Crystal Polymorphism and hydrate formation

The existence of different crystalline forms (polymorphs, hydrates and solvates) represents one of the most challenging, but also a very exciting phenomenon in solid state chemistry and related sciences, since we are still not able to predict the number of practically relevant forms and under which conditions these will be formed and exist. The relevance of polymorphism arises from the fact that solid state forms of a compound usually show clearly different physical properties, e.g. solubility, density, hardness, melting point, etc. Polymorphism and solvate (hydrate) formation is important for both fundamental research and the applied (industrial) field. This is true for pharmaceuticals (more than 80% are applied as solids), because polymorphism, hydrate/solvate formation and the degree of crystallinity can profoundly influence the manufacturing properties, the storage stability and the performance of drug products but also for many other materials used in chemical industry (plant protection substances, dyes, explosives, etc.). Therefore, the interest in computational ab initio crystal structure prediction (CSP) methods is increasing. Such predictions would be helpful for many reasons and would have great practical value in avoiding problems in the manufacturing and patenting of crystalline forms. Though we have to admit that the CSP from the chemical diagram of an organic molecule is still in his infancy, a number of studies showed already that the hypothetical structures are a very valuable complement to experimental polymorph screenings. Such predictions can help to discover new forms and provide the scientific understanding of the properties of experimentally discovered solid state forms. The proposed research project is aimed to systematically explore a homologous series of small organic model compounds in terms of polymorphism and solvate (hydrate) formation. To comprehensively understand the formation and stability of the different structures on the molecular level and to evaluate the structure-property relationships of these compounds, promising experimental and computational strategies will be combined. Due to the careful selection of the compounds and at the basis of own reliable experimental data this project implies highly innovative aspects, from the computational point of view: The selected set of model compounds (hydroxybenzenes, benzenecarboxylic and hydroxybenzoic acids) comprises substances that form polymorphs and hydrates, polymorphic hydrates and hydrates with different stoichiometries (different amount) of water. The experimental data should confirm the correctness of the calculations and vice versa. The research project aims at a better understanding of the supramolecular association of organic compounds (particularly polymorphism and hydrate formation) and explores the potential of crystal structure prediction. These efforts will contribute to the ultimate goal to predict realistic polymorphic forms as well as hydrates.