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 , similar 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, similar to 50 K in the case of virtual forms being separated by 10 kJ/mol at 0 K.