Pushing the Limits of Molecular Crystal Structure Determination From Powder Diffraction Data in High-Throughput Chemical Environments

Abstract

Crystal structure determination from powder diffraction data (SDPD) using the DASH software package is evaluated for data recorded using transmission capillary, transmission flat plate, and reflection flat plate geometries on a selection of pharmaceutical compounds. We show that transmission capillary geometry remains the best option when crystal structure determination is the primary consideration and, as expected, reflection flat plate geometry is not recommended for SDPD because of preferred orientation effects. However, the quality of crystal structures obtained from transmission plate instruments can be excellent, and the convenience factor for sample preparation, throughput, and retrieval is higher than that of transmission capillary instruments. Indeed, it is possible to solve crystal structures within an hour of a polycrystalline sample arriving in the laboratory, which has clear implications for making small-molecule crystal structures more routinely available to the practicing laboratory medicinal chemist. With appropriate modifications to crystal structure determination software, it can be imagined that SDPD could become a rapid turn-around walk-up analytical service in high-throughput chemical environments.

A Million Crystal Structures: The Whole Is Greater than the Sum of Its Parts

“…Over the last 20 years, the determination of crystal structures from powder diffraction data has become increasingly viable using laboratory equipment (i.e., without the need for a synchrotron source) and the number of “powder structures” in the CSD has risen sharply. , It can be a very attractive option when it proves difficult or impossible to grow a crystal suitable for single-crystal diffraction. Methods for structure solution from powder data have been summarized by Shankland et al Overlap of reflections and a rapid decline in scattering with increasing diffraction angle lead to relatively low information content in powder diffraction patterns.…”

Small-Angle X-ray Scattering (SAXS) Used for the Identification of Nicomorphine Polymorphic Changes at the Early Stage to Avoid Varied Stability and Possible Side Effects

“…However, there are already reports and works about [ 17 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] polymorphism in solids using mainly X-ray powder diffraction (XRD), presenting it as a common phenomenon in drugs, which can lead to compromised quality due to changes in their physicochemical properties. Due to these issues, an increase in resources on this topic is crucial, including new and deeper methods, since polymorphism must be controlled to prevent possible ineffective therapy and/or improper dosage.…”

“…Therefore, the message of this paper is simply to show that the use of additional non-standard methods with extended resolution scale for structure quality (such as SAXS) can be very useful for detecting such objections in the drug and thereby avoiding possible side effects of the drug in human body. The fact is that SAXS is also used like WAXS, XRD or other methods [ 17 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ] in the study of polymorphism [ 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ,…”

Crystalline Forms of 4,4'-Methylenediantipyrine: Crystallographic Unit Cell for the Anhydrous Form, from Laboratory Powder XRD Pattern by DASH Program Package

“…Conditions, such as low degree of torsional freedom and presence of only one molecule in the asymmetric cell, increase the opportunity of finding at least an "approximate" structure description based of powder XRD pattern fitting [4,9,34] with help of single crystal structural skeleton data obtained previously and available in CSD as rigid body model. Actually, because of the high initial Pawley profile fitting difficulties, arising mainly from usage of a laboratory X-ray tube radiation and of reflection plate sample holder system [35], the precise unit cell structure could not be achieved, it should further be validated from single crystal growth and XRD structure resolution, but unfortunately, we were not able to obtain a single crystal of the anhydrous compound. Anyhow, the previously described single crystal structure of monohydrate have been found very useful, and comparisons of FT-IR spectrum and thermal behavior of the anhydrous and monohydrated forms have definitely confirmed differences in degree of hydration and solid state structure, while those of 1 H-and 13 C-NMR spectra proved the molecular identity of the two forms.…”