The development of small-molecule fluorescent probes for the detection of ions and biomacromolecules and for cellular and in vivo imaging has been a very active research area. Nevertheless, many problems exist for traditional probes including their poor water solubility, toxicity and the inability to target specific tissues. Because of the enhanced water solubility, biocompatibility and targeting ability for specific cells, there has been an emerging movement to use carbohydrates as either the backbone or as a warhead to decorate conventional fluorescent probes, producing “glycoprobes” with enhanced properties. This feature article provides an overview of recently developed glycoprobes for ion and protein detection as well as targeted (receptor targeting) cellular imaging and theranostics. Here, we summarise the tactics for preparing small molecular glycoprobes and their supramolecular 2D material composites.

Here we demonstrate that low-dimensional materials (LDMs) enhance the conjugation between fluorogenic boronic acids (BAs) and saccharides. Among the LDMs investigated, 1D carbon nanotubes significantly lower the limit of detection and enhance the binding of the BA with D-fructose.

Fluorescent chemosensors for ions and neutral analytes have been widely applied in many diverse fields such as biology, physiology, pharmacology, and environmental sciences. The field of fluorescent chemosensors has been in existence for about 150 years. In this time, a large range of fluorescent chemosensors have been established for the detection of biologically and/or environmentally important species. Despite the progress made in this field, several problems and challenges still exist. This tutorial review introduces the history and provides a general overview of the development in the research of fluorescent sensors, often referred to as chemosensors. This will be achieved by highlighting some pioneering and representative works from about 40 groups in the world that have made substantial contributions to this field. The basic principles involved in the design of chemosensors for specific analytes, problems and challenges in the field as well as possible future research directions are covered. The application of chemosensors in various established and emerging biotechnologies, is very bright.

The ability to simultaneously monitor multiple analytes in, for example, a single microplate well, is important for both basic research and clinical applications. In particular, for disease diagnosis there is a growing awareness that determination of a single disease biomarker is insufficient to pathologically confirm a disease state. Consequently, much recent literature has been directed towards the development of multiplexed photoluminescent sensors which can simultaneously detect multiple and diverse biomarkers that exist in a homogenous solution or a single cell, accelerating the progress towards precise disease diagnosis. This tutorial review highlights a selection of recent contributions towards this emerging interdisciplinary field that incorporates chemistry, chemical biology, materials sciences and medical sciences.

A naphthalimide-based chemosensing motif turns ON the fluorescence emission in solution in the presence of aqueous iron(III) chloride, and maintains this property in living cancer cells. The emission response to Fe(III) ions occurs simultaneously with a change in pH. The protonation of methyl piperazine-conjugated naphthalimide promotes its lysosomal localisation as assessed by co-localisation tests and fluorescence lifetime imaging microscopy (FLIM) in vitro.

Two boronate fluorescent probes have been developed for the detection of peroxynitrite (TCFB1 and TCFB2). TCFB1 was shown to have a low sensitvity towards peroxynitrite and have a poor solubility in aqueous solution whereas TCFB2 demonstrated high sensitivity towards peroxynitrite and mitochondria localisation with the ability to detect exogenous and endogenous peroxynitrite in live cells (Hep-G2, RAW 264.7, HeLa and A459).

Two boronate fluorescent probes have been developed for the detection of peroxynitrite (TCFB1 and TCFB2). TCFB1 was shown to have a low sensitvity towards peroxynitrite and have a poor solubility in aqueous solution whereas TCFB2 demonstrated high sensitivity towards peroxynitrite and mitochondria localisation with the ability to detect exogenous and endogenous peroxynitrite in live cells (Hep-G2, RAW 264.7, HeLa and A459).

With this research, we have developed a bodipy based system as the first “turn-on” fluorescence system for the detection hydroxylamine.

Based on the complexation of phenylboronic acid (PBA) with Alizarin Red S (ARS), we developed a new chemosensor for the detection of hydrogen peroxide (H2O2) in aqueous media. This platform has demonstrated its ability to detect H2O2via colorimetric, fluorometric, and electrochemical measurements. The experimental observations reveal that the system displays a red-shifted visible colour change, on–off fluorescence response indicating release of indicator (ARS) and turn-on electrochemical signal indicating generation of phenol, after reaction with H2O2. With this work we have demonstrated that our reaction-based indicator displacement assay (RIA) systems, can be employed as an assay for H2O2 and hydrogen peroxide-related species for environmental and physiological detection.

Low cost and in situ fluoride detection by non-experts is important for the determination of drinking water safety in developing countries. Colour reagents can provide results quickly without expensive equipment, but colorimetric fluoride indicators are often nonspecific, complex to use or do not work in water. Here we show that azulene–boronate indicators respond selectively to fluoride at concentrations relevant to the WHO limit of 1.5 mg L−1.

