benzoboroxole - VOLUME 73, NUMBER 17 September 5, 2008...

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Benzoboroxoles as EfFcient Glycopyranoside-Binding Agents in Physiological Conditions: Structure and Selectivity of Complex ±ormation Marie Be ´rube ´, Meenakshi Dowlut, and Dennis G. Hall* Department of Chemistry, Uni V ersity of Alberta, Edmonton, Alberta T6G 2G2, Canada Recei V ed April 10, 2008 In contrast to normal boronic acids, o -hydroxymethyl phenylboronic acid (benzoboroxole) has the capability of complexing glycopyranosides efFciently 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. Introduction The selective recognition of natural biopolymers by small molecules has been captivating organic chemists for several decades. High levels of efFciency and selectivity have been attained in targeting two of the three major biopolymers: polypeptides and oligonucleic acids. There has been much less success in targeting oligosaccharides. Although a number of synthetic receptors have been described for the recognition of complex carbohydrates in organic solvents, 1 it is notoriously difFcult to achieve the same success under physiological conditions (i.e., water, at neutral pH). 2 The essence of the problem lies in large part with the competition between the multiple hydroxyl groups on the carbohydrates and the over- whelming ones from the bulk solvent, water. The challenge of aqueous carbohydrate recognition presents several exciting opportunities in chemical biology and medicine. ±or example, the development of a selective and noninvasive molecular sensor for monitoring blood glucose has long been sought as a key component of insulin-releasing implants for diabetes patients. 3 Other potential applications include the sensing, transport, and puriFcation of complex carbohydrates. Any approach to the recognition of carbohydrates in water should take advantage of the intrinsic geometrical orientation of the sugar’s hydroxyl groups on the rigid oxacarbocyclic skeleton. In this regard, boronic acids have the ability to form boronic esters reversibly with polyols and sugars in water (eq 1, ±igure 1). 4,5 While the * To whom correspondence should be addressed. Tel: 780-492-3141. ±ax: 780-492-8231.
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This note was uploaded on 06/13/2011 for the course CHEMISTRY 213 taught by Professor Chale during the Spring '11 term at Beacon FL.

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benzoboroxole - VOLUME 73, NUMBER 17 September 5, 2008...

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