The Recent Advances of Fluorescent Sensors Based on Molecularly Imprinted Fluorescent Nanoparticles for Pharmaceutical Analysis

Fluorescent nanoparticles have good chemical stability and photostability,controllable optical properties and larger stokes shift.In light of their designability and functionability,the fluorescent nanoparticles are widely used as the fluorescent probes for diverse applications.To enhance the sensitivity and selectivity,the combination of the fluorescent nanoparticles with the molecularly imprinted polymer,i.e.molecularly imprinted fluorescent nanoparticles(MIFN),was an effective way.The sensor based on MIFN(the MIFN sensor)could be more compatible with the complex sample matrix,which was especially widely adopted in medical and biological analysis.In this mini-review,the construction method,detective mechanism and types of MIFN sensors are elaborated.The current applications of MIFN sensors in pharmaceutical analysis,including pesticides/herbicide,veterinary drugs/drugs residues and human related proteins,are highlighted based on the literature in the recent three years.Finally,the research prospect and development trend of the MIFN sensor are forecasted.

6-(N,N-Dimethylamino)-2-naphthoylacryl Acid:a Highly Selective and Sensitive Fluorescent Sensor of Copper(Ⅱ)

A novel fluorescent probe,6-（N,N-dimethylamino）-2-naphthoylacryl acid（ACADAN） was designed and synthesized as a fluorescent sensor for Cu^2＋ in aqueous media.Significant amplification of fluorescence signals without causing any discernible change of maximum fluorescence emission wavelength（λ max） was observed upon the addition of Cu^2＋.Importantly,ACADAN is capable of recognizing Cu^2＋ selectively in aqueous media in the presence of various biologically relevant metal ions and the prevalent toxic metal ions in the environment with high sensitivity（detection limit was 0.1 μmol/L）.

Sensitive measurement of silver ions in environmental water samples integrating magnetic ion-imprinted solid phase extraction and carbon dot fluorescent sensor

Increasing use of silver in various fields has caused Ag^(+)pollution in water environment,taking great threats to people’s health.As a consequence,establishing rapid and reliable methods for sensitive determination of Ag^(+)is of great significance.Fluorescent(FL)sensors based on carbon dots(CDs),an excellent carbonaceous nanomaterial with strong and stable fluorescence,have absorbed extensive attentions in analysis of pollutants due to its advantages of carbon sources being readily available,low cost,easy operation and fast response.Moreover,ion-imprinting is a better way to increase the selectivity of the proposed method.Present work described an effective method for the sensitive measurement of silver ion in water samples in combination with magnetic ion-imprinted solid phase extraction and CDs based fluorescent sensor,which took full advantages of easy separation and high enrichment of magnetic solid phase extraction,high selectivity of ion-imprinting technology,and sensitivity and rapid response of fluorescent sensor from CDs.Sulfur-doped CDs derived from dithizone and magnetic ion-imprinted nanomaterial were prepared,and characterized with Fourier transform infrared spectroscopy and transmission electron microscope,etc.Magnetic Ag^(+)imprinted nanomaterial based solid phase extraction was employed for separating and enriching Ag^(+)from water samples.The significant parameters were optimized in detail.Under the optimal conditions,the proposed method provided good linearity in the range of 0.01-0.4μmol/L and low detection limit of 3 nmol/L.The reliability of the proposed method was validated with real water samples,and the results demonstrated that the proposed method was simple,robust,selective and sensitive detection tool for Ag^(+)in real water samples.

