Insights into the Crystallization and Structural Evolution of Glycine Dihydrate by In Situ Solid‐State NMR Spectroscopy

Abstract

In situ solid‐state NMR spectroscopy is exploited to monitor the structural evolution of a glycine/water glass phase formed on flash cooling an aqueous solution of glycine, with a range of modern solid‐state NMR methods applied to elucidate structural properties of the solid phases present. The glycine/water glass is shown to crystallize into an intermediate phase, which then transforms to the β polymorph of glycine. Our in situ NMR results fully corroborate the identity of the intermediate crystalline phase as glycine dihydrate, which was first proposed only very recently.

Monitoring Crystallization Processes in Confined Porous Materials by Dynamic Nuclear Polarization Solid-State Nuclear Magnetic Resonance

“…For the sample quenched at 15 min, the T 1ρ relaxation filtered 13 C CPMAS NMR spectrum ( Figure 3 c) comprises a broad signal that is different from the spectrum of the amorphous glycine/water frozen solution ( Figure 3 b). The intensity maximum of this broad signal (173.5 ppm) does not correspond to the 13 C chemical shift of any crystalline polymorph of glycine in the same temperature region 25 (α polymorph, 176.8 ppm; β polymorph, 175.5 ppm; γ polymorph, 174.3 ppm), although it is very close to the 13 C chemical shift of crystalline glycine dihydrate 25 (173.5 ppm). However, the new signal is significantly broader than that observed previously for crystalline glycine dihydrate in bulk crystallization experiments.…”

“…However, the new signal is significantly broader than that observed previously for crystalline glycine dihydrate in bulk crystallization experiments. 25 …”

“…To further explore this issue, the standard temperature sequence to generate glycine dihydrate in bulk solution 24 , 25 was carried out for the mesoporous silica material after impregnation with an aqueous [1- 13 C] glycine solution (7.7% w/w). However, following this procedure, the 13 C NMR spectrum ( Figure S1 ) does not show a sharp signal at 173.5 ppm characteristic of crystalline glycine dihydrate.…”

“…All measured 13 C chemical shifts are referenced against the COOH resonance for the β polymorph of glycine recorded at 100 K, which was set to 175.5 ppm. 25 …”

Monitoring the influence of additives on the crystallization processes of glycine with dynamic nuclear polarization solid-state NMR

“…Nuclear magnetic resonance (NMR) is a valuable method to discriminate polymorphs [5][6][7][8][9][10][11][12] and to establish the sequence of the different phases produced during the crystallization process [13][14][15][16][17]. Interestingly, in-situ methods, based on NMR, have been developed to identify the sequence of solid and liquid phases formed over time [18][19][20][21][22]. Unfortunately, the time-resolution of NMR is limited by the time required to record a spectrum, which ranges from several minutes for a one-dimensional spectrum to hours when more complex experiments are required to access structural information.…”