Heat of formation distributions of components involved in bi-component cocrystals and simple binary eutectic mixtures

Abstract

A computationally inexpensive screening tool was formulated allowing for rational pre-selection of components as the most promising candidates for synthesis of two-component cocrystals. The proposed procedure relies on the scoring function quantifying dissimilarity of 2D histograms, which describe distributions of heat of formation resulting from two counterparts of database consisting of 1599 cocrystals and 492 cases of pairs immiscible in the solid state. It has been observed that higher probability of cocrystal formation is to be expected if components differ by heat of formation (Hf) values and at least one of components is hydrophilic. This observation was also validated based on an additional 1590 cocrystals not included in the training set. On the contrary, the high probability of simple eutectic systems is expected for cases of high similarities and positive values of Hf. Based on the formulated scoring function, the regions of observed highest probability of cocrystallization can be identified. Although the proposed phenomenological approach cannot provide absolute prediction of cocrystal formation, it does offers practical and simple guidance for rationalizing the selection of potential components for real practical purposes.