Microsolvation of triazole in water: structural and energetic behaviors

Abstract

In this study, the hydration process of the triazole heterocycle is explored, considering different isomers of triazole–(H₂O)_n (n = 1–8) clusters. Among the used (28) density functional (DFT) exchange–correlation functionals, the M11 functional exhibits the lowest mean absolute deviation (MAD) with respect to the high-level DLPNO-CCSD(T)/CBS method used as reference. Subsequently, we analyzed the relative stabilities of these clusters over a temperature range of 20–400 K. Results indicate that triazole–water clusters are stabilized by strong hydrogen-bond interactions, and that the most stable configurations adopt compact, folded, cage-like structures. The hydration free energies per water molecule (ΔG) and hydration enthalpies per water molecule (ΔH) at room temperature and over the 20–400 K have been obtained in the framework of the cluster-continuum solvation approach (SMD). Results show that the hydration free energy follows a linear dependence on temperature, while the enthalpy remains nearly constant. For the TZ(H₂O)₈ cluster, the estimated hydration free energy is computed to be 0.56 kcal mol⁻¹, which is in good agreement with the available experimental counterpart (≈0.48 kcal mol⁻¹), supporting the reliability of the used computational approach.