The challenge in achieving precision medicine relies on how to advance and/or enhance new as well as old therapeutic strategies. Here, we highlight the significant role hydrophilicity of biotinylated fluorescent probe's plays on their cellular uptake behaviour.

Here we demonstrate that 2D MoS2 can enhance the receptor-targeting and imaging ability of a fluorophore-labelled ligand. The 2D MoS2 has an enhanced working concentration range when compared with graphene oxide, resulting in the improved imaging of both cell and tissue samples.

“Fluorescence imaging” is a particularly exciting and rapidly developing area of research; the annual number of publications in the area has increased ten-fold over the last decade. The rapid increase of interest in fluorescence imaging will necessitate the development of an increasing number of molecular receptors and binding agents in order to meet the demand in this rapidly expanding area. Carbohydrate biomarkers are particularly important targets for fluorescence imaging given their pivotal role in numerous important biological events, including the development and progression of many diseases. Therefore, the development of new fluorescent receptors and binding agents for carbohydrates is and will be increasing in demand. This review highlights the development of fluorescence imaging agents based on boronic acids a particularly promising class of receptors given their strong and selective binding with carbohydrates in aqueous media.

A practically simple derivatization protocol for determining the enantiopurity of chiral diols by 1H NMR spectroscopic analysis is described. Diols were treated with 0.5 equiv of 1,3-phenyldiboronic acid to afford mixtures of diastereomeric boronate esters whose homochiral/heterochiral ratios are an accurate reflection of the diol’s enantiopurity.

Structural studies of a three-component assembly—a host and two distinct guests—were carried out using a combination of 11B and 1H NMR. In aprotic solvent, the imino group that forms ortho to the boronic acid or boronate ester group can form a dative N–B bond. In protic solvent, a molecule of solvent inserts between the nitrogen and boron atoms, partially ionizing the solvent molecule. Additionally, 11B NMR was used in combination with a seventh-order polynomial to calculate five binding constants for each of the individual steps in protic solvent. Comparison of these binding constants was used to establish positive cooperativity in the binding of the two guests.

A graphical abstract is available for this content

A graphical abstract is available for this content

Using the self-assembly of aromatic boronic acids with Alizarin Red S (ARS), we developed a new chemosensor for the selective detection of peroxynitrite. Phenylboronic acid (PBA), benzoboroxole (BBA) and 2-(N,N-dimethylaminomethyl)phenylboronic acid (NBA) were employed to bind with ARS to form the complex probes. In particular, the ARS–NBA system with a high binding affinity can preferably react with peroxynitrite over hydrogen peroxide and other ROS/RNS due to the protection of the boron via the solvent-insertion B–N interaction. Our simple system produces a visible colorimetric change and on–off fluorescence response towards peroxynitrite. By coupling a chemical reaction that leads to an indicator displacement, we have developed a new sensing strategy, referred to herein as RIA (Reaction-based Indicator displacement Assay).

A novel electrochemically and fluorescence active boronic ester sensor molecule has been developed containing ferrocene and naphthalimide as the redox and fluorophore units. The combinations of iron (Fe3+) ions, sodium L-ascorbate, and fluoride (F−) ions can be used to produce a molecular system displaying INHIBIT logic, due to indirect fluorescence quenching.

Boronic acids can bind with 1,2- or 1,3-diols to form five or six-membered cyclic complexes and also can interact with Lewis bases to generate boronate anions. Therefore, boronic acid functionalised compounds and materials are highly topical and now employed in (i) functional materials, (ii) for attaching/sensing bio-molecules and proteins, and (iii) for microbial electrochemistry as well as being widely developed as chemical sensors and tools in health diagnostics. In this review, we address the recent progress of boronic acid-based electrochemical sensors both in solution processes and surface processes for the detection of biological analytes. This feature article will be of interest to chemists, chemical engineers, biochemists, the sensor community, but also researchers working with protein and microbial systems.

A biocompatible fluoride receptor has been developed where the interaction between the boronic acid ester and amine (NH) results in fluoride ion selectivity and enhanced fluorescence quenching.

