0022-4766/15/5602-0317 © 2015 by Pleiades Publishing, Ltd. 317 Journal of Structural Chemistry. Vol. 56, No. 2, pp. 317-323, 2015. Original Russian Text © 2015 D. A. Druzhbin, T. N. Drebushchak, V. S. Min`kov, E. V. Boldyreva. CRYSTAL STRUCTURE OF TWO PARACETAMOL POLYMORPHS AT 20 K: A SEARCH FOR THE “STRUCTURE–PROPERTY” RELATIONSHIP D. A. Druzhbin 1,2 , T. N. Drebushchak 1,2 , V. S. Min`kov 1,2 , and E. V. Boldyreva 1,2 UDC 548.737:548.33 At a temperature of 20 K the crystal structures of two paracetamol polymorphs (monoclinic, form I, SPG P2 1 /n and orthorhombic, form II, SPG Pbcа) are solved by single crystal X-ray diffraction and a comparative analysis of the geometric characteristics of intra- and intermolecular interactions is performed. Polymorphous transformations were not observed until cooling to this temperature. It is shown that in form II hydrogen bonds remain longer than those in form I up to a temperature of 20 K, and the density of metastable form II remains higher than that of stable form I. At the same time, in form II, thermal parameters of nitrogen and oxygen atoms remain higher than those in form I. The features observed in the behavior of the heat capacity of both forms at temperatures below 100 K are not directly related to a change in the geometry of hydrogen bonds. The methyl group orientation determined from the electron density maps does not alter as compared to higher temperatures in both modifications. Thus, changes in the Raman spectra observed in the orthorhombic paracetamol form below 100 K are explained by the features of its dynamics rather than a change in the overall average orientation of the methyl group determined by X-ray diffraction. DOI: 10.1134/S002247661502016X Keywords: polymorphism, paracetamol, single crystal X-ray diffraction analysis, hydrogen bonds, low temperatures. INTRODUCTION Weak intermolecular interactions, including also hydrogen bonds, play an important role in the formation of the crystal structures of molecular crystals. Information on these interactions is necessary to understand the properties of molecular crystals. From the practical standpoint, the knowledge of the “structure–properties” relationship provides the controlled design of new drugs with improved properties. Compounds crystallizing in diverse polymorphs are convenient objects for the study of the role of various types of intermolecular interactions in the manifestation of different properties. Paracetamol (acetaminophen, panadol) is an antipyretic and analgesic drug having several polymorphs in the solid state [1–3]. Two paracetamol forms have been widely studied: stable monoclinic (form I, SPG P2 1 /n) and metastable orthorhombic (form II, SPG Pbcа). The literature about these two forms is vast and diverse (e.g., see the works devoted to the 1 Institute of Solid State Chemistry and Mechanochemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia; tanya@xray.nsu.ru. 2 Novosibirsk National Research State University, Scientific Educational Center “Molecular Design and Ecologically Safe Technologies”, Novosibirsk, Russia. Translated from Zhurnal Strukturnoi Khimii, Vol. 56, No. 2, pp. 332-338, March-April, 2015. Original article submitted April 22, 2014.