I. Rozas et al., INTERRELATION BETWEEN ELECTROSTATIC AND LIPOPHILICITY POTENTIALS ON MOLECULAR-SURFACES, Journal of molecular graphics, 13(2), 1995, pp. 98-108
Molecular electrostatics and lipophilicity are two important propertie
s included in quantitative structure-activity relationships (QSARs) em
ployed for rational drug design. The molecular electrostatic potential
(MEP) provides information on the position, distribution, and extent
of electrophilic and nucleophilic regions around a molecule. Similarly
, the solvent affinity can be represented by a local phenomenological
potential of semiempirical nature: the molecular lipophilicity potenti
al (MLP). Although a simultaneous, three-dimensional display of MEP an
d MLP is possible, it may not provide a practical tool for comparing m
olecules. In this work, we deal with the simpler two-dimensional maps
of the entire molecular surface projected onto an MEP-MLP plane. We an
alyze how these maps change with the following factors: (1) compositio
n and molecular geometry, (2) the quality of the computation of MEP, a
nd (3) the parameter set used for evaluating the lipophilicity potenti
al. The approach is used to compare series of pyrazole derivatives. Th
e methodology is useful in assessing molecular similarity, as well as
in establishing the nature of differences between compounds.