Ratiometric dual fluorescent receptors for anions under intramolecular charge transfer mechanism

A series of the intramolecular charge transfer (ICT) dual fluorescent receptors with anion binding site in the electron acceptor were designed and synthesized. These receptors exhibited dual fluorescence in acetonitrile and the charge transfer (CT) emission energy was found to correlate linearly with the Hammett constant of the substituent existing in the electron acceptor, which is the basis for anion sensing. Dual fluorescence of these receptors was found to be sensitive to the presence of anions such as fluoride and acetate and the receptors can be employed as ratiometric fluorescent sensors for anions.     

Fluorometric sensing of biogenic amines with aggregation-induced emission-active tetraphenylethenes

A fluorometric sensor for detection and identification of biogenic amines with carboxylic acid modified tetraphenylethenes (TPEs) based on aggregation-induced emission (AIE) is reported. A mixture of the carboxylic acid substituted TPE and biogenic amines displayed a blue emission on aggregation, which serves as a "turn-on" fluorescent sensor for the amines, the degree of fluorescence enhancement being dependent on the amine. The chromic responses were utilized to distinguish the amines. A fluorometric sensor array of three TPEs with carboxylic acid groups was shown to identify accurately 10 different amines, including biogenic amines. The response patterns were systematically classified by using linear discriminant analysis (LDA) with 98% classification accuracy. Additional information on the concentration of histamine in a "tuna fish matrix" as an example was assessed by the further analysis of the fluorescence intensity, demonstrating a test for food freshness and quality.     

A unique NH-spacer for N-benzamidothiourea based anion sensors. Substituent effect on anion sensing of the ICT dual fluorescent N-(p-dimethylaminobenzamido)-N'-arylthioureas

A series of N-(p-dimethylaminobenzamido)-N'-(substituted-phenyl)thioureas (substituent = p-CH3, H, p-Cl, p-Br, m-Br, m-NO2, and p-NO2) were designed as anion sensors in order to better understand the -NH-spacer via a substituent effect investigation. In these molecules the dual fluorescent intramolecular charge transfer (ICT) fluorophore p-dimethylaminobenzamide as the signal reporter was linked to the anion-binding site, the thiourea moiety, via an N-N single bond. Correlation of the NMR signals of the aromatic and -NH protons with substituents in these molecules indicated that the N-N single bond stopped the ground-state electronic communication between the signal reporter and the anion-binding site. Dual fluorescence was observed in highly polar solvents such as acetonitrile with the former five derivatives. The fact that the CT emission wavelength and the CT to LE emission intensity ratio of the sensors were independent of the substituent existing in the anion-binding moiety suggested that the substituent electronic effect could not be communicated to the CT fluorophore in the excited-state either. Yet in acetonitrile both the CT dual fluorescence and the absorption of the sensors were found to be highly sensitive toward anions. A conformation change around the N-N bond in the sensor molecules was suggested to occur upon anion binding that established the electronic communication between the signal reporter and the anion-binding site. The anion binding constants of the N-(p-dimethylaminobenzamido)thiourea sensors were found higher than those of the corresponding traditional N-phenylthiourea counterparts and the substituent effect on the anion binding constant was much higher than that in the latter. "-NH-" was shown to be a unique spacer that affords N-benzamidothiourea allosteric anion sensors.     

Evaluation of a simple and novel fluorescent anion sensor, 4-quinolone, and modification of the emission color by substitutions based on molecular orbital calculations

4-Quinolone (4-QO) was evaluated as a simple and novel fluorescent anion sensor, and the modification of its emission color was carried out. The series of 4-QO derivatives having molecular orbitals with different energy levels was designed by substitutions at the 6 and 7 positions based on the molecular orbital calculations. All derivatives showed drastic fluorescence enhancements in the presence of F⁻ via the intramolecular charge transfer mechanism, and the successful modification of the emission color was achieved. The anion-induced emission colors of these derivatives as well as their binding affinities for F⁻ could be predicted by ab initio quantum chemical calculations, indicating that the present calculations are useful in designing new anion sensors.     

