A new boronic acid fluorescent reporter that changes emission intensities at three wavelengths upon sugar binding

The boronic acid moiety is a very useful functional group for the preparation of sugar sensors. Along this line, water-soluble boronic acids that change fluorescent properties upon sugar binding are especially useful as reporter units in fluorescent sensors for carbohydrates. Herein, we report the discovery of a new water-soluble boronic acid (1, dibenzofuran-4-boronic acid) that exhibits unique fluorescence changes at three wavelengths upon binding with sugars under near physiological conditions.     

6,6′-Bis-substituted BINOL boronic acids as enantioselective and chemoselective fluorescent chemosensors for d-sorbitol

A new chiral fluorescent BINOL boronic acid 1 has been synthesized. The chiral recognition properties of 1 are drastically different from BINOL boronic acid c. Sensor 1 shows improved enantioselectivity as well as chemoselectivity toward sugar alcohols, such as d-sorbitol and d-mannitol.The enantioselectivity of sensor 1 toward d-sorbitol (K_R/K_S) is 1:35 (pH 9.0), and the chemoselectivity for d-sorbitol/d-mannitol is 20:1.     

A highly fluorescent water-soluble boronic acid reporter for saccharide sensing that shows ratiometric UV changes and significant fluorescence changes

One water-soluble naphthalene-based fluorescent boronic acid, 6-(dimethylamino)-naphthalene-2-boronic acid (6-DMANBA, 1), has been synthesized. 6-DMANBA shows significant ratiometric UV absorbance changes upon addition of a sugar. For example, addition of 50 mM fructose shifted the UV absorption wavelengths of 6-DMANBA from 306 and 251 to 280 and 244 nm, respectively. In addition, 6-DMANBA is highly fluorescent with a quantum yield of 89% in the absence of a sugar and shows significant fluorescence intensity changes with the addition of a saccharide in aqueous phosphate buffer at physiological pH. For example, with the addition of 50 mM fructose, 6-DMANBA shows an 80% fluorescent intensity decrease at 432 nm. All these spectroscopic properties make compound 1 unique and useful.     

Photophysical properties of phenanthro[9,10-d]imidazole-type fluorescent hosts upon inclusion of organic solvent molecules

The crystal of phenanthro[9,10-d]imidazole-type fluorescent clathrate host (1) exhibits fluorescence enhancement behavior with a blue-shift of the emission maximum upon enclathration of organic solvent molecules such as 1-butanol and morpholine, whereas the crystal of 1 exhibits fluorescence enhancement behavior with a red-shift of the emission maximum upon enclathration of carboxylic acid such as acetic acid and propionic acid. The crystal structures of the guest-free and the guest-inclusion compounds of 1 have been determined by X-ray analysis. On the bases of the spectral data and the crystal structures, the effects of the enclathrated guest molecule on the solid-state photophysical properties of the guest-inclusion compounds are discussed.     

Synthesis, evaluation, and computational studies of naphthalimide-based long-wavelength fluorescent boronic Acid reporters

Boronic acids that change fluorescence properties upon sugar binding are very useful for the synthesis of carbohydrate sensors. Along this line, boronic acids that fluoresce beyond 500 nm are especially useful. A series of boronic acid fluorescent reporter compounds based on the 4-amino-1,8-naphthalimide structure have been synthesized (1a-d) and evaluated under near physiological conditions. These compounds showed good water solubility and significant changes in fluorescence properties after binding with sugars, with the emission wavelength being at around 570 nm. Analogues in this series with different substitutions showed similar properties. We have also examined the mechanism of the observed fluorescence changes for these compounds.     

Adenine-based receptor for dicarboxylic acids

The adenine-based fluorescent receptor 1 was designed and synthesized for the selective recognition of dicarboxylic acids in CH₃CN. The recognition takes place through the Hoogsteen binding site of adenine with concomitant PET quenching of the anthracene moiety. The carboxylic acid binding to 1 was investigated by ¹H NMR, X-ray, UV-vis, and fluorescence spectroscopic methods. The Hoogsteen (HG) cleft of receptor 1 is found to be selective for glutaric acid.     

