X-Ray Crystallography Suzanna Ward PhD student Pharmaceutical Salt Selection Supervisor: Professor Mike Hursthouse Data-Learning-Prediction-Design

The Process Identify which salts are likely to form using pK values Set up an array of acids, bases and solvents using the Liquid Handling System Vary conditions such as temperature, stirring rate, pressure, solvent evaporation speed etc Analyse the crystals obtained Huge amounts of data to be interpreted Use the data to predict which acids/bases will readily form salts with any given parent molecule and what alterations in properties this will give rise to

The Importance of pK a Values in Salt Selection electronegative electropositive Salt formation involves proton transfer – it is an acid-base reaction pK values: -determine whether salt formation occurs - measure of stability of the resulting salt For a Stable Salt – pK (conjugate acid)< pK (conjugate base) with a minimum difference of 3 units Difficult to calculate – Environment/solvent Dependent Have to rely on experimental values pK a - determines the amount of protonated and non-protonated forms at a specific pH. Spartan- Molecular modelling package Electrostatic potential maps

Summary The Way Forward Find a way to calculate pk values Statistical fitting to identify key experiments to be performed Automated way of analysing products Use robotics to aid structural analysis Use pattern recognition programs to identify frameworks Predict stable salts and their properties