Electrostatic interactions in molecular mechanics (MM2) calculations via PEOE partial charges I. Haloalkanes

The PEOE (partial equalization of orbital electronegativity) procedure has been modified slightly and reparametrized for haloalkanes to calculate partial atomic charges suitable for evaluation of dipole moments and electrostatic energies in conjunction with molecular mechanics (MM2) calculations. Dipole moments of 66 haloalkanes are calculated with an average absolute deviation of 0.14 D from experimental values. The conformational energies of 40 compounds have been calculated and the agreement with experimental data is generally good and compares well with calculations by the IDME (induced dipole moment and energy) method. In addition, carbon and proton charges correlate well with C-1s core binding energies and ¹H-NMR (nuclear magnetic resonance) shifts for halomethanes. The most striking benefit of treating electrostatics through a set of partial charges compared to the standard MM2 bond dipole approach is demonstrated by calculations on 1,4-disubstituted cyclohexanes, for which standard MM2 fails to predict the most stable conformation.