Department of Chemistry, Durham University, South Road, Durham DH1 3LE, UK.
Nat Chem. 2010 Dec;2(12):1037-43. doi: 10.1038/nchem.859. Epub 2010 Oct 10.
We describe the use of low-molecular-weight supramolecular gels as media for the growth of molecular crystals. Growth of a range of crystals of organic compounds, including pharmaceuticals, was achieved in bis(urea) gels. Low-molecular-weight supramolecular gelators allow access to an unlimited range of solvent systems, in contrast to conventional aqueous gels such as gelatin and agarose. A detailed study of carbamazepine crystal growth in four different bis(urea) gelators, including a metallogelator, is reported. The crystallization of a range of other drug substances, namely sparfloxacin, piroxicam, theophylline, caffeine, ibuprofen, acetaminophen (paracetamol), sulindac and indomethacin, was also achieved in supramolecular gel media without co-crystal formation. In many cases, crystals can be conveniently recovered from the gels by using supramolecular anion-triggered gel dissolution; however, crystals of substances that themselves bind to anions are dissolved by them. Overall, supramolecular gel-phase crystallization offers an extremely versatile new tool in pharmaceutical polymorph screening.
我们描述了将低分子量超分子凝胶用作生长分子晶体的介质。在双（脲）凝胶中实现了包括药物在内的一系列有机化合物晶体的生长。与传统的明胶和琼脂糖等水性凝胶相比，低分子量超分子凝胶剂可以使用无限范围的溶剂系统。我们详细研究了在四种不同的双（脲）凝胶剂（包括金属凝胶剂）中卡马西平晶体的生长情况。在超分子凝胶介质中还实现了其他一些药物物质的结晶，例如司帕沙星、吡罗昔康、茶碱、咖啡因、布洛芬、对乙酰氨基酚（扑热息痛）、舒林酸和吲哚美辛，而没有形成共晶。在许多情况下，可以通过利用超分子阴离子触发凝胶溶解方便地从凝胶中回收晶体；然而，本身与阴离子结合的物质的晶体则被其溶解。总体而言，超分子凝胶相结晶为药物多晶型筛选提供了一种极其通用的新工具。
