Wootten Matthew M, Le Bailly Bryden A F, Tshepelevitsh Sofja, Leito Ivo, Clayden Jonathan
School of Chemistry, University of Bristol Cantock's Close Bristol BS8 1TS UK
Institute of Chemistry, University of Tartu Ravila 14a Tartu 50411 Estonia.
Chem Sci. 2022 Jan 17;13(8):2258-2269. doi: 10.1039/d1sc06812a. eCollection 2022 Feb 23.
Molecules that change shape in response to environmental conditions are central to biological molecular communication devices and their synthetic chemical analogues. Here we report a molecular system in which a series of chiral anionic ligands of differing basicity are selectively protonated according to the pH of the medium. A cationic circular dichroism (CD) reporter complex responds to anion binding by selecting one of two alternative enantiomeric conformations. Exploiting the principle that less basic anions have, in general, weaker electrostatic interactions than more basic anions, a set of three chiral acids with large (>5 unit) p differences and differing configurations were sequentially deprotonated in acetonitrile by addition of base, allowing the most basic anion in the mixture at any time to bind to the reporter complex. A characteristic CD output resulted, which changed in sign as the next-most basic anion was revealed by the next deprotonation in the series. Four cycles of switching between three ligand-bound states were achieved with minimal changes in signal magnitude, by alternating addition of base and acid. The pH-dependent conformational response was used to transduce a signal by appending to the binding site a 2-aminoisobutyric acid (Aib) oligomer, whose or helical conformation depended on the chirality of the bound ligand, and was reported by a remote C-labelled NMR reporter group. The multicomponent system thus converts a pH signal into a programmable conformational response which induces a remote spectroscopic effect.
能够根据环境条件改变形状的分子是生物分子通信设备及其合成化学类似物的核心。在此，我们报告了一种分子系统，其中一系列不同碱性的手性阴离子配体根据介质的pH值被选择性地质子化。一种阳离子圆二色性（CD）报告复合物通过选择两种对映体构象中的一种来响应阴离子结合。利用一般来说碱性较弱的阴离子比碱性较强的阴离子具有较弱静电相互作用这一原理，通过添加碱，在乙腈中依次使一组三个具有大的（>5个单位）pKa差异且构型不同的手性酸去质子化，从而使混合物中任何时刻碱性最强的阴离子与报告复合物结合。产生了特征性的CD输出，随着该系列中下一次去质子化揭示出次碱性最强的阴离子，CD输出的符号发生变化。通过交替添加碱和酸，在信号幅度变化最小的情况下实现了三种配体结合状态之间的四个切换循环。通过在结合位点连接一个2-氨基异丁酸（Aib）低聚物来利用pH依赖性构象响应来转导信号，该低聚物的α-螺旋或β-螺旋构象取决于结合配体的手性，并由一个远程的13C标记的NMR报告基团报告。因此，该多组分系统将pH信号转化为可编程的构象响应，从而诱导远程光谱效应。
