Substituted naphthoxy-phthalonitrile derivatives: Synthesis, substituent effects, DFT, TD-DFT Calculations, antimicrobial properties and DNA interaction studies

Abstract

Herein, substituted-naphthol derivatives 4a-e were synthesized in two steps, namely the Diels Alder cycload-dition and Cu-catalyzed aromatization reactions, respectively. Then, pththalonitrile derivatives 7-12 have been prepared by a nucleophilic displacement reaction of 3-nitrophthalonitrile with the naphthol derivatives 4a-e, 5 and, obtained in excellent yields. Structural characterization of the compounds was identified by different spectroscopic techniques. Antimicrobial properties of the synthesized compounds were determined by the microdilution procedure against Gram-positive, Gram-negative bacteria, and yeast. Furthermore, the DNA interaction of the compounds were determined by gel electrophoresis. One of the most prominent findings is that compounds 9 and 10 have more inhibitory effects on Gram-positive bacteria than Gram-negative bacteria. These compounds especially exhibited the highest antibacterial potency against S. aureus (625 mu g/mL) among Gram-positive bacteria. According to the plasmid DNA interaction results, the synthesized compounds caused changes in the structure and mobility of the plasmid DNA. Then, geometry optimizations and frequency calcu-lations were conducted at B3LYP/6-311 G(d,p) level of DFT, and optimized structures were used for further analyses. The NBO results revealed that the rc -> rc * and n -> rc * interactions were greatly contributed to lowering the stabilization energy of all compounds (7-12). FMO energy analyses showed that compound 9 has the biggest electrodonating power.