A simple fluorescent sensor for highly sensitive detection of UO_(2)2+

Extensive application of nuclear energy has caused widespread environmental uranium contamination.New detection approaches without complicated sample pretreatment and precision instruments are in demand for on-site and in-time determination of uranyl ions in environmental monitoring, especially in an emergency situation. In this work, a simple and effective fluorescent sensor(Z)-N’-hydroxy-4-(1,2,2-triphenylvinyl)benzimidamide(TPE-A) with aggregation-induced emission(AIE) character was established and studied. It could realize to detect UO_(2)2+via quenching the fluorescence of its aggregation-induced emission, with good selectivity and sensitivity. Such strategy shows a wide linear range from 5.0 × 10^(-8)mol/L to 4.5 × 10^(-7)mol/L(R^(2)= 0.9988) with exceptional sensitivity reaching 4.7 × 10^(-9)mol/L, which is far below the limit for uranium in drinking water(30 μg/L, ca. 1.1 × 10-7mol/L) stipulated by the WHO.A response time less than four minutes make it rapid for uranyl ion measurement. It was applied for detection of uranyl ion in spiked river water samples with recoveries in the range of 98.7%-104.0%, comparable to those obtained by ICP-MS. With the advantages of portable apparatus, rapid detection process and high sensitivity, TPE-A can serve as a promising fluorescent sensor for the detection of UO_(2)2+in environmental water samples.

Self-assembly of a quadrangular prismatic covalent cage templated by zinc ions:A selective fluorescent sensor for palladium ions

Herein we report a covalent cage TPE-Zn_(4)based on a tetraphenylethylene molecule via subcomponent self-assembly,which is templated by zinc ions.TPE-Zn_(4)features a quadrangular prismatic cage structure,which is characterized by NMR,mass spectrum,and single-crystal X-ray diffractions.TPE-Zn_(4)emitted orange fluorescence(λ_(em)=620 nm)in DMSO solution under the irradiation of UV light(λ_(ex)=395 nm)and can be applied as a fluorescence sensor for selectively detecting Pd^(2+).The fluorescence of TPE-Zn_(4)was quenched by Pd^(2+)in DMSO solution,and a very low detection limit of 62.3 n M was achieved.Mechanism studies reveal that the Pd^(2+)can replace the Zn^(2+),and the heavy atom effect and chelation-enhanced quenching effect between the Pd^(2+)and the cage probably cause the fluorescence quenching.

Isomeric fluorescence sensors for wide range detection of ionizing radiations

In order to achieve a wider range of ionizing radiations detection,novel fluorescence sensing materials have been developed that utilize the fluorescence enhancement phenomenon caused by the intramolecular photoinduced electron transfer(PET)effect.Two perylene diimide isomers PDI-P and PDI-B were designed and synthesized,and their molecular structures were characterized by high-resolution Fourier transform mass spectrometry(HRMS),nuclear magnetic resonance hydrogen and carbon spectroscopy(~1H and~(13)C NMR).The interaction between ionizing radiation and fluorescent molecules was simulated by HCl titration.The results show that combining PDIs and HCl can improve fluorescence through the retro-PET process.Despite the similarities in chemical structures,the fluorescent enhancement multiple of PDI-B with aromatic amine as electron donor is much higher than that of PDI-P with alkyl amine.In the direct irradiation experiments of ionizing radiation,the emission enhancement multiples of PDI-P and PDI-B are 2.01 and 45.4,respectively.Furthermore,density functional theory(DFT)and time-dependent density functional theory(TDDFT)calculations indicate that the HOMO and HOMO-1 energy ranges of PDI-P and PDI-B are 0.54 e V and 1.13 e V,respectively.A wider energy range has a stronger driving force on electrons,which is conducive to fluorescence quenching.Both femtosecond transient absorption spectroscopy(fs-TAS)and transient fluorescence spectroscopy(TFS)tests show that PDI-B has shorter charge separation lifetime and higher electron transfer rate constant.Although both isomers can significantly reduce LOD during PET process,PDI-B with aromatic amine has a wider detection range of 0.118—240 Gy due to its larger emission enhancement,which is a leap of three orders of magnitude.It breaks through the detection range of gamma radiation reported in existing studies,and provides theoretical support for the further study of sensitive and effective new materials for ionizing radiation detection.

