Molecules such as glycine, the simplest amino acid, can crystallise into different polymorphs with the same chemical composition but different structures. The two phases of glycine are α-glycine, which forms easily and is stable in bulk conditions, and β-glycine, which is difficult to produce and unstable in the bulk. However, β-glycine is piezoelectric; it generates electricity when compressed or bent and is therefore technologically useful.

In this work, the researchers developed a new method to produce glycine crystals. Using an electric field, they sprayed a glycine solution to create nanoscale droplets in which crystals form. By controlling the spraying conditions, they confined crystal growth at the nanoscale, thereby controlling how the crystals form. Crystals below 120 nm in size were pure β-glycine, above 130 nm were mostly α-glycine, and sizes between 120-130 nm produced a mixture of both polymorphs. This shows that crystal size (nanoconfinement) is the key parameter controlling which polymorph forms, and β-glycine is stable between 5 and 120 nm.

The crystals form in two steps. Firstly, nanoclusters form, then these clusters rearrange into crystals. β-glycine forms first because it has a lower interfacial energy, making it easier to create surfaces, and a lower nucleation barrier, so it forms faster. Overall, β-glycine is kinetically favourable. However, α-glycine has a lower bulk free energy and better packing. As crystals grow larger, they can rearrange into α-glycine, which is thermodynamically more stable. Under nanoconfinement, molecular rearrangement is restricted, preventing the formation of the more ordered α-phase and stabilising β-glycine.
This research is important because it shows how to precisely control which crystal form a material takes using nanoscale confinement, rather than relying on trial and error methods. It also provides a general strategy for stabilising metastable but functional materials, with potential applications in sensors, energy harvesting, and advanced functional materials.