A water-soluble boronate-based fluorescent probe was evaluated for the detection of peroxynitrite (ONOO−) in the presence of a monosaccharide. The enhanced fluorescence of the probe when bound with D-fructose was switched off in the presence of peroxynitrite. In contrast, other reactive oxygen/nitrogen species (ROS/RNS) led to only slight fluorescence decreases due to protection by an internal N–B interaction. The interaction of the probe with D-fructose not only strengthens the fluorescence signal, but also protects the boronic acid from oxidation by other ROS/RNS. Therefore, under conditions generating various ROS/RNS, the boronate-based saccharide complex preferentially reacts with peroxynitrite. The probe was used in cell imaging experiments for the detection of endogenous and exogenous peroxynitrite. The sensor displays good “on–off” responses towards peroxynitrite, both in RAW 264.7 cells and HeLa cells.

A novel near-infrared (NIR) and colorimetric fluorescent molecular probe based on a dicyanomethylene-4H-pyran chromophore for the selective detection of glutathione in living cells has been developed. The fluorescence OFF–ON switch is triggered by cleavage of the 2,4-dinitrobenzensulfonyl (DNBS) unit by the interaction with GSH.

Copper ions are essential for many biological processes. However, high concentrations of copper can be detrimental to the cell or organism. A novel naphthalimide derivative bearing a monoboronic acid group (BNP) was investigated as a Cu2+ selective fluorescent sensor in living cells. This derivative is one of the rare examples of reversible fluorescent chemosensors for Cu2+ which uses a boronic acid group for a binding site. Moreover, the adduct BNP–Cu2+ displays a fluorescence enhancement with fructose. The uptake of this novel compound in HeLa cancer cells was imaged using confocal fluorescence microscopy techniques including two-photon fluorescence lifetime imaging microscopy.

Palladium catalysed, aryl boronic acid homocoupling, is explored as a fluorescence sensing regime for saccharides. The catalytic formation rate of fluorescent bi-aryls, under control of a palladium catalyst, is modulated by the presence of saccharides. The nature of the aryl group, rate of biaryl formation and limits of detection are investigated.

Aggregates of an amphiphilic monoboronic acid bearing a hydrophobic pyrene fluorophore were employed for highly modulating, sensitive, and selective ratiometric fluorescent sensing of glucose in aqueous solution. The selectivity for glucose was improved by “knock-out” binding of fructose by phenylboronic acid.

Amine alkylation reactions of alcohols have been performed in the presence of boronic ester groups to provide products which are known to have use as molecular sensors. The boronic ester moiety could be present in either the alcohol or amine starting material and was not compromised in the presence of a ruthenium catalyst.

A practically simple three-component chiral derivatization protocol for determining the enantiopurity of chiral hydroxylamines by 1H NMR spectroscopic analysis is described, involving their treatment with 2-formylphenylboronic acid and enantiopure BINOL to afford a mixture of diastereomeric nitrono-boronate esters whose ratio is an accurate reflection of the enantiopurity of the parent hydroxylamine.

We have developed a simple and robust fluorescence based boronic-acid molecular sensor for determining the concentration of fluoride in water at environmentally significant levels. The simplicity of the method and the ability to measure fluoride in water between 0.1 and 1.5 ppm is particularly noteworthy given the WHO requirements for detecting levels of fluoride in drinking water below 1.5 ppm.

An operationally simple colorimetric method for enantioselective detection of chiral secondary alcohols via hydrogen bonding interactions using a chiral ferrocene derivative is reported.

Integrated and insulated boronate-based fluorescent probes have been evaluated for the detection of hydrogen peroxide in the presence of saccharides.

A bis-boronic acid modified electrode for the sensitive and selective determination of glucose concentrations has been developed. The electrochemical characteristics of the sensor with added saccharides were investigated using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The bis-boronic acid modified electrode was both sensitive and selective for glucose.

Upon mixing a chiral amine, enantiopure BINOL, and o-formyl phenyl boronic acid, the three components assemble efficiently and rapidly into chiral host–guest structures that produce distinct circular dichroism signals for each enantiomer of the amine. Employing BINOL and two derivatives to create an array of receptors, the CD signals resulting from several α-chiral primary amines were processed by principal component analysis and linear discriminant analysis to give satisfactory discrimination of the amines studied. Not only was the system able to differentiate the analytes chemoselectively and enantioselectively, but it also allowed for the rapid determination of chiral amineee values.

