Methods for determining the reliability of semiempirical electrostatic potentials and potential derived charges

The reliability of the ZDO semiempirical molecular electrostatic potential (i.e. the potential determined without deorthogonalization) was investigated with regard to its ability to reproduce the negative potential well above aromatic systems and to generate potential derived atomic charges. The negative well above benzene and 5-hydroxytryptophan derivatives has indeed been observed; this is an important observation as this well plays an important role in many recognition processes, such as the clustering of aromatic rings within enzymes. The well may also be observed in classical molecular electrostatic potentials calculated using atomic charges derived from the semiempirical molecular electrostatic potential. The potential derived charges were assessed using an energy-based criterion which involves a comparison of the electrostatic interaction energy between two small molecules. The electrostatic interaction energy was determined for both a full quantum mechanical system, using the Morokuma-Kitaura energy decomposition analysis and for a quantum-classical hybrid system, using a simplified decomposition procedure. The semiempirical potential derived charges were found to be of similar quality to the ab initio potential derived charges and superior to ab initio Mulliken charges.