Comparison of two molecular design strategies for the development of an ammonium ionophore more highly selective than nonactin

A series of ionophores for ammonium ion-selective electrodes was designed and synthesized, and their characteristics were examined. The design of the ionophores is based on two different strategies: (1) introduction of bulky blocking subunits (decalino groups) in 20- or 21-membered crown ethers (TD20C6 and TD21C6), the ring size of which is expected to be suitable for selective NH₄⁺ recognition, as compared to the slightly smaller K⁺; and (2) preorganized tripodal ionophores based on a 6-fold substituted benzene ring in order to complementarily recognize the tetrahedral NH₄⁺, in contrast to the spherical K⁺. Compared to nonactin, a natural product that is used as a representative NH₄⁺ ionophore, the newly developed TD20C6 showed higher NH₄⁺ selectivity over K⁺ while retaining the selectivity over Na⁺(log K_NH4+,K+^pot≡ -1.5 and log K_NH4+,Na+^pot = -2.5). On the other hand, a tripodal ionophore with pyrazole nitrogen atoms as NH4⁺ binding sites showed high NH₄⁺/K⁺. selectivity but suffered from increased Ca²⁺ interference (log K_NH4+,K+^pot = -2.1 and log K_NH4+,Ca2+^pot = -1.6). As an overall conclusion, the cyclic ionophores TD19C6 and TD20C6 are the best ammonium-selective ionophores developed to date.