Issue 8, 2022

Inducing a pH-dependent conformational response by competitive binding to Zn2+ of a series of chiral ligands of disparate basicity

Abstract

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) pKa 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 M or P helical conformation depended on the chirality of the bound ligand, and was reported by a remote 13C-labelled NMR reporter group. The multicomponent system thus converts a pH signal into a programmable conformational response which induces a remote spectroscopic effect.

Graphical abstract: Inducing a pH-dependent conformational response by competitive binding to Zn2+ of a series of chiral ligands of disparate basicity

Supplementary files

Article information

Article type
Edge Article
Submitted
06 12 2021
Accepted
09 1 2022
First published
17 1 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2022,13, 2258-2269

Inducing a pH-dependent conformational response by competitive binding to Zn2+ of a series of chiral ligands of disparate basicity

M. M. Wootten, B. A. F. Le Bailly, S. Tshepelevitsh, I. Leito and J. Clayden, Chem. Sci., 2022, 13, 2258 DOI: 10.1039/D1SC06812A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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