NMR crystallization: in situ NMR strategies for monitoring the evolution of crystallization processes

Abstract

We present a discussion of the range of NMR techniques that have been utilized for in situ monitoring of crystallization processes, highlighting the opportunities that now exist for exploiting the versatility of NMR techniques to reveal insights into the changes that occur in both the solid phase and the liquid phase as a function of time during crystallization processes from solution. New results are presented from in situ NMR studies of a range of crystallization processes using the CLASSIC NMR strategy and other techniques, specifically covering the following topics: (i) crystallization of glycine from aqueous solution at low temperature, revealing the relatively long-lived existence of a pure phase of the highly meta-stable β polymorph, (ii) the complementarity of ¹H→¹³C cross-polarization NMR and direct-excitation ¹³C NMR techniques in probing the evolution of the solid and liquid phases in in situ NMR studies of crystallization processes, (iii) in situ NMR studies of the process of guest exchange between a crystalline host–guest material in contact with the liquid phase of a more favourable type of guest, and (iv) systematic studies of the influence of magic-angle sample spinning on the behaviour of a crystallization system.