Solvent impact on the photochemical properties of anticancer drug PLX4720; a computational study

The advancement in pharmaceutical research has led to a successful era but limitations because of the drug's photochemical behavior triggered the researchers to explore the promising revolution. In terms of molecular properties rationalizing, the photosensitive drug photochemical response is essential for knowing the associated potential phototoxicity. It is the need of the hour to check the influence of the molecular microenvironment on photochemical and the physicochemical properties of the PLX4720 B-RAFV600E inhibitor. The geometry optimization was done with functional wB97XD. TD-DFT calculation has been performed to study the PLX4720 absorption spectra in different solvents and hydrogen bonding. The polarity-dependent spectral properties are indicative of the microenvironments that influenced the structural properties of PLX4720. In polar solvents, a notable enhancement is observed in the oscillation strength of HOMO -> LUMO, the main electronic transition affects the photochemical properties of PLX4720. The charge delocalization is enhanced by these effects on the heteroatoms that comprise electron lone pairs. The inter-molecular hydrogen bonding among PLX4720 and the microenvironment study is also carried out. As a result, a substantial effect on the spectral properties of PLX4720 is reported. The physiochemical properties of PLX4720 complex are investigated using DMSO through hydrogen bonding interaction, NBO and DOS analyses. These results have exposed considerable changes in the structural properties of the PLX4720 which is an indication of the impact of intermolecular hydrogen bonding on photochemical properties. The results also reveal a notable charge density change in the selected atoms, leading to greater electronic transitions. The final results provided here give an insight into understanding about PLX4720 photochemical behavior at the molecular level in biologically mimicked microenvironments.

Automated summary

The advancement in pharmaceutical research has led to a successful era, but limitations due to the photochemical behavior of drugs have triggered researchers to explore a promising revolution in order to understand the potential phototoxicity. This study used different tools and methods to investigate the absorption spectra and photochemical properties of the PLX4720 inhibitor, focusing on the molecular microenvironment and interactions, and obtained significant results.