Polypod Carboxylic Acid-Rare Earth Complex with High Cyclic Stability for Nitrobenzene Compound Detection.

The 5',5''-bis(4-carboxyphenyl)-[1,1':3',1'':3'',1'''-quaterphenyl]-4,4'''-dicarboxylic (H4L1) ligand has a large conjugated rigid planar structure and good absorption of ultraviolet radiation, which can provide effective "antenna effect". However, rare earth complexes using H4L1 as the sole ligand have not been reported. In this paper, rare earth Eu was combined with H4L1 ligand to produce organic rare earth composite L1-Eu by solvothermal synthesis method. It was found through fluorescence spectroscopy that the emission of L1-Eu complex has a linear response to nitrobenzene compounds. The L1-Eu composite material has a low detection limit for nitrobenzene compounds, with detection limits of 0.910, 8.401, 24.510, and 8.171 µM for nitrobenzene, o-nitrophenol, m-nitrophenol, and p-nitrophenol, respectively. Further more the L1-Eu complex can sensitively respond to nitrobenzene compounds while resisting interference from common metal ions and organic solvents. In particular, L1-Eu composite material has good stability and recyclability. Therefore, L1-Eu composite material can serve as a fluorescent probe for specific detection of nitrobenzene compounds. We believe that the L1-Eu complex provides a new method for fluorescence detection of nitrobenzene compounds.

Construction of UCNPs-aptamer-AuNPs luminescence energy transfer probe for ratio detection of Staphylococcus aureus.

A ratio luminescence probe was developed for detecting Staphylococcus aureus (S. aureus) based on luminescence energy transfer (LET) using double-wavelength emission (550 nm and 812 nm) upconversion nanoparticles (UCNPs) as donor, gold nanoparticles (AuNPs) as acceptor and the aptamer for S. aureus as the specific recognition and link unit. The LET process could cause luminescence quenching because of the spectral overlap between the acceptor and the donor at 550 nm. In the presence of S. aureus, S. aureus selectively combined with the aptamer, and the AuNPs left the surface of UCNPs, which weakened the quenching effect and restored the luminescence of UCNPs. Based on this, the ratio detection was realized by monitoring the change of the luminescence signal of the probe at 550 nm and taking the luminescence signal at 812 nm as the reference signal. Crucially, the probe has a fast reaction speed, with a reaction time of 25 min, and the detection of S. aureus is realized in the concentration range of 5.0 × 103-3.0 × 105 CFU/ml, with the detection limit of 106 CFU/ml. Therefore, the ratio probe has great potential for detecting of S. aureus in food because of its high sensitivity, fast speed and good selectivity.

Luminescence Probes in Bio-Applications: From Principle to Practice.

Bioanalysis based on optical imaging has gained significant progress in the last few decades. Luminescence probes are capable of detecting, monitoring, and tracing particular biomolecules in complex biological systems to figure out the roles of these molecules in organisms. Considering the rapid development of luminescence probes for bio-applications and their promising future, we have attempted to explore the working principles and recent advances in bio-applications of luminescence probes, in the hope of helping readers gain a detailed understanding of luminescence probes developed in recent years. In this review, we first focus on the current widely used luminescence probes, including fluorescence probes, bioluminescence probes, chemiluminescence probes, afterglow probes, photoacoustic probes, and Cerenkov luminescence probes. The working principles for each type of luminescence probe are concisely described and the bio-application of the luminescence probes is summarized by category, including metal ions detection, secretion detection, imaging, and therapy.

A novel iridium(III) complex-based ratiometric luminescence probe for monitoring hydrogen sulfide in living cells and zebrafish.

