Electrostatic and Allosteric Cooperativity in Ion-Pair Binding: A Quantitative and Coupled Experiment-Theory Study with Aryl-Triazole-Ether Macrocycles
Electrostatic and Allosteric Cooperativity in Ion-Pair Binding: A Quantitative and Coupled Experiment-Theory Study with Aryl-Triazole-Ether Macrocycles
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DOI：
10.1021/jacs.5b05839
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发表时间：
2015-08-05
影响因子：
15
通讯作者：
Flood, Amar H.
中科院分区：
文献类型：
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作者：
Qiao, Bo;Sengupta, Arkajyoti;Flood, Amar H.
离子对与受体的合作结合对盐的操纵至关重要，但对合作性的全面理解一直难以捉摸。为此，我们将实验与理论相结合，量化离子对结合，并将变构与静电分离，以了解它们的相对贡献。我们将芳基三唑醚大环（MC）设计成半柔性的，允许离子对（NaX; X =阴离子）接触，并且是单环的，以简化分析。多平衡模型使我们首次量化了平衡MC中心点Na+ + MC中心点X- (sic) MC中心点NaX + MC的实验协同性α，这与NaI (α = 1300, δ G（α) = -18 kJ mol(-1)）和NaClO4 (α = 400, δ G（α) = -15 kJ mol(-1)）在4:1二氯甲烷-乙腈中的接触离子对结合有关。我们使用密度泛函理论的精确能量来反卷积静电效应和受体几何上的变构变化如何单独促进协同性。使用连续溶剂化模型（二氯甲烷）进行的计算表明，变构对总体正协同性的贡献接近30%。计算得到的球形离子对（NaCl > NaBr > NaI）的静电协同性趋势与实验观察结果（NaI > NaClO4）相吻合。我们表明，决定接触离子对中电荷分离距离的固有离子尺寸控制着静电协同性。这一发现支持了半柔性受体可以促进最佳静电协同的设计原则。虽然库仑定律预测了尺寸依赖的趋势，但它高估了静电协同性；我们认为单个阴离子和阳离子与其各自的结合位点的结合稀释了它们的有效电荷。这种全面的理解对于合理设计离子对受体来操纵盐是至关重要的。
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, alpha, for the equilibrium MC center dot Na+ + MC center dot X- (sic) MC center dot NaX + MC, which is associated with contact ion-pair binding of NaI (alpha = 1300, Delta G(alpha) = -18 kJ mol(-1)) and NaClO4 (alpha = 400, Delta G(alpha) = -15 kJ mol(-1)) 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 similar to 30% to overall positive cooperativity. The calculated trend of electrostatic cooperativity using pairs of spherical ions (NaCl > NaBr > NaI) correlates to experimental observations (NaI > NaClO4). 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 Coulombs 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.