Diazole-based powdered cocrystal featuring a helical hydrogen-bonded network: Structure determination from PXRD, solid-state NMR and computer modeling
Diazole-based powdered cocrystal featuring a helical hydrogen-bonded network: Structure determination from PXRD, solid-state NMR and computer modeling
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DOI：
10.1016/j.ssnmr.2014.12.005
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发表时间：
2015-02-01
影响因子：
3.2
通讯作者：
Mafra, Luis
中科院分区：
文献类型：
--
作者：
Sardo, Mariana;Santos, Sergio M.;Mafra, Luis
我们提出了一种新的等摩尔1：1共晶形成的3，5-二甲基-1H-吡唑（dmpz）和4，5-二甲基-1H-咪唑（dmim）的结构，确定通过粉末X射线衍射数据结合固态NMR，提供洞察氢键连接性和弱相互作用，如C-H中心点中心点π接触的拓扑细节。各种1D/2D C-13，N-15和H-1高分辨率固态NMR技术的使用提供了对局部长度尺度的结构洞察，揭示了所研究的共晶的dmim和dmpz分子构建块之间的核间接近性和相对取向。分子建模和DFT计算也被用来产生有意义的结构。INT精修能够将品质因数R（F-2）从近似11%（仅PXRD）降低至5.4%。尝试使N-H中心点N和C-H中心点π接触在稳定所报道的共晶中的作用合理化。为了这个目的，四个咪唑衍生物与不同的甲基取代基的位置与dmpz反应，以了解甲基化在阻断或使某些分子间接触的效果。只有一个咪唑衍生物（dmim）能够纳入dmpz三聚体基序，从而产生共晶体，其中含有疏水（甲基）和亲水组分，自组装形成螺旋氢键模式的非典型ID网络，具有与蛋白质中α-螺旋排列的结构相似性。1：1 dmpz DMIM化合物I是由两种不同唑类形成的共晶的第一个实例。(C)2014爱思唯尔公司All rights reserved.
We present the structure of a new equimolar 1:1 cocrystal formed by 3,5-d imethy1-1H-pyrazole (dmpz) and 4,5-dimethy1-1H-imidazole (dmim), determined by means of powder X-ray diffraction data combined with solid-state NMR that provided insight into topological details of hydrogen bonding connectivities and weak interactions such as C-H center dot center dot center dot pi contacts. The use of various 1D/2D C-13, N-15 and H-1 high-resolution solid-state NMR techniques provided structural insight on local length scales revealing internuclear proximities and relative orientations between the dmim and dmpz molecular building blocks of the studied cocrystal. Molecular modeling and DFT calculations were also employed to generate meaningful structures. INT refinement was able to decrease the figure of merit R(F-2) from similar to 11% (PXRD only) to 5.4%. An attempt was made to rationalize the role of N-H center dot center dot center dot N and C-H center dot center dot center dot pi contacts in stabilizing the reported cocrystal. For this purpose four imidazole derivatives with distinct placement of methyl substituents were reacted with dmpz to understand the effect of methylation in blocking or enabling certain intermolecular contacts. Only one imidazole derivative (dmim) was able to incorporate into the dmpz trimeric motif thus resulting in a cocrystal, which contains both hydrophobic (methyl groups) and hydrophilic components that self-assemble to form an atypical ID network of helicoiclal hydrogen bonded pattern, featuring structural similarities with alpha-helix arrangements in proteins. The 1:1 dmpz...dmim compound I is the first example of a cocrystal formed by two different azoles. (C) 2014 Elsevier Inc. All rights reserved.