Exploring the solvation, structural stability, and molecular interactions of telmisartan: DFT and molecular dynamics simulations

In the present study, solvation effects, structural properties, and stability of Telmisartan (TS) have been studied using experimental and computational methods. Telmisartan and TS-Ag and TS-Cu nanocages have been optimized at the B3LYP/6-31G level. Geometric analysis revealed that both TS and its metal complexes with Ag and Cu adopt non-planar geometries, and coordination to these metals increases stability. The calculated solvation free energy indicated that water and ethanol are the most stable environments for TS, whereas chloroform and the metal complexes (TS-Ag and TS-Cu) are less stable. Molecular electrostatic potential and frontier molecular orbital analyses revealed that polar solvents increase the reactivity of TS. TS has been docked with the 4YHJ protein, inhibitory concentration of 0.92 µM, forming key interactions in the binding pocket. Molecular dynamics simulations were also performed, as well as discussed, to study the stability of the TS-4YHJ complex. These results emphasize the importance of solvent selection, metal complexation, and molecular interactions in improving the stability and reactivity of TS for future pharmaceutical uses. KEY WORDS: Telmisartan, DFT, Solvent effects, Docking, Molecular dynamics simulations Bull. Chem. Soc. Ethiop. 2026, 40(4), 893-906. DOI: https://dx.doi.org/10.4314/bcse.v40i4.12