NEW STRATEGIES FOR EXPLORING CRYSTALLIZATION PROCESSES OF ORGANIC MATERIALS*

Crystal growth processes are crucially important in many aspects of biological and physical sciences. In many situations, however, the outcome of crystallization processes (in terms of the polymorphic form or the morphological properties of the crystals obtained) can be difficult to control, such that it is often challenging to achieve a desired outcome in a reliable and reproducible manner. Progress in this regard will rely to a large extent on improving the current level of fundamental physico-chemical understanding of crystallization processes. This paper gives an overview of two experimental strategies that have been developed recently for exploring fundamental aspects of crystallization processes. First, we describe an in-situ solid-state NMR strategy for monitoring the evolution of the different polymorphs (or other solid forms) that are present as a function of time during crystallization from solution. As an illustrative example, we describe the application of this strategy to investigate the evolution of polymorphic forms during the crystallization of glycine from different solvent systems. Second, we highlight a strategy for retrospective analysis of the growth history of crystals, based on analysis of well-defined variations in the composition of the crystal using confocal Raman microspectrometry. The utility of this strategy to yield insights on changes in crystal morphology during crystal growth is illustrated in the case of urea inclusion compounds prepared by crystallization under conditions of competitive co-inclusion of two different types of guest molecule.