A red-emitting BODIPY-based fluorescent-resonance-energy-transfer (FRET) molecular probe 1 for selective detection of cysteine and homocysteine was designed. The fluorescence OFF–ON switch is triggered by cleavage of the 2,4-dinitrobenzensulfonyl (DNBS) unit from the fluorophore by thiols. The FRET energy donor (λabs = 498 nm, λem = 511 nm) is a parent BODIPY moiety and the energy acceptor is based on 4-hydroxylstyryl BODIPY moiety (λabs = 568 nm, λem = 586 nm). The unique C–C linker between the energy donor and acceptor was established using a Suzuki cross-coupling reaction. A polyether chain was also introduced into the probe to improve solubility in aqueous solution. While probe 1 itself is non-fluorescent, in the presence of cysteine or homocysteine a red emission at 590 nm is switched on (excitation at 505 nm), producing a pseudo-Stokes shift of up to 77 nm, which is in stark contrast to the small Stokes shift (ca. 10 nm) observed for typical BODIPY dyes. Excitation of the energy donor leads to the red emission from the acceptor of the probe, and demonstrates a high energy transfer efficiency. The probe was used for in vivo fluorescent imaging of cellular thiols. The fluorescence sensing mechanism of the probe and the photophysical properties of the fluorescent intermediates were fully rationalized by DFT calculations. The lack of fluorescence of probe 1 is attributed to the dark excited state S1 (oscillator strength f = 0.0007 for S0 → S1, based on the optimized S1 state geometry), which is due to the electron sink effect of the DNBS moiety. Cleavage of the DNBS moiety from the fluorophore by thiols re-establishes the emissive S1 state of the fluorophore (f = 1.4317 for S0 → S1), thus the red emission can be observed in the presence of thiols (fluorescence is turned on). The FRET effect of the probe was rationalized by DFT calculations which indicated that upon excitation into the S4 excited state (localized on the energy donor unit), the S1 state (localized on the energy acceptor, i.e. styryl-BODIPY) is populated via internal conversion (IC), thus red emission from the styryl-BODIPY energy acceptor is observed (Kasha's rule).

We report the controlled synthesis of boronic-acid terminated polylactides via the use of a protected boronic acid-functionalised ring-opening polymerisation initiator and the subsequent deprotection of the resultant polymer. We have demonstrated the utility of this approach to biocompatible polymer conjugates of biologically-relevant diols using an indicator-displacement assay.

A rapid and facile TLC staining method is reported for the qualitative analysis of boronic acids and related boron-containing derivatives. A red colouration is observed when boron is present due to the formation of a boron–curcumin complex. The structure of the phenylboronic acid–curcumin complex was confirmed using single crystal X-ray diffraction data.

Dynamic covalent functionality has been acknowledged as a powerful tool for the construction of organised architectures, the reversible nature thermodynamically facilitates self-control and self-correction. The use of boronic acids complexation with diols and their congeners has already shown great promise in realising and developing reversible boron-containing multicomponent systems with dynamic covalent functionality. The structure-directing potential has lead to the development of a variety of self-organisation involving not only macrocycles, cages and capsules, but also porous covalent organic frameworks and polymers. Structure controls as well as remarkable synthesis are highlighted in this feature article.

In this feature article the use of boronic acids to monitor, identify and isolate analytes within physiological, environmental and industrial scenarios is discussed. Boronic acids recognise diol motifs through boronic ester formation and interact with anions generating boronates, as such they have been exploited in sensing and separation protocols for diol appended molecules such as saccharides and anions alike. Therefore robust molecular sensors with the capacity to detect chosen molecules selectively and signal their presence continues to attract substantial attention, and boronic acids have been exploited with some success to monitor the presence of various analytes. Reversible boronic acid-diol interactions have also been exploited in boronaffinity chromatography realising new separation domains through the same binding events. Boronic acid diol and anion interactions pertaining to sensing and separation are surveyed.

A practically simple three-component Strecker reaction for the asymmetric synthesis of enantiopure α-arylglycines has been developed. Addition of a range of aryl-aldehydes to a solution of sodium cyanide and (S)-1-(4-methoxyphenyl)ethylamine affords highly crystalline (S,S)-α-aminonitriles that are easily obtained in diastereomerically pure form. Heating the resultant (S,S)-α-aminonitriles in 6 M aqueous HCl at reflux resulted in cleavage of their chiral auxiliary fragments and concomitant hydrolysis of their nitrile groups to afford enantiopure (S)-α-arylglycines. The enantiopurities of these (S)-α-arylglycines were determined via derivatization of their corresponding methyl esters with 2-formylphenylboronic acid and (S)-BINOL, followed by 1H NMR spectroscopic analysis of the resultant mixtures of diastereomeric iminoboronate esters.

This critical review will explore some of the recent research into the use of boron based anion receptors and focus on those receptors that have been designed to transduce the binding event into a measurable output signal. In particular the review will concentrate on optical chemosensors, where the signal produced is in the form of a colour or fluorescence change (116 references).

The exciplex formation between a pyridinium boronic acid and phenyl group connected via a propylene linker can be monitored using fluorescence. Addition of pinacol affords a cyclic boronate ester with enhanced Lewis acidity that increases the strength of its cation–π stacking interaction causing a four-fold fluorescence enhancement.

