"Using CSP to Help Solve Powder Diffraction Structures was presented by Tom Darden, PhD, Senior Scientist, Physics Group at OpenEye, on Friday, April 10, 2020 at 1 pm EDT / 10am PDT (US).
Most drugs are delivered to patients as crystalline form tablets. The dose of medicine delivered by the tablet depends on its solid state properties such as solubility. If a drug is to be successfully marketed, it is critically important that the solid state properties of the drug be understood and controlled. To this end, extensive experimental screens are applied, searching for all thermodynamically viable crystal forms. Theoretical approaches for Crystal Structure Prediction (CSP) are also beginning to be used to supplement the experimental screens. A key experimental technique for identifying crystalline forms found during screening is X-ray Powder Diffraction (XRPD). This can be used to determine structures when experimental conditions or insufficient crystalline material preclude other techniques. However, the first and often rate limiting step in structure solution by XRPD is indexing the unit cell from the diffraction pattern. If the peaks in the pattern are too broad, or the powder represents a mixture of crystals, indexing may be impossible. An alternative approach, illustrated in this talk, is to use CSP technology to propose a set of viable low-energy crystal structures, whose predicted diffraction pattern can then be compared to the experimental pattern to choose the closest match.
