Experimental and computational studies on the tautomerism of N-substituted 3-amino-5-oxo-4-phenyl-1H-pyrazolo-1-carboxamides with antibacterial activity Agnieszka A. Kaczor a,b , Tomasz Wróbel a , Zbigniew Karczmarzyk c , Waldemar Wysocki c , Ewaryst Mendyk d , Antti Poso b , Dariusz Matosiuk a , Monika Pitucha e,⇑ a Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, 4A Chodz ´ki St., PL-20093 Lublin, Poland b School of Pharmacy, University of Eastern Finland, Yliopistoranta 1, P.O. Box 1627, FI-70211 Kuopio, Finland c Department of Chemistry, Siedlce University, 3 Maja 54 St., PL-08110 Siedlce, Poland d Analytical Laboratory, Faculty of Chemistry, M. Curie-Skłodowska University, 3 M. Curie-Skłodowska Sq., PL-20031 Lublin, Poland e Department of Organic Chemistry, Faculty of Pharmacy with Division of Medical Analytics, 4A Chodz ´ki St., PL-20093 Lublin, Poland highlights  Tautomerism of N-substituted 3-amino-5-oxo-4-phenyl-1H- pyrazolo-1-carboxamides.  The form with the keto group is the preferred one in the crystalline state and DMSO.  Some fraction with the corresponding hydroxy group also occurs in both states.  This finding was related to the antibacterial activity of the studied compounds. graphical abstract article info Article history: Received 8 May 2013 Received in revised form 9 August 2013 Accepted 9 August 2013 Available online 14 August 2013 Keywords: Antibacterial compounds Pyrazolones Quantum chemical calculations Tautomerism X-ray structure determination abstract The tautomerism of N-substituted 3-amino-5-oxo-4-phenyl-1H-pyrazolo-1-carboxamides with antibac- terial activity is studied with X-ray crystallography, IR, 1 H and 13 C NMR (including NOESY spectra) and quantum chemical calculations. It is found that the form with the keto group at position 5 is the preferred one in the crystalline state and in DMSO, although some fraction with the corresponding hydroxy group also occurs in both states. This finding was related to the antibacterial activity of the studied compounds as the energetic stabilization of the keto group may determine their proper hydrogen bond interactions with the bacterial enzyme. Ó 2013 Elsevier B.V. All rights reserved. 1. Introduction Azoles are medicinally important compounds with a wide range of activity. Azole ring occurs in many biological molecules, which play an important role in the transmission of genetic information and cell division. It is a part of the purine which forms nucleic acids, DNA and RNA. There are many reports about the activity and possible practical application of pyrrole, imidazole, oxadiazole and triazole derivatives [1–4]. However, among azoles pyrazoles deserve special attention. They are known as herbicides, fungi- cides, insecticides, MDR modulators and also antibacterial, 0022-2860/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.molstruc.2013.08.010 ⇑ Corresponding author. Tel.: +48 815357374. E-mail address: monika.pitucha@umlub.pl (M. Pitucha). Journal of Molecular Structure 1051 (2013) 188–196 Contents lists available at ScienceDirect Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstruc