Incorporating active pharmaceutical ingredients into a molecular salt using a chiral counterion

The molecular salt structures of three active pharmaceutical ingredients with the pure enantiomers of the amine 1-phenylethylamine contain a predictable hydrogen bonded heterosynthon. The APIs containing a carboxylic acid functional group, namely (S)-ibuprofen, diclofenac and niflumic acid, transfer their acid proton to the amine and form three charge-assisted N(+)-H center dot center dot center dot O(-) hydrogen bonds. These three hydrogen bonds form hydrogen bonded columns with repeating R(4)(3)(10) rings. The formation of the heterosynthon is predicted from a Cambridge Structural Database search, where the heterosynthon is formed in 87% of the structures containing carboxylate and ammonium functional groups, even in the presence of other hydrogen bonding functional groups such as alcohols.