Hydrogen sulfide exhibits crucial functions in many biological and physiological processes. The abnormal levels of H2S have been revealed to be associated with numerous human diseases. The majority of existing fluorescent probes toward H2S may still need to be improved in terms of single output signal, water solubility, biotoxicity and photostability. The construction of a ratiometric fluorescent probe based on metal complex is one effective strategy for avoiding the mentioned problems for precisely detecting H2S. Herein, we report an iridium(III) complex-based ratiometric luminescence probe (Ir-PNBD), which is designed by coupling the 7-nitro-2,1,3-benzoxadiazoles (NBD) to one of the bipyridine ligands of Ir (III) complex luminophore through a piperazition moiety. Ir-PNBD owns high selectivity and sensitivity toward H2S, and an excellent ability to target mitochondria. Moreover, Ir-PNBD was further successfully utilized to visualize exogenous and endogenous H2S in HeLa cells and zebrafish. Our work offers new opportunities to gain deeper insights into the construction of transition metal complex-based ratiometric luminescent probes and expands their applications in biomedical imaging and disease diagnosis.

Glutathione ligand self-assembly enables luminescence from Au15 nanoclusters for highly sensitive and selective monitoring of blood Pb(II) ions.

Lead Pb(II) ions is a cumulative toxicant that impacts several biological systems and poses severe harm to young children. Accurate Pb(II) ions monitoring is thus of paramount importance. Here, we present the synthesis and application of glutathione-capped Au15 nanoclusters (Au15(SG)13) as a luminescence probe for the accurate and selective monitoring of blood Pb(II). The introduction of Pb(II) ions triggers orderly self-assembly of Au15 nanoclusters, resulting in the formation of rigid shell around Au nuclei. This limits the localized vibration of the glutathione ligands and their interaction with water molecules, greatly reducing non-radiative energy loss, and thereby enhancing the photoluminescence signal. Consequently, Au15(SG)13 nanoclusters exhibit high sensitivity for Pb(II) detection. The detection signal displays a linear relationship with Pb(II) over a wide detection range (0-800 µg/L), demonstrating a substantial sensitivity of 35.29 µg/L. Moreover, the developed nanoclusters show superior selectivity for Pb(II) ions, distinguishing them from other prevalent heavy metals. This work pave the way for the development of advanced Pb(II) sensors with high sensitivity and selectivity.

Visualization of the elevated levels of hypochlorous acid in Alzheimer's disease with a ruthenium(II) complex-based luminescence probe.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that devastatingly affects people's lives. Accumulating evidence indicates that the pathological progression of AD is inseparably connected with hypochlorous acid (HClO). However, further exploring the biological function remains an open challenging due to a lack of effective tools to image HClO in AD brains. To this end, a ruthenium(II) luminescence probe, Ru-HClO, is developed for quantitative detection and visualization of HClO in nerve cells and AD brains. Ru-HClO shows quenched luminescence due to the PET process (excited electron transfer from Ru(II) center to diaminomaleonitrile) and the CN bond isomerization in the excited state. The HClO-triggered specific cleavage reaction with Ru-HClO cleaves the CN bond to form highly luminescent Ru-COOH. Ru-HClO shows rapid response speed, high sensitivity and selectivity, excellent biocompatibility, which makes the probe to be applied to semi-quantitative analysis of HClO in nerve cells and high-throughput screening of anti-AD drugs in the AD cell model. Moreover, using Ru-HClO as a probe, present work further validated that the elevated levels of HClO secretion were accompanied by the AD progressed. These findings may provide valuable results for figuring out the biological roles that HClO played in AD but also for accelerating anti-AD therapeutic discovery.

Ratiometric lysosome-targeting luminescent probe based on a coumarin-ruthenium(II) complex for formaldehyde detection and imaging in living cells and mouse brain tissues.

Ratiometric luminescence probes have attracted widespread attention because of their self-calibration capability. However, some defects, such as small emission shift, severe spectral overlap and poor water solubility, limit their application in the field of biological imaging. In this study, a unique luminescence probe, Ru-COU, has been developed by combining tris(bipyridine)ruthenium(II) complex with coumarin derivative through a formaldehyde-responsive linker. The probe exhibited a large emission shift (Δλ > 100 nm) and good water solubility, achieving ratiometric emission responses at 505 nm and 610 nm toward formaldehyde under acidic conditions. Besides, ratiometric luminescence imaging of formaldehyde in living cells and Alzheimer disease mouse's brain slices demonstrates the potential value of Ru-COU for the diagnosis and treatment of formaldehyde related diseases.

