Crystallising a drug inside a tiny droplet of water can change its molecular structure—and that could make the medicine work better or allow a smaller dose to have the same effect. Many organic compounds, including drugs and biological molecules, can exist in multiple crystal forms called polymorphs. Only one form is usually stable; the others are metastable and vanish quickly. Yet metastable forms often have superior properties—better solubility, for instance—so controlling which form appears is a major goal in pharmaceuticals and materials science. Current methods using capillaries or porous materials offer limited control. This project takes a radically different approach: crystallising molecules in ultra-thin liquid films, possibly just one molecule thick. By confining the crystal to a two-dimensional puddle, the researchers aim to fine-tune its structure, thickness, and composition with unprecedented precision. If it works, the technique could enable personalised drug manufacturing—tiny, precisely structured crystals tailored to an individual patient’s dose. It could also produce novel 2D crystalline polymers for use in electronic devices, bypassing current synthesis bottlenecks. The work is fundamental science, driven by curiosity about how matter behaves under extreme confinement, but its practical payoffs—in drug delivery, device fabrication, and chemical engineering—could be substantial.
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Metastable phases are key in our life: majority of condensed phases of organic compounds are metastable, including lipids and proteins. However, metastable phases are typically very difficult to access and to further exploit in applications, as they are separated by small energy barriers and have very short lifetimes. In the case of organic compounds, the presence of metastable forms (polymorphs) makes very challenging to control the crystal's size, shape and structure, which ultimately determine their physical properties. A large effort has been spent in developing and designing techniques that allow to control polymorphism. One of the most attractive strategy is based on confinement, achieved by using capillaries, microporous materials, nanoporous media, and surfaces. However, the control of size and polymorphism by confinement is still not fully understood, by limiting further exploitation of these crystals in applications. 2DROP focuses on a ground breaking approach that will enable to access crystallization in thin molecular layers and to fine-tuning the crystal composition, structure and thickness, possibly down to the monolayer. This approach will be used to get the insights on crystallization under extreme confinement, where the discrete nature of the medium is expected to arise; to establish a new way to make complex crystals, such as 2D crystalline polymers, bypassing the limitations of liquid-interface synthesis and allowing the integration of such new crystals in devices; and, finally, to establish a ground breaking way to manufacture and ingest drugs, which will ensure bioavailability and dose personalization. 2DROP will establish a disruptive technology whose results will be of strong interest in several fields, ranging from soft matter, colloidal chemistry, chemical engineering, material science, nanotechnology and electrical engineering. This strong multidisciplinary project fully reflects the unique background of the PI.
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