Developing the Application of the Crystalline Sponge Method

Abstract

The crystalline sponge (CS) method made waves in the scientific community when first published in 2013. It removes the necessity of sample crystallisation for single crystal X-ray diffraction (SCXRD) by utilising the crystallinity and porosity of metal organic frameworks. However, adoption of the technique has been primarily limited to the pharmaceutical industry and academic work has rarely strayed outside of original authors’ laboratories. Our work seeks to showcase the suitability of the CS method to the wide diversity of chemistry undertaken in academia and further develop understanding of the technique as a standard analytical tool. A number of firsts are presented, including the largest systematic studies undertaken for CS analysis, development of a quantitative grading system for assessing data quality, and quantification of interactions in the pore environment.

This thesis reports exploration of a family of novel biaryl molecules sourced from a synthetic organic laboratory at the University of Southampton. Characterisation experiments have enabled elucidation of the molecular structure of 13 synthetic oils via SCXRD and represents the first systematic library of compound structures generated by CS research. The systematic structural differences provide a range of comparable data to investigate host – guest and guest – guest interactions. Subsequent analysis provides insights into analyte preferences for intermolecular interactions through consideration of steric and electronic effects. These fundamental observations also provide preliminary insight into the mechanism by which the stable host-guest complexes form.

This preliminary work is followed by a statistical design of experiments study to assess the influence of experimental variables on the reliability and quality of crystallographic data obtained from a successful CS experiment. This approach focuses on a single analyte tested via 60 experiments (20 unique conditions). This enables investigation of a wider range of experimental conditions than would conventionally be applied to analytes during CS experimentation to uncover two-factor influences and identify more broadly applicable trends for future experiments. This collection of data is employed as a basis for the development of a novel molecular structure grading system which enables quantification of guest exchange quality.

Finally, combination of CS data with conventional SCXRD, spectroscopic analysis, and computational methods has enabled thorough analysis and quantification of the pore environment experienced by guest molecules. Through consideration of guest three-dimensional geometries and their relative energies, a spectrum of conformational flexibility is constructed to understand the impact of confinement effects on guest molecules. This is complemented with evaluation of intermolecular interaction energies and provides quantitative detail for unique guest exchange sites to inform researchers to what extent their analyte is adopting a relaxed conformation within the CS.

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Identifiers

ORCID for Robert Christopher Carroll: orcid.org/0000-0001-9249-4033

ORCID for Simon Coles: orcid.org/0000-0001-8414-9272

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