High Affinity Crown Ether Complexes in Water: Thermodynamic Analysis, Evidence of Crystallography and Binding of NAD+

Improving traditional crown ether to the water-soluble and high binding ability host molecule is critical to our efforts to model or mimic biological supramolecular systems. In this paper, we converted two traditional crown ethers, 1,5-dinaphtho-32-crown-8 and 1,5-dinaphtho-38-crown-10, into the water-soluble tetrasulfonated 1,5-dinaphtho-32-crown-8 and tetrasulfonated 1,5-dinaphtho-38-crown-10, evaluated their complexation with three dicationic bipyridiniums in aqueous solution by microcalorimetric titration, UV–vis, and NMR experiments, and then determined the crystal structures of three tetrasulfonatocrown ether-bipyridinium complexes. The equilibrium association constants of tetrasulfonated 1,5-dinaphtho-32-crown-8 with these bipyridiniums reach up to 107 M–1, while those of tetrasulfonated 1,5-dinaphtho-38-crown-10 are just in the range of 105 M–1 order of magnitude. The thermodynamic data obtained show that the complexation of two tetrasulfonatocrown ethers with dicationic bipyridiniums is absolutely enthalpy-driven in water with an accompanying little entropic gain, and each monocationic pyridinium moiety in guest molecules can provide about −10 to −15 kJ·mol–1 enthalpy contribution irrespective of the size of ether crowns. Moreover, we also investigated the recognition capability of the two water-soluble crown ethers with NAD+ and NADH by microcalorimetric titration and NMR experiments, indicating that tetrasulfonated 1,5-dinaphtho-32-crown-8 shows exclusive selectivity to NAD+. The water-solubility and high affinity of this system as well as the flexible and non-preorganized characteristic of these crown ethers make it suitable to serve as a model for mimicking biological systems.将传统冠醚改造为水溶性且具备高结合能力的主体分子，对于我们开展生物超分子体系的建模与模拟研究至关重要。本研究将两种传统冠醚——1,5-二萘并-32-冠-8与1,5-二萘并-38-冠-10——改造为水溶性的四磺酰化1,5-二萘并-32-冠-8与四磺酰化1,5-二萘并-38-冠-10；通过微量热滴定、紫外-可见光谱（UV-vis）与核磁共振波谱（NMR）实验，评价了它们在水溶液中与三种双阳离子联吡啶鎓盐的络合行为，并解析了三种四磺酰化冠醚-联吡啶鎓盐配合物的晶体结构。四磺酰化1,5-二萘并-32-冠-8与上述联吡啶鎓盐的平衡结合常数最高可达10⁷ M⁻¹，而四磺酰化1,5-二萘并-38-冠-10的平衡结合常数仅处于10⁵ M⁻¹数量级区间。所得热力学数据表明，两种四磺酰化冠醚与双阳离子联吡啶鎓盐在水溶液中的络合过程完全由焓驱动，仅伴随少量熵增益；且无论冠醚环尺寸如何，客体分子中每个单阳离子吡啶鎓基团均可提供约-10至-15 kJ·mol⁻¹的焓贡献。此外，本研究还通过微量热滴定与NMR实验，探究了两种水溶性冠醚对烟酰胺腺嘌呤二核苷酸（NAD+）与还原型烟酰胺腺嘌呤二核苷酸（NADH）的识别性能，结果显示四磺酰化1,5-二萘并-32-冠-8对NAD+具有专一选择性。该体系的水溶性与高结合亲和力，加之这类冠醚所具备的柔性非预组织特性，使其适合作为模拟生物体系的模型。