de Armas Héctor Novoa, Peeters Oswald M, Blaton Norbert, Van den Mooter Guy, De Ridder Dirk J A, Schenk Henk
Laboratorium voor Biokristallografie, Katholieke Universiteit Leuven, Faculteit Farmaceutische Wetenschappen, O & N2 Campus Gasthuisberg, Herestraat 49 Bus 822, B-3000 Leuven, Belgium.
J Pharm Sci. 2006 Oct;95(10):2123-36. doi: 10.1002/jps.20645.
The crystal structure of carnidazole form II, O-methyl [2-(2-methyl-5-nitro-1H-imidazole-1-yl)ethyl]thiocarbamate, has been determined using synchrotron X-ray powder diffraction in combination with simulated annealing and whole profile pattern matching, and refined by the Rietveld method. For structure solution, 12 degrees of freedom were defined: one motion group and six torsions. Form II crystallizes in space group P2(1)/n, Z=4, with unit cell parameters after Rietveld refinement: a=13.915(4), b=8.095(2), c=10.649(3) A, beta=110.83(1) degrees, and V=1121.1(5) A3. The two polymorphic forms, as well as the hydrate, crystallize in the monoclinic space group P2(1)/n having four molecules in the cell. In form II, the molecules are held together by forming two infinite zig-zag chains via hydrogen bonds of the type N--H...N, the same pattern as in form I. A conformational study of carnidazole, at semiempirical PM3 level, was performed using stochastic approaches based on modification of the flexible torsion angles. The values of the torsion angles for the molecules of the two polymorphic forms and the hydrate of carnidazole are compared to those obtained from the conformational search. Form I and form II are enantiotropic polymorphic pairs this agrees with the fact that the two forms are conformational polymorphs.
已使用同步加速器X射线粉末衍射结合模拟退火和全谱图匹配确定了卡硝唑晶型II(O-甲基[2-(2-甲基-5-硝基-1H-咪唑-1-基)乙基]硫代氨基甲酸酯)的晶体结构,并通过Rietveld方法进行了精修。对于结构解析,定义了12个自由度:一个运动基团和六个扭转角。晶型II属于空间群P2(1)/n,Z = 4,经Rietveld精修后的晶胞参数为:a = 13.915(4),b = 8.095(2),c = 10.649(3) Å,β = 110.83(1)°,V = 1121.1(5) ų。两种多晶型以及水合物均结晶于单斜空间群P2(1)/n,晶胞中有四个分子。在晶型II中,分子通过形成两条无限之字形链,经由N–H...N型氢键结合在一起,这与晶型I中的模式相同。在半经验PM3水平上,使用基于柔性扭转角修饰的随机方法对卡硝唑进行了构象研究。将卡硝唑两种多晶型以及水合物分子的扭转角值与构象搜索得到的值进行了比较。晶型I和晶型II是对映异构多晶型对,这与两种晶型是构象多晶型这一事实相符。