At the interface between chemistry and physics, the crystallization process is ubiquitous in nature and industry. It is the basis of the formation of snowflakes but also of certain active principles used in pharmacology. For the phenomenon to occur for a given substance, it must first go through a so-called nucleation stage, during which the molecules organize themselves and create the optimal conditions for the formation of crystals. While it was difficult to observe this pre-nucleation dynamic, this key process has just been revealed by the work of a research team from the University of Geneva (UNIGE). Scientists have successfully visualized this process using real-time, microscale spectroscopy, paving the way for the design of safer and more stable active substances. These results are in the Proceedings of the National Academy of Sciences (PNAS).
Crystallization is a chemical and physical process used in many fields, from the pharmaceutical industry to the food industry. It is used to isolate a gaseous or liquid substance in the form of crystals. However, this phenomenon is not unique to the industry; it is ubiquitous in nature and can be seen, for example, in snowflakes, coral or kidney stones.
For crystals to form from substances, they must first go through a crucial step called nucleation. It is during this first phase that the molecules begin to organize themselves to form “nuclei”, stable clusters of molecules, which leads to the development and growth of the crystal. This process occurs stochastically, meaning it is unpredictable when and where a nucleus forms. “Until now, scientists have struggled to visualize this first step at the molecular level. The microscopic picture of crystal nucleation has been the subject of intense debate. Recent studies suggest that the molecules appear to form a disordered organization before the formation of ‘nuclei.’ how does crystal order emerge from it? That’s a big question!” explains Takuji Adachi, lecturer in the Department of Physico-Chemistry of the Faculty of Science of the UNIGE.
Capture one crystal nucleation event at a time
Takuji Adachi’s team, supported by two researchers from the Department of Chemistry at McGill University (Nathalie LeMessurier and Lena Simine), has taken a decisive step by successfully observing the nucleation process of an individual crystal at the scale micrometric by optical spectroscopy. “We succeeded in demonstrating and visualizing the organization and formation of molecular aggregates that precede crystallization,” explains Johanna Brazard, researcher in the Department of Physical Chemistry and co-first author of the research.
To observe this phenomenon, the scientists combined Raman microspectroscopy – a technique based on the interaction of light with matter to obtain information on its composition – and optical trapping. “We used lasers to highlight the molecular structure during nucleation but also to induce the nucleation phenomenon and thus be able to observe it and record its spectral fingerprint”, explains Oscar Urquidi, doctoral student in the Department of Physical Chemistry and co -first author of this research. The model substance chosen to conduct these experiments was glycine, an amino acid that is an essential building block of life, dissolved in water.
“Our work has revealed a crystallization step that was previously invisible,” says Takuji Adachi. Visualizing more precisely and better understanding what is happening at the molecular level is very useful for directing certain manipulations more effectively. This discovery could in particular facilitate the obtaining of purer and more stable crystalline structures for certain substances used in the design of many drugs or materials.
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