Theoretical study of the thermodynamic, electronic, and pharmacokinetic stability of 2-[(benzimidazolyl) methylthio]-4,5-diphenylimidazole derivatives: implications for the development of new antibacterial agents

Infectious diseases remain a major challenge for public health, reinforcing the need for new effective antimicrobial agents. In this context, five derivatives of 2-[(benzimidazolyl)methylthio]-4,5-diphenylimidazole were studied using theoretical calculations based on density functional theory (DFT, B3LYP/6-31+G(d,p)) to evaluate their thermodynamic stability, electronic properties, and pharmacokinetic potential. The results show that all compounds exhibit good energy stability, with negative values for enthalpy of formation (∆_fH), Gibbs free energy (∆G⁰), and total energy (E_T), reinforced in the aqueous phase by the solvation effect. Frontier orbital analysis reveals a small HOMO – LUMO gap for compound 3, indicating increased electronic reactivity and enhanced electron transfer capacity. At the same time, the dipole moment in aqueous phase is highest for this same compound (µ = 16.420 D), highlighting high polarity and an ability to interact with polar biomolecules. The physicochemical and pharmacokinetic properties (molar mass, LogP, TPSA, HBD/HBA) confirm that compound 3 combines high polarity, moderate lipophilicity, and favorable hydrogen bonding potential. These results suggest that this derivative has a promising profile for biological and pharmaceutical applications, in line with the principles of rational design of bioactive molecules.