Experimental Electron Density and Neutron Diffraction Studies on the Polymorphs of Sulfathiazole

High resolution X-ray diffraction data on forms I–IV of sulfathiazole and neutron diffraction data on forms II–IV have been collected at 100 K and analyzed using the Atoms in Molecules topological approach. The molecular thermal motion as judged by the anisotropic displacement parameters (adp’s) is very similar in all four forms. The adp of the thiazole sulfur atom had the greatest amplitude perpendicular to the five-membered ring, and analysis of the temperature dependence of the adps indicates that this is due to genuine thermal motion rather than a concealed disorder. A minor disorder (∼1–2%) is evident for forms I and II, but a statistical analysis reveals no deleterious effect on the derived multipole populations. The topological analysis reveals an intramolecular S–O···S interaction, which is consistently present in all experimental topologies. Analysis of the gas-phase conformation of the molecule indicates two low-energy theoretical conformers, one of which possesses the same intramolecular S–O···S interaction observed in the experimental studies and the other an S–O···H–N intermolecular interaction. These two interactions appear responsible for “locking” the molecular conformation. The lattice energies of the various polymorphs computed from the experimental multipole populations are highly dependent on the exact refinement model. They are similar in magnitude to theoretically derived lattice energies, but the relatively high estimated errors mean that this method is insufficiently accurate to allow a definitive stability order for the sulfathiazole polymorphs at 0 K to be determined.

本数据集包含磺胺噻唑（sulfathiazole）晶型I~IV的高分辨X射线衍射数据，以及晶型II~IV的中子衍射数据，所有数据均在100 K条件下采集，并采用分子中原子（Atoms in Molecules）拓扑分析方法进行解析。通过各向异性位移参数（anisotropic displacement parameters，ADPs）评估的分子热运动，在四种晶型中均高度相似。噻唑环上硫原子的各向异性位移参数在垂直于五元环的方向上具有最大振幅，对位移参数的温度依赖性分析表明，该现象源于真实的热运动，而非隐性无序。晶型I与II存在约1%~2%的轻微无序，但统计分析显示该无序不会对拟合得到的多极子布居产生不利影响。拓扑分析结果显示存在分子内S–O···S相互作用，该作用在所有实验拓扑密度分析中均稳定存在。对该分子气相构象的分析显示存在两种低能理论构象：其中一种具有实验研究中观察到的分子内S–O···S相互作用，另一种则存在S–O···H–N分子间相互作用。这两种相互作用似乎是“锁定”分子构象的关键因素。基于实验多极子布居计算得到的各多晶型晶格能，高度依赖于具体的精修模型，其数值量级与理论计算得到的晶格能相近，但由于估算误差相对较大，该方法的精度尚不足以确定0 K下磺胺噻唑多晶型的确切稳定性顺序。