Boronic Acids with Saccharides

In the field of observation, chance favours only the prepared mind 

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The interaction of boronic acids with saccharides " and anions has been extensively investigated, and boronic acids have also been exploited in a range of applications as diverse as sensing and separation, " NMR (nuclear magnetic resonance) shift reagents, functional polymers for electrophoresis, and molecular self-assembled capsules and materials. 

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-... 

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 reversible interaction of boronic acids with diol motifs has been exploited in separation science to great effect. Incorporation of boronic acids into the various stationary phases employed in chromatographic techniques has allowed for saccharide-selective or specific separation protocols to be developed. A particularly noteworthy area that lies out with the remit of this current chapter is the development of boron affinity columns used in HPLC, a collection of pertinent references are, however, provided. 

James and co-workers have prepared a ferrocene monoboronic acid (73) and di-boronic acid (74) as electrochemical saccharide sensors (Figure 12.14) [141]. Monoboronic acid system 73 has also been prepared and proposed as an electrochemical sensor for saccharides by Norrild [142]. Electrochemical saccharide sensor 74 contains two boronic acid units (saccharide selectivity), one ferrocene unit (electrochemical read out) and a hexamethylene linker imit (for D-glucose selectivity). Electrochemical sensor 74 displays enhanced D-glucose (40x) and D-galactose (17x) selectivity compared with the monoboronic acid 73. 

Scheme 17 In addition to the pair-wise interaction of boronic acids with polyhydroxyl species discussed, boronic acids also form stable complexes with buffer conjugate bases. These complexes can be formed between both the free boronate anion and Lewis bases as well as between saccharide boronate complexes and Lewis bases. Not recognised until 2004, these species persist into acidic solution and under certain stoichiometric conditions can become the dominant component in the solution. The two modes of interaction between the phenylboronate anion and phosphate are illustrated here.

Computational data and observed experimental results indicate that strong binding between boronic acids and saccharides occurs preferentially with saccharides that have an available anomeric hydroxyl pair, which has the capacity to conform to a j yn-periplanar alignment. In the vast majority of cases, this requires formation of the furanose form of the saccharide. 

Fig. 42. A series of boronic acids 159-166 with chromophoric groups has been evaluated with respect to its capacity to selectively bind d-glucose or other saccharides...

Boronic acid-containing polyaniline has also been utilized in diabetes-related research. One such polymer (23) (Fig. 17) has been observed to exhibit a linear near-infrared optical response to saccharides.43 The polymer was prepared by the copolymerization of aniline with 3-aminophenylboronic acid using lOmM (NH4)S208 in 1M HC1. The films were observed to undergo changes in the absorption spectra on addition of saccharides at pH 7.2. 

T.D. James, K.R.A.S. Sandanayake, S. Shinkai, Saccharide sensing with molecular receptors based on boronic acid , Angew. Chem, Int. Ed. EngL 1996, 35, 1910-1922. 

Shinkai et al. described the synthesis of dendritic saccharide sensors based on a PAMAM dendrimer labeled with eight boronic acid residues [183]. The dendritic compound showed enhanced binding affinity for D-galactose and d-fructose. The fact that the dendritic boronic acid functions as a saccharide sponge is ascribed primarily to the cooperative action of two boronic acids to form an intramolecular 2 1 complex. When one boronic acid binds a saccharide, its counterpart cannot participate in dimer formation and seeks a guest. 

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). 

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