Crystal structures of a new oral iron chelator, 1,2-dimethyl-3-hydroxy-4-pyridone, and its solvates with acetic acid and formic acid.
The crystal structures of a new oral iron chelator, 1,2-dimethyl-3-hydroxy-4-pyridone (DMHP), and of its 1:1 solvates with formic acid (DMHP,F) and acetic acid (DMHP,A) were determined by single-crystal X-ray diffraction. The data were collected at temperatures of 23 +/- 1 degrees C for DMHP, -64 +/- 1 degrees C for DMHP,F, and -120 +/- 1 degrees C for DMHP,A. The iron chelator DMHP is orthorhombic [Pbca, a = 7.290(5) A, b = 13.046(4) A, c = 13.748(6) A, Z = 8]. The DMHP molecules form centric dimers, each in a 10-membered ring in which the OH group of one molecule is hydrogen-bonded to the CO oxygen of the other [O-H...O; 0.91(4) A, 153(3)degrees, 1.85(4) A]. In each DMHP molecule, the OH group and CO oxygen are insignificantly intramolecularly hydrogen-bonded [O-H...O; 0.91(4) A, 107(3)degrees, 2.33(4) A]. DMHP,F is monoclinic [C2/c, a = 21.825(9) A, b = 3.811(5) A, c = 20.491(6) A, beta = 92.80(3)degrees, Z = 8]. The fundamental intermolecular and insignificant intramolecular hydrogen-bonded dimer structure of DMHP is maintained but is distorted and is supplemented by hydrogen bonds between the CO oxygen of each DMHP molecule and the OH group of one formic acid molecule [O-H...O; 0.99(5) A, 176(3)degrees, 1.53(4) A]. However, the two DMHP and the two formic acid molecules are twisted out of plane like the blades of a four-bladed propeller. DMHP,A is triclinic [P1, a = 8.458(2) A, b = 8.471(2) A, c = 6.986(3) A, alpha = 104.33(2)degrees, beta = 92.57(2)degrees, gamma = 88.78(2)degrees, Z = 2].(ABSTRACT TRUNCATED AT 250 WORDS)
Chan
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HK
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis 55455.
Ghosh
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Venkataram
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Rahman
Y E
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Grant
D J
DJ
D000085:Acetates / Q000737:chemistry*; D019342:Acetic Acid; D002626:Chemistry, Pharmaceutical; D000077543:Deferiprone; D005561:Formates / Q000737:chemistry*; D007502:Iron Chelating Agents / Q000737:chemistry; D015394:Molecular Structure; D011728:Pyridones / Q000737:chemistry*; D014961:X-Ray Diffraction
D000085:Acetates; D005561:Formates; D007502:Iron Chelating Agents; D011728:Pyridones; C030544:formic acid; D000077543:Deferiprone; D019342:Acetic Acid