Confined Crystallization - Netting Nuclei

The crystallization of molecular solids is a process of key industrial and economic significance, as well as being of enduring fundamental interest. Crystallization is an everyday purification method used throughout the chemical industry. In particular it has tremendous importance in the pharmaceutical field where the solid form of a drug substance directly affects its solubility, dissolution rate, bioavailability, stability, processing and tableting characteristics. Crystals nucleate from elusive molecular aggregates termed nuclei. It is well-defined pre-critical molecular aggregates as model (and real!) crystal nuclei that this project addresses by means of confining them in large container frameworks and hence preventing their uncontrolled growth, while at the same time stabilising their unfavourable interface with the medium. In order to isolate and study molecular aggregates of a size that is close to the size of a critical nucleus we believe that it is key to confine and stabilise the assembly in order to prevent both its growth and dissolution. In order to do this we propose to trap the nucleus within very large, discrete, well-defined coordination polymers. The role of the polymer will be to provide an inner surface to passivate the exterior surface of the high energy crystal nucleus and to sterically confine the assembly in a controllable way to prevent its run-away growth under supersaturation conditions. Confinement thus offers the possibility of producing a structured array of caged molecules of size comparable to a crystal nucleus or pre-nucleation cluster for structural characterisation without the nuclei growing into bulk crystals. Crystallizing the coordination polymers themselves (either from a solution or from a melt of the guest, or by guest exchange from previously formed crystals) will allow full structural elucidation of the confined assembly by single crystal X-ray diffraction.