Tautomerisation and polymorphism in molecular complexes of piroxicam with mono-substituted benzoic acidsElectronic supplementary information (ESI) available: Description of the crystal structures of the 19 new molecular complexes; PXRD for PXZ:2FBA before and after annealing at 140 °C with calculated patterns for both polymorphs for comparison; pictures showing colour change due to solid-solid transformation. CCDC reference numbers 890547-890565. For ESI and crystallographic data in CIF or other

• Main Authors: Wales, Craig, Thomas, Lynne H, Wilson, Chick C
• Format: Article
• Language: English
• ISSN: 1466-8033
• DOI: 10.1039/c2ce26069g

A series of nineteen piroxicam (PX) molecular complexes with mono-substituted benzoic acid co-molecules are reported. The piroxicam molecule can exist in two possible tautomers, one of which is zwitterionic; the PX tautomer obtained in these complexes is not related to the type of substituent or substitution position. Instead, a correlation is seen between the p K a of the benzoic acid co-molecule and the preference towards a particular PX tautomer. The complexes with 2-, 3- and 4-fluorobenzoic acids exhibit the rare phenomenon of tautomeric polymorphism. DSC measurements have been used to identify the most thermodynamically stable polymorph in these cases and this has been rationalised by consideration of the intermolecular interactions in the crystal structures. The complexes containing zwitterionic piroxicam (PXZ) display a highly predictable and reproducible four-molecule tetrameric hydrogen bonding pattern whereas the complexes containing non-ionised piroxicam have more than one possible hydrogen bonding synthon. A study of nineteen piroxicam molecular complexes shows the piroxicam molecule to adopt either a neutral or a zwitterionic tautomer, showing some correlation with the p K a of the co-molecule used. Three complexes exhibit the rare phenomenon of tautomeric polymorphism.