A new type of boronic acid fluorescent reporter compound for sugar recognition Wenqian Yang, a Li Lin a and Binghe Wang a,b, * a Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204, USA b Department of Chemistry and Center for Biotechnology and Drug Discovery, Georgia State University, Atlanta, GA 30302-4089, USA Received 23 August 2005; accepted 13 September 2005 Available online 30 September 2005 Abstract—Fluorescent boronic acids that change fluorescent properties upon carbohydrate binding are very useful for the prepara- tion of fluorescent sensors for sugars. Herein we report 5-quinolineboronic acid (5-QBA) that shows significant fluorescent property changes through a unique pK a -switching mechanism upon binding a diol in aqueous solution. Ó 2005 Elsevier Ltd. All rights reserved. Carbohydrates play a critical role in a variety of biolo- gical processes. 1 Lectin 2 mimetics that can recognize cer- tain carbohydrates with high affinity and specificity under near physiological conditions can be used in sens- ing, diagnostic, and therapeutic applications. In prepar- ing compounds for carbohydrate recognition, the boronic acid moiety holds a special place because of the ability for boronic acid to form tight and reversible complexes with diols, 3 which are commonly found on carbohydrates. Several laboratories have devoted much effort in this area to developing boronic acid-base fluo- rescent sensors for carbohydrates. 4,5 Our laboratory and others have been especially interested in the devel- opment of boronic acid compounds that can recognize complex carbohydrate biomarkers. 6 These compounds are essentially lectin mimetics and are therefore referred to as boronolectins. 3d,4e,h Our aim is to develop these boronolectins for diagnostic and therapeutic applica- tions. Along this line, we have studied fluorescent label- ing of mammalian cells based on their cell-surface carbohydrate biomarkers using small molecule chemo- sensors. 6a,b In our continuing effort to search for fluores- cent boronolectins for various biologically important carbohydrates, we are interested in developing a combi- natorial approach. In order to increase the structural and spectroscopic diversity in our libraries, we are in need of boronic acids of different structural classes that (1) change fluorescent properties upon binding and (2) are water soluble. 3d,4g,7 Herein we report 5-quinolineboronic acid (5-QBA) as a fluorescent reporter for carbohydrates, which shows large fluorescence intensity changes upon binding with carbohydrates in aqueous solution at physiological pH. More important, 5-QBA also shows an unique pK a -switching between the quinolinium and boronic acid groups upon binding with a diol and has much stronger binding with each individual sugar compared with 8-QBA. 5-QBA itself is essentially non-fluorescent at pH above 5 and weakly fluorescent at lower pH in aqueous solution. However, upon addition of D-fructose, the fluorescence intensity increased dramatically in a concentration- dependent manner (Fig. 1). In an effort to examine the N B OH HO 5-quinolineboronic acid (5-QBA) N B HO OH N B HO OH 5-QBA 8-QBA 0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2005.09.074 Keywords: Boronic acid; Sensing; Sensor; Fluorescent; Quinoline; pK a ; Sugar recognition; Heterocycles. * Corresponding author. Tel.: +1 4046 510289; fax: +1 4046 545827; e-mail: wang@gsu.edu Tetrahedron Letters 46 (2005) 7981–7984 Tetrahedron Letters