Disaggregation is a Mechanism for Emission Turn-On of ortho-Aminomethylphenylboronic Acid-Based Saccharide Sensors

Abstract

ortho-Aminomethylphenylboronic acid-based receptors with appended fluorophores are commonly used as molecular sensors for saccharides in aqueous media. The mechanism for fluorescence modulation in these sensors has been attributed to some form of photoinduced electron transfer (PET) quenching, which is diminished in the presence of saccharides. Using a well-known boronic acid-based saccharide sensor (3), this work reveals a new mechanism for fluorescence turn-on in these types of sensors. Compound 3 exhibits an excimer, and the associated ground-state aggregation is responsible for fluorescence modulation under certain conditions. When fructose was titrated into a solution of 3 in 2:1 water/methanol with NaCl, the fluorescence intensity increased. Yet, when the same titration was repeated in pure methanol, a solvent in which the sensor does not aggregate, no fluorescence response to fructose was observed. This reveals that the fluorescence increase is not fully associated with fructose binding, but instead disaggregation of the sensor in the presence of fructose. Further, an analogue of the sensor that does not contain a boronic acid (4) responded nearly identically to 3 in the presence of fructose, despite having no functional group with which to bind the saccharide. This further supports the claim that fluorescence modulation is not primarily a result of binding, but of disaggregation. Using an indicator displacement assay and isothermal titration calorimetry, it was confirmed that fructose does indeed bind to the sensor. Thus, our evidence reveals that while binding occurs with fructose in the aqueous solvent system used, it is not related to the majority of the fluorescence modulation. Instead, disaggregation dominates the signal turn-on, and is thus a mechanism that should be investigated in other ortho-aminomethylphenylboronic acid-based sensors.

A boronic acid-based fluorescent hydrogel for monosaccharide detection

“…This pioneering work has led to the development of other ortho-aminomethylphenylboronic acid-containing fluorescence sensors improving selectivity, increasing excitation/emission profile and binding affinities [10][11][12]. While there was never any doubt that the orthoaminomethylphenylboronic acid group was important to improve saccharide binding at neutral pH the mechanism of action had been under debate for a number of years [13][14][15]. Recently, the debate was concluded and the fluorescence enhancement on saccharide binding is caused by modulation of internal conversion resulting in different levels of quenching.…”

A new approach to developing diagnostics and therapeutics: Aggregation‐induced emission‐based fluorescence turn‐on

“…In addition, normal level of steroids is important to health and disorder of the steroid metabolism causes series of diseases. Traditional ACQ probes can be used to recognize and quantify these biomolecules . Considering the advantages of AIEgens, they are more suitable for accurate detection of biomarkers (Figure ).…”

“…94 Traditional ACQ probes can be used to recognize and quantify these biomolecules. [96][97][98] Considering the advantages of AIEgens, they are more suitable for accurate detection of biomarkers ( Figure 6). Liu et al 99 synthesized 12 ( Figure 2) for detection of D-glucose.…”

Modeling Boronic Acid Based Fluorescent Saccharide Sensors: Computational Investigation of d-Fructose Binding to Dimethylaminomethylphenylboronic Acid

“…40 Saccharide binding to the sensors has been shown to increase sensor solubility and therefore cause disaggregation which allows fluorescence to reemerge. 40 However, in fact, more recent work by Anslyn and coworkers has arrived at a unifying "loose-bolt effect" explanation for the fluorescence mechanism in potentially all o-aminomethylphenylboronic acid based saccharide sensors. 41 (-BOH 2 N, the reactant state) to 2.0 (-BOH NH, the product state), geometry optimizations were conducted at each step along the reaction coordinate restraining H 18 at each given r val , energies were collected at every step and are shown in Figure 6.…”