Prediction of Solid Solution Formation in a Family of Diastereomeric Salts. A Molecular Modeling Study

The possibility of solid solution behavior of diastereomeric salts, containing multiple resolving agents of the same family (Dutch Resolution), is predicted by molecular modeling. Super-cells containing different ratios of resolving agents in the diastereomeric salt are constructed and optimized, and their lattice energy is computed. The energy difference between these “simulated solid solutions” and the native structures is related in an understandable fashion to the probability of solid solution formation. This procedure is applied to a family of diastereomeric salts of ephedrine and cyclic phosphoric acids, for which the ternary diagrams have been determined experimentally at 25 °C in ethanol. Good agreement between experimental and computational results indicates that this relatively simple and fast method could predict the stable character of solid solution behavior in binary systems.