Solid-Form Transition Temperature Prediction from a Virtual Polymorph Screening: A Reality Check

The focus of this study is an estimation of uncertainty of solid-form transition temperature ( T tr ) prediction based on modern virtual polymorph screening calculations. That was done through error propagation, utilizing estimated uncertainties of the relative free energy predictions at 0 K as well as of finite-temperature contribution to the polymorphic relative free energy. It was found that the uncertainty of the T tr prediction displays an inverse dependence on the difference of slopes of the intersecting relative free energy curves—the lower the difference, the higher the uncertainty of T tr prediction. The results demonstrated that the error of T tr prediction is expected to be high (up to ∼260–270 K), especially at the temperature range close to ambient and above. The lowest uncertainty of T tr prediction at room temperature is expected to be ∼50 K in the case of virtual forms being separated by 10 kJ/mol at 0 K.