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

Abstract

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 Kd of 19 mm, but the Kd 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 Kd values (Kd (K+) =45 mm and Kd (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.

1,2,3‐Triazol‐1,4‐diyl‐Fluoroionophores for Zn2+, Mg2+ and Ca2+ based on Fluorescence Intensity Enhancements in Water

“…These φ f values are low, caused by a PET process from the aniline unit to the coumarin moiety, which quenches the fluorescence. Further, similar low φ f values were also found for a set of π ‐conjugated 1,2,3‐triazol‐1,4‐diyl–fluoroionophores [11a–e,12a−c] . Herein, the regioisomeric triazole linkage in Zn1 is responsible for a better fluorescence quenching than in Zn3 .…”

“…In a further study, they developed selective fluorescent probes for K + by using the highly K + /Na + selective ionophore the N ‐(o‐2‐methoxyethoxy)phenylaza‐18‐crown‐6 (cf. K1 and K2 , Scheme 2) [11a–e] and for Na + by using the highly Na + /K + selective ionophore the N ‐(o‐methoxyphenyl)aza‐15‐crown‐5 (cf. Na1 and Na2 , Scheme 2).…”

Na+ Selective Fluorescent Tools Based on Fluorescence Intensity Enhancements, Lifetime Changes, and on a Ratiometric Response

“…Scheme , see highly K + selective fluorescent probes K1 ‐ K4 ). Representatives for highly K + selective PET fluoroionophores are K1 and K2 consisting of highly K + selective building blocks the N ‐( o ‐2‐methoxyethoxy)phenylaza‐18‐crown‐6 in K1 and the isopropoxy substituted N ‐phenylaza‐18‐crown‐6 in K2 and of a diethylaminocoumarin unit as a fluorophore in both K1 and K2 , respectively. The PET fluoroionophore K3 consisting of a [1,3]dioxolo[4,5‐ f ][1,3]benzodioxole (DBD) fluorophore and of a highly K + selective ionophore (cf.…”

State-of-the-art: functional fluorescent probes for bioimaging and pharmacological research

“…Photoluminescent Carbon dots have been used as a fluorescent probe for the label-free detection of the potassium level in serum and red blood cells [47]. This fluorescent probe was reported to have an outstanding selectivity for K + /Na + and to be a suitable fluorescent tool to measure the physiological level of K + levels in the range of 10-80 mmol/L in vitro [48]. Another probe, TLSHalo, is useful to examine the K + transition in cells with high resolution and sensitivity, capable of visualizing dramatic changes of K + in cells [49].…”