Recognition of d-Glucose in Water with Excellent Sensitivity, Selectivity, and Chiral Selectivity Using γ-Cyclodextrin and Fluorescent Boronic Acid Inclusion Complexes Having a Pseudo-diboronic Acid Moiety

Abstract

Fluorescence recognition of d-glucose in water with excellent sensitivity, selectivity, and chiral selectivity is desired because d-glucose is an essential component in biological and pathological processes. We report an innovative approach that exploits the 1:2 stoichiometric inclusion complexes of γ-cyclodextrin (γ-CyD) with two molecules of fluorescent monoboronic acid-based receptors, which form a pseudo-diboronic acid moiety as the recognition site for d-glucose in water. Two monoboronic acids (1F and 2N) were easily synthesized without heating or column purification. The 1:2 stoichiometric inclusion complexes (1F/γ-CyD and 2N/γ-CyD) were prepared in a mixture of dimethyl sulfoxide/water (2/98 in v/v) by mixing γ-CyD and the corresponding monoboronic acids. Both 1F/γ-CyD and 2N/γ-CyD exhibited strong turn-on response to d-glucose with excellent selectivity over nine other saccharides in the water-rich solvent at pH 7.4 owing to the ditopic recognition of d-glucose by the pseudo-diboronic acid moieties. The limits of detection of 1F/γ-CyD and 2N/γ-CyD for d-glucose were 1.1 and 1.8 μM, respectively, indicating the remarkable sensitivity for the detection of d-glucose at μM levels. 1F/γ-CyD and 2N/γ-CyD also demonstrated chiral-selective recognition of d-glucose, which is apparent from the 2.0- and 6.3-fold enhancement of fluorescence by the addition of d-glucose relative to l-glucose addition, owing to the chiral pseudo-diboronic acid moieties produced by the chiral γ-CyD cavity. To the best of our knowledge, 2N/γ-CyD has the highest d/l selectivity among hitherto reported fluorescent diboronic acid-based receptors.

Enantioselective and Chemoselective Optical Detection of Chiral Organic Compounds without Resorting to Chromatography

“…In accordance with the findings [28] of Hashimoto et al, two fluorescent receptors based on γ-CD and two fluorescent molecules (i) 3-fluorophenylboronic acid and (ii) pyridyl boronic acid (Figure 3) were developed [29] by Suzuki et al The receptors formed a pseudo-diboronic acid moiety as the recognition site for D-glucose as inclusion complexes (1 : 2 stoichiometric) in water at pH 7.4. Both γ-CD based inclusion complexes showed much stronger dimeric fluorescence recognition of D-glucose by the pseudo-diboronic acid moieties in terms of strong turnon response to D-glucose with excellent selectivity over nine other saccharides (such as D-fructose, D-galactose, and Lglucose).…”

“…The experimental method to use any of the sensors for determining enantioselectivity or chemoselectivity or to establish the absolute configuration and ee/er of the chiral analyte should be considered as simple and quite normal in terms of treating the solution of sensor with the solution(s) of the chiral analyte followed by use of fluorescence, UV and CD spectrometers. Nevertheless, prior to use of sensor, the experimental approach additionally required application of very expensive multiple instrumentation, for example, (i) to establish the saccharide complex stoichiometry use of 1 H NMR and MS; [17] 1 H NMR, IR and elemental analysis; [12] ESI-MS, 1 H NMR and molecular modelling; [24] photoluminescence quantum yield measurement system, fluorescence lifetime measurement system, single-crystal X-ray diffractometer, and HPLC; [29] (ii) use of NMR, UV-Vis, and fluorescence spectroscopy, X-ray diffraction, SEM, and fluorescence microscopy for understanding the insights of the structure of the precipitate [41] (or the gel [42] ) and its strong fluorescence in the recognition of α-hydroxycarboxylic acids using the 1,1'-binaphthyl based sensor [(S)-c]; [41,42] (iii) application of 13 C NMR (600 MHz), gel permeation chromatography, laser refractometer, and HRMS to use chiral conjugated polymers for simultaneous determination of concentration and enantiomeric composition of chiral amino alcohols, prior to fluorescence measurement [52] made the overall method very cumbersome, time consuming and expensive; (iv) The synthesis of the sensor [(S)-f] required stirring of reaction mixture for 2 days at different steps followed by open column chromatographic purification and characterization using 1 H, 13 C, 19 F NMR, HRMS, and the compound was stored in refrigerator and the fluorescence measurement was to be completed within 2 h at room temperature. Though the authors have not mentioned about the stability parameters it is apparent that the sensor so prepared and used was not sufficiently stable at room temperature; [53] (iv) HPLC, gel permeation chromatography, 13 C NMR, MALDI-TOF-MS for synthesis and characterization of chiral binphthyl based dendrimers; [36] 1 H and 13 C NMR, MS, and HPLC; [68] 1 H NMR, MALDI-TOF-MS, conductivity measuring instrument, elemental analysis, and X-ray crystallography for ECCD analysis of chiral amines derivatized with quinoline chromophores, [85] because determination of geometry of any of the complexes (including derivatives in the form of simple inorganic complexes) formed by the binding of chiral analyte(s) is to be established with the help of such instrumental techniques, (v) COSY and NOESY NMR spectroscopy, and MALDI-TOF MS analyses on t...…”

“…It confirmed the chiral‐selective recognition of D‐glucose by the pseudo‐diboronic acid moieties. Overall, the method and the sensors [29] showed an improvement in terms of ease of synthesis, high solubility in water and the highest D/L selectivity among the methods reported till then [21,24,26] on fluorescent diboronic acid‐based receptors, for such monosaccharides.…”

“…In accordance with the findings [28] of Hashimoto et al ., two fluorescent receptors based on γ‐CD and two fluorescent molecules (i) 3‐fluorophenylboronic acid and (ii) pyridyl boronic acid (Figure 3) were developed [29] by Suzuki et al . The receptors formed a pseudo‐diboronic acid moiety as the recognition site for D‐glucose as inclusion complexes (1 : 2 stoichiometric) in water at pH 7.4.…”

Cyclodextrin Host–Guest Recognition in Glucose-Monitoring Sensors

“…In recent research, Suzuki et al presented a novel approach utilizing 1:2 stoichiometric inclusion complexes of γ-cyclodextrin with two molecules of fluorescent monoboronic-acid-based receptors for glucose recognition in water . The resulting complexes exhibited strong selectivity and sensitivity toward d -glucose, with limits of detection of 1.1 and 1.8 μM for 1F/γ-CyD and 2N/γ-CyD, respectively.…”