Boronic acid-based fluorescent sensors

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

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

Badugu R, Lakowicz JR, Geddes CD. Fluorescence sensors for monosaccharides based on the 6-methylquinolinium nucleus and boronic acid moiety potential application to ophthalmic diagnostics. Talanta 2005, 65, 762-768. 

Fang H, Kaur G, Wang B. Progress in boronic acid-based fluorescent glucose sensors. Journal of Fluorescence 2004, 14, 481 489. 

Figure 4 The boronic acid-based fluorescent monomer (18) used for the preparation of imprinted polymeric sensors for carbohydrates.

The most popnlar class of the boronic acid-based sensors utilize an amine gronp proximal to boron coupled to a fluorescence outpnL The Lewis acid-Lewis base interaction between the boronic acid and the tertiary amine has a dual role. Firstly, it enables molecular recognition at nentral pH. Secondly, it can be nsed to signal binding by modnlating the intensity of flnorescence emissions. 

Figure 3 The first rationally designed boronic acid-based fluorescent PET sensor to display selectivity for D-glucose. The receptor-spacer-fiuorophore-spacer-receptor assembly requires binding to occur at both receptors in order to restore fluorescence.

Boronic acid-based biosensors to detect saccharides The recognition of saccharides, especially o-glucose, is of particular interest, owing to their correlation to diabetes and human cancers. The specific recognition of boronic acid for -diols provides a sensing selectivity. In the sugar sensors based on boronic acids (Figure 8), fluorescent, colorimetric, or electrochemical methods can be used as readout units. 

Heinrichs G, Schellentrager M, Kubik S (2006) An enantioselective fluorescence sensor for glucose based rai a cyclic tetrapeptide containing two boronic acid binding sites. Eur J Org Chem 18 4177-4186... 

Boronic acid-based fluorescent probes have been developed as sensors for fluoride ions as a consequence of the fact that trivalent boron forms strong covalent bonds with this ion. Because the B-0 bond in arylboronic acids is labile under protic conditions, in the presence of fluoride a series of equilibria is established (Scheme 4.1),in which boron participates in a OH"/F exchange process. 

The chiral unit is also important in the design of carbohydrate-selective boronic acid-based probes. " PET-based fluorescent probes containing the stereogenic centers were also developed to enhance selectivities towards sugars. Representative examples include the chiral sensors (R)-C-l, (iS)-C-l, (R)-C-2 and (iS )-C-2 and the achiral probes C-3a, C-3b and C-4 (Figure 4.4). The results of this study show that the chiral probes are more selective... 

Figure 6.10 a-Methylnaphthylamine based chiral fluorescent bis-boronic acid sensors (R,i )-(-)-7 and (S,5 )-(+)-7. 

Boronic acid-derived fluorescent chemosensors are unique in that the inter-molecular interaction is a covalent bond, and not hydrogen bonding as is the case for most conventional fluorescent molecular sensors used for the selective reeognition of hydroxyl carboxylic acids. This chapter summarizes the development of the boronic acid-based chiral fluorescent chemosensors over recent years and the enantioselective fluorescent reeognition of chiral a-hydroxyl carboxylic acids analytes in aqueous solutions. The fundamental scaffolds of these chiral sensors include a fluorophore, an arylboronie aeid binding site, and linker between the two units. The systems usually consist of a bis-boronic acid unit, which is required for enantioselective recognition of the chiral a-hydroxyl carboxylic acid analytes. However, mono-boronic acid fluorescent chemosensors have also been developed. All three components of the chiral boronic acid sensors play an important role in determining 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. 

Zhao and co-workers describe boronic acid based systems for enantioselec-tive fluorescent recognition. The scaffold used for the chiral sensors employs a fluorophore, arylboronic acid binding sites (two are best) and a linker (of appropriate size for the guest) between the two receptors. 

I 72 Boronic Acid-based Receptors and Sensors for Saccharides FLUORESCENT NON-FLUORESCENT NON-FLUORESCENT... 

In this review, we discussed sugar recognition by boronic acid-based fluorescent sensors and azoprobes in combination with CD, with focus on our research. Among the... 

Boronic acid-based fluorescent PET sensors developed for the recognition of simple monosaccharides have been extended to include ditopic recognition sites and so introduce selectivity for a diverse range of guest species. 

The introduction of a carefully located tertiary amine proximal to the boron centre of a fluorescent sensor permits the sensor to function at lower pH and introduces an off on optical response to the system via photoinduced electron transfer (PET). The tertiary amine boronic acid (N-B) interaction in a boronic acid-based PET sensor has strength in the range of 15 25 kJ mol . In an aprotic solvent, the N B dative bond is usually present. However, in a protic media, solvent insertion of the N-B occurs to afford a hydrogen-bonded zwitterionic species. 

Yang W, Yan J, Fang H et al (2003) The first fluorescent sensor for D-glucarate based on the cooperative action of boronic acid and guanidinium groups. Chem Commun 792-793... 

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). 

Carbohydrate detection is important for applications such as glucose monitors these are arguably one of the most successful and relevant biosensors. An interesting fluorescence recovery-type saccharide sensor based on the reactivity of carbohydrates with boronic acids was reported in 2002 [36]. Specifically, modification of the cationic viologen-linked boronic acid derivative 40 to a zwitterionic species 41 upon covalent and reversible reaction of boronic acid with monosaccharides (Scheme 1) can cause the dissociation of the ion-pair in-... 

A new PET-based chemosensor for uronic and sialic acids utilizing the cooperative action of boronic acid and metal chelate was reported by Shinkai and co-workers. This group synthesized a novel fluorescent chemosensor molecule bearing both an o-aminomethylphenylboronic acid group for diol binding to a saccharide and a l,10-phenanthroline-Zn(II)chelate moiety for the carboxylate binding, which enables this sensor to discriminate between neutral monosaccharides and acidic compounds [110],... 

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... 

More recently the boronic acid PET system has been used in combination with other binding sites. The D-glucosamine selective fluorescent systems 31 and 32 based on a boronic acid and azacrown ether have been explored [73,74], Sensors 31 and 32 consist of monoaza-18-crown-6 ether or monoaza-15-crown-5 as a binding site for the ammonium terminal of D-glucosamine hydrochloride, while a boronic acid serves as a binding site for the diol (carbohydrate) part... 

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