250 nm Glycine-Rich Nanodroplets Are Formed on Dissolution of Glycine Crystals But Are Too Small To Provide Productive Nucleation Sites

Abstract

Recent theoretical and experimental studies have proposed a two-step mechanism for crystal formation in which crystal nucleation is preceded by formation of disordered molecular assemblies. Here, we investigated whether similar intermediates might also form as crystals dissolve, effectively the reverse process. A model system of glycine in water was studied, and the resultant solutions were characterized using small-angle X-ray scattering, dynamic light scattering, and nanoparticle tracking analysis. Invariably, dissolution of glycine crystals into water was observed to produce scattering nanospecies with liquid-like properties and a mean diameter of about 250 nm, at near saturation concentration. The nanospecies persisted indefinitely in solution in the presence of excess glycine crystals and were identified as glycine-rich nanodroplets with an equilibrium population of about 10 9 per mL. The time to appearance of glycine crystals from quiescent supersaturated solution (S = 1.1) containing either a low population of nanodroplets (nanofiltered) or a high population of nanodroplets (unfiltered) was indistinguishable with typically only a single crystal forming after about 30 h. However, a very significant acceleration of crystal formation was observed whenever a gently tumbling stirrer-bar was introduced into the vial; thousands of microcrystals appeared after an incubation period of only 3−5 h. The possibility of this being caused by factors such as secondary nucleation, bubbles, or glass splinters or scratches was eliminated via control experiments. Further investigation of the glycine solution, just prior to appearance of microcrystals, revealed an additional subpopulation of extremely large glycine-rich nanodroplets (diameter >750 nm), not observed in quiescent solutions. It is proposed that productive nucleation of glycine crystals occurs exclusively within these larger glycine-rich nanodroplets because a critical mass of glycine is required to form nascent crystals large enough to survive exposure to bulk more dilute solution. We hypothesize that nucleation occurs frequently but nonproductively within subcritical mass nanodroplets and infrequently but productively within very rare critical mass solute-rich nanodroplets. Such a model provides a new compelling way of bridging classical mechanisms of crystal nucleation with the more recently proposed two-step processes.

Effect of mixing, concentration and temperature on the formation of mesostructured solutions and their role in the nucleation of dl-valine crystals

“…These mesostructured liquid phases appear to be thermodynamically stable over a range of valine concentrations and temperatures. Similar phase behaviour was observed before in aqueous solution of other amino acids, glycine and DL-alanine 43 , and the role of such as 55 structures in the nucleation mechanism of glycine crystals was investigated 44 . The question addressed further here will be, what is the role of the mesoscale clusters in valine crystal nucleation and how the presence of such structure will affect the antisolvent crystallization process of valine.…”

“…Figure 7 provides a pictorial summary of the proposed nucleation crystallization pathways. Borrowing from the classical nucleation theory and building on what we proposed previously 44 smaller mesoscale clusters may 30 not contain sufficient amount of valine to be able to form stable nuclei able to survive and grow in the surrounding bulk solution. This could certainly be the case if as anticipated the mesoscale clusters were to contain a significant volume fraction of solvent.…”

“…It has been concluded that the mesoscale clusters are not a separate phase and the system has been described as a thermodynamically stable mesostructured liquid containing solute-rich domains dispersed within bulk solution 43 . We have previously reported presence of submicron size 35 mesospecies in supersaturated aqueous glycine solutions and their likely role in nucleation of glycine crystals 44 . We have also previously studied crystallization of DL-valine from 2-propanolwater solutions using Small Angle Static Light Scattering and turbidimetry measurements, which indicated presence of 40 mesoscale clusters in optically clear supersaturated solutions 45 .…”

Influence of History of Solution in Crystal Nucleation of Fenoxycarb: Kinetics and Mechanisms

“…The likely mechanism is that the 0.2 µm filtration step removes some prenucleation clusters/nanodroplets of fenoxycarb, similar to a recent study on glycine in aqueous solutions. 27 According to this hypothesis, nucleation-promoting clusters then re-form during subsequent nucleation and dissolution.…”

Nucleation of crystals that are mixed composites of all three polymorphs in the Gaussian core model

“…Despite its importance, the mechanism by which one polymorph is selected preferentially during crystallization is currently poorly understood, and the subject of active research. 1,[5][6][7][8][9]12 Here, our focus is on nucleation, the first stage of crystallization, during which a microscopically small nucleus of the crystal phase is formed in the metastable fluid phase. It is well known that what happens at nucleation can determine important physical properties of much larger crystals.…”