Preparation, properties and synthetic potentials of fluorous boronates

A fluorous approach to the chemistry of boronic acids and its application in fluorous-phase techniques are described. Treatment of fluorous bromosilane 2 with allyl Grignard reagent followed by dihydroxylation provided fluorous diol 1. A series of boronic acids were attached to 1 by esterification. The formed fluorous boronates 4 were moisture sensitive and thus their synthetic potentials were limited. Thus a fluorous pinacol, 5, was designed and synthesized by treatment of fluorous bromosilane 2 with excess 2,3-dimethyl-2-butyenylmagnesium bromide 9 to afford fluorous tetramethyl ethene 8, and was dihydroxylated. Compound 5 was successfully used to prepare fluorous boronates in a one-pot process from organic bromides. We have demonstrated that olefin cross-metathesis can be carried out in a fluorous version. It is noteworthy that all of the fluorinated compounds reported in this paper were purified by simple liquid extraction.     

Fluorescent detection of amidinium-carboxylate and amidinium formation using anthracene-based diamidine: an application for the analysis of dicarboxylic acid binding

An anthracene-based diamidine (1) ‘turn-on’ fluorescent probe for the detection of dicarboxylic acids has been designed and synthesized. The fluorescence spectra of the diamidine 1 with carboxylic acids that showed two different fluorescence bands, which corresponded to the amidinium-carboxylate (λ_em=430-440 nm), and amidinium (λ_em=460-470 nm as a broad band) formation, were confirmed by DOSY NMR and TD-DFT calculations. These different fluorescence bands showed the binding mode of carboxylic acids and the stability of formed complexes toward diamidine 1. The fluorescent detection of amidinium-carboxylate formation using diamidine 1 was applicable to the detection of α,ω-dicarboxylic acids (C₆-C₁₃) and succeeded in the detection of α,ω-dicarboxylic acid (adipic acid) in human urine.     

Triphenylamine-based novel PET sensors in selective recognition of dicarboxylic acids

The triphenylamine-based chemosensors 1 and 2 have been designed and synthesized, for the first time, for the selective recognition of dicarboxylic acids. Carboxylic acid binding takes place through charge neutral pyridyl amide receptor sites with concomitant quenching of fluorescence of the triphenylamine moiety. The bindings were examined using ¹H NMR, fluorescence and UV-vis spectroscopic methods. The receptor 1 was found to be selective for glutaric and adipic acids and the macrocycle 2 was specific for 2,2-dimethylmalonic acid.     

Mono- and oligosaccharide sensing by phenylboronic acid-appended 5,15-bis(diarylethynyl)porphyrin complexes

Porphyrin derivatives bearing a pair of boronic acid groups (1, 1·Zn, and 1·Cu) were designed and synthesized from 2 to construct a saccharide sensing system. Compounds 1, 1·Zn, and 1·Cu have a diethynyl porphyrin rotational axis, which is expected to act as a saccharide-binding modulator. Saccharide binding studies were conducted by UV-vis, fluorescence, and circular dichroism (CD) spectroscopies. In a water-methanol 1:1 (v/v) mixed solvent, we have found that 1·Zn can bind mono- and oligosaccharides including Lewis oligosaccharides to produce 1:1 host-saccharide complexes with the association constants of 10²−10³ M⁻¹ range. This paper thus demonstrates a new principle to design a boronic acid-based saccharide receptor.     

Characterization of 2-phenylbenzo[g]quinoxaline derivatives as viscosity-sensitive fluorescent probes

To develop viscosity-sensitive fluorescent probes, five different substituted 2-phenylbenzo[g]quinoxaline derivatives (3a-e) were designed and synthesized by using benzo[g]quinoxaline as a fluorophore and phenyl ring bearing a rotatable single bond as a viscosity-sensitive unit. The fluorescence properties of these compounds were investigated in the media of the ethylene glycol-glycerol mixture with varied viscosity. It is found that 2-(4-hydroxyphenyl)benzo[g]quinoxaline (3d) and 2-(4-dimethylaminophenyl)-benzo[g]quinoxaline (3e) carrying stronger electron-donating groups in the phenyl ring show more sensitive fluorescence response to viscosity, revealing their potential use in viscosity detection and the key role of the substituted groups. The effects of solvent polarity and pH on the fluorescent properties of 3d and 3e were also discussed. The present study might be useful in developing viscosity-sensitive fluorescent probes.     

