Electrostatic and Allosteric Cooperativity in Ion-Pair Binding: A Quantitative and Coupled Experiment-Theory Study with Aryl-Triazole-Ether Macrocycles.

Cooperative binding of ion pairs to receptors is crucial for the manipulation of salts, but a comprehensive understanding of cooperativity has been elusive. To this end, we combine experiment and theory to quantify ion-pair binding and to separate allostery from electrostatics to understand their re...

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Publicado en:Journal of the American Chemical Society Vol. 137; no. 30; pp. 9746 - 9758
Autores principales: Bo Qiao, Sengupta, Arkajyoti, Yun Liu, McDonald, Kevin P., Pink, Maren, Anderson, Joseph R., Raghavachari, Krishnan, Flood, Amar H.
Formato: Artículo
Publicado: American Chemical Society 8/5/2015
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Acceso en línea:Ver este registro en EBSCOhost
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      dt: 8/5/2015
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        10.1021/jacs.5b05839
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        atl: Electrostatic and Allosteric Cooperativity in Ion-Pair Binding: A Quantitative and Coupled Experiment-Theory Study with Aryl-Triazole-Ether Macrocycles.
      aug:
        au:
          Bo Qiao
          Sengupta, Arkajyoti
          Yun Liu
          McDonald, Kevin P.
          Pink, Maren
          Anderson, Joseph R.
          Raghavachari, Krishnan
          Flood, Amar H.
        affil: Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, Indiana 47405, United States
      su:
        Allosteric regulation
        Ion pairs
        Physiological control systems
        Density functional theory
        Ions
      sug:
        subj:
          Allosteric regulation
          Ion pairs
          Physiological control systems
          Density functional theory
          Ions
      ab: Cooperative binding of ion pairs to receptors is crucial for the manipulation of salts, but a comprehensive understanding of cooperativity has been elusive. To this end, we combine experiment and theory to quantify ion-pair binding and to separate allostery from electrostatics to understand their relative contributions. We designed aryl-triazole-ether macrocycles (MC) to be semiflexible, which allows ion pairs (NaX; X = anion) to make contact, and to be monocyclic to simplify analyses. A multiequilibrium model allows us to quantify, for the first time, the experimental cooperativity, α, for the equilibrium MC·Na + MC·X ⇄ MC·NaX + MC, which is associated with contact ion-pair binding of NaI (α = 1300, ΔG = -18 kJ mol) and NaClO (α = 400, ΔG = -15 kJ mol) in 4:1 dichloromethane-acetonitrile. We used accurate energies from density functional theory to deconvolute how the electrostatic effects and the allosteric changes in receptor geometry individually contribute to cooperativity. Computations, using a continuum solvation model (dichloromethane), show that allostery contributes ~30% to overall positive cooperativity. The calculated trend of electrostatic cooperativity using pairs of spherical ions (NaCl > NaBr > NaI) correlates to experimental observations (NaI > NaClO). We show that intrinsic ionic size, which dictates charge separation distance in contact ion pairs, controls electrostatic cooperativity. This finding supports the design principle that semiflexible receptors can facilitate optimal electrostatic cooperativity. While Coulomb's law predicts the size-dependent trend, it overestimates electrostatic cooperativity; we suggest that binding of the individual anion and cation to their respective binding sites dilutes their effective charge. This comprehensive understanding is critical for rational designs of ion-pair receptors for the manipulation of salts.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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          year: 2015
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