A simple three step synthesis was developed to provide six novel modular sensors, consisting of three para sensors, and three meta sensors with naphthalene, anthracene and pyrene fluorophores. The interaction of the six sensors with the saccharides: D-glucose, D-fructose, D-galactose, and D-mannose, were evaluated. All sensors displayed increasing fluorescence intensity upon the addition of these saccharides, with all of the sensors showing enhanced selectivity for D-glucose over D-galactose, D-fructose and D-mannose. High affinity (Kobs) was also observed for the meta sensors with respect to the para sensors. The naphthalene and anthracene meta sensors showed particularly high affinity (Kobs) for D-galactose. Circular dichroism spectroscopy was used to probe the structures of the complexes formed. Cyclic complexes were formed between all six sensors and D-glucose. Whilst naphthalene and anthracene meta sensors which displayed high affinity for D-galactose also formed cyclic complexes with that saccharide.

We have developed a permethylated ferrocene redox system with a butylamine substituent for application in liquid | liquid ion sensors. The steric hindrance associated with the methyl groups results in an electrochemical system where the ferricenium derivative is chemically inert and the redox system remains chemically reversible, even for applications in aqueous or biphasic media. N,N-Butyl-decamethylferrocenyl-amine is soluble in hydrophobic organic solvents, such as 4-(3-phenylpropyl)pyridine (PPP) and N-octyl-pyrrolidone (NOP), and is employed here under “microphase” conditions, deposited in the form of microdroplets onto an electrode and immersed in aqueous buffer solutions. It is shown that under these conditions, electron transfer and proton transfer are only weakly coupled, and that anion transfer dominates the microphase redox process over the entire pH range. The corresponding biphasic Pourbaix diagram is discussed.

A fluorescent molecular tweezer for carbohydrates has been prepared which utilises two boronic acid receptor groups.

Reaction of 2-formyl-aryl-boronic acids with 1,2-amino alcohols results in dynamic covalent self assembly to quantitatively afford tetracyclic macrocyclic Schiff base boracycles containing bridging boron–oxygen–boron functionality.

Addition of chloride ions to boron bis(phenolate) 5 in dichloromethane solution produces a selective fluorescence decrease. The fluorescence change is believed to be caused by associative hydrogen bonding between the chloride ion and two boronic acid groups. While addition of fluoride ions to bis(phenolate) 5 generates a purple colorimetric response, the colorimetric response is caused by fluoride induced B−O bond cleavage and air oxidation of the phenolate anion formed by this dissociation.

Bisboronic acid 3 binds strongly and enantioselectively with six-carbon sugar alcohols but does not bind strongly with five- or four-carbon sugar alcohols or monosaccharides.

Selective anion-induced organization of phenylboronic acids and alizarin results in a new TURN-ON fluorescent sensor for anions in MeOH.

The addition of D-tartaric acid to R,R-2 causes a large increase in fluorescence. While addition of L-tartaric acid to R,R-2 only produces small changes in fluorescence.

The addition of potassium fluoride ‘switches on’ the fluorescence of sensors 1 and 2 while potassium chloride and bromide cause no fluorescence change; the fluorescence can be ‘switched off’ by removing the potassium cation from the benzocrown ether receptors of sensors 1 and 2 through the addition of [2.2.2]-cryptand and restored by the addition of the potassium cation as potassium chloride.

Non-linear effects reveal that the use of chiral BINOL–boron reagents for aza-Diels–Alder reactions results in an enantioselective catalytic species containing at least 2 equiv. of BINOL. Dynamic ligand exchange and ligand accelerated catalysis occurs in these reactions, consistent with the formation of a cyclic borate ester of BINOL with enhanced Lewis acidity.Graphic

A modular electrochemical saccharide sensor using ferrocene has been prepared which contains two boronic acid receptor groups and hexamethylene linker.

Modular photoinduced electron transfer (PET) sensors bearing two phenylboronic acid groups, a pyrene group and alkylene linkers, from trimethylene to octamethylene, have been prepared and evaluated. The diboronic acid systems with tetramethylene 3444 pentamethylene 3555 and hexamethylene 3666 linkers display the greatest enhancement in binding relative to monoboronic acid 4 with D-glucose. The diboronic acid system with the hexamethylene 3666 linker is particularly D-glucose selective and sensitive. Whilst the diboronic acid systems with the longer heptamethylene 3777 and octamethylene 3888 linkers display the greatest enhancement in binding relative to monoboronic acid 4 with D-galactose. All saccharide titrations were performed in methanolic aqueous solution.