New TEMPO-Appended 2,2'-Bipyridine-Based Eu(III), Tb(III), Gd(III) and Sm(III) Complexes: Synthesis, Photophysical Studies and Testing Photoluminescence-Based Bioimaging Abilities.

Linked to Alzheimer's disease (AD), amyloids and tau-protein are known to contain a large number of cysteine (Cys) residues. In addition, certain levels of some common biogenic thiols (cysteine (Cys), homocysteine (Hcy), glutathione (GSH), etc.) in biological fluids are closely related to AD as well as other diseases. Therefore, probes with a selective interaction with the above-mentioned thiols can be used for the monitoring and visualizing changes of (bio)thiols in the biological fluids as well as in the brain of animal models of Alzheimer's disease. In this study, new Eu(III), Tb(III), Gd(III) and Sm(III) complexes of 2,2'-bipyridine ligands containing TEMPO fragments as receptor units for (bio)thiols are reported. The presence of free radical fragments of the ligand in the complexes was proved by using the electronic paramagnetic resonance (EPR) method. Among all the complexes, the Eu(III) complex turned out to be the most promising one as luminescence- and spin-probe for the detection of biogenic thiols. The EPR and fluorescent titration methods showed the interaction of the resulting complex with free Cys and GSH in solution. To study the practical applicability of the probes for the monitoring of AD in-vivo, by using the above-mentioned Eu(III)-based probe, the staining of the brain of mice with amyloidosis and Vero cell cultures supplemented with the cysteine-enriched medium was studied as well as the fluorescence titration of Bovine Serum Albumin, BSA (as the model for the thiol moieties containing protein), was carried out. Based on the results of fluorescence titration, the formation of a non-covalent inclusion complex between the above-mentioned Eu(III) complex and BSA was suggested.

Development of a fluorescein modified ruthenium(II) complex probe for lysosome-targeted ratiometric luminescence detection and imaging of peroxynitrite in living cells.

Ratiometric luminescence (fluorescence/phosphorescence) probes have attracted widespread attention of researchers in the field of biological detection and noninvasive imaging of bioactive molecules in living systems. However, most of them suffer from some defects such as small emission shift, different excitation wavelength and spectral overlap, which eventually affect the luminescence ratio, thus leading to limitations in ratiometric bioimaging applications. In this paper, we present a novel "ruthenium(II) complex-fluorescein" scaffold probe (Ru-FL-ONOO) for ratiometric luminescence detection of peroxynitrite (ONOO-), in which a Ru(II) complex was conjugated to fluorescein serving as the dual-emissive moiety and the spirocyclic structure of fluorescein-phenylhydrazine was used as the specifically-reactive moiety for recognizing ONOO-. The probe possesses not only favourable specificity but also high sensitivity for responding to ONOO-, exhibiting a large emission shift (Δλem > 120 nm) at a single excitation wavelength. After being transferred into living cells, the probe localized within lysosomes, allowing ONOO- therein to be imaged at ratiometric mode. The imaging results reveal that the ratiometric probe bearing the Ru(II) complex-fluorescein scaffold could be a useful approach for overcoming the drawback of spectral overlap of dual-emissive moiety under single-wavelength excitation so as to improve the signal-to-noise ratio, thus benefiting the development of ratiometric bioimaging.

Dye-sensitized core-shell NaGdF4:Yb,Er@NaGdF4:Yb,Nd upconversion nanoprobe for determination of H2S.

The core-shell NaGdF4:Yb,Er@NaGdF4:Yb,Nd upconversion nanoparticles (UCNPs) were successfully obtained with the method of co-precipitation, and the water-solubility of UCNPs was improved by the ligand exchange reaction between nitrosyl tetrafluoroborate (NOBF4) and nanoparticles. The IR-783 dye with negative charge and NOBF4-UCNPs with positive charge can bind together by electrostatic action to sensitize UCNPs through the energy transfer from IR-783 to UCNPs. However, with the presence of Na2S (a commonly used H2S donor), a highly selective reaction between H2S and IR-783, which destoried the structure of IR-783 and blocked the energy transfer, thus led to the quenching of luminescent intensity. Based on this, a sensing system for determination of H2S has been constructed successfully. The linear range of H2S detection by this system is 0.5-15 µM, and the detection limit is 34.17 nM. Furthermore, the dye-sensitized core-shell NaGdF4:Yb,Er@NaGdF4:Yb,Nd upconversion nanoprobe was applied to real sample analysis with satisfactory results.

