A multi-technique approach for probing the evolution of structural properties during crystallization of organic materials from solution

Abstract

We are engaged in a multidisciplinary study of fundamental aspects of the crystallization of organic molecular materials from solution, focusing on polymorphic systems under the recognition that such systems represent an ideal opportunity for obtaining a systematic understanding of competing pathways in crystallization processes. The range of techniques employed in this work are sensitive to structural properties on different length scales and are thus appropriate for mapping the changes that occur at different stages of the crystallization process, starting from the early aggregation events in solution (probed by solution-state NMR and molecular dynamics simulations, including studies of diffusion properties), leading to the growth of molecular aggregates (probed by small-angle neutron scattering), then the emergence of solid microcrystals dispersed in the crystallization solution (probed by small-angle neutron scattering and solid-state NMR) and finally the formation of the bulk solid crystalline phase (probed by powder X-ray diffraction). This paper reports preliminary results on the application of this multi-technique approach to study the crystallization of glycine (which has three known polymorphic forms under ambient conditions) from aqueous solution.

Microscopic mechanism of nanocrystal formation from solution by cluster aggregation and coalescence

“…Constant temperature conditions were maintained with the Hoover thermostat, 31 using a mass of 10 3 kcal mol −1 ps 2 (scaled units). The side length of the simulation cell was initially set at ∼4.7 nm and filled with pure water (3491 molecules), yielding an average density of ∼0.993 g/cm 3 after equilibration.…”

“…2 Prenucleation clusters during crystallization of glycine have also been detected with a combination of NMR, and x-ray and neutron scattering methods. 3 Recently, analytical ultracentrifugation and ion-selective electrode data have provided evidence of large ion clusters in unsaturated solutions of calcium carbonate. 4 It was suggested that these clusters are the relevant species that initiate precipitation of the solid phase, an amorphous aggregate that evolves into a particular polymorph depending on the pH of the solution.…”

Now You See Them

“…Yet, nucleation from solution is poorly understood, because experimental studies of nucleation are highly challenging (1). Recent studies have highlighted the possible role of clusters in nucleus formation (2,3). On page 1819 of this issue, Gebauer et al provide support for this thesis (4) by demonstrating the presence of large, well-defined clusters before nucleation of one of the phases of calcium carbonate.…”

Macromolecular crowding studies of amino acids using NMR diffusion measurements and molecular dynamics simulations

“…Diffusion is a natural method to study the effects of crowded solutions [19][20][21]. A number of diffusion studies have been used to characterize aggregation in amino acids [22][23][24][25]. The diffusion coefficient of both small and large molecules inside a cell has been found to be smaller compared to their infinite dilution diffusion coefficient due to crowding effects [17,19,21,26,27].…”

“…The clustering of amino acids such as glycine has been studied using NMR diffusion experiments and molecular dynamics (MD) simulations as a function of concentration, pH and temperature [22][23][24][34][35][36][37][38]. Hughes et al [23] used a multidisciplinary approach (i.e., NMR diffusion, MD simulations and small-angle neutron scattering) to investigate the crystallization of glycine in aqueous solutions. Hamad et al [34] have attempted to explain the size of glycine clusters using radial distribution functions (RDFs) and hydrogen bonding.…”