Sensors for saccharides

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

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. 

The first fluorescence PET sensors for saccharides were based on fluorophore boronic acids. Czarnik and Yoon showed that 2- and 9-anthryboronic acid [50] 19 and 20 could be used to detect saccharides. However, the fluorescence change was small [/ (in the presence of saccharide)// (in the absence of saccharide) = ca. 0.7], The pA/a of the fluorophore boronic acids are shifted by saccharide present in the medium. The extent of the effect is in line with the inherent selectivity of phenylboronic acid [49], The PET from the boronate anion is believed to be the source of the fluorescence quenching. Although... 

James TD, Samankumara KRAS, Shinkai S. Novel photoinduced electron-transfer sensor for saccharides based on the interaction of boronic acid and amine. Chemical Communications 1994, 4, 477 178. 

James, T.D. (2005) Boronic Acid-Based Receptors and Sensors For Saccharides, in Boronic Acids (ed. D.G. Hall), Wiley-VCH, Weinheim, Ch. 12,... 

Recently, Fabre et al. [31] and Freund et al. [7, 8] used electro-chemically deposited, self-doped, boronic-acid-substituted, conducting polymers for saccharide and fluoride detection. Freund et al. prepared a potentiometric sensor for saccharides using self-doped PABA [7, 8]. The transduction mechanism in that system is reportedly the change in pKa of polyaniline that accompanies complexation, and the resulting change in the electrochemical potential. Sensors produced with this approach exhibit reversible responses with selectivity to various saccharides and 1,2-diols (Figure 3.22) that reflect their binding constants with phenylboronic acid observed in bulk solutions. The sensitivity... 

The primary interaction of a boronic acid with a diol is covalent and involves the reversible and rapid formation of a cyclic boronate ester. An array of hydroxyl groups presented by saccharides provides an ideal architecture for these interactions and has led to the development of boronic acid-based sensors for saccharides (Scheme 1). 

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. 

Colorimetric sensors for saccharides are of particular interest in a practical sense. If a system with a large color change can be developed, it could be incorporated into a diagnostic test paper for saccharides, similar to universal indicator paper for pH. Such a system would make it possible to measure o-glucose concentrations without the need of specialist instrumentation. This would be of particular benefit to diabetic patients in developing countries. 

James has prepared a ferrocene monoboronic acid 64 and diboronic acid 65 as electrochemical saccharide sensors. The monoboronic acid system 64 has also been prepared and proposed as an electrochemical sensor for saccharides by Norrild and Sotofte. The electrochemical saccharide sensor 65 contains two boronic acid units (saccharide selectivity), one ferrocene unit (electrochemical read out), and a hexamethylene linker unit (for D-glucose selectivity). The electrochemical sensor 65 displays enhanced D-glucose (40 times) and D-galactose (17 times) selectivity when compared to the monoboronic acid 64. 

Figure 17 Fluorescence-based PET sensors for saccharides utilize the ability of 2-aminomethylphenyl boronate moieties to form a boron-nitrogen bond, which results in modulation of the sensor fluorescence. (Reproduced from Ref. 190. Wiley-VCH, 1994.)...

I 12 Boronic Acid-based Receptors and Sensors for Saccharides... 

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). 

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). 

Nakashima has prepared a phenylboronic acid terminated redox active self-assembled monolayer on a gold electrode as an electrochemical sensor for saccharides. Self-assembled monolayers of 89, a phenylboronic acid terminated viologen alkyl disulfide, function as a sensitive saccharide sensor in aqueous soluhon [168]. 

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