A Highly K+‐Selective Fluorescent Probe – Tuning the K+‐Complex Stability and the K+/Na+ Selectivity by Varying the Lariat‐Alkoxy Unit of a Phenylaza[18]crown‐6 Ionophore

A desirable goal is to synthesize easily accessible and highly K⁺/Na⁺‐selective fluoroionophores to monitor physiological K⁺ levels in vitro and in vivo. Therefore, highly K⁺/Na⁺‐selective ionophores have to be developed. Herein, we obtained in a sequence of only four synthetic steps a set of K⁺‐responsive fluorescent probes 4 , 5 and 6 . In a systematic study, we investigated the influence of the alkoxy substitution in ortho position of the aniline moiety in π‐conjugated aniline‐1,2,3‐triazole‐coumarin‐fluoroionophores 4 , 5 and 6 [R=MeO ( 4 ), EtO ( 5 ) and iPrO ( 6 )] towards the K⁺‐complex stability and K⁺/Na⁺ selectivity. The highest K⁺‐complex stability showed fluoroionophore 4 with a dissociation constant K_d of 19 mm , but the K_d value increases to 31 mm in combined K⁺/Na⁺ solutions, indicating a poor K⁺/Na⁺ selectivity. By contrast, 6 showed even in the presence of competitive Na⁺ ions equal K_d values (K_d^K+=45 mm and K_d^K+/Na+=45 mm ) and equal K⁺‐induced fluorescence enhancement factors (FEFs=2.3). Thus, the fluorescent probe 6 showed an outstanding K⁺/Na⁺ selectivity and is a suitable fluorescent tool to measure physiological K⁺ levels in the range of 10–80 mm in vitro. Further, the isopropoxy‐substituted N‐phenylaza[18]crown‐6 ionophore in 6 is a highly K⁺‐selective building block with a feasible synthetic route.