Computer predictions of organic crystal structures and properties
Sarah L. Price · Acta Crystallographica Section A Foundations of Crystallography · 2002
How do intermolecular forces determine the crystal structure adopted by an organic molecule?The challenge of predicting the quantitative crystal structure from the chemical diagram of a molecule requires reliable quantitative models for the intermolecular forces.We have been deriving anisotropic atom-atom model potentials from the ab initio molecular charge density, which automatically represent the effects of lone pair and π electron density on the intermolecular interactions.These have proved necessary to compare the relative thermodynamic stability of different hypothetical structures as the first stage in crystal structure prediction.However, often many more energetically feasible structures are predicted than known polymorphs.Thus, the second challenge is to model how these forces determine the kinetic factors that can affect the polymorph obtained [1].The computed mechanical and morphological properties of the hypothetical structures can be used [2] as a starting point to eliminate kinetically improbable structures.Computer crystal structure predictions are at an exciting stage for simple organic molecules.There have been many successes, including in blind tests [3].However, even after eliminating structures on the basis of both energy and properties, we are often predicting more potential polymorphs than had been observed.Such predictions are leading to the discovery of new polymorphs.These early examples show that considerable experimental and theoretical collaboration is required for a predictive understanding of polymorphism.