Benzoboroxoles as Efficient Glycopyranoside-Binding Agents in Physiological Conditions: Structure and Selectivity of Complex Formation

Abstract

In contrast to normal boronic acids, o-hydroxymethyl phenylboronic acid (benzoboroxole) has the capability of complexing glycopyranosides efficiently in neutral water. The measurement of association constants with a panel of model hexopyranosides indicates that the preferred mode of binding is through a cis-3,4-diol, such as that found in galactopyranosides, and mass spectrometric studies support a 1:1 binding stoichiometry. The complexation of glucopyranosides is weaker, and they are bound through their 4,6-diol unit. Although several factors may explain the exceptional carbohydrate-binding behavior of this class of hemiboronic acids, the relatively high Lewis acidity of benzoboroxoles is a likely contributing factor along with subtle factors such as intramolecular hydrogen bonds with other hydroxyl groups in the resulting anionic complex. These results with hexopyranosides suggest that biologically relevant cell-surface oligosaccharides could be targeted in water using oligomeric benzoboroxole receptors.

Recent Advances in the Synthesis and Applications of Organoborane Polymers

“…Sumerlin and coworkers demonstrated that linkage of the phenylboronic acid moiety through the electronwithdrawing carboxyl rather than amino group of an amide (54) results in similarly enhanced sugar binding at neutral pH [41]. In a different approach, Kiser and coworkers incorporated more acidic boroxoles [139,140] into polymer structures [141][142][143][144]. Related block copolymers (55,56) were investigated by Kim and coworkers as building blocks of responsive vesicles for insulin release applications [36,40].…”

Reversible Covalent Bond Toolbox

“…As a prelude, in 2006, the Hall lab first reported ortho-hydroxymethyl phenylboronic acid (5, Figure 1), which has a weak but encouraging binding with a model of hexopyranosides (methyl α-D-glucopyranoside). 23,24 This is especially important, since carbohydrates found in glycoproteins, glycolipids, and lipopolysaccharides are almost always six-membered ring sugars and linear diols, while most boronic acids normally show a preference for furanose sugars in binding. Compound 5 binds methyl α-D-glucopyranoside with a K a of 22 M −1 in neutral aqueous media by complexing hexopyranosides primarily using their 4,6-diol.…”

Covalent Interactions in Chemosensor Design

“…This was followed by a decade of very active work in the design and synthesis of sensors for monosaccharides and oligosaccharides. Efforts in recent years have moved to a more biological direction, with applications in glycan analysis [29,[53][54][55][56][57], recognitions of cell-surface carbohydrate biomarkers [5,58], and glycoproteins [57], as well as array analyses [59][60][61], which is the subject of Chapter 17. For biological applications, these boronic-acid-based sensors and receptors function in a manner similar to lectins (carbohydrate-binding proteins).…”

“…Several recent reviews and research papers comprehensively summarize the use of boronic acids in sensor designs for carbohydrates [9,[14][15][16]66], fluoride [47][48][49][50][51], and cyanides [45,46], and have in-depth discussions of factors [15,19,67] that should be considered in designing such sensors. In addition, there have also been quite a few reviews [8,15,66] and research papers [54,[68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85] on boronic acids that change their fluorescent properties upon binding to a nucleophilic analyte or pH changes. Obviously, it would not be possible to describe all these findings here; therefore, readers are referred to the above-referenced papers for details.…”

“…In the first example, the Hall laboratory in 2006 reported an ortho-hydroxymethyl phenylboronic acid (5, Scheme 3.2), which was shown to be superior in carbohydrate binding to the well-established diaklyamino (Wulfftype) analogs with better binding affinity and solubility [29,54]. The most significant finding of compound 5 is the weak but encouraging binding with model glycopyranosides.…”