X-ray diffraction and infrared spectroscopy of N,N-dimethylformamide and dimethyl sulfoxide solvatomorphs of betulonic acid.

Stanisław Boryczka, Maria Jastrzebska, Ewa Bębenek, Joachim Kusz, Maciej Zubko, Monika Kadela, Ewa Michalik

Department of Organic Chemistry, Medical University of Silesia, Sosnowiec 41-200, Poland.

Journal of pharmaceutical sciences 2012 Dec

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X-ray diffraction and infrared spectroscopy measurements for the N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) solvatomorphs of betulonic acid (BA) were investigated. BA [3-oxolup-20(29)-en-28-oic acid, C(30)H(46)O(3)] exhibits a wide spectrum of biological activities and is considered to be a promising natural agent for the treatment of various cancer diseases. BA as a noncrystalline substance was obtained by oxidation of betulin. Crystal structures and the spectral data allowed analysis of hydrogen bonding (H-bonding), molecular conformation, and crystal packing differences in the solvatomorphs. Crystals of BA solvates were grown from the DMF-acetone (1:10, v/v) and DMSO-water (9:1, v/v) solutions. BA-DMF (1:1) solvate crystallizes in the monoclinic P2(1) space group, Z = 2. The unit cell parameters are as follows: cell lengths a = 13.2458(5) Å, b = 6.6501(2) Å, c = 17.9766(7) Å, and β = 110.513(4)°. BA-DMSO (1:1) solvate crystallizes in the orthorhombic P2(1)2(1)2(1) (Z = 4) space group with the following unit cell parameters: a = 6.6484(4) Å, b = 13.3279(8) Å, and c = 32.6821(19) Å. Conformational analysis of the six-membered rings, cyclopentane ring, and isopropenyl group showed differences in comparison with other betulin derivatives examined earlier. For both solvates, the intermolecular packing arrangement was governed mainly by H-bonds. The shortest H-bonds with D···A distances of 2.604 and 2.657 Å, and almost linear DH···A connection occurred between OH of carboxylic group of BA and oxygen atoms from O=C and O=S groups of DMF and DMSO, respectively. Copyright © 2012 Wiley Periodicals, Inc.

Citation

Stanisław Boryczka, Maria Jastrzebska, Ewa Bębenek, Joachim Kusz, Maciej Zubko, Monika Kadela, Ewa Michalik. X-ray diffraction and infrared spectroscopy of N,N-dimethylformamide and dimethyl sulfoxide solvatomorphs of betulonic acid. Journal of pharmaceutical sciences. 2012 Dec;101(12):4458-71