SCXRD, CSP-NMRX and microED in the quest for three elusive polymorphs of meloxicam.

Crystal structure determination is a crucial aspect of almost every branch of the chemical sciences, bringing us closer to understanding crystallization, polymorphism, phase transitions, and the relationship between a structure and its physicochemical and functional properties. Unfortunately, many molecules notoriously crystallize as microcrystalline powders, providing a significant challenge in establishing their structures. In this work, we describe the crystal structure determination of three elusive polymorphs of the anti-inflammatory drug meloxicam (MLX) using three approaches, of which only one was successful for each crystal phase.

Large-Scale Parameter Estimation for Crystal Structure Prediction. Part 1: Dataset, Methodology, and Implementation.

Crystal structure prediction (CSP) seeks to identify all thermodynamically accessible solid forms of a given compound and, crucially, to establish the relative thermodynamic stability between different polymorphs. The conventional hierarchical CSP workflow suggests that no single energy model can fulfill the needs of all stages in the workflow, and energy models across a spectrum of fidelities and computational costs are required. Hybrid /empirical force-field (HAIEFF) models have demonstrated a good balance of these two factors, but the force-field component presents a major bottleneck for model accuracy.

The seventh blind test of crystal structure prediction: structure generation methods.

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern.