Breakthrough in Crystal Chemistry could Impact Discovery Pipeline

Scientists at the University of Newcastle led by Dr Michael Hall and Dr Mike Probert, have successfully developed a way of growing crystals of organic soluble molecules from nanoscale encapsulated droplets. Along with chemistry experts at the University of Durham and in collaboration with SPT Labtech, the innovative method - Encapsulated Nanodroplet Crystallisation - involving the use of inert oils to control evaporative solvent loss, has the potential to enhance the drug development pipeline.

Whilst crystallisation of organic soluble molecules is a technique used by scientists all over the world, the ability to do so with such small quantities of analyte is ground-breaking. The scientists used just a few micrograms of molecular analyte dissolved in a few nanolitres of organic solvent in an automated process that offers rapid set up of hundreds of unique experiments with ease.

Dr Hall, Senior Lecturer in Chemistry, Newcastle University, said: “We have developed a nanoscale crystallisation technique for organic-soluble small molecules, using high-throughput liquid-handling robotics to undertake multiple crystallisation experiments simultaneously with minimal sample requirements and high success rates.

“This new method has the potential to have far-reaching impact within the molecular sciences and beyond. Fundamental research will benefit from highly detailed characterisation of new molecules, such as natural products or complex synthetic molecules, by X-ray crystallography, whilst the development of new drugs by the pharmaceutical industry will be accelerated, through rapid access to characterised crystalline forms of new active pharmaceutical ingredients.”

Understanding these new crystalline forms, known as polymorphs, is essential to the successful generation of new pharmaceutical agents and drugs. The ability to investigate these forms quickly and on a vast scale, whilst minimising the amount of analyte required, could be a key breakthrough enabled by the new ENaCT protocol.

Dr Probert, Senior Lecturer in Inorganic Chemistry and Head of Crystallography, Newcastle University, commented “…this new approach to crystallisation has the ability to transform the scientific landscape for the analysis of small molecules, not only in the drug discovery and delivery areas but also in the more general understanding of the crystalline solid state.”

Reference: Encapsulated Nanodroplet Crystallization of Organic-Soluble Small Molecules Tyler, et al.,Chem (2020).