Fluorinated Boronic Acid-Appended Pyridinium Salts and ¹⁹F NMR Spectroscopy for Diol Sensing

Abstract

The identification and discrimination of diols is of fundamental importance in medical diagnostics, such as measuring the contents of glucose in the urine of diabetes patients. Diol sensors are often based on fluorophore-appended boronic acids, but these severely lack discriminatory power and their response is one-dimensional. As an alternative strategy, we present the use of fluorinated boronic acid-appended pyridinium salts in combination with F NMR spectroscopy. A pool of 59 (bio)analytes was screened, containing monosaccharides, phosphorylated and N-acetylated sugars, polyols, carboxylic acids, nucleotides, and amines. The majority of analytes could be clearly detected and discriminated. In addition, glucose and fructose could be distinguished up to 1:9 molar ratio in mixtures. Crucially, the receptors feature high sensitivity and selectivity and are water-soluble, and theirF-NMR analyte fingerprint is pH-robust, thereby making them particularly well-suited for medical application. Finally, to demonstrate this applicability, glucose could be detected in synthetic urine samples down to 1 mM using merely a 188 MHz NMR spectrometer.

Single‐Molecule Determination of the Isomers of d‐Glucose and d‐Fructose that Bind to Boronic Acids

“…Thev alues of t on and t off were determined by fitting dwell-time histograms for each catechol concentration to single exponential functions.T he forward and reverse rate constants derived from the t values (Table 1) yield an equilibrium association constant of catechol to the boronic acid of K a = 2.4 AE 0.2 10 3 m À1 at 21 AE 1 8 8C( n = 3), consistent with literature values. [5] Short, spike events of varying amplitudes observed in the baseline of single-channel recordings with aP B pore (Supporting Information, Figure S6), which can be seen in addition to the dominant binding events of catechol in Figure 1c,w ere attributed to intrinsic fluctuations within the pore and were neglected during analysis.…”

Rational Design of Self-Healing Tough Hydrogels: A Mini Review

“…The stability (self-healing ability) of phenylboronic ester complex also depends on the conformation of the diol groups in the polymer chains. Schiller et al determined binding constants between phenylboronic acid and different polysaccharides with different diol conformations (Axthelm et al, 2017 ). It was found that phenylboronic acid has a higher affinity for the cis -diol groups than that for the trans -diol groups.…”

Single‐Molecule Determination of the Isomers of d‐Glucose and d‐Fructose that Bind to Boronic Acids

“…[3] Forexample,boronic acid-containing hydrogels have been used recently for biocompatible continuous glucose monitoring. [4] Despite the growing number of sophisticated boronic acid-based chemosensors that can detect and discriminate sugars, [5] knowledge of the structural interactions between saccharides and boronic acids remains limited.…”

“…[9] Ther eciprocal of the mean inter-event interval (t on )i s proportional to the catechol concentration, which is consistent with abimolecular interaction for which 1/t on = k on [catechol].I nc ontrast, ap lot of the reciprocal of the mean lifetime of the complex (t off )v ersus the catechol concentration has anear zero slope,which is consistent with au nimolecular dissociation mechanism (1/ t off = k off )( Figure 1d). [5] Short, spike events of varying amplitudes observed in the baseline of single-channel recordings with aP B pore (Supporting Information, Figure S6), which can be seen in addition to the dominant binding events of catechol in Figure 1c,w ere attributed to intrinsic fluctuations within the pore and were neglected during analysis. [5] Short, spike events of varying amplitudes observed in the baseline of single-channel recordings with aP B pore (Supporting Information, Figure S6), which can be seen in addition to the dominant binding events of catechol in Figure 1c,w ere attributed to intrinsic fluctuations within the pore and were neglected during analysis.…”

“…Because the d-glucose pyranose anomer a-d-glucopyranose has 1,2-hydroxy groups positioned cis at C 1 and C 2 ,a nd b-dglucopyranose has hydroxy groups at C 1 through C 4 positioned trans to each other (Figure 2g), our results suggest that a-d-glucopyranose binds to ab oronic acid through the cishydroxy groups at C 1 and C 2 .T his proposition was further supported by the lack of interaction of a-d-glucose 1phosphate with the P B pore (Figure 2f and the Supporting Information, Figure S17), consistent with previous reports that this phosphorylated sugar does not bind to afluorinated boronic acid-appended pyridinium salt receptor. [5] We next examined the binding of d-fructose to the P B pore (Figure 3a nd the Supporting Information, Figure S19). Similar to the binding of d-glucose,the addition of d-fructose to the trans compartment resulted in reversible current blockades (DI =+7.5 AE 0.3 pA;F igure 3a).…”