Protic pharmaceutical ionic liquids and solids: Aspects of protonics

A series of new protic compounds based on active pharmaceutical ingredients have been synthesised and characterised. Some of the salts synthesised produced ionic liquids, while others that were associated with rigid molecular structures tended to produce high melting points. The protonic behaviour of these compounds was found to be a major determinant of their properties. Indicator studies, FTIR-ATR and transport properties (Walden plot) were used to probe the extent of proton transfer and ion association in these ionic liquids. While proton transfer was shown to have taken place in all cases, the Walden plot indicated strong ion association in the primary amine based examples due to hydrogen bonding. This was further explored via crystal structures of related compounds, which showed that extended hydrogen bonded clusters tend to form in these salts. These clusters may dictate membrane transport properties of these compounds in vivo.