Interrelation between electrostatic and lipophilicity potentials on molecular surfaces.
Molecular electrostatics and lipophilicity are two important properties included in quantitative structure-activity relationships (QSARs) employed 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 potential (MLP). Although a simultaneous, three-dimensional display of MEP and MLP is possible, it may not provide a practical tool for comparing molecules. In this work, we deal with the simpler two-dimensional maps of the entire molecular surface projected onto an MEP-MLP plane. We analyze how these maps change with the following factors: (1) composition and molecular geometry, (2) the quality of the computation of MEP, and (3) the parameter set used for evaluating the lipophilicity potential. The approach is used to compare series of pyrazole derivatives. The methodology is useful in assessing molecular similarity, as well as in establishing the nature of differences between compounds.
Rozas
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Department of Chemistry, Queen's University, Kingston, Ontario, Canada.
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Arteca
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D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D003626:Data Display; D015195:Drug Design; D004560:Electricity; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry; D013329:Structure-Activity Relationship
D011720:Pyrazoles