Research
most |
The main focus of our research group lies in the field of crystal engineering and crystallization process development, with a strong emphasis on designing and understanding multi-component solid forms. By combining principles of crystal engineering, crystallization, and mechanochemistry, we explore the solid-state landscape to uncover novel routes for material synthesis. Our research aims not only at the discovery of new crystalline systems but also at developing practical processes - optimisation, resolution, and purification - based on the intrinsic properties of these new-found solid forms.
Crystal Engineering
Crystal engineering is the design and synthesis of solid-state structures with desired properties by controlling molecular packing and intermolecular interactions. It uses principles of supramolecular chemistry to guide the formation of predictable crystal architectures. Applications include polymorph control, co-crystal formation, and tuning of physical properties such as solubility and stability. Crystal engineering enables the development of new formulations, purification strategies, and chiral resolution methods. By combining fundamental understanding with practical design, it bridges solid-state chemistry and industrial process innovation.
Crystallization Process Development
Crystallization is a critical final step in producing organic and inorganic compounds, affecting yield, purity, and product quality. Challenges such as caking, yield loss, uncontrolled particle size, or unexpected polymorphs often occur, even at industrial scale, but can be mitigated through a deep understanding of the crystallization process. Key steps include studying the solid state (polymorphism, solvatism, phase behavior), solvent selection and solubility, process parameters (stirring, seeding, particle size), and scale-up.
Our group focuses on formation of new and alternative solid forms and multi-component crystals, development of new pharmaceutical formulations, which in turn could enable resolution, purification, and separation, while controlling critical properties such as hygroscopicity and stability. We work on both drug candidates and marketed compounds, bridging fundamental solid-state insights with industrial process development.
Cocrystals
Cocrystals are crystalline solids of two or more neutral components connected by non-covalent interactions, preserving molecular identity while modifying properties. Guided by crystal engineering, we screen and design cocrystals, including using mechanochemical, solvent-free methods. Applications of cocrystals span pharmaceuticals, agrochemicals, and food science, including (but not limited to) improvement of solubility, stability, and bioavailability, as well as enabling chiral resolution via diastereomeric cocrystals. As an example of this, our group has successfully resolved racemic Levetiracetam (an antiepileptic drug) using S-mandelic acid as a chiral coformer. We leverage cocrystals for process development, resolution, and purification, emphasizing sustainable, solvent-minimized approaches to advance both academic research and industrial applications.
Mechanochemistry
Mechanochemistry is an emerging field of chemistry that uses mechanical energy to drive chemical reactions in the solid state. Unlike traditional solution-based chemistry, where solvents act as the medium for molecular motion and reactivity, mechanochemistry enables reactions to proceed without (or with minimal) solvent, making it both sustainable and highly efficient.
In recent years, mechanochemistry has gained attention for its ability to access novel materials and reaction pathways that are difficult or even impossible to achieve in solution. It has become an important tool in crystal engineering, enabling the preparation of multi-component solids, co-crystals, salts, and polymorphs. Moreover, it provides unique opportunities in chiral chemistry, where processes such as resolution and deracemization can be performed efficiently under solvent-free conditions.
Our group applies mechanochemistry as both a synthetic method and a process development strategy, contributing to greener, scalable, and innovative approaches to solid-state chemistry.
Deracemization
Deracemization refers to the transformation of a racemic mixture into an enantiopure product. Since enantiomers often exhibit dramatically different biological activities, achieving enantiopurity is of central importance in the pharmaceutical, agrochemical, and fine chemical industries.
Unlike classical resolution, which separates enantiomers but discards half of the material, deracemization has the advantage of converting the unwanted enantiomer into the desired one, offering higher efficiency and sustainability. Several different strategies have been used to deracemize various compounds, such as Viedma ripening, crystallization-induced asymmetric transformations (CIAT), cocrystal-based deracemization, but our research group has pioneered mechanochemical deracemization (MCDR) as a sustainable, solvent-minimized approach to obtaining enantiopure compounds.
We successfully transposed deracemization in solid-state for six different types of compounds to ball milling conditions: ketones, isoindolinones, imines, an ester, and an inorganic compound. Using MCDR, we achieved quantitative enantiomeric excesses, reduced reaction times by up to 97%, and eliminated solvent use, establishing a versatile and scalable strategy that merges crystal engineering and mechanochemistry for efficient chiral resolution.As part of our research we focus on developing and upscaling crystallization processes for pharmaceutically active as well as food compounds. We do this for industrial as well as academic partners, working on drugs in development, as well as drugs/food compounds which are already marketed but which require an optimized process.