TY - JOUR
T1 - Tautomeric polymorphism of the neuroactive inhibitor kynurenic acid
AU - Pogoda, Dorota
AU - Janczak, Jan
AU - Pawlak, Sylwia
AU - Zaworotko, Michael
AU - Videnova-Adrabinska, Veneta
N1 - Publisher Copyright:
© 2019 International Union of Crystallography.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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 (β-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.
AB - 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 (β-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.
KW - Crystal structure
KW - Hirshfeld surface analysis
KW - Hydrogen bonding
KW - Keto-Enol tautomers
KW - Kynurenic acid
KW - Molecular drug
KW - Neuroactive inhibitor
KW - Polymorphism
KW - Trypto-phan metabolite
UR - http://www.scopus.com/inward/record.url?scp=85066960798&partnerID=8YFLogxK
U2 - 10.1107/S2053229619005990
DO - 10.1107/S2053229619005990
M3 - Article
C2 - 31166934
AN - SCOPUS:85066960798
SN - 2053-2296
VL - 75
SP - 793
EP - 805
JO - Acta Crystallographica Section C: Structural Chemistry
JF - Acta Crystallographica Section C: Structural Chemistry
ER -