parameters. In this context, we discuss the hi gh flexibility of the cation-pi interactions in the framework of molecular recognition in biological systems.