Synthesis and Evaluation of Dual Wavelength Fluorescent Benzo[b]thiophene Boronic Acid Derivatives for Sugar Sensing

Abstract

Cell surface glycoproteins have been known to play very important roles in various physiologic and pathologic processes. Small molecule compounds capable of carbohydrate recognition can be very useful for the development of sensing, diagnostic, and therapeutic agents. Along this line, we are interested in developing water-soluble fluorescent boronic acid compounds for carbohydrate recognition. As such, a series of benzo[b]thiophene boronic acid derivatives have been synthesized and their fluorescent properties analyzed at physiologic pH. Benzo[b]thiophene derivatives were found to be a new type of fluorescent reporter compounds capable of dual fluorescent emission under physiologic pH conditions. Compounds 1, 3, 4, 5, and 6 showed unusual emission wavelength shifts upon binding of sugars. These boronic acids will be useful tools for building glycoprotein biosensors for biologic applications.

Fluorescent Analogs of Biomolecular Building Blocks: Design, Properties, and Applications

“…These design principles have been refined and advanced, resulting in a multitude of colorimetric and fluorometric sensors for carbohydrates. Examples include N -phenylnaphthalimide sensors ( 3.3 ),82–84 stilbenes ( 3.4 ),81 as well as boronic acids derived from quinoline ( 3.5 ),85 naphthalene ( 3.6 ),86 nitrophenol ( 3.7 ),87 and benzothiophene ( 3.8 ) 88. Their structures and properties are discussed in a number of overview articles 86,89–94…”

Carbohydrate recognition by boronolectins, small molecules, and lectins

“…Recent work in the Wang lab includes compounds shown in Figure 4. Among them, six benzo[b]thiophene boronic acid (BTBA) analogs ( 9a–f ) (Figure 4) were reported as fluorescent reporters 249. All six compounds showed significant fluorescent property changes upon sugar binding with good water solubility under physiological condition.…”

Covalent Interactions in Chemosensor Design

“…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.…”