Anion Sensing through Redox-Modulated Fluorescent Halogen Bonding and Hydrogen Bonding Hosts**

Anion sensing via either optical or electrochemical readouts has separately received enormous attention, however, a judicious combination of the advantages of both modalities remains unexplored. Toward this goal, we herein disclose a series of novel, redox-active, fluorescent, halogen bonding (XB) and hydrogen bonding (HB) BODIPY-based anion sensors, wherein the introduction of a ferrocene motif induces remarkable changes in the fluorescence response. Extensive fluorescence anion titration, lifetime and electrochemical studies reveal anion binding-induced emission modulation through intramolecular photoinduced electron transfer (PET), the magnitude of which is dependent on the nature of both the XB/HB donor and anion. Impressively, the XB sensor outperformed its HB congener in terms of anion binding strength and fluorescence switching magnitude, displaying significant fluorescence turn-OFF upon anion binding. In contrast, redox-inactive control receptors display a turn-ON response, highlighting the pronounced impact of the introduction of the redox-active ferrocene on the optical sensing performance. Additionally, the redox-active ferrocene motif also serves as an electrochemical reporter group, enabling voltammetric anion sensing in competitive solvents. The combined advantages of both sensing modalities were further exploited in a novel, proof-of-principle, fluorescence spectroelectrochemical anion sensing approach, enabling simultaneous and sensitive read out of optical and electrochemical responses in multiple oxidation states and at very low receptor concentration.     

Bidirectional photoinduced electron-transfer quenching is observed in 4-amino-1,8-naphthalimide-based fluorescent anion sensors

The synthesis and photophysical evaluations of two new fluorescent photoinduced electron-transfer (PET) anion sensors, 1 and 2, is described. These are based on 4-amino-1,8-naphthalimide fluorophores and diarylthiourea anion receptors, connected via a methylene spacer to the imide. The sensing of acetate, phosphate, and fluoride, on all occasions, gave rise to quenching in the fluorescence of 1 and 2, similar to that seen for the structural isomer 3. These results demonstrate that bidirectional PET sensing occurs in such naphthalimide-based anion sensors.     

Anion recognition and sensing in organic and aqueous media using luminescent and colorimetric sensors

This review article focuses primarily on the work carried in our laboratories over the last few years using luminescent and colorimetric sensors, where the anion recognition occurs through hydrogen bonding in organic or aqueous solvents. This review begins with the story of the discovery of fluorescent photoinduced electron transfer (PET) sensors for anions using charged neutral urea or thiourea receptors where both fluorescent and NMR spectroscopic methods monitored anion recognition. This work led to the development of dual luminescent and colorimetric anion sensors based on the use of the ICT based naphthalimide chromophore, where ions such as fluoride gave rise to changes in both the fluorescence and the absorption spectra of the sensors, but at different concentrations. Here, the former changes were due to hydrogen bonding interactions, whereas the latter was due to the deprotonation of acidic protons, giving rise to the formation of the bifluoride anion (HF₂⁻). Modification of the 4-amino-l,8-naphthalimide moiety has facilitated the formation of colorimetric anion sensors that work both in organic or aqueous solutions. Such charge neutral receptor motifs have also been incorporated into organic scaffolds with norbomyl and calixarene backbones, which have enabled us to produce anion directed self-assembled structures.     

A modular strategy for tailoring fluorescent biosensors from ribonucleopeptide complexes

Fluorescent biosensors that facilitate reagentless sensitive detection of small molecules are crucial tools in the areas of therapeutics and diagnostics. However, construction of fluorescent biosensors with desired characteristics, that is, detection wavelengths and concentration ranges for ligand detection, from macromolecular receptors is not a straightforward task. An ATP-binding ribonucleopeptide (RNP) receptor was converted to a fluorescent ATP sensor without chemically modifying the nucleotide in the ATP-binding RNA. The RNA subunit of the ATP-binding RNP and a peptide modified with a pyrenyl group formed a stable fluorescent RNP complex that showed an increase in the fluorescence intensity upon binding to ATP. The strategy to convert the ATP-binding RNP receptor to a fluorescent ATP sensor was applied to generate fluorescent ATP-binding RNP libraries by using a pool of RNA subunits obtained from the in vitro selection of ATP-binding RNPs and a series of fluorophore-modified peptide subunits. Simple screening of the fluorescent RNP library based on the fluorescence emission intensity changes in the absence and presence of the ligand afforded fluorescent ATP or GTP sensors with emission wavelengths varying from 390 to 670 nm. Screening of the fluorescence emission intensity changes in the presence of increasing concentrations of ATP allowed titration analysis of the fluorescent RNP library, which provided ATP sensors responding at wide concentration ranges of ATP. The combinatorial strategy using the modular RNP receptor reported here enables tailoring of a fluorescent sensor for a specific ligand without knowledge of detailed structural information for the macromolecular receptor.     