An Eu(III)-functionalized Sr-based metal-organic framework for fluorometric determination of Cr(III) and Cr(VI) ions.

An Eu(III)-functionalized strontium-organic framework (Eu3+@Sr-MOF) was synthesized by encapsulating Eu3+ ions into the pores of Sr-MOF via postsynthetic modification (PSM) and fully characterized by XRD, SEM, EDS, FTIR, and TGA. The luminescent properties of Eu3+@Sr-MOF were measured and investigated in detail, which demonstrated that Eu3+@Sr-MOF not only possessed excellent water and chemical stabilities in a wide pH range (5-10) but also displayed red luminescence with excitation/emission maxima at 332/617 nm. The Eu3+@Sr-MOF can be considered as a highly selective and sensitive recyclable luminescence probe for sensing Cr(III) and Cr(VI) based on strong luminescence quenching effects; it can be recycled at least five times. The luminescence probe for Cr3+, CrO42-, and Cr2O72- shows low detection limits (0.15 µM, 0.17 µM, and 0.13 µM, respectively), relatively broad linear ranges (0.6-150 µM, 0.1-200 µM and 0.4-180 µM, respectively), and high quenching constants KSV. The signals can be observed by the naked eye under UV light of 365 nm. The method was applied to the determination of total Cr in environmental water samples. Graphical abstract.

Guanine-guided time-resolved luminescence recognition of DNA modification and i-motif formation by a terbium(III)-platinum(II) complex.

Site-specific recognition of DNA modification or the formation of noncanonical structures has important applications in molecular biology, disease diagnosis, and gene expression analysis. In this study, we introduce a guanine-guided sensing tool using a terbium(III)-platinum(II) complex (TPC) as a time-resolved luminescence probe to site-specifically recognize DNA modification and i-motif formation in aqueous solution. The probe is composed of a TbIII center as the luminescent reporter and two PtII units as the receptor for guanine (G) nucleobase. TPC exhibits remarkable reaction selectivity for guanine nucleotides over other nucleotides, giving rise to a significant increase in luminescence. The luminescence enhancement of TPC is mainly attributed to an energy transfer from G base to the TbIII center after the specific coordination of PtII with N7 of guanine (N7-G), which would be facilitated by the phosphates through promoting the departure of coordinated water and bringing G closer to TbIIIvia noncovalent interactions. Based on such sensing feature, the enhanced luminescence of TPC sensitized by G nucleotides can correspondingly decrease upon N7-G modifications of DNA or i-motif formation through constructing simple guanine-guided sensing tools. This probe would provide a useful strategy for site-specific recognition of DNA for extensive purposes.

Ln-CPs constructed from unsymmetrical tetracarboxylic acid ligand: Tunable white-light emission and highly sensitive detection of CrO42-, Cr2O72-, MnO4- in water.

A series of isostructural lanthanide coordination polymers (Ln-CPs), [Ln(Hbptc)(H2O)4]·H2O [Ln = Er (1), Pr (2), Dy (3), Sm (4), Gd (5), Nd (6) and Tb(7); H4bptc = 2,3,3',4'-biphenyl tetracarboxylic acid] have been isolated based on an unsymmetrical tetracarboxylic acid. Single-crystal X-ray diffraction analysis reveals that all CPs featured a two dimensional (2D) layer with (6, 6, 6)-connected 63 topology. Luminescent spectra demonstrate that CPs 1-7 exhibit impressive UV-visible luminescence in the solid state at room temperature. More significantly, a single-component white-light material with International Commission on Illumination (CIE) coordinates of (0.335, 0.334) for 4 (Sm-CP), very closing to the pure white-light of (0.333, 0.333) was obtained by finely tuning of the excitation wavelength. In addition, the luminescent detection for anions of 7 is investigated. Fluorescence measurements show that 7 can detect oxoanion pollutants Cr2O72-, CrO42-, and MnO4- anions in aqueous solutions with high selectivity and sensitivity, which suggests that the Tb-CP is a promising functional luminescence probe for toxic oxoanions. The possible mechanisms of the quenching effect were also discussed in detail.

