Crystal structure prediction lattice energy calculation

The lattice energies of the single-molecule crystals and co-crystal are assumed to be those for the most stable forms of each. To predict the stability of a given co-crystal it is therefore necessary to perform crystal structure prediction on each molecule independently and on the co-crystal itself. If it is necessary to predict which stoichiometry of co-crystal is the most stable, it is also necessary to perform crystal structure prediction on crystals with each possible stoichiometry. Since the cost and difficulty of a crystal structure prediction calculation increases considerably with the number of independent molecules in the asymmetric unit, this becomes a very hard problem which few have ventured to tackle. The role of crystal structure prediction is to identify the lowest energy structures that are possible for both co-crystal and its single-molecule crystalline components. The prediction of stoichiometry for a co-crystal requires consideration of all dissociation processes available for a given number of molecules in the asymmetric unit, for example ... 

There are various theoretical methods for calculating the lattice energy of a molecular crystal. It is important to note that the accuracy of these methods is key to the correct prediction of co-crystal stability. Some verification of the accuracy of the method for calculating the lattice energy is possible using experimental information. If the method, when used in crystal structure prediction, fails to predict the known polymorphs of the molecular crystals as low energy structures, then it is clear that, unless there is some fortuitous cancellation of errors, the method will not be able to predict co-crystal stability reliably. 

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