Design, synthesis and photophysical studies of simple fluorescent anion PET sensors using charge neutral thiourea receptors

The synthesis of four fluorescent photoinduced electron transfer (PET) chemosensors 1-4 for anions is described. These are all based on a simple design employing charge neutral aliphatic or aromatic thiourea anion receptors connected to an anthracene fluorophore via a methylene spacer. Here the anion recognition occurred through 1 : 1 hydrogen bonding between the thiourea protons and the anion, as demonstrated by observing the changes in the (1)H NMR in DMSO-d(6) where the two thiourea protons were shifted downfield upon addition of anions. Whereas 1-3 were designed for the detection of anions such as fluoride, acetate or phosphate, 4 was made for the recognition of N-protected amino acids. All the sensors showed 'ideal' behaviour where only the fluorescence emission was quenched upon anion recognition, due to enhanced efficiency of electron transfer quenching from the receptor to the excited state of the fluorophore. By simply varying the nature of the thiourea substituent it was possible to modulate, or tune, the acidity of the thiourea receptor moiety, altering the sensitivity of the anion recognition. For, the anion selectivity and the degree of the fluorescence quenching were in the order of F(-) > AcO(-) > H(2)PO(4)(-), with Cl(-) or Br(-) not being detected.     

Mechanically Modulating the Photophysical Properties of Fluorescent Protein Biocomposites for Ratio‐ and Intensiometric Sensors

Mechanically sensitive biocomposites comprised of fluorescent proteins report stress through distinct pathways. Whereas a composite containing an enhanced yellow fluorescent protein (eYFP) exhibited hypsochromic shifts in its fluorescence emission maxima following compression, a composite containing a modified green fluorescent protein (GFPuv) exhibited fluorescence quenching under the action of mechanical force. These ratio‐ and intensiometric sensors demonstrate that insights garnered from disparate fields (that is, polymer mechanochemistry and biophysics) can be harnessed to guide the rational design of new classes of biomechanophore‐containing materials.     

An Ultrafast Molecular-Rotor-Based Fluorescent Turn-On Sensor for the Perrhenate Anion in Aqueous Solution

Devising sensors for the perrhenate anion in aqueous media is extremely challenging, and has seldom been reported in the literature. Herein, we report a fluorescence turn-on sensor for the perrhenate anion in aqueous media based on the aggregation-induced emission of a popular ultrafast molecular rotor dye, Thioflavin-T. The selective response towards the perrhenate anion has been rationalized in terms of matching water affinity, with the weakly hydrated perrhenate anion spontaneously forming a contact ion pair with the weakly hydrated ultrafast molecule-rotor-based organic cation, Thioflavin-T, which in turn leads to an aggregate assembly that provides a fluorescence turn-on response towards perrhenate. The sensing response of Thioflavin-T has been found to be quite selective towards the perrhenate anion when tested against anions that are ubiquitously present in the environment, such as chloride, nitrate, and sulfate anions. The formation of self-assembled Thioflavin-T aggregates has also been investigated by time-resolved emission and temperature-dependent measurements.     

A new series of 2,5-bis(4-methylphenyl)-1,3,4-oxadiazole derivatives: their synthesis and fluorescence properties for anion sensors

A new series of 2,5-bis(4-methylphenyl)-1,3,4-oxadiazole derivatives containing various substituted groups on the ortho-position to oxadiazole ring was synthesized and their fluorescent sensor properties were investigated. The fluorescent sensor molecules showed UV absorption shift as well as fluorescence emission shift upon exposure to fluoride anion in DMF solution, which was considerably dependent on the substituent attached on the phenyl group. The new sensory compound, 1d can be used as a fluoride anion sensor in terms of naked-eye detection and fluorescent sensing with high selectivity.     

Enantioselective recognition of mandelic acid by a 3,6-dithiophen-2-yl-9H-carbazole-based chiral fluorescent bisboronic acid sensor

We have prepared chiral fluorescent bisboronic acid sensors with 3,6-dithiophen-2-yl-9H-carbazole as the fluorophore. The thiophene moiety was used to extend the π-conjugation framework of the fluorophore in order to red-shift the fluorescence emission and, at the same time, to enhance the novel process where the fluorophore serves as the electron donor of the photoinduced electron transfer process (d-PET) of the boronic acid sensors; i.e., the background fluorescence of the sensor 1 at acidic pH is weaker compared to that at neutral or basic pH, in stark contrast to the typical a-PET boronic acid sensors (where the fluorophore serves as the electron acceptor of the photoinduced electron transfer process). The benefit of the d-PET boronic acid sensors is that the recognition of the hydroxylic acids can be achieved at acidic pH. We found that the thiophene moiety is an efficient π-conjugation linker and electron donor; as a result, the d-PET contrast ratio of the sensors upon variation of the pH is improved 10-fold when compared to the previously reported d-PET sensors without the thiophene moiety. Enantioselective recognition of tartaric acid was achieved at acid pH, and the enantioselectivity (total response K(D)I(F)(D)/K(L)I(F)(L)) is 3.3. The fluorescence enhancement (I(F)(Sample)/I(F)(Blank)) of sensor 1 upon binding with tartaric acid is 3.5-fold at pH 3.0. With the fluorescent bisboronic acid sensor 1, enantioselective recognition of mandelic acid was achieved for the first time. To the best of our knowledge, this is the first time that the mandelic acid has been enantioselectively recognized using a chiral fluorescent boronic acid sensor. Chiral monoboronic acid sensor 2 and bisboronic acid sensor 3 without the thiophene moiety failed to enantioselectively recognize mandelic acid. Our findings with the thiophene-incorporated boronic acid sensors will be important for the design of d-PET fluorescent sensors for the enantioselective recognition of α-hydroxylic acids such as mandelic acid, given that it is currently a challenge to recognize these analytes with boronic acid fluorescent molecular sensors.     

