Vibrational frequency Analysis, DFT and in Vitro Fungicidal Activity Studies of Biphenyl-4-Carboxylic Acid, 2,4-Difluorobiphenyl and 4-Acetylbiphenyl- A Comparative Study

Abstract

Comparative spectroscopic investigation of Biphenyl-4-carboxylic acid (BCA), 4-Acetylbiphenyl (ACB) and 2,4-difluorobiphenyl (DFB) are obtained by using Density Functional Theory (DFT) with B3LYP functional at 6-311++G(d, p) basis set. The vibrational assignments have been proposed with aid of the results of Normal Coordinate Analysis (NCA). The effects of carboxyl, acetyl and fluoro substituents on the vibrational frequencies of biphenyl have been investigated and compared. The molecular stability and bond strength was investigated by applying the Natural Bond Orbital (NBO) analysis. The other molecular properties like Mulliken charge analysis, HOMO-LUMO analysis and Molecular Electrostatic Potential (MESP) of the title compounds have been reported. In vitro analysis have been performed with two fungal pathogens Aspergillus niger and Candida albicans using well diffusion method. BCA compound exhibited excellent activity against the Aspergillus niger with zone of inhibition values in the range of 22 and 25 mm in 40 and 80 µl with 10 mg/ml. Molecular docking studies of the most active compound are carried out, and results showed reasonable binding modes in the fungicide active site of phytase protein Fophys and Succinate dehydrogenase (SDH) proteins. A preliminary Structure-Activity Relationship study of the biphenyl derivatives has led to the recognition of some important structural requirements for antifungal activity. Furthermore the fungicide-likeness analysis of BCA, DFB and ACB compounds have been developed to predict its fungicide activity by using fungiPAD webtool.