Design and synthesis of a more highly selective ammonium ionophore than nonactin and its application as an ion-sensing component for an ion-selective electrode

A novel ammonium ionophore, which exhibits superior NH₄⁺ selectivity compared with that of the natural antibiotic nonactin, was successfully designed and synthesized based on a 19-membered crown compound (TD19C6) having three decalino subunits in the macrocyclic system. This bulky decalino subunit is effective for (1) increasing the structural rigidity of the cyclic compound, (2) introducing the 'block-wall effect', which prevents forming a complex with a large ion, and (3) increasing the lipophilicity of the ionophore molecule. In the ammonium ionophore design, the first factor contributes to increasing the NH₄⁺ selectivity relative to smaller ions such as Li⁺, Na⁺, or even the closest size, K⁺, and the second factor increases the NH₄⁺ selectivity over larger ions such as Rb⁺ and Cs⁺. The X-ray structural analysis proved that TD19C6 forms a size-fit complex with NH₄⁺ in its crown ring cavity. As an application of this ionophore, an ion sensor (ion-selective electrode) was prepared, which exhibited NH₄⁺ to K⁺ and Na⁺ selectivity of 10 and 3000 times, respectively. This electrode showed a better performance compared to the electrode based on nonactin, which is the only ammonium ionophore presently used in practical applications.