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.

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.

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

1-Pyrenecarboxaldehyde thiosemicarbazone:A novel fluorescent molecular sensor towards mercury(Ⅱ) ion

A novel and simple fluorescent molecular sensor,1-pyrenecarboxaldehyde thiosemicarbazone（Hpytsc）,was synthesized.Its higher sensitivity and selectivity to mercury（Ⅱ） ion were studied through absorption and emission channels.The UV-vis spectra show that the increasing mercury（Ⅱ） ion concentrations result in the decreasing absorption intensity.The fluorescence monomer emission of Hpytsc is enhanced upon binding mercury（Ⅱ） ion,which should be due to the 1：1 complex formation between Hpytsc and metal ion.

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.

Novel synthesis of N-substituted-calix[4]azacrown derivatives

A novel series of calix[4]azacrown derivatives with the reaction between calix[4]azacrown and the different fluorophore derivatives,which may be useful fluorescent receptors,have been synthesized and structurally characterized by IR,~1H NMR,^（13）C NMR and MS.From their analysis data,it was found those compounds adopted a cone conformation.

Monitoring NAD(H) and NADP(H) dynamics during organismal development with genetically encoded fluorescent biosensors

Cell metabolism plays vital roles in organismal development,but it has been much less studied than transcriptional and epigenetic control of developmental programs.The difficulty might be largely attributed to the lack of in situ metabolite assays.Genetically encoded fluorescent sensors are powerful tools for noninvasive metabolic monitoring in living cells and in vivo by highly spatiotemporal visualization.Among all living organisms,the NAD(H)and NADP(H)pools are essential for maintaining redox homeostasis and for modulating cellular metabolism.Here,we introduce NAD(H)and NADP(H)biosensors,present example assays in developing organisms,and describe promising prospects for how sensors contribute to developmental biology research.

Multifunctional N,S-doped and methionine functionalized carbon dots for on−off−on Fe^(3+)and ascorbic acid sensing,cell imaging,and fluorescent ink applying

Fluorescent carbon dots(CDs)have been identified as potential nanosensors and attracted tremendous research interests in wide areas including anti-counterfeiting,environmental and biological sensing and imaging in considering of the attractive optical properties.In this work,we present a CDs based fluorescent sensor from polyvinylpyrrolidone,citric acid,and methionine as precursors by hydrothermal approach.The selective quantifying of Fe^(3+)and ascorbic acid(AA)are based on the fluorescent on-off-on process,in which the fluorescent quenching is induced by the coordination of the Fe^(3+)on the surface of the CDs,while the fluorescence recovery is mainly attributed to redox reaction between Fe^(3+)and AA,breaking the coordination and bringing the fluorescence back.Inspired by the good water solubility and biocompatibility,significant photostability,superior photobleaching resistance as well as high selectivity,sensitivity,and interference immunity,which are constructed mainly from the N,S-doping and methionine surface functionalization,the CDs have not only been employed as fluorescence ink in multiple anticounterfeiting printing and confidential document writing or transmitting,but also been developed as promising fluorescence sensors in solution and solid by CDs doped test strips and hydrogels for effectively monitoring and removing of Fe^(3+)and AA in environmental aqueous solution.The CDs have been also implemented as effective diagnostic candidates for imaging and tracking of Fe^(3+)and AA in living cells,accelerating the understanding of their function and importance in related biological processes for the prevention and treatment specific diseases.

Ratiometric Fluorescence Detection of 6-Mercaptopurine Based on the Nanohybrid of Fluorescence Carbon Dots and Gold Nanoclusters

The development of a simple and accurate quantitative method for the determination of 6-mercaptopurine (6-MP) is of great importance because of its serious side effects. Ratiometric fluorescence (RF) sensors are not subject to interference from environmental factors, and exhibit enhanced precision and accuracy. Therefore, a novel RF sensor for the selective detection of 6-MP was developed. The present work reports a sensitive and selective RF sensor for the detection of 6-mercaptopurine, by hybridizing carbon nanodots (CDots) and gold nanoclusters (AuNCs) capped with bovine serum albumin (BSA). The CDots serve as the reference signal and the AuNCs as the reporter. On addition of the 6-MP, AuNCs formed aggregates, because the existing cross-links within the AuNCs and BSA structure were broken in favour of the Au-S bonds, which can enhance the fluorescence of AuNCs, while the fluorescence of CDots is stable against 6-MP, leading to distinct ratiometric fluorescence changes when exposed to 6-MP. 6-MP could be detected in the range of 0 - 30.22 μM with a detection limit of 54 nM. The developed sensor was applied for the determination of 6-MP in human serum samples and satisfactory results were obtained.