A novel fluorescence sensor for milk clotting enzyme chymosin using peptide as substrate and covalent organic framework nanosheet as fluorescence quencher

Chymosin is one of the critical enzymes in cheese making.Herein,we proposed a novel fluorometric assay for chymosin determination.Firstly,covalent organic frameworks(COF)were synthesized and exfoliated to 2-dimensional COF nanosheets(COF NS)by ultrasound treatment.Gold nanoparticles(Au NPs)were loaded with COF NS to prepare AuNPs/COF NS(Au@COF NS).Secondly,rhodamine B(RhB)modified substrate peptide(Pep)for chymosin was linked with Au@COF NS to construct a Pep-Au@COF NS nanocomposite.For the sensing principle,fluorescence of RhB was quenched by Au@COF NS and the fluorescence intensity was weak due to the fluorescence resonance energy transfer between COF NS and RhB of Pep.However,in the presence of chymosin,the RhB was released by specific cleavage of the substrate peptide by chymosin and resulted in the recovery of fluorescence.The increased fluorescence intensity was proportional to the increase of chymosin concentration and thus a“turn on”fluorescent sensor for chymosin was constructed.The sensor showed a linear range in the concentration of 0.05-60.00μg/mL for the detection of chymosin with a detection limit of 20 ng/mL.The sensor was used to quantify chymosin in rennet product with good selectivity,which has the potential applications in cheese manufacturing.

Spatiotemporal Imaging of Cellular Energy Metabolism with Genetically-Encoded Fluorescent Sensors in Brain

The brain has very high energy requirements and consumes 20% of the oxygen and 25% of the glucose in the human body. Therefore, the molecular mechanism under- lying how the brain metabolizes substances to support neural activity is a fundamental issue for neuroscience studies. A well-known model in the brain, the astrocyte- neuron lactate shuttle, postulates that glucose uptake and glycolytic activity are enhanced in astrocytes upon neu- ronal activation and that astrocytes transport lactate into neurons to fulfill their energy requirements. Current evidence for this hypothesis has yet to reach a clear consensus, and new concepts beyond the shuttle hypothesis are emerging. The discrepancy is largely attributed to the lack of a critical method for real-time monitoring of metabolic dynamics at cellular resolution. Recent advances in fluorescent protein-based sensors allow the generation of a sensitive, specific, real-time readout of subcellular metabolites and fill the current technological gap. Here,we summarize the development of genetically encoded metabolite sensors and their applications in assessing cell metabolism in living cells and in vivo, and we believe that these tools will help to address the issue of elucidating neural energy metabolism.

Synthesis and properties of three novel rhodamine-based fluorescent sensors for Hg^(2+)

Three novel rhodamine-based Hg^2＋ fluorescent sensors were designed and synthesized. The sensors could work in semi-aqueous solutions with nearly neutral p H and showed high selectivity and sensitivity to Hg^2＋ with remarkable fluorescence enhancement. For these three sensors, the linear working range broadened（0–80, 0–100 and 0–140 μmol/L, respectively） and the sensitivity increased（7.7, 15.5 and 17.6 folds of the fluorescence enhancement and 512, 66.2 and 37.6 ppb of the detection limit） with the rising of the thiourea-unit numbers. Furthermore the sensors exhibited excellent interference immunity to multiple environmentally and biologically relevant metal ions. Pond and tap water assay showed good practicability of the sensors. The number of the bound Hg^（2＋） equaling to that of the thiourea units and the irreversible recognition process implied a new interaction way between Hg^（2＋） and the sensor.

A pillar[5]arene-based side-chain pseudorotaxanes and polypseudorotaxanes as novel fluorescent sensors for the selective detection of halogen ions

A pseudorotaxane and its polypseudorotaxanes formed between pillar[5]arene moieties and noctylpyrazinium cations as novel fluorescent sensors for the selective detection of halogen ions were reported.A collapse of these pillar[5]arene-based pseudorotaxanes and polypseudorotaxanes occurred upon the addition of Cl,Br,and I（tetrabutylammonium salts）,respectively,leading to their fluorescence recovery.The fluorescence enhancement of the pseudorotaxane and the polypseudorotaxanes increases in the order of I

Thiourea functionalized CdSe/CdS quantum dots as a fluorescent sensor for mercury ion detection

