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Electrostatic Potential as a Descriptor of Anti-Bacterial Activities of Some Anacardic Acid Derivatives: A Study Using Density Functional Theory

Structures and minimum molecular electrostatic potential (MEP) distributions in anacardic acid and some of its derivatives have been studied by full geometry optimization at the M06-2X/6-31G(d,p), WB97XD/6-31G(d,p) and B3LYP/6-31G(d,p) levels of density functional theory (DFT) in gas phase as well as in DMSO and aqueous solutions. Solvent effect was treated employing the integral equation formalism of the polarizable continuum model. Effects of modifications of the C1-side chain on the minimum MEP values in various regions were studied. Minimum MEP values near the oxygen atoms of the C2-OH group, oxygen or sulfur atoms of the C1-attached urea or thiourea groups and above or below the ring plane considered to be involved in interaction with the receptor were used to perform multiple linear regression. Experimentally observed anti-bacterial activities of these molecules against S. aureus are thus shown to be related to minimum MEP values in the above mentioned regions. Among the three DFT functionals used in the study, the M06-2X functional is found to yield most reliable results. Anti-bacterial activities have been predicted for certain molecules of the class which need to be verified experimentally.