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

Matthew M. Wootten, Bryden A. F. Le Bailly, Sofja Tshepelevitsh, Ivo Leito, Jonathan Clayden

Research output: Contribution to journalArticle (Academic Journal)peer-review

4 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)2258-2269
Number of pages12
JournalChemical Science
Volume13
Issue number8
DOIs
Publication statusPublished - 17 Jan 2022

Bibliographical note

Funding Information:
This work was funded by the EPSRC Programme Grant ‘Molecular Robotics’ (EP/P027067) and the ERC Advanced Grant ‘DOGMATRON’ (AdG 883786). The work at Tartu was supported by the Estonian Research Council grants (PRG690) and by EU through the European Regional Development Fund under project TK141 “Advanced materials and high-technology devices for energy recuperation systems” (2014-2020.4.01.15-0011). The computations were carried out at the High Performance Computing Centre of the University of Tartu (www.etais.ee).

Publisher Copyright:
© The Royal Society of Chemistry.

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