Compositional Polymorphism through Crystalline Solid Solutions and Its Interpretation for Thermodynamic Stability

The thermodynamic stability of polymorphs of a molecular compound can vary with changes in temperature, pressure and composition. Compositional polymorphism occurs when a polymorphic compound incorporates a guest species into its crystal lattice, forming a crystalline solid solution (CSS). The incorporation of the guest molecules causes strains and disorder that are specific to the lattice of the host crystal, thereby resulting in different changes in the thermodynamic properties of the polymorphs with composition. The imparted thermodynamic changes cause the polymorphs to either converge or diverge in thermodynamic stability, in some cases making a metastable polymorph the most stable form at the same temperature and pressure. This contribution provides a comprehensive analysis of compositional polymorphism that includes thermodynamic stability relationships of polymorphs as a function of solid phase composition. The report starts with a description of CSSs and how compositional alterations cause changes in the thermodynamic properties of the host structure, leading to melting point depression and liquid solubility enhancement. Particular focus is given to the thermodynamic expressions that describe free energy of mixing in the solid state, as derived from the heat of fusion of CSS and their respective pure components. Recent experimental examples of T–X phase diagrams are included that detail thermodynamic modifications observed by changes in melting properties and liquid solubility. This is followed by thermodynamic derivations and experimental data showing how the compositions of the solvus correlate to thermodynamic changes of the host. These relationships are subsequently used to delineate rules of thumb for inferring polymorphic stability relationships while introducing new nomenclature relevant for polymorphic solid solutions. Finally, theoretical T–X phase diagrams are presented, showcasing possible stability scenarios involving polymorphic solid solutions relevant for molecular compounds.