Design of Na⁺‐Selective Fluorescent Probes: A Systematic Study of the Na⁺‐Complex Stability and the Na⁺/K⁺ Selectivity in Acetonitrile and Water

Abstract

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 ) to investigate the Na /K selectivity and Na - complex stability in CH CN and H O. 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 CH CN 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 CH CN 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 CH CN 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 H O, 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 =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 K 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.

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

“…[5d, 8] The long-wavelength CT absorptions for the coumarin-derived derivatives are centered at 425 nm for 2,a t4 27 nm for 4 and at 420 nm for 10, which is comparable to the coumarin CT absorption at 422 nm for 1.As lightly red-shifted long wavelength CT is found for 5 at 430 nm and for 6 at 435 nm. For 2, 4, 5, 6 and 10,t he second CT absorption band, whichi st ypical for p-conjugated anilino-1,2,3-triazol-1,4-diyl-fluoroionophores, [8] can be found for 2, 4, 5, 6 and 10 at around 300 nm corresponding to aC T from the nitrogen lone pair of the aromatic ring (donor) to the 1,2,3-triazole acceptor unit. Further,w es tudied the influence of Na + and K + towards the UV/Vis absorption of 2, 4, 5, 6 and 10 in aH 2 O/DMSO( v/v,9 9/1) mixture.F or 2, 4, 5, 6 and 10,w e found no change of the long-wavelength absorptioni nt he presenceo fN a + or K + (cf.…”

A Ratiometric Fluorescent Probe for K+ in Water Based on a Phenylaza‐18‐Crown‐6 Lariat Ether

“…Furthermore, the CT absorption band of 1 at 330 nm belongs to a CT from the anilinotriazole donor moiety to the anthryl acceptor unit, as also shown for probe 3 . Herein, we observed for 1 compared with 3 (CT at 423 nm) a blue‐shifted and less intense CT band about 330 nm (Figure S1 a in the Supporting Information), because 1 possesses a weaker electron donor unit than the reference compound 3 , as already discussed for the series of crown compounds with a bulky substituent in the ortho position of the aniline donor moiety . Further, we found for 2 superimposed absorptions about 370 nm, which partially corresponding to a CT from the anilinotriazole donor moiety to the pyrenyl acceptor unit.…”

Benzo[g]coumarin-Based Fluorescent Probes for Bioimaging Applications

“…Accordingly, a development of tools for selective detection of Na + over K + is very important and challenging. Recently, Holdt et al designed a Na + selective fluorescent probe based on the benzo[ g ]coumarin derivatives which have an N -( o -methoxyphenyl)aza-15-crown-5 moiety ( 23 ; Figure 5 ) [ 20 ]. A higher Na + /K + selectivity of 23 was observed, but also, it gives a higher K d value (223 mM) as a limitation for detection of lower concentration of Na + .…”