Efficacy of bi-component cocrystals and simple binary eutectics screening using heat of mixing estimated under super cooled conditions

• Distinguishing of two component cocrystals from simple binary eutectic mixtures is possible based on excess heat computations.
• Maximizing percentages of true positives and minimizing fractions of false positives was done based on predictive analytical tool.
• Among six considered approximations the BP-TZVPD-FINE approach offers the highest precision of cocrystal screening but still includes 12.8% of false positives.
• Application of Hmix criterion for cocrystal screening at this level excludes 41% positive cases classifying them as false negatives.
• Much less computationally demanding semiempirical quantum chemistry methods are also worth considering offering only slightly worse precision.

The values of excess heat characterizing sets of 493 simple binary eutectic mixtures and 965 cocrystals were estimated under super cooled liquid condition. The application of a confusion matrix as a predictive analytical tool was applied for distinguishing between the two subsets. Among seven considered levels of computations the BP-TZVPD-FINE approach was found to be the most precise in terms of the lowest percentage of misclassified positive cases. Also much less computationally demanding AM1 and PM7 semiempirical quantum chemistry methods are likewise worth considering for estimation of the heat of mixing values. Despite intrinsic limitations of the approach of modeling miscibility in the solid state, based on components affinities in liquids under super cooled conditions, it is possible to define adequate criterions for classification of coformers pairs as simple binary eutectics or cocrystals. The predicted precision has been found as 12.8% what is quite accepted, bearing in mind simplicity of the approach. However, tuning theoretical screening to such precision implies the exclusion of many positive cases and this wastage exceeds 31% of cocrystals classified as false negatives.

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