BENZENE DIMER - A GOOD MODEL FOR PI-PI INTERACTIONS IN PROTEINS - A COMPARISON BETWEEN THE BENZENE AND THE TOLUENE DIMERS IN THE CAS PHASE AND IN AN AQUEOUS-SOLUTION

We have investigated the relative orientational preference of two benz ene and two toluene molecules in a vacuum and in water, by means of fr ee energy calculations. The gas-phase simulations reveal that, whereas the T-shaped benzene dimer is 0.78 kcal/mol lower in free energy than its stacked homologue, the sandwich arrangement of the toluene dimer is preferred over the T-shaped structure by 0.18 kcal/mol. MP2/TZP ab initio binding energies, evaluated for both dimers, were found to be c onsistent with the molecular mechanical estimates, hence suggesting th at the van der Waals and the electrostatic contributions to the macrom olecular force field employed herein are well balanced. We further not e that our results agree quite nicely with the experimental binding en ergies of Neusser and Krause, obtained from breakdown measurements. Th e tendency witnessed in the gas phase is magnified in an aqueous solut ion, with differences in free energy between the T-shaped and the sand wich arrangements of the benzene and the toluene dimers equal to -1.47 and 1.12 kcal/mol, respectively. The calculated association constants and osmotic second virial coefficients also correlate reasonably well with the experimental data of Tucker and Christian. The conflict betw een the orientational preferences of the benzene and the toluene dimer s is suggestive that trends in ''pi-pi'' interactions in proteins shou ld be rationalized by other factors than simple electrostatic/dispersi on considerations. The analysis of Phe-Phe pairs in protein crystallog raphic structures sheds light on the influence of both sterical hindra nces and ancillary interactions between the aromatic moities and neigh boring functional groups on the orientational preference of the phenyl rings.