CdSe/CdS quantum dots （QDs） functionalized by thiourea （TU） were synthesized and used as a fluorescent sensor for mercury ion detection. The TU-functionalized QDs were prepared by bonding TU via electrostatic interaction to the core/shell CdSe/CdS QDs after capping with thioglycolic acid （TGA）. It was observed that the fluorescence of the functionalized QDs was quenched upon the addition of Hg^2＋. The quantitative detection of Hg^2＋ with this fluorescent sensor could be conducted based on the linear relationship between the extent of quenching and the concentration of Hg^2＋ added in the range of 1-300 μg.L^-1, A detection limit of 0.56 μg.L^-1 was achieved. The sensor showed superior selectivity for Hg^2＋ and was successfully applied to the determination of mercury in environmental samples with satisfactory results

A novel colorimetric and ratiometric NIR fluorescent sensor for glutathione based on dicyanomethylene-4H-pyran in living cells

Glutathione(GSH)plays a critical role in maintaining oxidation-reduction homeostasis in biological systems.Considering the detection of GSH by fluorescence sensors is limited by either the short wavelength emission or the poor photostability,a highly stable colorimetric and ratiometric NIR fluorescent sensor(DCM-S)for GSH detection has been constructed on the basis of dicyanomethylene-4H-pyran(DCM)chromophore.The specific disulfide bond is incorporated via a carbamate linker as the GSH responsive group,which simultaneously blue-shifts and quenches the fluorescence.Upon addition of GSH,DCM-S exhibits outstanding colorimetric(from yellow to red)and ratiometric fluorescent response with the 6-fold enhancement of NIR fluorescence at 665 nm in quantum yield.More importantly,the GSH-treated DCM-S(DCM-NH_2 actually)possesses 20-fold longer fluorescence half-life period as well as much better photostability than the FDA-approved ICG.Finally,the ratiometric detection of GSH is also successfully operated in the living cell imaging,exhibiting NIR fluorescence and large Stokes shift(215 nm)with nearly no background fluorescence interference.As a consequence,DCM-S can be utilized as colorimetric and ratiometric NIR fluorescent sensor for GSH,with a great potential in the development of GSH-induced drug delivery system.

One enantiomeric fluorescent sensor pair to discriminate four stereoisomers of threonines

The BINOL-amino alcohol enantiomeric pair （S）-I and （R）-I are discovered to conduct both enantioselective and diastereose- lective fluorescent discrimination of the four stereoisomers of threonine derivatives. This study utilizes different fluorescence responses of one sensor at two emission wavelengths toward the stereoisomeric substrates which expands the capability of the sensor in chiral recognition. In addition, the sensor pair also allows visual recognition of the N-protected L-allo-threonine and D-allo-threonine by enantioselective precipitation.

Label-free Fluorescent Sensor for Probing Heparin-Protein Interaction Based on Supramolecular Assemblies

In this paper a label-free fluorescent sensor for probing the interaction between heparin and protein was reported.Heparin,the bioactive polyanions,formed supramolecular assemblies with cationic surfactant cetyltrimethyl ammonium bromide (CTAB).The environment-dependent dye pyrene,encapsulated in hydrophobic interiors of the supramolecular assemblies worked as the fluorescence probe.Once the heparin-binding protein was added,competing interactions of protein with heparin would weaken the interaction between CTAB and heparin.As a result,the noncovalently sequestered pyrene would be released upon disassembly and the fluorescence of the released pyrene was subsequently decreased.The binding events were exemplified by protamine and Tat peptide,these processes were also verified by DLS and TEM.Such a strategy is appealing as organic synthesis was traded off against supramolecular assembly.This label-free fluorescent system is simple,selective,convenient,and can serve as a good complement to other existing methods,also this method has the potential for preprimary drug screening.

