Effect of the solvent H/D isotope substitution on enthalpy-interaction parameters for the pharmaceutical urotropine (hexamethylenetetramine) in aqueous solutions at 298.15 K

The enthalpies of dilution of solutions of hexamethylenetetramine (HMTA), the well-known pharmaceutical urotropine, in water (H₂O) and heavy water (D₂O) were determined with a new heat conduction calorimeter at 298.15 K. The enthalpy-related homotactic coefficients of pairwise, $h_{22}$, and triplet, $h_{222}$, interactions between hydrated solute molecules were computed using the excess thermodynamic function concept (based on the McMillan-Mayer theory formalism). The $h_{22}$ and $h_{222}$ values were found to be large and positive in both H₂O and D₂O due to a partial overlapping of solute hydrophobic hydration shells and appearance of solute – solute correlations at rather large distances. This phenomenon is stronger pronounced in heavy water both for pairwise and for triplet HMTA – HMTA interactions indicating a highly ordered hydration structure in D₂O. The established correlation between the $h_{22}$ values and the corresponding solvent isotope effects, ${\mathrm{\delta h}}_{22}$(H₂O → D₂O), for HMTA and tetramethylurea mono- and bicyclic derivatives as solute species confirms the hypothesis of the differentiating effect of a solvent isotopic substitution on both the energetics of solvation and solute – solute interactions in aqueous solutions of proton-accepting non-electrolytes. In other words, the more negative or positive the $h_{22}$ value due to stronger homo- and heterocomponent D-bonds, the more negative or positive the corresponding isotopic effect is.