Fluorescent detection of amidinium-carboxylate and amidinium formation using a 1,8-diphenylnaphthalene-based diamidine: dicarboxylic acid recognition with high fluorescence efficiency

A 1,8-diphenylnaphthalene-based diamidine (1) ‘turn-on’ fluorescent probe for the detection of dicarboxylic acids has been designed and synthesized. The fluorescence spectra of the diamidine 1 with carboxylic acids that showed two different fluorescence bands, which corresponded to the amidinium-carboxylate (λ_em=410–430 nm) and amidinium (λ_em=440–470 nm as a broad band, which consisted from two peaks) formation, were confirmed by DOSY NMR and TD-DFT calculations. The complexation of diamidine 1 with dicarboxylic acids, which have sufficient distances between the two carboxylic groups for binding to the diamidine 1 (dicarboxylic acids 3, 4, and α,ω-dicarboxylic acids 6 (C₆–C₂₀)), showed the formation of 1:1 complexes (i.e., amidinium-carboxylate formation). On the other hand, for the complexation with monocarboxylic acids and dicarboxylic acids having insufficient distances between the two carboxylic groups (benzoic acid 5, acetic acid 7, and α,ω-dicarboxylic acids 6 (C₃–C₅)), formation of the amidinium (1·2H⁺) was observed. Relatively similar binding constants (10⁻⁵) for the complexation of the diamidine 1 with dicarboxylic acids 6, which depend on their chain length (strain), were observed due to the flexibility of the 1,8-diphenylnaphthalene unit. Additionally, for the complexation of the diamidine 1 with dicarboxylic acids, higher fluorescence quantum yields (Φ_fl: up to 80%) were observed when compared to the binding of the diamidine 2 (Φ_fl: up to 35%).     

A new fluorescent sensor for the detection of pyrophosphate based on a tetraphenylethylene moiety

We have developed a new fluorescent sensor 1-2Zn based on a tetraphenylethylene (TPE) moiety for the detection of PPi. This TPE-based chemosensor showed ‘turn-on’ fluorescence emission according to the concentration of PPi. The fluorescence enhancement upon binding of PPi to 1-2Zn resulted from the restriction of intramolecular rotation of phenyl rings in 1-2Zn.     

Synthesis of novel fluorescent 3-aryl- and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines by Suzuki cross-coupling reactions

Two series of compounds, 3-aryl- (series A, compounds 2a-j) and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines (series B, compounds 3a-j) have been synthesized by Suzuki cross-coupling reactions, with a triazolopyridine halide and an aryl or heteroaryl boronic acid in moderate to good yields. All compounds obtained are fluorescents, the quantum yields, particularly those of compounds 3f-j, are very high.     

Amphiphilic pyrenecarboxylic acids: incorporation into vesicle membrane and ability as sensitizer for electron transport reactions

The novel pyrenecarboxylic acids 1-3 having a single or double hydrophobic alkyl chain were synthesized, and their photophysical properties were investigated in solutions and vesicle membranes. In analogy with parent 1-pyrenecarboxylic acid, the absorption and fluorescence spectra of 1-3 were changed with the H⁺ concentration. The amphiphilic pyrenecarboxylic acids 1-3 had good solubility in the vesicle membranes, and acted as an excellent sensitizer for the electron transport from an electron donor in the inner waterpool of the vesicle to an electron acceptor in the outer aqueous phase across vesicle membranes.     

Pyrenyl-appended imidazolium receptor for selective fluorescence sensing of oxalic acid

A new fluorescent imidazolium-based cholestane receptor 4 bearing a pyrene moiety was synthesized. The binding ability of 4 toward various dicarboxylic acids was examined by UV-vis and fluorescence spectroscopy. Receptor 4 showed the highest binding constant for oxalic acid among all the tested dicarboxylic acids (K_a = 5.06 × 10⁴ M⁻¹). Oxalic acid formed a complex with 4 with a 1:2 ratio in ethanol.     

Synthesis of novel halopyridinylboronic acids and esters. Part 4: Halopyridin-2-yl-boronic acids and esters are stable, crystalline partners for classical Suzuki cross-coupling

This paper describes some methods for the synthesis and the isolation of novel 5 or 6-halopyridin-2-yl-boronic acids and esters 3, 4, 7. These compounds are prepared via a regioselective halogen-metal exchange using n-butyllithium and subsequent quenching with triisopropylborate starting from appropriate dihalopyridines. All substrates studied to date provided a single regioisomeric boronic acid or ester product. Additionally, these compounds have been found to undergo Pd-catalysed coupling with arylhalides and authorise a strategy to produce new pyridines libraries.     

