Hu Xiaobo, Dawson Simon J, Mandal Pradeep K, de Hatten Xavier, Baptiste Benoit, Huc Ivan
Université de Bordeaux , CNRS , IPB , CBMN , UMR 5248 , Institut Européen de Chimie et Biologie , 2 Rue Escarpit , 33600 Pessac , France . Email:
Chem Sci. 2017 May 1;8(5):3741-3749. doi: 10.1039/c7sc00430c. Epub 2017 Mar 8.
The growth of crystals of aromatic compounds from water much depends on the nature of the water solubilizing functions that they carry. Rationalizing crystallization from water, and structure elucidation, of aromatic molecular and supramolecular systems is of general value across various fields of chemistry. Taking helical aromatic foldamers as a test case, we have validated several short polar side chains as efficient substituents to provide both solubility in, and crystal growth ability from, water. New 8-amino-2-quinolinecarboxylic acids bearing charged or neutral aminomethyl, carboxymethyl, sulfonic acid, or bis(hydroxymethyl)-methoxy side chains in position 4 or 5, were prepared on a multi gram scale. Fmoc protection of the main chain amine and suitable protections of the side chains ensured compatibility with solid phase synthesis. One tetrameric and five octameric oligoamides displaying these side chains were synthesized and shown to be soluble in water. In all cases but one, crystals were obtained using the hanging drop method, thus validating the initial design principle to combine polarity and rigidity. The only case that resisted crystallization appeared to be due to exceedingly high water solubility endowed by eight sulfonic acid functions. The neutral side chain did provide crystal growth ability from water but contributed poorly to solubility.
芳香族化合物从水中结晶的过程很大程度上取决于它们所携带的水溶性官能团的性质。对芳香族分子和超分子体系从水中结晶以及结构解析进行合理化研究,在化学的各个领域都具有普遍价值。以螺旋状芳香折叠体为例,我们验证了几种短极性侧链作为有效的取代基,既能使其在水中溶解,又能使其从水中结晶生长。我们以多克规模制备了在4位或5位带有带电荷或中性的氨甲基、羧甲基、磺酸或双(羟甲基)甲氧基侧链的新型8-氨基-2-喹啉羧酸。主链胺的芴甲氧羰基(Fmoc)保护和侧链的适当保护确保了与固相合成的兼容性。合成了一种显示这些侧链的四聚体和五种八聚体寡酰胺,并证明它们可溶于水。除了一个例外情况,在所有情况下都使用悬滴法获得了晶体,从而验证了结合极性和刚性的初始设计原则。唯一抗拒结晶的情况似乎是由于八个磺酸官能团赋予了极高的水溶性。中性侧链确实能使晶体从水中生长,但对溶解性的贡献很小。