TY - JOUR A1 - Schwarze, Thomas A1 - Schneider, Radu A1 - Riemer, Janine A1 - Holdt, Hans-Jürgen T1 - 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 JF - Chemistry : an Asian journal ; an ACES journal N2 - 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 -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 19mm, but the K-d value increases to 31mm 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+)=45mm and K-d(K+/Na+)=45mm) 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 10-80mm 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. KW - crown compounds KW - fluorescence KW - fluorescent probes KW - potassium KW - sodium Y1 - 2016 U6 - https://doi.org/10.1002/asia.201500956 SN - 1861-4728 SN - 1861-471X VL - 11 SP - 241 EP - 247 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Ast, Sandra A1 - Schwarze, Thomas A1 - Müller, Holger A1 - Sukhanov, Aleksey A1 - Michaelis, Stefanie A1 - Wegener, Joachim A1 - Wolfbeis, Otto S. A1 - Körzdörfer, Thomas A1 - Dürkop, Axel A1 - Holdt, Hans-Jürgen T1 - A highly K+-Selective Phenylaza-[18]crown-6-Lariat-Ether-Based Fluoroionophore and its application in the sensing of K+ Ions with an optical sensor film and in cells JF - Chemistry - a European journal N2 - Herein, we report the synthesis of two phenylaza-[18]crown-6 lariat ethers with a coumarin fluorophore (1 and 2) and we reveal that compound 1 is an excellent probe for K+ ions under simulated physiological conditions. The presence of a 2-methoxyethoxy lariat group at the ortho position of the anilino moiety is crucial to the substantially increased stability of compounds 1 and 2 over their lariat-free phenylaza-[18] crown-6 ether analogues. Probe 1 shows a high K+/Na+ selectivity and a 2.5-fold fluorescence enhancement was observed in the presence of 100 mm K+ ions. A fluorescent membrane sensor, which was prepared by incorporating probe 1 into a hydrogel, showed a fully reversible response, a response time of 150 s, and a signal change of 7.8% per 1 mm K+ within the range 1-10 mm K+. The membrane was easily fabricated (only a single sensing layer on a solid polyester support), yet no leaching was observed. Moreover, compound 1 rapidly permeated into cells, was cytocompatible, and was suitable for the fluorescent imaging of K+ ions on both the extracellular and intracellular levels. KW - crown compounds KW - fluorescence KW - gels KW - potassium KW - sensors Y1 - 2013 U6 - https://doi.org/10.1002/chem.201302350 SN - 0947-6539 SN - 1521-3765 VL - 19 IS - 44 SP - 14911 EP - 14917 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Schwarze, Thomas A1 - Riemer, Janine A1 - Holdt, Hans-Jürgen T1 - A Ratiometric Fluorescent Probe for K+ in Water Based on a Phenylaza-18-Crown-6 Lariat Ether JF - Chemistry - a European journal N2 - This work presents two molecular fluorescent probes 1 and 2 for the selective determination of physiologically relevant K+ levels in water based on a highly K+/Na+ selective building block, the o-(2-methoxyethoxy)phenylaza-18-crown-6 lariat ether unit. Fluorescent probe 1 showed a high K+-induced fluorescence enhancement (FE) by a factor of 7.7 of the anthracenic emission and a dissociation constant (K-d) value of 38mm in water. Further, for 2+K+, we observed a dual emission behavior at 405 and 505nm. K+ increases the fluorescence intensity of 2 at 405nm by a factor of approximately 4.6 and K+ decreases the fluorescence intensity at 505nm by a factor of about 4.8. Fluorescent probe 2+K+ exhibited a K-d value of approximately 8mm in Na+-free solutions and in combined K+/Na+ solution a similar K-d value of about 9mm was found, reflecting the high K+/Na+ selectivity of 2 in water. Therefore, 2 is a promising fluorescent tool to measure ratiometrically and selectively physiologically relevant K+ levels. KW - charge transfer KW - crown compounds KW - fluorescence KW - potassium KW - ratiometric sensors Y1 - 2018 U6 - https://doi.org/10.1002/chem.201802306 SN - 0947-6539 SN - 1521-3765 VL - 24 IS - 40 SP - 10116 EP - 10121 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Schwarze, Thomas A1 - Mueller, Holger A1 - Schmidt, Darya A1 - Riemer, Janine A1 - Holdt, Hans-Jürgen T1 - Design of Na+-Selective Fluorescent Probes: A Systematic Study of the Na+-Complex Stability and the Na+/K+ Selectivity in Acetonitrile