具有聚集诱导发光特性的四苯基乙烯研究进展

具有聚集诱导发光(aggregation-induced emission,AIE)性质的四苯基乙烯及其衍生物(tetraphenylethenes,TPEs)因其发光性能优良、合成简便、易多功能化而越来越受到关注.本文着重对最近几年TPEs的AIE性质研究进展进行综述.在阐述结构与AIE性质之间关系的同时,介绍了TPEs在生物、化学传感器及其它方面的应用, 并对TPEs的设计与应用给予展望.     

Dual responsive chemosensors for anions: the combination of fluorescent PET (Photoinduced Electron Transfer) and colorimetric chemosensors in a single molecule

The design and synthesis of two novel fluorescent PET anion sensors is described, based on the principle of ‘fluorophore-spacer-(anion)receptor’. The sensors 1 and 2 employ simple diaromatic thioureas as anion receptors, and the fluorophore is a naphthalimide moiety that absorbs in the visible part of the spectrum and emits in the green. Upon recognition of anions such as F⁻ and AcO⁻ in DMSO, the fluorescence emission of 1 and 2 was ‘switched off’, with no significant changes in the UV-vis spectra. This recognition shows a 1:1 binding between the receptor and the anions. In the case of F⁻, further additions of the anion, gave rise to large changes in the UV-vis spectra, where the λ_max at 455 nm was shifted to 550 nm. These changes are thought to be due to the deprotonation of the 4-amino moiety of the naphthalimide fluorophore. This was in fact found to be the case, using simple naphthalimide derivatives such as 6. Sensors 1 and 2 can thus display dual sensing action; where at low concentrations, the fluorescence emission is quenched, and at higher concentrations the absorption spectra are modulated.     

Synthesis of functionalized core-modified sapphyrins and covalently linked porphyrin–sapphyrin dyads

We adopted simple synthetic strategy to synthesize mono-functionalized thiasapphyrins containing functionalized aryl group in the meso-position at thiophene side. The thiasapphyrin building block containing iodophenyl functional group was coupled with three different porphyrin building blocks with N₄, N₃S and N₂S₂ cores containing meso-ethynylphenyl functional group under mild Pd(0) coupling conditions to synthesize three covalently linked diphenyl ethyne bridged porphyrin–thiasapphyrin dyads. The porphyrin–thiasapphyrin dyads were characterized by mass, NMR, absorption, electrochemical and fluorescence techniques. The NMR, absorption and electrochemical studies indicated that the two components in dyads interact weakly and retain their individual identities. The steady state fluorescence studies indicated that the porphyrin fluorescence is reduced to a significant extent because of energy and/or electron transfer to the thiasapphyrin unit. The protonation studies indicated that N₄ porphyrin unit is more basic, whereas N₃S and N₂S₂ porphyrin units are less basic compared to thiasapphyrin unit in respective dyads. We explored the potential of dyads as fluorescent anion sensors and showed that two out of three dyads can be used as fluorescent anion sensors.     

A unique approach to development of near-infrared fluorescent sensors for in vivo imaging

