Tautomeric polymorphism of the neuroactive inhibitor kynurenic acid

Abstract

Kynurenic acid (KYN; systematic name: 4-hydroxyquinoline-2-carboxylic acid, C10H7NO3) displays a therapeutic effect in the treatment of some neurological diseases and is used as a broad-spectrum neuroprotective agent. However, it is understudied with respect to its solid-state chemistry and only one crystal form (α-KYN·H2O) has been reported up to now. Therefore, an attempt to synthesize alternative solid-state forms of KYN was undertaken and six new species were obtained: five solvates and one salt. One of them is a new polymorph, β-KYN·H2O, of the already known KYN monohydrate. All crystal species were further studied by single-crystal and powder X-ray diffraction, thermal and spectroscopic methods. In addition to the above methods, differential scanning calorimetry (DSC), in-situ variable-temperature powder X-ray diffraction and Raman microscopy were applied to characterize the phase behaviour of the new forms. All the compounds display a zwitterionic form of KYN and two different enol–keto tautomers are observed depending on the crystallization solvent used.