Thermochemical, spectral and biological activity prediction of some methylpyridine derivatives: a computational approach

Pyridine and its derivatives play a vital role in pharmaceutical and pesticide applications. However, prolonged exposure to pyridine can lead to significant health risks due to its ability to enter the body via inhalation and absorption. This study employed density functional theory (DFT) at the B3LYP/6–311 g++(d, p) level to systematically investigate the thermochemical properties—including free energy, dipole moment, molecular orbitals, and electrostatic potential—as well as the spectral characteristics (FT-IR, Raman, and UV-Vis spectra) of some selected methylpyridine derivatives bearing functional groups such as–F,–Br,–OH,–NH2,–CN, and–COOCH2CH3. Thermodynamic assessments and molecular orbital analysis offer insights into the thermodynamic stability and chemical reactivity of the analyzed pyridine derivatives. Molecular docking and non-bonding interaction analyses were performed against human kinesin Eg5, a key mitotic motor protein and a promising cancer chemotherapy target. All methylpyridine derivatives showed higher binding affinities than unsubstituted pyridine (–4.0 kcal/mol), with 6-bromo-2-methylpyridin-3-amine displaying the highest affinity (–6.0 kcal/mol). Complementary molecular dynamics simulations, alongside ADMET and PASS predictions, offered insights into their biochemical and toxicological profiles. This comprehensive computational study highlights the thermochemical and biological activity of selected methylpyridine derivatives, aiming to contribute to the development of safer reagents and chemicals.