Thiosquaramides: pH switchable anion transporters.
Thiosquaramides: pH switchable anion transporters.
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DOI：
10.1039/c4sc01629g
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发表时间：
2014-09-01
期刊：
影响因子：
8.4
通讯作者：
Gale PA
中科院分区：
文献类型：
--
作者：
Busschaert N;Elmes RB;Czech DD;Wu X;Kirby IL;Peck EM;Hendzel KD;Shaw SK;Chan B;Smith BD;Jolliffe KA;Gale PA
阴离子在细胞膜上的运输是一种重要的生物功能，由特殊蛋白质控制。近年来，出现了许多模仿这些蛋白质的阴离子运输行为的小分子，但这些合成分子中只有几个还表现出生物系统中的门控/开关行为。合成了一小系列硫代石酰胺，并用1H核磁共振滴定、单晶X射线衍射和各种囊泡技术研究了它们随pH变化的氯离子结合和阴离子传输行为。分光光度滴定和密度泛函计算表明，硫代石酰胺的酸性明显强于它们的氧代石酰胺类似物，pKa值在4.0到9.0之间。这导致观察到，在pH 7.2时，由于受体的去质子化，硫代石酰胺的阴离子传输能力完全关闭，但在较低pH时完全开启。
The transport of anions across cellular membranes is an important biological function governed by specialised proteins. In recent years, many small molecules have emerged that mimick the anion transport behaviour of these proteins, but only a few of these synthetic molecules also display the gating/switching behaviour seen in biological systems. A small series of thiosquaramides was synthesised and their pH-dependent chloride binding and anion transport behaviour was investigated using 1H NMR titrations, single crystal X-ray diffraction and a variety of vesicle-based techniques. Spectrophotometric titrations and DFT calculations revealed that the thiosquaramides are significantly more acidic than their oxosquaramide analogues, with pKa values between 4.0 and 9.0. This led to the observation that at pH 7.2 the anion transport ability of the thiosquaramides is fully switched OFF due to deprotonation of the receptor, but is completely switched ON at lower pH.