Fluorescent sensors saccharide

James TD (2007) Saccharide-Selective Boronic Acid Based Photoinduced Electron Transfer (PET) Fluorescent Sensors. 277 107-152... 

Arimori S, Bell ML, Oh CS et al (2001) Molecular fluorescence sensors for saccharides. Chem Commun 18 1836—1837... 

Appropriate combinations of boronic acid and fluorophores lead to a remarkable class of fluorescent sensors of saccharides (Shinkai et ah, 1997, 2000, 2001). The concept of PET (photoinduced electron transfer) sensors (see Section 10.2.2.5 and Figure 10.7) has been introduced successfully as follows a boronic acid moiety is combined intramolecularly with an aminomethylfluorophore consequently, PET from the amine to the fluorophore causes fluorescence quenching of the latter. In the presence of a bound saccharide, the interaction between boronic acid and amine is intensified, which inhibits the PET process (Figure 10.42). S-l is an outstanding example of a selective sensor for glucose based on this concept (see Box 10.4). 

Fig. 10.42. Fluorescent sensors of saccharides based on boronic acids (adapted from James T. D. et al. (1996) Chem.

Fluorescence sensors for saccharides are of particular interest in a practical sense. This is in part due to the inherent sensitivity of the fluorescence technique. Only small amounts of a sensor are required (typically 10-6 M), offsetting the synthetic costs of such sensors. Also, fluorescence spectrometers are widely available and inexpensive. Fluorescence sensors have also found applications in continuous monitoring using an optical fiber and intracellular mapping using confocal microscopy. 

Related optical and fluorescent sensor systems have been widely used. For instance, the fluorescence of the pyrene unit in species (187) is quenched upon saccharide binding to the boron center. Boronic acid groups were also attached to dendrimers and polymers. The benefit of systems containing at least two boronic acid centers, as shown for the luminescent saccharide sensor (187), is that two-point binding can more effectively control saccharide binding. Similar... 

Bis-boronate 7 forms a 1 1 complex with glucose selectively relative to other saccharides, and its enhanced fluorescence can be used as a glucose-selective molecular fluorescence sensor at physiological glucose concentrations." ... 

The use of boronic acids in the development of fluorescent sensors for saccharides is a comparatively new field (Scheme 3). Following the first report by Yoon and Czamik" o-glucose selectivity was achieved in 1994 by James et al. A year later, this was followed up by enan-tioselective saccharide recognition. The intervening years have seen the field grow to the point where hundreds of publications now report on boronic acid-saccharide recog-... 

As mentioned above, the first fluorescent sensor for saccharides was reported by Yoon and Czamik." The internal charge transfer (ICT) sensor 1 consisted of a boronic acid fragment directly attached to anthracene. On addition of saccharide, it was noted that the intensity of the fluorescence emission for the 2-anthrylboronic acid 1 was reduced by 30%. This change in fluorescence emission intensity is ascribed to the change in electronics that accompanies rehybridization at boron. For boronic acid 1 (below its pA a). the nentral sp hybridized boronic acid displayed a strong flnorescence emission (above its pA a) and the anionic sp boronate displayed a reduction in the intensity of fluorescence emission. 

We designed boronic acid receptor units in an AIDA-based (see Figure 5.22) fluorescent sensor array to differentiate neutral mono- and disaccharides in aqueous solution at neutral pH. With this array we were able to diseriminate among 12 saccharides at 2 mM concentration. The array consists of the... 

Fluorescent Sensors. As boronic acids can bind to saccharides reversibly, when attached to a fluorophore, the fluorescence of the fluoro-phore can be modulated upon the formation of boronate-saccharide complex. Numerous boronic acid-based fluorescence glucose sensors have been reported in the literature. However, most systems were designed for solution measurements, which are inconvenient for real-time and real-space measurements and can not be used repetitively. For a glucose sensor to be useful in a device, the sensing components must be immobilized to allow for real-time monitoring. 

T. D. James, K. R. A. S. Sandanayake and S. Shinkai, A glucose-specific molecular fluorescence sensor, Angem Chem.,1994,106(21), 2287-2289. T. D. James, K. R. A. S. Sandanayake, R. Iguchi and S. Shinkai, Novel Saccharide-Photoinduced Electron-Transfer Sensors Based on the Interaction of Boronic Acid and Amine,/ Am. Chem. Soc., 1995, 117(35), 8982-8987. 

A. Schiller, R. A. Wessling and B. Singaram, A fluorescent sensor array for saccharides based on boronic acid appended bipyridinium salts, Angew. Chem., Int. Ed., 2007,46(34), 6457-6459. 

The first fluorescent sensors for saccharides were based on fluorophore appended boronic acids. Czarnik showed that 2- and 9- anthrylboronic acid [36, 37] (1 and 2) could be used to detect saccharides (Figure 12.2). With these systems, the negatively charged boronate has a lower fluorescence than the neutral boronic acid. Since the pFC of a boronic acid is lowered on saccharide binding, the fluorescence of these systems at a fixed pH decreases when saccharides are added. The observed stability constant (f pp) for 1 was 270 with D-fructose at pH 7.4 (phosphate buffer). 

James and co-workers have prepared 12a, a monoboronic acid fluorescent sensor that shows large shifts in emission wavelength on saccharide binding [50]. The dual fluorescence of 12a, can be ascribed to locally excited (LE) and twisted internal charge transfer (TICT) states of the aniline fluorophore [51]. When saccharides interact with sensor 12a in aqueous solution at pH 8.21 the emission maxima at 404 nm (TICT state) shifts to 362 nm 274 nm, LE state). The band at 404 nm is due to the TICT state of 12a containing a B-N bond i.e. the lone pair is coordinated with the boron and perpendicular to the jt-system. The band at 274 nm (LE state) corresponds to the situation where the B-N bond in 12a has been broken with formation of the boronate (Scheme 12.3). 

With 14 the free amine reduces the intensity of the fluorescence (quenching by PET). This is the off state of the fluorescent sensor. When sugar is added, the amine becomes coordinatively bound to the boron center. The boron-bound amine cannot quench the fluorescence and hence a strong fluorescence is observed. This is the on state of the fluorescent sensor. The system described above illustrates the basic concept of an off-on fluorescent sensor for saccharides (Scheme 12.4). 

Photoinduced electron transfer (PET) has been wielded as a tool of choice in fluorescent sensor design for protons and metal ions. Design of fluorescent sensors for neutral organic species presents a harsher challenge due to the lack of electronic changes upon inclusion. The design of a fluorescent sensor based on the boronic acid saccharide interaction has been difficult due to the lack of sufficient electronic changes found in either the boronic acid moiety or in the saccharide moiety. Furthermore, facile boronic... 

Figure 15 The first fluorescent sensor for saccharides 2-anthrylboronic acid 36, as well as its isomer 9-anthrylboronic acid 37. Recognition of saccharides was mediated by an apparent decrease in fluorescence intensity, due to the formation of the boronate anion.

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