Ramadhar Timothy R, Zheng Shao Liang, Chen Yu Sheng, Clardy Jon
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts, 02115, USA.
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts, 02138, USA.
Acta Crystallogr A Found Adv. 2015 Jan;71(Pt 1):46-58. doi: 10.1107/S2053273314019573. Epub 2015 Jan 1.
A detailed set of synthetic and crystallographic guidelines for the crystalline sponge method based upon the analysis of expediently synthesized crystal sponges using third-generation synchrotron radiation are reported. The procedure for the synthesis of the zinc-based metal-organic framework used in initial crystal sponge reports has been modified to yield competent crystals in 3 days instead of 2 weeks. These crystal sponges were tested on some small molecules, with two being unexpectedly difficult cases for analysis with in-house diffractometers in regard to data quality and proper space-group determination. These issues were easily resolved by the use of synchrotron radiation using data-collection times of less than an hour. One of these guests induced a single-crystal-to-single-crystal transformation to create a larger unit cell with over 500 non-H atoms in the asymmetric unit. This led to a non-trivial refinement scenario that afforded the best Flack x absolute stereochemical determination parameter to date for these systems. The structures did not require the use of PLATON/SQUEEZE or other solvent-masking programs, and are the highest-quality crystalline sponge systems reported to date where the results are strongly supported by the data. A set of guidelines for the entire crystallographic process were developed through these studies. In particular, the refinement guidelines include strategies to refine the host framework, locate guests and determine occupancies, discussion of the proper use of geometric and anisotropic displacement parameter restraints and constraints, and whether to perform solvent squeezing/masking. The single-crystal-to-single-crystal transformation process for the crystal sponges is also discussed. The presented general guidelines will be invaluable for researchers interested in using the crystalline sponge method at in-house diffraction or synchrotron facilities, will facilitate the collection and analysis of reliable high-quality data, and will allow construction of chemically and physically sensible models for guest structural determination.
基于使用第三代同步辐射对方便合成的晶体海绵进行分析，报告了一套详细的晶体海绵法合成和晶体学指南。用于初始晶体海绵报告的锌基金属有机框架的合成程序已被修改，以便在3天而不是2周内得到合格的晶体。这些晶体海绵对一些小分子进行了测试，其中两个小分子在用内部衍射仪分析时，在数据质量和正确的空间群确定方面意外地遇到了困难情况。通过使用同步辐射，数据收集时间不到一小时，这些问题很容易得到解决。其中一个客体诱导了单晶到单晶的转变，形成了一个更大的晶胞，不对称单元中有超过500个非氢原子。这导致了一个不平凡的精修方案，为这些系统提供了迄今为止最好的弗拉克x绝对立体化学测定参数。这些结构不需要使用PLATON/SQUEEZE或其他溶剂掩蔽程序，是迄今为止报道的最高质量的晶体海绵系统，其结果得到数据的有力支持。通过这些研究制定了一套完整晶体学过程的指南。特别是，精修指南包括精修主体框架、定位客体和确定占有率的策略，讨论几何和各向异性位移参数约束和限制的正确使用，以及是否进行溶剂挤压/掩蔽。还讨论了晶体海绵的单晶到单晶转变过程。所提出的一般指南对于有兴趣在内部衍射或同步辐射设施中使用晶体海绵法的研究人员将是非常宝贵的，将有助于收集和分析可靠的高质量数据，并将允许构建用于客体结构确定的化学和物理合理模型。