Near-infrared (NIR) fluorescent sensors have emerged as promising molecular tools for imaging biomolecules in living systems. However, NIR fluorescent sensors are very challenging to be developed. Herein, we describe the discovery of a new class of NIR fluorescent dyes represented by 1a/1c/1e, which are superior to the traditional 7-hydroxycoumarin and fluorescein with both absorption and emission in the NIR region while retaining an optically tunable hydroxyl group. Quantum chemical calculations with the B3LYP exchange functional employing 6-31G(d) basis sets provide insights into the optical property distinctions between 1a/1c/1e and their alkoxy derivatives. The unique optical properties of the new type of fluorescent dyes can be exploited as a useful strategy for development of NIR fluorescent sensors. Employing this strategy, two different types of NIR fluorescent sensors, NIR-H(2)O(2) and NIR-thiol, for H(2)O(2) and thiols, respectively, were constructed. These novel sensors respond to H(2)O(2) or thiols with a large turn-on NIR fluorescence signal upon excitation in the NIR region. Furthermore, NIR-H(2)O(2) and NIR-thiol are capable of imaging endogenously produced H(2)O(2) and thiols, respectively, not only in living cells but also in living mice, demonstrating the value of the new NIR fluorescent sensor design strategy. The new type of NIR dyes presented herein may open up new opportunities for the development of NIR fluorescent sensors based on the hydroxyl functionalized reactive sites for biological imaging applications in living animals.     

Fluorescent assemblies: Synergistic of amphiphilic molecules and fluorescent elements

In recent years, fluorescent assemblies based amphiphilic molecules have gained attention as unique and powerful materials for multiple applications that cover sensors, optoelectronics and bioimaging because of amphiphilic molecules self-assembly with outstanding flexibility and diversity spanning assembly structure from micelles, vesicles and nano-assemblies to gels. Weak and noncovalent interactions are important driving force for assemblies. The combination of the structural characteristics of self-assembly and the fluorescent properties of the fluorescent building element render the fluorescent material versatility and their easy-to-tune properties. Amphiphilic molecules can be used as building elements to co-assemble with dye molecules, aggregation-induced emission (AIE) gens, fluorescent nanoparticles and new amphiphilic molecules containing fluorescent groups can also be designed and prepared with self-assembly capability. Concomitantly, the improvement of fluorescence performance including fluorescence intensity, quantum yield, stability and controllability during assembly proved outstanding properties of fluorescence assemblies. These promising fluorescent assemblies are by far not exhaustive in construction method and mechanism explanation but foreshadow their more potential applications. Here, we will understand deeper the fluorescent assemblies and inspire future developments and applications employing this emerging fluorescence soft materials.     

Synthesis and photophysical evaluation of charge neutral thiourea or urea based fluorescent PET sensors for bis-carboxylates and pyrophosphate

The synthesis of the fluorescent photoinduced electron transfer (PET) chemosensors 1-3 for bis-anions such as bis-carboxylates and pyrophosphate in organic solvents is described herein. These sensors are based on the receptor-spacer-fluorophore-spacer-receptor motif where the receptors are charge neutral aromatic thiourea or urea receptors and the fluorophore is anthracene. The anion recognition was evaluated using 1H NMR as well as absorption and fluorescence spectroscopy in DMSO. For simple anions such as acetate or fluoride, the recognition was shown to be through hydrogen bonding of the corresponding anion to the receptors. This gave rise to only minor changes in the absorption spectra, but significant changes in the fluorescence emission spectra, which was substantially (70-95%) quenched. Analysis of these recognition events implied a 1 : 2 (sensor : anion) binding and ideal PET behaviour for ions such as AcO- and H2PO4-. For F-, the luminescent quenching indicated a 1 : 1 binding, but we deduced that this was due more to complete quenching of the excited state after the addition of one equivalent of the anion. For all of the anions, the quenching contributed to enhanced efficiency of PET from the receptors to the excited state of the fluorophore. In the case of the bis-anions (ambient), such as di-carboxylates, similar fluorescence quenching was observed. However, here either a 1 : 1 or a 1 : 2 binding was observed depending on the length of the spacer separating the two carboxylate moieties and the nature of the receptor. Whereas both pyrophosphate and malonate gave rise to a 1 : 1 binding, glutarate gave rise to approximately 1 : 2 binding for the thiourea sensors 1 and 2. However, for the urea based sensor 3, the binding was found to be 1 : 1 for all the bis-anions. For such a 1 : 1 binding we propose that the anion most likely bridges the fluorophore moiety. This was also evident from the 1H NMR (DMSO-d6) spectrum where the anthracene resonances were significantly affected. By simply modifying the electronic structure of the receptor, the sensitivity of the recognition process could also be modified; e.g. compound 1, bearing the trifluoromethyl substituent, showed stronger binding to the bis-anions than 2, which possessed a simple phenyl moiety.     

Fluorescent sensor for fluoride anion based on a sulfonamido-chromone scaffold

New scaffolds of sulfonamido-chromone derivatives recently synthesized were found to be effective fluorescent sensors for fluoride anion. This new class of fluorophore showed a blue shift in the emission spectra upon addition of various equivalents of fluoride. These compounds also exhibit excellent selectivity for the fluoride anion via a deprotonation process. They were also shown to have a detection limit of F^? down to 0.5?ppm.