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 i PrO ( 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 m m , but the K d value increases to 31 m m 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 m m and K d K+/Na+ =45 m m ) 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 m m 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.