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