Intermolecular interactions, including hydrogen bonding, are important for governing many processes, including solvation, protein ligand binding and crystallisation. Previously in the Hunter group, the Surface Site Interaction Point (SSIP) model of intermolecular interactions has been used to describe molecules as a set of discrete hydrogen bonding sites. In this thesis I describe the prediction of phase properties using this molecular description, after giving an introduction to the wider area of phase property prediction. Experimental equilibrium constants for formation of hydrogen bonded complexes was collated to allow for the reparameterisation of the relationship used to convert calculated electrostatic potentials into the hydrogen bond parameters used to describe the interaction properties of SSIPs, and a curated database of this information was created. An overhaul of the software infrastructure, to allow greater exploitation of automation in the workflow, was undertaken. Canonicalisation of data formats for information produced during the calculation has also been undertaken to provide a foundation for work in the following chapters. Calculation of partition coefficients for a series of molecular datasets have been used to benchmark the performance of the surface site interaction model for liquids at equilibrium (SSIMPLE) which uses the SSIP description for molecules to calculate free energies. Functional Group Interaction Profiles (FGIP) describe the energy change of two solute SSIPs interacting as a function of solute SSIP values. These profiles provide insight into the strength of interactions within different solvents. A selection of profiles for a range of solvents are included as examples. The profiles provide a useful guide for how to tune interactions when designing systems which rely on intermolecular interactions for association. Consideration of the solvation free energy of a single SSIP in a solvent as a function of SSIP value, has led to the development of a metric for solvent similarity. The comparison of solvation free energy curves for different solvents and solvent mixtures led to the construction of similarity dendrograms that can be used for solvent selection in experimental systems. Expansion of the approach to be used to examine the temperature dependence of the interactions, allowed the exploration of vapour liquid equilibria.
Solvation, logP, VLE, chemistry, SSIP, SSIMPLE, simulation, prediction, computational, modelling, FGIP, Similarity
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