Eu3+ as a luminescence probe in DNA studies: Structural and conformational implications.

Lanthanide ions are widely used as luminescent probes for structural studies of various biomolecules, including DNA. Latest developments of circularly polarized luminescence (CPL) methodology further boosted interest to luminescence techniques. However, an effect of the lanthanide probes themselves on the DNA structure and conformation was investigated only partially and not for all lanthanides. In the present work, we performed a detailed spectroscopic study of Eu3+ complexes with native double-stranded DNA and compared them to the relevant complexes with single-stranded DNA. We employed infrared (IR), vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectroscopic methods to investigate Eu3+ effect on DNA structure and conformational transitions. It was shown that Eu3+ ions can induce significant alteration of the native DNA structure at the concentrations often used in luminescence studies. While no DNA denaturation was observed at these metal ion concentrations, significant unstacking of the base pairs and disordering of the sugar-phosphate backbone, partial appearance of the A-form backbone geometry, and DNA transition into condensed ψ-type form took place. Eu3+ binding to single-stranded DNA was more pronounced than the binding to double-stranded DNA. We detected the main Eu3+ binding sites and determined the metal ion concentration range in which DNA geometry remains largely unaltered. The results obtained in the current study could be used for tuning the luminescence and CPL structural studies of DNA utilizing Eu3+ ions as probes.

A ratiometric time-gated luminescence probe for hydrogen sulfide based on copper(II)-coupled lanthanide complexes.

Time-gated luminescence (TGL) bioassay technique using luminescent lanthanide complexes as probes has exhibited excellent practicability in detection of various analytes in autofluorescence-rich biosamples. Herein, a novel copper(II)-coupled lanthanide complex-based luminescence probe has been developed for the ratiometric TGL detection of hydrogen sulfide (H2S) in vitro and in vivo. The probe is constructed based on a dual-functional ligand that was synthesized by conjugating di(2-picolyl)amine with terpyridine polyacid (DATP) using the "click chemistry" method. The as-prepared ligand can coordinate to Eu3+ and Tb3+ ions with its terpyridine polyacid moiety to display long-lived emissions of Eu3+ and Tb3+ ions, while the further coordination of its di(2-picolyl)amino moiety to Cu2+ induces to the luminescence quenching of the Eu3+ complexes, which allows the probe consisting of the heterometallic Cu2+-DATP-Eu3+/Tb3+ complexes to be constructed. After the probe was reacted with H2S to lead to the release of Cu2+ from the complexes, the emission of Eu3+ at 610 nm was remarkably enhanced, while that of Tb3+ at 540 nm was changed slightly. This luminescence response feature allowed the probe to be conveniently applied for the ratiometric TGL determination of H2S with I610/I540 as the signal. The applicability of the probe for quantitative detection of H2S in human sera as well as for imaging of H2S in living cells and zebrafish were evaluated. All of the results proved the potential of the probe for in vitro and in vivo applications.

Polyethyleneimine protected silver nanoclusters luminescence probe for sensitive detection of cobalt (II) in living cells.

A simple luminescence sensor, based on polyethyleneimine protected silver nanoclusters (AgNCs@PEI) is successfully fabricated via one-pot reduction method. The obtained AgNCs@PEI are characterized by high-resolution transmission electron microscopy (HR-TEM), Dynamic light scattering (DLS), transient and steady-state fluorescence, and UV-vis spectroscopy. The NCs show large Stocks-shift (∼130nm), high tolerability to extreme pH and high ionic strengths, and excellent photo-stability under UV irradiation, laying the basement for the practical applications. In addition, the sensor is used to detect the Co2+ basing on the luminescence quenching, which is interfered by pH conditions (from pH4.0 to pH7.4). As a luminescence probe for Co2+ ions, the detection limit of AgNCs@PEI is as low as 0.25nM, which is much lower than that of many other reports. Additionally, the AgNCs@PEI possess the advantages of good selectivity, fast response and abroad linear detection. A linear response range in 0.5nM-50µM is achieved for Co2+ when using 20µM AgNCs@PEI in BR buffer solution (neutral condition pH7.4). Incubation time of AgNCs@PEI toward Co2+ is only 2min and it can distinguish Co2+ from other 13 metal ions. Furthermore, the probe (AgNCs@PEI) is applied to sensing and imaging of HeLa cells, showing low cytotoxicity and good sensitivity.