Terpyridine-derived Zn^(2+) Selective Fluorescence Sensor: Ratiometric Fluoroionophoric Behavior Study

A sensitive and selective zinc ion ratiometric fluorescence sensor has been synthesized and characterized. This material displays dual fluorescence. After the material was bonded to a closed-shell metal ion, such as Zn2＋, the recovery of the local excited fluorescence of the material-Zn2＋ complex, largely at the expense of the intramolecular charge transfer fluorescence, is consistent with the difference between selected orbital transitions of the free dye and the metal-chelated complex. For instance, the contribution of the πtpy→πtpy, transition becomes more prominent. This is also consistent with the results of the fluorescence decay behavior, measured via a time-correlated single photon counting setup. In contrast, the corresponding open shell Ni2＋ -bound complex quenches both kinds of photoluminescence, due to spin-orbit coupling.

A Fluorescence Optical Fiber Sensor for Amrinon Using a New Oxazole Compound

A new oxazole compound, 1,4 bis(naphtho[1,2 d][1,3]oxazol 2 yl)benzene(BNOB) was synthesized and incorporated into a thin plasticized polymeric membrane for sensing Amrinon. The sensor exhibits a linear response to Amrinon in the range of 7 98×10 -7 —1 52×10 -4 mol/L at pH 3 28—4 04. The response mainly originates from the Primary Inner Filter Effect, which causes a decrease in the fluorescence intensity of the sensor membrane. The distinct advantages of the proposed sensor are of full reversibility, high sensitivity and selectivity as well as short response time(<1 min), indicating that the sensor can be used to monitor Amrinon in serum samples.

Synthesis of fluorescent bisboronic acid sensors and their recognition of mono-/oligo-saccharides

Sensors capable of recognizing cell surface carbohydrates,such as sialyl Lewis X（sLe-x）,are invaluable research tools and for the diagnosis and early detection of many forms of cancer.In this paper,we report the design and synthesis of a series of bisboronic acids 6（a-f） as fluorescent sensors towards mono-/oligosaccharides.Among them,compounds 6d and 6e showed strong binding affinities with glucose and fructose,while compound 6c,in which two anthracene-based boronic acid units were linked by a hexamethylene spacer,was able to recognize sLe-x selectivity and stained HEPG2 cells at 1 μmoI/L.

Application of TIRFM in Biomolecule Research and Clinical Medicine

With the increasing demand for imaging quality, many scientists constantly explore new imaging instruments to meet the requirements. The total internal reflection fluorescence microscopy has some incomparable superiorities, so it has become one of the research hotspots in recent years. It can show great performance in single-molecule imaging because it has unique imaging principles. This apparatus is used mainly in two fields, biomolecule research and clinical medicine. To know this instrument’s function, the summary of applications in these two parts was given in this article. Now, scientists who have been focusing on this apparatus try to make this microscope combined with other late-model precise instruments that probe some unknown interaction mechanism of action. The TIRFM will show extraordinary talents in many aspects, and it will become a powerful tool for people to explore the mysteries of life.

A Fiber Optic Sensor for 2-cholrophenol Analysis based on Oxygen Sensing System

A fiber optic 2-cholrophenol（2-CP） sensor was developed based on the fluorescence quenching of molecular oxygen on the oxygen-sensitive membrane and O2 consumption during catalytic oxidation reaction of 2-CP. The 2-CP concentration can be determined by utilizing a lock-in amplifier to measure the change in the fluorescence lifetime of an oxygen-sensitive membrane, in which the tris（2,2′-bipyridyl） ruthenium（II） chloride complexes（Ru（II）（byp）3Cl2） were immobilized in cellulose acetate（CA） via simple hybridized approach. The experimental results show the good linear relationship between the phase delay of sensitive membrane and 2-CP concentration in its detection range of 1×10-7 to 1×10-5 mol/L and 1×10-5 to 1×10-4 mol/L. The detection limit of the sensor is 7×10-8 mol/L（S/N=3） and the response time is 5 min. Our experimental measurements confirmed good response characteristics of the as-prepared fiber optic 2-CP sensor, as well as its capability to detect the 2-CP concentration in practical water samples.

Surfactant-regulated acetylpyrene assemblies as fluorescent probes for identifying heme proteins in an aqueous solution

Heme proteins play various important roles in a variety of physiological and pathological processes.Surfactant assemblies have drawn great attention in fabricating fluorescent sensors to detect and identify proteins.In this study,an acetylpyrene fluorophore containing imidazole HP-1 was synthesized,and it could be well modulated by an anionic surfactant sodium dodecyl sulfate(SDS).The selected ensemble based on HP-1/SDS assemblies exhibited selective fluorescence sensing performance towards the heme proteins,including neuroglobin(Ngb),myoglobin(Mb)and cytochrome c(Cyt c).Besides,phospholipid DMPC vesicles as membrane models were particularly explored the association process between the heme protein Mb and membrane.The present work showed that Mb induced the lysis of DMPC liposomes visualized by transmission electron microscopy and optical microscope.