Pavlovic, Radoslav Z;
Lalisse, Remy F;
Hansen, Alexandar L;
Waudby, Christopher A;
Lei, Zhiquan;
Guney, Murat;
Wang, Xiuze;
... Badjic, Jovica D; + view all
(2021)
From Selection to Instruction and Back: Competing Conformational Selection and Induced Fit Pathways in Abiotic Hosts.
Angewandte Chemie International Edition
, 60
(36)
10.1002/anie.202107091.
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Abstract
Two limiting cases of molecular recognition, induced fit (IF) and conformational selection (CS), play a central role in allosteric regulation of natural systems. The IF paradigm states that a substrate “instructs” the host to change its shape after complexation, while CS asserts that a guest “selects” the optimal fit from an ensemble of preexisting host conformations. With no studies that quantitatively address the interplay of two limiting pathways in abiotic systems, we herein and for the first time describe the way by which twisted capsule M-1, encompassing two conformers M-1(+) and M-1(−), trap CX4 (X=Cl, Br) to give CX4⊂M-1(+) and CX4⊂M-1(−), with all four states being in thermal equilibrium. With the assistance of 2D EXSY, we found that CBr4 would, at its lower concentrations, bind M-1 via a M-1(+)→M-1(−)→CBr4⊂M-1(−) pathway corresponding to conformational selection. For M-1 complexing CCl4 though, data from 2D EXSY measurements and 1D NMR line-shape analysis suggested that lower CCl4 concentrations would favor CS while the IF pathway prevailed at higher proportions of the guest. Since CS and IF are not mutually exclusive, we reason that our work sets the stage for characterizing the dynamics of a wide range of already existing hosts to broaden our fundamental understanding of their action. The objective is to master the way in which encapsulation takes place for designing novel and allosteric sequestering agents, catalysts and chemosensors akin to those found in nature.
| Type: | Article |
|---|---|
| Title: | From Selection to Instruction and Back: Competing Conformational Selection and Induced Fit Pathways in Abiotic Hosts |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/anie.202107091 |
| Publisher version: | https://doi.org/10.1002/anie.202107091 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Physical Sciences, Chemistry, Multidisciplinary, Chemistry, encapsulation mechanisms, molecular encapsulation, molecular recognition, NMR dynamics, ROTATIONAL BARRIERS, BINDING, ENCAPSULATION, NMR, EXCHANGE, COOPERATIVITY, COMPLEXES, MECHANISM, ALLOSTERY, DYNAMICS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10167548 |
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