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

Autor: Aspelin V; Division of Theoretical Chemistry, Department of Chemistry, Lund University, Lund SE 221 00, Sweden., Lidskog A; Center for Analysis and Synthesis (CAS), Department of Chemistry, Lund University, Lund SE 221 00, Sweden., Solano Arribas C; Center for Analysis and Synthesis (CAS), Department of Chemistry, Lund University, Lund SE 221 00, Sweden., Hervø-Hansen S; Division of Theoretical Chemistry, Department of Chemistry, Lund University, Lund SE 221 00, Sweden., Stenqvist B; Division of Physical Chemistry, Department of Chemistry, Lund University, Lund SE 221 00, Sweden., Chudoba R; Division of Theoretical Chemistry, Department of Chemistry, Lund University, Lund SE 221 00, Sweden., Wärnmark K; Center for Analysis and Synthesis (CAS), Department of Chemistry, Lund University, Lund SE 221 00, Sweden., Lund M; Division of Theoretical Chemistry, Department of Chemistry, Lund University, Lund SE 221 00, Sweden.; Lund Institute of Advanced Neutron and X-ray Science (LINXS), Scheelevägen 19, Lund SE 223 70, Sweden.
Jazyk: angličtina
Zdroj: Journal of the American Chemical Society [J Am Chem Soc] 2022 Feb 23; Vol. 144 (7), pp. 2921-2932. Date of Electronic Publication: 2022 Feb 10.
DOI: 10.1021/jacs.1c08507
Abstrakt: 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 2 SO 4 . A counterintuitive result was observed: the enthalpy change associated with the binding of the second ion is more negative than that of the first (Δ H bind,2 ° < Δ H 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 Δ H bind,2 ° < Δ H bind,1 ° . While the observed trend is independent of the counterion, the origin of the significantly larger magnitude of the difference Δ H bind,2 ° - Δ H 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.
Databáze: MEDLINE