We use the formation of supramolecular species to probe fundamental phenomena observed in aqueous solution. In particular, we are interested in garnering information about the Hydrophobic Effect (why oil and water don’t mix), and the Hofmeister Effect (why co-solute salts modulate the solubility of organic solutes). Both phenomena are of immense importance to the biological realm where they control biomolecule structure and function, and medicinal chemistry where they modulate drug delivery and binding. They are also key factors in a host of other fields of chemistry including green chemistry and environmental remediation.
We use a combination of Isothermal Titration Calorimetry (ITC), Nuclear Magnetic Resonance (NMR) spectroscopy, UV-vis and fluorescence spectrometry, and osmometry to probe how changes to a solution influences the thermodynamics of host-guest complexation. The hosts and guests associate through mutually complementary hydrophobic surfaces, and it is the interaction of these surfaces that is controlled by their solvation and how they interact with co-solutes such as chaotropic salts. We also collaborate with computational chemists who provide an in silico perspective on the systems under study.
A typical study begins with the design and synthesis of a concave host molecule that possesses a large hydrophobic pocket, yet is fully water-soluble. The smaller and less elaborate guest molecules used are usually commercially available; however occasionally these are also synthesized. ITC directly measures the enthalpy of interaction between two molecules. Consequently it is the fastest and most accurate technique for determining ΔH˚ and consequently ΔG˚, and TΔS˚. In addition, a series of ITC experiments at different temperatures yields how ΔH˚ varies as a function of temperature (the heat capacity of a system). Where ITC experiments are not possible, NMR can be used instead. Furthermore, NMR also provides a detailed picture of how solutes interact with each other. Other spectroscopic techniques can also provide thermodynamic data of solute associations, whilst osmometry is useful in determining the activity of solutions under high salt concentration. Finally, computational work also yields information such as the degree of solvation of the host hydrophobic pocket, the thermodynamics of waters of solvation, and mechanisms of guest complexation.