FUNCTIONAL CORRELATION OF MOLECULAR ELECTRONIC-PROPERTIES WITH POTENCY OF SYNTHETIC CARBINOLAMINE ANTIMALARIAL AGENTS

Specific calculated molecular electronic properties of structurally di verse synthetic aromatic carbinolamines containing phenanthrene, quino line, and N-substituted biphenyl rings are associated with antimalaria l potency allowing use of these electronic features in the prediction of antimalarial efficacy, thus aiding the design of new antimalarial a gents. These electronic features include the magnitude and location of 3-dimensional molecular electrostatic potentials, lowest unoccupied m olecular orbitals, and highest occupied molecular orbitals. Stereoelec tronic properties were calculated using quantum chemical AM1 methods o n the optimized geometry of the lowest energy or most populated confor mer in both gaseous and aqueous environments. In the phenanthrene carb inolamines, the aliphatic nitrogen atom and the hydroxyl proton are in trinsically more nucleophilic and less electrophilic, respectively, th an in the nonphenanthrene compounds. Hydrogen bonding ability and the electrophilic nature of the aromatic ring appear to be two important f eatures responsible for interaction with receptor molecules. Published by Elsevier Science Ltd.