Novel chemosensor for alkaline earth metal ion based on 9-anthryl aromatic amide using a naphthalene as a TICT control site and intramolecular energy transfer donor

Novel fluorescent chemosensors 1 and 2 with two different fluorophores (naphthalene and anthracene) at the both ends of polyether was synthesized. These compounds based on 9-anthryl aromatic amide adopted a naphthalene as a TICT controller and an intramolecular energy transfer source. Compound 1 shows high fluorescence efficiency upon complexation with metal ion, and the fluorescence efficiency of 2 is regulated by metal ionic size.     

Intramolecular charge transfer dual fluorescent sensors from 4-(dialkylamino)benzanilides with metal binding site within electron acceptor

Three fluoroionophores (2a-c) were designed as the intramolecular charge transfer (CT) dual fluorescent sensors for metal cations with metal binding site within the electron acceptor. These sensors were derived from 4-dialkylaminobenzanilides (alkyl=methyl, ethyl, and n-butyl) with the amido phenyl ring being an arm of 15-crown-5 thus bearing binding site for alkaline and alkaline earth metal cations. Compounds 2a-c were expected to have two possible CT channels of opposite direction. The absorption and fluorescence spectra of 2a-c and their crown-ether free model molecules 3a-c in a variety of solvents were recorded. Dual fluorescence was observed with 2a-c and was assigned to the LE and the CT states, respectively. In nonpolar or less polar solvents the CT occurring with 2a-c was identified as that occurred with benzanilides (BA) with the amido anilines being the electron donor (the BA-like CT), while in polar solvents such as acetonitrile (ACN), the CT was still mainly the BA-like. In the presence of alkali and alkaline earth metal cations in ACN, the CT dual fluorescence underwent substantial changes so as increased total quantum yield, red-shifted LE band and enhanced CT to LE intensity ratio. Binding of the metal cations at the 15-crown-5 moiety of 2a-c was shown to turn the CT direction that the dialkylamino group in the binding complexes being the electron donor while the benzo-15-crown-5 moiety now being within the electron acceptor. The occurrence of this CT enhances metal cation binding to 15-crown-5 ether in 2a-c, which was confirmed by the observed higher metal binding constants. Compounds 2a-c as the CT dual fluorescent sensors were shown to operate under the mechanism of the metal cation binding induced switching of the CT character from the BA-like to that occurred with 4-(dimethylamino)benzamides (the DMABA-like). Compounds 2a-c therefore represent successful examples for the CT dual fluorescent sensors for cations with the metal binding site within the electron acceptor and can be employed as sensitive ratiometric fluorescent sensors for metal cations of improved sensing performance.     

Microwave-assisted synthesis of 3-hydroxy-4-pyridinone/naphthalene conjugates. Structural characterization and selection of a fluorescent ion sensor

Two novel 3-hydroxy-4-pyridinone/naphthalene conjugates (L1 and L2) with different distances between the chelating and the fluorescent moieties were synthesized using conventional heating and microwave irradiation achieving a shorter reaction time. The structure of both compounds was confirmed by X-ray crystallography, revealing that these compounds were isolated as hydrochloride salts in dihydroxypyridinium forms. In solution and in the presence of a base, the tautomeric keto forms may be obtained as it was elucidated by NMR analysis. The dihydroxypyridinium form of L1 exhibits fluorescence at 450 nm, both in ACN and DMSO, whereas the corresponding keto form exhibits fluorescence at 365 nm. In contrast, the dihydroxypyridinium form of L2 only fluoresces in DMSO, exhibiting a band at 340 nm, while the keto form is non-fluorescent. These distinct fluorescent behaviors reveal that the tautomeric form in which the ligands are isolated and the distance between the chelating and fluorescent functions strongly influences their fluorescence properties. Ligand L1 exhibits better fluorescence properties and its fluorescence intensity is quenched in the presence of variable concentration of Cu²⁺, Zn²⁺, and Fe³⁺, thus making it suitable to be used as ion sensor.