Boronic Acid Appended Naphthyl-Pyridinium Receptors as Chemosensors for Sugars

Angel Resendez,Sanjay V Malhotra

doi:10.1038/s41598-019-42812-8

Abstract

There remains a need in clinics and research to have simple and sensitive detection systems that allow the detection and quantification of sugar markers of biomedical relevance such as sugars lactulose and mannitol for noninvasive gut permeability assessment. We have prepared a new class of boronic acid-appended naphthyl-pyridinium receptor compounds as chemosensors. These were studied for their ability to act as modular internal charge transfer (ICT) fluorescent probes or donor/acceptor pair ensembles where the receptor compound can act as a quencher for an anionic dye. As an ICT sensor, fluorescence intensity increased upon diol recognition, which stems from the neutralization of the pyridinium nitrogen that is perturbing the chromophoric properties. We found these ICT probes provide good sensitivity for disaccharide lactulose with low micromolar detection and quantification limits. In addition, their ability to form a non-fluorescent ground state complex with anionic reporter dyes, such as HPTS or TSPP, was examined as probes for various sugars. We have identified three receptor/quencher compounds with high quenching efficiency for anionic dyes. Subsequently, a range of sugars and sugar derivatives were tested for chemosenstivity of our probes. This study illustrates an approach for designing boronic acid-based chemoreceptors for the recognition and quantification of sugars and sugar derivatives.

Highlights

Indicator displacement assays (IDA) have been reported as competitive binding assay systems26–32, where the receptor and indicator units are two discrete entities which can provide advantages, such as signal modulation and ease of modification of receptor system over direct sensing (Fig. 1)
With the ability to overcome sensitivity and/or selectivity challenges that come with boronic acid-based recognition systems, we pursued a naphthalene moiety as a new quencher along with anionic dyes such as HPTS and tetrakis (4-sulfophenyl) porphine (TSPP)
We envisioned designing a new type of boronic acid-based chemosensor that relies on quaternary nitrogen that is separate from the fluorophore unit, and primarily responsible for the internal charge transfer (ICT) mechanism

Summary

Introduction

Indicator displacement assays (IDA) have been reported as competitive binding assay systems, where the receptor and indicator (or reporter) units are two discrete entities which can provide advantages, such as signal modulation and ease of modification of receptor system over direct sensing (i.e., one-component systems) (Fig. 1). The two-component system relies on the cationic nature of the receptor compound to form a non-fluorescent ground state complex with the anionic fluorescent dye, 8-hydroxypyrene, 1,3,6-trisulfonic acid trisodium salt (HPTS), and a boronic acid–appended viologen (BBV) that acts as both a quencher and receptor. Studies of several boronic acid-appended viologens that possess both bipyridinium or phenanthrolinium cores have been previously reported35 The ability of these viologens to quench the fluorescence of various anionic reporters is directly proportional to the number of cationic charges on the quencher. To alleviate the need for a large number of cationic groups, we investigated new boronic acid-appended quenchers with ortho substitution for improved ability to [1] quench the fluorescence of an anionic reporter and [2] improve the sensitivity for the recognition of sugars and sugar derivatives. The combination of each probe (receptor-dye) was investigated for their performance in recognizing various sugars and sugar derivatives

Methods

Results

Conclusion