A number of boronic acid functionalised azo dye molecules have been prepared using a simple 3-step synthesis and their spectral properties upon complexation with monosaccharides investigated. The dyes undergo visible colour changes in aqueous solution upon addition of monosaccharide.

Twenty substituted N-benzylidineaniline derivatives have been synthesised and their kinetic behaviour investigated. The rate of hydrolysis of the boronic acid imines was found to be accelerated by added saccharide. Catalytic activity was only observed below the pKa of the boronic acid. Altering the concentration or type of saccharide revealed a Brønsted-like linear free energy relationship, indicating that intramolecular general acid catalysis was operating. Structure–activity relationship studies demonstrated that the system's electronic demands were independent of the boronic acid moiety.

The first reported fluorescent sensor for boronic and boric acids is actually not a sensor for boronic and boric acids but rather is a sensor for protons; the system is also not the first fluorescent sensor since Alizarin has been used as a fluorescent sensor for boric acids since 1936.

We have developed a novel class of simple materials for sensing monosaccharides by the functionalization of graphene oxide (GO) with boronate-based fluorescence probes (BA1 and BA2). The composite materials were characterized by atomic force microscopy, Raman spectroscopy, and UV–vis/fluorescence spectroscopy. The strong fluorescence of the BA probes is quenched in the presence of GO through fluorescence resonance energy transfer. The BA@GO composite sensors formed provide a useful platform for fluorogenic detection of monosaccharides based on the strong affinity between the boronic acid receptor and monosaccharides. The BA@GO composite sensor displayed a “turn-on” fluorescence response with a good linear relationship toward fructose over a range of other saccharides.

A novel near-infrared (NIR) and colorimetric fluorescent molecular probe based on a dicyanomethylene-4H-pyran chromophore for the selective detection of glutathione in living cells has been developed. The fluorescence OFF–ON switch is triggered by cleavage of the 2,4-dinitrobenzensulfonyl (DNBS) unit by the interaction with GSH.

A water-soluble boronate-based fluorescent probe was evaluated for the detection of peroxynitrite (ONOO−) in the presence of a monosaccharide. The enhanced fluorescence of the probe when bound with D-fructose was switched off in the presence of peroxynitrite. In contrast, other reactive oxygen/nitrogen species (ROS/RNS) led to only slight fluorescence decreases due to protection by an internal N–B interaction. The interaction of the probe with D-fructose not only strengthens the fluorescence signal, but also protects the boronic acid from oxidation by other ROS/RNS. Therefore, under conditions generating various ROS/RNS, the boronate-based saccharide complex preferentially reacts with peroxynitrite. The probe was used in cell imaging experiments for the detection of endogenous and exogenous peroxynitrite. The sensor displays good “on–off” responses towards peroxynitrite, both in RAW 264.7 cells and HeLa cells.

A graphical abstract is available for this content

A graphical abstract is available for this content

This critical review will explore some of the recent research into the use of boron based anion receptors and focus on those receptors that have been designed to transduce the binding event into a measurable output signal. In particular the review will concentrate on optical chemosensors, where the signal produced is in the form of a colour or fluorescence change (116 references).

Integrated and insulated boronate-based fluorescent probes have been evaluated for the detection of hydrogen peroxide in the presence of saccharides.

A fluorescent molecular tweezer for carbohydrates has been prepared which utilises two boronic acid receptor groups.

Using the self-assembly of aromatic boronic acids with Alizarin Red S (ARS), we developed a new chemosensor for the selective detection of peroxynitrite. Phenylboronic acid (PBA), benzoboroxole (BBA) and 2-(N,N-dimethylaminomethyl)phenylboronic acid (NBA) were employed to bind with ARS to form the complex probes. In particular, the ARS–NBA system with a high binding affinity can preferably react with peroxynitrite over hydrogen peroxide and other ROS/RNS due to the protection of the boron via the solvent-insertion B–N interaction. Our simple system produces a visible colorimetric change and on–off fluorescence response towards peroxynitrite. By coupling a chemical reaction that leads to an indicator displacement, we have developed a new sensing strategy, referred to herein as RIA (Reaction-based Indicator displacement Assay).

The exciplex formation between a pyridinium boronic acid and phenyl group connected via a propylene linker can be monitored using fluorescence. Addition of pinacol affords a cyclic boronate ester with enhanced Lewis acidity that increases the strength of its cation–π stacking interaction causing a four-fold fluorescence enhancement.

A rapid and facile TLC staining method is reported for the qualitative analysis of boronic acids and related boron-containing derivatives. A red colouration is observed when boron is present due to the formation of a boron–curcumin complex. The structure of the phenylboronic acid–curcumin complex was confirmed using single crystal X-ray diffraction data.

