Microsolvation of triazole in water: structural and energetic behaviors

In this study, the hydration process of the triazole heterocycle is explored, considering different isomers of triazole-(H₂O)_<i>n</i> (<i>n</i> = 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 (Δ<i>G</i>) and hydration enthalpies per water molecule (Δ<i>H</i>) 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.