Pyrenoviologen-based fluorescent sensor for detection of picric acid in aqueous solution

Two highly emissive pyrenoviologen derivatives were synthesized and used to fabricate fluorescent sensors for detection of picric acid(PA)with good sensitivity and selectivity.The sensitivity of the sensor was attributed to the specific electrostatic association effect of the cationic pyrenoviologens to the picrate anions,which also gave the sensor special selectivity among other compounds with similar structure.The electron transfer between them was attributed to the fluorescence response.Fluorescence lifetime measurements revealed that the quenching is static in nature.The novel and efficient pyrenoviologen derivatives-based sensors offered a strategy to fabricate real-life PA sensor.

Salicyaldehyde-based fluorescent sensors with high sensitivity for amino acids

Structurally simple salicylaldehyde-based fluoreseent sensors for amino acids have been obtained by one-step or two-step synthesis.These sensors show significant fluorescence enhancement in the presence of many amino acids at concentrations as low as 10~5 mol/L.The reversible reaction of the aldehydes with amino acids to form imines in aqueous solution is proposed to account for the observed fluorescence enhancement.

A novel fluorescent sensor for cAMP based on E.coli CAP protein

cAMP is an important second messenger that is capable of controlling a wide array of cellular processes, including glycogen, sugar and lipid metabolism. Here we report the design and construction of a novel genetically encoded fluorescent sensor for cAMP. The sensor was realized by fusing E. coli CAP protein with cpYFP, and displayed a one-fold fluorescence change towards c AMP binding. Further characterization assays demonstrated that the sensor had high affinity for cAMP and fast response kinetics.The development of our sensor could be a useful supplement to existing methods for cAMP detection.

Rapid quantification of acid value in frying oil using iron tetraphenylporphyrin fluorescent sensor coupled with density functional theory and multivariate analysis

A metalloporphyrin-based fluorescent sensor was developed to determine the acid value in frying oil.The electronic and structural performances of iron tetraphenylporphyrin(FeTPP)were theoretically investigated using time-dependent density functional theory and density functional theory at the B3LYP/LANL2DZ level.The quantified FeTPP-based fluorescent sensor results revealed its excellent performance in discriminating different analytes.In the present work,the acid value of palm olein was determined after every single frying cycle.A total of 10 frying cycles were conducted each day for 10 consecutive days.The FeTPP-based fluorescent sensor was used to quantify the acid value,and the results were compared with the chemical data obtained by conventional titration method.The synchronous fluorescence spectrum for each sample was recorded.Parallel factor analysis was used to decompose the three-dimensional spectrum data.Then,the support vector regression(SVR),partial least squares,and back-propagation artificial neural network methods were applied to build the regression models.After the comparison of the constructed models,the SVR models exhibited the highest correlation coefficients among all models,with 0.9748 and 0.9276 for the training and test sets,respectively.The findings suggested the potential of FeTPP-based fluorescent sensor in rapid monitoring of frying oil quality and perhaps also in other foods with higher oil contents.

CO_2-responsive Polymeric Fluorescent Sensor with Ultrafast Response

Response speed is one of the most important evaluation criteria for CO2 sensors. In this work, we report an ultrafast CO2 fluorescent sensor based on poly[oligo（ethylene glycol） methyl ether methacrylate]-b-poly[N,N-diethylaminoethyl methacrylate-r-4-（2- methylacryloyloxyethylamino）-7-nitro-2,1,3-benzoxadiazole] [POEGMA-b-P（DEAEMA-r-NBDMA）], in which DEAEMA units act as the CO2-responsive segment and 4-nitrobenzo-2-oxa-l,3-diazole （NBD） is the chromophore. The micelles composed of this copolymer could disassemble in 2 s upon CO2 bubbling, accompanying with enhanced fluorescence emission with bathochromic shift. Furthermore, the quantum yield of the NBD chromophore increases with both the CO2 aeration time and the NBD content. Thus we attribute the fluorescent enhancement to the inhibition of the photo-induced electron transfer between unprotonated tertiary amine groups and NBD fluorophores. The sensor is durable although it is based on ＂soft＂ materials. These micellar sensors could be facilely recycled by alternative CO2/Ar purging for at least 5 times, indicating good reversibility.