Aqueous synthesis of Ag and Mn co-doped In2S3/ZnS quantum dots with tunable emission for dual-modal targeted imaging.

Here, we present the microwave-assisted synthesis of In2S3/ZnS core/shell quantum dots (QDs) co-doped with Ag+ and Mn2+ (referred to as AgMn:In2S3/ZnS). Ag+ altered the optical properties of the host QDs, whereas the spin magnetic moment (S=5/2) of Mn2+ efficiently induced the longitudinal relaxation of water protons. To the best of our knowledge, this is the first report of the aqueous synthesis of color-tunable AgMn:In2S3/ZnS core/shell QDs with magnetic properties. The synthetic procedure is rapid, facile, reproducible, and scalable. The obtained QDs offered a satisfactory quantum yield (45%), high longitudinal relaxivity (6.84s-1mM-1), and robust photostability. In addition, they exhibited excellent stability over a wide pH range (5-12) and high ionic strength (0.15-2.0M NaCl). As seen by confocal microscopy and magnetic resonance imaging, AgMn:In2S3/ZnS conjugated to hyaluronic acid (referred to as AgMn:In2S3/ZnS@HA) efficiently and specifically targeted cluster determinant 44, a receptor overexpressed on cancer cells. Moreover, AgMn:In2S3/ZnS@HA showed negligible cytotoxicity in vitro and in vivo, rendering it a promising diagnostic probe for dual-modal imaging in clinical applications. STATEMENT OF SIGNIFICANCE: In this manuscript, we reported a facial and rapid method to prepare In2S3/ZnS core/shell quantum dots (QDs) co-doped with Ag+ and Mn2+ (referred to as AgMn:In2S3/ZnS). Ag+ dopants were used to alter the optical properties of the In2S3 host, whereas Mn2+ co-dopants with their unpaired electrons provided paramagnetic properties. The emission wavelength of the core/shell QDs could be tuned from 550 to 743nm with a maximum PL quantum yield of 45%. The resulting core/shell QDs also maintained a stable emission in aqueous solution at broad ranges of pH (5-12) and ionic strength (0.15-2.0M NaCl), as well as a high photostability under continuous irradiation. In vivo cytotoxicity experiments showed that up to 500µg/mL AgMn:In2S3/ZnS@HA did not cause obvious toxicity to zebrafish embryos. In vitro targeted cell luminescence and magnetic resonance imaging showed that AgMn:In2S3/ZnS conjugated to hyaluronic acid was selectively and efficiently internalized in CD44-expressing tumor cells, confirming that the resultant QDs could function as dual-modal imaging probes for accurate diagnosis.

Enabling the Triplet of Tetraphenylethene to Sensitize the Excited State of Europium(III) for Protein Detection and Time-Resolved Luminescence Imaging.

A tetraphenylethene (TPE) group that exhibits aggregation-induced emission is incorporated into the ligand of a Eu(III) complex (TPEEu) to sensitize the excited state of Eu(III). In steady-state measurements, TPEEu exhibits weak luminescence when dissolved in aqueous solutions even at a high concentration level, but emits strong fluorescence of TPE and phosphorescence of Eu(III) upon binding with bovine serum albumin. With a delay time of 0.05 ms and a gate time of 1.0 ms in time-resolved measurements, only phosphorescent emission of Eu(III) is observed with a high on/off ratio. Moreover, this probe is successfully used in time-resolved luminescence imaging to eliminate the background signal from biological autofluorescence without a washing process. This work provides a general strategy in designing Ln(III) complexes for detecting a broad range of biological molecules.