A common theoretical approach to determine pK values uses ideal-gas electronic structure (ES) calculations in conjunction with conductor-like polarizable continuum models (CPCM), universal solvation models (SMD, SM8), or their explicit solvent variants (the inclusion of explicit solvent molecules in the first solvation shell). The calculation of solvation free energy using such models requires five temperature-dependent solvent-based parameters based on experimental data: dielectric constant, bulk surface tension, refractive index, and acidity and basicity parameters. The accuracy of these models is often unsatisfactory, in part because their development and application has generally been limited to small rigid molecules; furthermore, the models have only been parameterized at 298.15 K. Their static nature also hampers extensions to flexible molecules in solution, in which the contribution of different molecular conformers to the solvation free energy is non-negligible. In a notable study, Coote et al. demonstrated different criteria for obtaining the most stable conformer in the solution phase, and showed how an erroneous result may be obtained if the commonly used gas-phase geometry is adopted for the solution phase solvation free energy calculation in the case of larger flexible amine molecules.