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Counterintuitive Electrostatics upon Metal Ion Coordination to a Receptor with Two Homotopic Binding Sites

Aspelin, Vidar LU ; Lidskog, Anna LU ; Solano Arribas, Carlos ; Hervø-Hansen, Stefan LU ; Stenqvist, Björn LU ; Chudoba, Richard LU orcid ; Wärnmark, Kenneth LU and Lund, Mikael LU orcid (2022) In Journal of the American Chemical Society 144(7). p.2921-2932
Abstract
The consecutive binding of two potassium ions to a bis(18-crown-6) analogue of Tröger’s base (BCETB) in water was studied by isothermal titration calorimetry using four different salts, KCl, KI, KSCN, and K2SO4. A counterintuitive result was observed: the enthalpy change associated with the binding of the second ion is more negative than that of the first (ΔH°bind,2 < ΔH°bind,1). This remarkable finding is supported by continuum electrostatic theory as well as by atomic scale replica exchange molecular dynamics simulations, where the latter robustly reproduces experimental trends for all simulated salts, KCl, KI, and KSCN, using multiple force fields. While an enthalpic... (More)
The consecutive binding of two potassium ions to a bis(18-crown-6) analogue of Tröger’s base (BCETB) in water was studied by isothermal titration calorimetry using four different salts, KCl, KI, KSCN, and K2SO4. A counterintuitive result was observed: the enthalpy change associated with the binding of the second ion is more negative than that of the first (ΔH°bind,2 < ΔH°bind,1). This remarkable finding is supported by continuum electrostatic theory as well as by atomic scale replica exchange molecular dynamics simulations, where the latter robustly reproduces experimental trends for all simulated salts, KCl, KI, and KSCN, using multiple force fields. While an enthalpic K+–K+attraction in water poses a small, but fundamentally important, contribution to the overall interaction, the probability of the collapsed conformation (COL) of BCETB, where both crown ether moieties (CEs) of BCETB are bent in toward the cavity, was found to increase successively upon binding of the first and second potassium ions. The promotion of the COL conformation reveals favorable intrinsic interactions between the potassium coordinated CEs, which further contribute to the observation that ΔH°bind,2 < ΔH°bind,1. While the observed trend is independent of the counterion, the origin of the significantly larger magnitude of the difference ΔH°bind,2 - ΔH°bind,1 observed experimentally for KSCN was studied in light of the weaker hydration of the thiocyanate anion, resulting in an enrichment of thiocyanate ions close to BCETB compared to the other studied counterions. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the American Chemical Society
volume
144
issue
7
pages
12 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:35142499
  • scopus:85124892200
ISSN
1520-5126
DOI
10.1021/jacs.1c08507
language
English
LU publication?
yes
id
bc6da2c2-28cc-47b1-877a-bafc8553a5ba
date added to LUP
2022-03-14 13:10:28
date last changed
2024-03-06 02:53:48
@article{bc6da2c2-28cc-47b1-877a-bafc8553a5ba,
  abstract     = {{The consecutive binding of two potassium ions to a bis(18-crown-6) analogue of Tröger’s base (BCETB) in water was studied by isothermal titration calorimetry using four different salts, KCl, KI, KSCN, and K<sub>2</sub>SO<sub>4</sub>. A counterintuitive result was observed: the enthalpy change associated with the binding of the second ion is more negative than that of the first (ΔH°<sub>bind,2</sub> &lt; ΔH°<sub>bind,1</sub>). This remarkable finding is supported by continuum electrostatic theory as well as by atomic scale replica exchange molecular dynamics simulations, where the latter robustly reproduces experimental trends for all simulated salts, KCl, KI, and KSCN, using multiple force fields. While an enthalpic K<sup>+</sup>–K<sup>+</sup>attraction in water poses a small, but fundamentally important, contribution to the overall interaction, the probability of the collapsed conformation (COL) of BCETB, where both crown ether moieties (CEs) of BCETB are bent in toward the cavity, was found to increase successively upon binding of the first and second potassium ions. The promotion of the COL conformation reveals favorable intrinsic interactions between the potassium coordinated CEs, which further contribute to the observation that ΔH°<sub>bind,2</sub> &lt; ΔH°<sub>bind,1</sub>. While the observed trend is independent of the counterion, the origin of the significantly larger magnitude of the difference ΔH°<sub>bind,2</sub> - ΔH°<sub>bind,1</sub> observed experimentally for KSCN was studied in light of the weaker hydration of the thiocyanate anion, resulting in an enrichment of thiocyanate ions close to BCETB compared to the other studied counterions.}},
  author       = {{Aspelin, Vidar and Lidskog, Anna and Solano Arribas, Carlos and Hervø-Hansen, Stefan and Stenqvist, Björn and Chudoba, Richard and Wärnmark, Kenneth and Lund, Mikael}},
  issn         = {{1520-5126}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{7}},
  pages        = {{2921--2932}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Journal of the American Chemical Society}},
  title        = {{Counterintuitive Electrostatics upon Metal Ion Coordination to a Receptor with Two Homotopic Binding Sites}},
  url          = {{http://dx.doi.org/10.1021/jacs.1c08507}},
  doi          = {{10.1021/jacs.1c08507}},
  volume       = {{144}},
  year         = {{2022}},
}