An operationally simple colorimetric method for enantioselective detection of chiral secondary alcohols via hydrogen bonding interactions using a chiral ferrocene derivative is reported.

A novel electrochemically and fluorescence active boronic ester sensor molecule has been developed containing ferrocene and naphthalimide as the redox and fluorophore units. The combinations of iron (Fe3+) ions, sodium L-ascorbate, and fluoride (F−) ions can be used to produce a molecular system displaying INHIBIT logic, due to indirect fluorescence quenching.

A red-emitting BODIPY-based fluorescent-resonance-energy-transfer (FRET) molecular probe 1 for selective detection of cysteine and homocysteine was designed. The fluorescence OFF–ON switch is triggered by cleavage of the 2,4-dinitrobenzensulfonyl (DNBS) unit from the fluorophore by thiols. The FRET energy donor (λabs = 498 nm, λem = 511 nm) is a parent BODIPY moiety and the energy acceptor is based on 4-hydroxylstyryl BODIPY moiety (λabs = 568 nm, λem = 586 nm). The unique C–C linker between the energy donor and acceptor was established using a Suzuki cross-coupling reaction. A polyether chain was also introduced into the probe to improve solubility in aqueous solution. While probe 1 itself is non-fluorescent, in the presence of cysteine or homocysteine a red emission at 590 nm is switched on (excitation at 505 nm), producing a pseudo-Stokes shift of up to 77 nm, which is in stark contrast to the small Stokes shift (ca. 10 nm) observed for typical BODIPY dyes. Excitation of the energy donor leads to the red emission from the acceptor of the probe, and demonstrates a high energy transfer efficiency. The probe was used for in vivo fluorescent imaging of cellular thiols. The fluorescence sensing mechanism of the probe and the photophysical properties of the fluorescent intermediates were fully rationalized by DFT calculations. The lack of fluorescence of probe 1 is attributed to the dark excited state S1 (oscillator strength f = 0.0007 for S0 → S1, based on the optimized S1 state geometry), which is due to the electron sink effect of the DNBS moiety. Cleavage of the DNBS moiety from the fluorophore by thiols re-establishes the emissive S1 state of the fluorophore (f = 1.4317 for S0 → S1), thus the red emission can be observed in the presence of thiols (fluorescence is turned on). The FRET effect of the probe was rationalized by DFT calculations which indicated that upon excitation into the S4 excited state (localized on the energy donor unit), the S1 state (localized on the energy acceptor, i.e. styryl-BODIPY) is populated via internal conversion (IC), thus red emission from the styryl-BODIPY energy acceptor is observed (Kasha's rule).

We have developed a simple and robust fluorescence based boronic-acid molecular sensor for determining the concentration of fluoride in water at environmentally significant levels. The simplicity of the method and the ability to measure fluoride in water between 0.1 and 1.5 ppm is particularly noteworthy given the WHO requirements for detecting levels of fluoride in drinking water below 1.5 ppm.

“Fluorescence imaging” is a particularly exciting and rapidly developing area of research; the annual number of publications in the area has increased ten-fold over the last decade. The rapid increase of interest in fluorescence imaging will necessitate the development of an increasing number of molecular receptors and binding agents in order to meet the demand in this rapidly expanding area. Carbohydrate biomarkers are particularly important targets for fluorescence imaging given their pivotal role in numerous important biological events, including the development and progression of many diseases. Therefore, the development of new fluorescent receptors and binding agents for carbohydrates is and will be increasing in demand. This review highlights the development of fluorescence imaging agents based on boronic acids a particularly promising class of receptors given their strong and selective binding with carbohydrates in aqueous media.

A biocompatible fluoride receptor has been developed where the interaction between the boronic acid ester and amine (NH) results in fluoride ion selectivity and enhanced fluorescence quenching.

Dynamic covalent functionality has been acknowledged as a powerful tool for the construction of organised architectures, the reversible nature thermodynamically facilitates self-control and self-correction. The use of boronic acids complexation with diols and their congeners has already shown great promise in realising and developing reversible boron-containing multicomponent systems with dynamic covalent functionality. The structure-directing potential has lead to the development of a variety of self-organisation involving not only macrocycles, cages and capsules, but also porous covalent organic frameworks and polymers. Structure controls as well as remarkable synthesis are highlighted in this feature article.

A simple probe for the detection of peroxynitrite was developed incorporating a benzyl boronic ester “protecting” unit. The “protecting” unit of the probe is removed by peroxynitrite to “turn-on” ESIPT fluorescence (4.5 fold enhancement). Furthermore, the probe was cell permeable and was used in cell imaging experiments showing an off–on response towards peroxynitrite, in HeLa and RAW 264.7 cells.

