Experimental and Theoretical Investigation of GS-441524 using Density Functional Theory, FTIR, Raman and UV-VIS Spectroscopy

GS-441524, a 1′ substituted C glycoside and an adenosine analogue, exhibits broad antiviral activity against RNA viruses. Previous research has primarily concentrated on its antiviral properties for humans and animals. Vibrational and electronic spectroscopy can enhance our understanding of its structure and function and serve as valuable tools in detection techniques and kinetic studies. In this paper, we employed IR and Raman spectroscopy to study its solid form, and UV-VIS spectroscopy to examine its aqueous solution. Density Functional Theory (DFT) calculations were utilized to analyze the spectra. Specifically, we evaluated the DFT functionals B3LYP, BP86, and CAM-B3LYP in conjunction with the basis sets 6-31G(d,p), 6-311G(d,p), and 6-311++G(d,p). The largest basis set, 6-311++G(d,p), performed significantly better than the smaller ones in reproducing the experimental results. The BP86 functional most accurately reproduced the vibrational spectra, while B3LYP best matched the electronic spectra. By increasing the basis set size, disregarding the Tamm-Dancoff approximation (TDA), and accounting for solvent effects using the polarizable continuum model, the wavelength, λmax, of the largest peak in the UV-VIS calculations, shifted (increased) by 2, 7.5, and 18 nm towards the experimental value, respectively. © (2024), (International Hellenic University - School of Science). All rights reserved.