Pharmacokinetics and molecular-level insights into 5-Methyl-3-(trifluoromethyl)-1H-pyrazole for anticancer action: Spectroscopic profiling, solvent interactions, topological analysis and ADME–QSAR predictions

Abstract

This study investigated the structural and spectroscopic characteristics of 5-methyl-3-(trifluoromethyl)-1H-pyrazole through PXRD/Rietveld refinement and DFT methods. A PES scan revealed two conformers, with Conformer I exhibiting the lowest energy at −602.619 Hartree (a.u.). Structural and topological analyses, including AIM, LOL, ELF, and RDG, were conducted, extended to dimeric and trimeric forms to elucidate intermolecular interactions. Vibrational analysis (FT-IR and FT-Raman) was performed to identify functional groups and bonding features, while ¹H/¹³C NMR studies were conducted to analyse chemical shift variations associated with the dimeric and trimeric forms. Solvent effect on reactivity was assessed using FMO analysis. Intermolecular hydrogen bonding and crystal structure were characterized using Hirshfeld-surface analysis. Experimental and theoretical UV–Vis absorption spectra across various solvents have pinpointed regions of electronic transitions. Solute-solvent interaction parameters (${\pi }^{\ast },\alpha$ and $\beta$) with a correlation (R² = 0.93789) revealed a strong influence of solvent polarity and hydrogen-bonding properties on the absorption maxima (λ_max) of the compound. ADMET predictions indicate strong drug-development potential with high blood–brain barrier (BBB) penetration, low metabolic liability, and good oral bioavailability, but minimal hERG inhibition. The compound showed binding energies of −8.47 and − 8.01 kcal mol⁻¹ against MAP3K14 (NIK) target proteins, suggesting potential anticancer activity.