Upon mixing a chiral amine, enantiopure BINOL, and o-formyl phenyl boronic acid, the three components assemble efficiently and rapidly into chiral host–guest structures that produce distinct circular dichroism signals for each enantiomer of the amine. Employing BINOL and two derivatives to create an array of receptors, the CD signals resulting from several α-chiral primary amines were processed by principal component analysis and linear discriminant analysis to give satisfactory discrimination of the amines studied. Not only was the system able to differentiate the analytes chemoselectively and enantioselectively, but it also allowed for the rapid determination of chiral amineee values.

In this feature article the use of boronic acids to monitor, identify and isolate analytes within physiological, environmental and industrial scenarios is discussed. Boronic acids recognise diol motifs through boronic ester formation and interact with anions generating boronates, as such they have been exploited in sensing and separation protocols for diol appended molecules such as saccharides and anions alike. Therefore robust molecular sensors with the capacity to detect chosen molecules selectively and signal their presence continues to attract substantial attention, and boronic acids have been exploited with some success to monitor the presence of various analytes. Reversible boronic acid-diol interactions have also been exploited in boronaffinity chromatography realising new separation domains through the same binding events. Boronic acid diol and anion interactions pertaining to sensing and separation are surveyed.

We report a strategy for modulating the electrogenerated chemiluminescence (ECL) response by integrating a boronic acid to the chemical structure of coreactants. Excellent selectivity for D-glucose was achieved by tuning the linker length of a bis-boronic acid amine coreactant.

Copper ions are essential for many biological processes. However, high concentrations of copper can be detrimental to the cell or organism. A novel naphthalimide derivative bearing a monoboronic acid group (BNP) was investigated as a Cu2+ selective fluorescent sensor in living cells. This derivative is one of the rare examples of reversible fluorescent chemosensors for Cu2+ which uses a boronic acid group for a binding site. Moreover, the adduct BNP–Cu2+ displays a fluorescence enhancement with fructose. The uptake of this novel compound in HeLa cancer cells was imaged using confocal fluorescence microscopy techniques including two-photon fluorescence lifetime imaging microscopy.

Boronic acids can bind with 1,2- or 1,3-diols to form five or six-membered cyclic complexes and also can interact with Lewis bases to generate boronate anions. Therefore, boronic acid functionalised compounds and materials are highly topical and now employed in (i) functional materials, (ii) for attaching/sensing bio-molecules and proteins, and (iii) for microbial electrochemistry as well as being widely developed as chemical sensors and tools in health diagnostics. In this review, we address the recent progress of boronic acid-based electrochemical sensors both in solution processes and surface processes for the detection of biological analytes. This feature article will be of interest to chemists, chemical engineers, biochemists, the sensor community, but also researchers working with protein and microbial systems.

Here we demonstrate that low-dimensional materials (LDMs) enhance the conjugation between fluorogenic boronic acids (BAs) and saccharides. Among the LDMs investigated, 1D carbon nanotubes significantly lower the limit of detection and enhance the binding of the BA with D-fructose.

Modular and modular polymer supported fluorescence photoinduced electron transfer (PET) sensors 2 and 3 with two boronic acid receptor units, a pyren-1-yl fluorophore, and hexamethylene linker show selective saccharide binding in aqueous methanolic solution at pH 8.21.

Here we demonstrate that 2D MoS2 can enhance the receptor-targeting and imaging ability of a fluorophore-labelled ligand. The 2D MoS2 has an enhanced working concentration range when compared with graphene oxide, resulting in the improved imaging of both cell and tissue samples.

The development of small-molecule fluorescent probes for the detection of ions and biomacromolecules and for cellular and in vivo imaging has been a very active research area. Nevertheless, many problems exist for traditional probes including their poor water solubility, toxicity and the inability to target specific tissues. Because of the enhanced water solubility, biocompatibility and targeting ability for specific cells, there has been an emerging movement to use carbohydrates as either the backbone or as a warhead to decorate conventional fluorescent probes, producing “glycoprobes” with enhanced properties. This feature article provides an overview of recently developed glycoprobes for ion and protein detection as well as targeted (receptor targeting) cellular imaging and theranostics. Here, we summarise the tactics for preparing small molecular glycoprobes and their supramolecular 2D material composites.

The challenge in achieving precision medicine relies on how to advance and/or enhance new as well as old therapeutic strategies. Here, we highlight the significant role hydrophilicity of biotinylated fluorescent probe's plays on their cellular uptake behaviour.