and Water JF - Chemistry - a European journal N2 - There is a tremendous demand for highly Na+-selective fluoroionophores to monitor the top analyte Na+ in life science. Here, we report a systematic route to develop highly Na+/K+ selective fluorescent probes. Thus, we synthesized a set of fluoroionophores 1, 3, 4, 5, 8 and 9 (see Scheme 1) to investigate the Na+/K+ selectivity and Na(+-)complex stability in CH3CN and H2O. These Na+-probes bear different 15-crown-5 moieties to bind Na+ stronger than K+. In the set of the diethylaminocoumarin-substituted fluoroionophores 1-5, the following trend of fluorescence quenching 1 > 3 > 2 > 4 > 5 in CH3CN was observed. Therefore, the flexibility of the aza-15-crown-5 moieties in 1-4 determines the conjugation of the nitrogen lone pair with the aromatic ring. As a consequence, 1 showed in CH3CN the highest Na+-induced fluorescence enhancement (FE) by a factor of 46.5 and a weaker K+ induced FE of 3.7. The Na+-complex stability of 1-4 in CH3CN is enhanced in the following order of 2 > 4 > 3 > 1, assuming that the O-atom of the methoxy group in the ortho-position, as shown in 2, strengthened the Na+-complex formation. Furthermore, we found for the N( o-methoxyphenyl) aza-15-crown-5 substituted fluoroionophores 2, 8 and 9 in H2O, an enhanced Na+-complex stability in the following order 8 > 2 > 9 and an increased Na+/K+ selectivity in the reverse order 9 > 2 > 8. Notably, the Na+-induced FE of 8 (FEF = 10.9), 2 (FEF = 5.0) and 9 (FEF = 2.0) showed a similar trend associated with a decreased K+-induced FE [8 (FEF = 2.7) > 2 (FEF = 1.5) > 9 (FEF = 1.1)]. Here, the Na+-complex stability and Na+/K+ selectivity is also influenced by the fluorophore moiety. Thus, fluorescent probe 8 (K-d = 48 mm) allows high-contrast, sensitive, and selective Na+ measurements over extracellular K+ levels. A higher Na+/K+ selectivity showed fluorescent probe 9, but also a higher Kd value of 223 mm. Therefore, 9 is a suitable tool to measure Na+ concentrations up to 300 mm at a fluorescence emission of 614 nm. KW - crown compounds KW - fluorescence KW - fluorescent probes KW - potassium KW - sodium Y1 - 2017 U6 - https://doi.org/10.1002/chem.201605986 SN - 0947-6539 SN - 1521-3765 VL - 23 SP - 7255 EP - 7263 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Schwarze, Thomas A1 - Riemer, Janine A1 - Müller, Holger A1 - John, Leonard A1 - Holdt, Hans-Jürgen A1 - Wessig, Pablo T1 - Na+ Selective Fluorescent Tools Based on Fluorescence Intensity Enhancements, Lifetime Changes, and on a Ratiometric Response JF - Chemistry - a European journal N2 - Over the years, we developed highly selective fluorescent probes for K+ in water, which show K+-induced fluorescence intensity enhancements, lifetime changes, or a ratiometric behavior at two emission wavelengths (cf. Scheme 1, K1-K4). In this paper, we introduce selective fluorescent probes for Na+ in water, which also show Na+ induced signal changes, which are analyzed by diverse fluorescence techniques. Initially, we synthesized the fluorescent probes 2, 4, 5, 6 and 10 for a fluorescence analysis by intensity enhancements at one wavelength by varying the Na+ responsive ionophore unit and the fluorophore moiety to adjust different K-d values for an intra- or extracellular Na+ analysis. Thus, we found that 2, 4 and 5 are Na+ selective fluorescent tools, which are able to measure physiologically important Na+ levels at wavelengths higher than 500 nm. Secondly, we developed the fluorescent probes 7 and 8 to analyze precise Na+ levels by fluorescence lifetime changes. Herein, only 8 (K-d=106 mm) is a capable fluorescent tool to measure Na+ levels in blood samples by lifetime changes. Finally, the fluorescent probe 9 was designed to show a Na+ induced ratiometric fluorescence behavior at two emission wavelengths. As desired, 9 (K-d=78 mm) showed a ratiometric fluorescence response towards Na+ ions and is a suitable tool to measure physiologically relevant Na+ levels by the intensity change of two emission wavelengths at 404 nm and 492 nm. KW - crown compounds KW - fluorescence lifetime KW - fluorescent probes KW - ratiometric KW - sodium Y1 - 2019 U6 - https://doi.org/10.1002/chem.201902536 SN - 0947-6539 SN - 1521-3765 VL - 25 IS - 53 SP - 12412 EP - 12422 PB - Wiley-VCH CY - Weinheim ER -