A ternary nucleotide-lanthanide coordination nanoprobe for ratiometric fluorescence detection of ciprofloxacin.

Ciprofloxacin (CIP) is a widely used broad-spectrum antibiotic and has been associated with various side effects, making its accurate detection crucial for patient safety, drug quality compliance, and environmental and food safety. This study presents the development of a ternary nucleotide-lanthanide coordination nanoprobe, GMP-Tb-BDC (GMP: guanosine 5'-monophosphate, BDC: 2-amino-1,4-benzenedicarboxylic acid), for the sensitive and ratiometric detection of CIP. The GMP-Tb-BDC nanoprobe was constructed by incorporating the blue-emissive ligand BDC into the Tb/GMP coordination polymers. Upon the addition of CIP, the fluorescence of terbium ion (Tb3+ ) was significantly enhanced due to the coordination and fluorescence sensitization properties of CIP, while the emission of the BDC ligand remained unchanged. The nanoprobe demonstrated good linearity in the concentration range of 0-10 µM CIP. By leveraging mobile phone software to analyze the color signals, rapid on-site analysis of CIP was achieved. Furthermore, the nanoprobe exhibited accurate analysis of CIP in actual drug and milk samples. This study showcases the potential of the GMP-Tb-BDC nanoprobe for practical applications in CIP detection.

Recent Advances in Photoswitchable Fluorescent and Colorimetric Probes.

In recent years, significant advancements have been made in the research of photoswitchable probes. These probes undergo reversible structural and electronic changes upon light exposure, thus exhibiting vast potential in molecular detection, biological imaging, material science, and information storage. Through precisely engineered molecular structures, the photoswitchable probes can toggle between "on" and "off" states at specific wavelengths, enabling highly sensitive and selective detection of targeted analytes. This review systematically presents photoswitchable fluorescent and colorimetric probes built on various molecular photoswitches, primarily focusing on the types involving photoswitching in their detection and/or signal response processes. It begins with an analysis of various molecular photoswitches, including their photophysical properties, photoisomerization and photochromic mechanisms, and fundamental design concepts for constructing photoswitchable probes. The article then elaborates on the applications of these probes in detecting diverse targets, including cations, anions, small molecules, and biomacromolecules. Finally, it offers perspectives on the current state and future development of photoswitchable probes. This review aims to provide a clear introduction for researchers in the field and guidance for the design and application of new, efficient fluorescent and colorimetric probes.

Recent Advances in Electrochemical Sensors for Formaldehyde.

Formaldehyde, a ubiquitous indoor air pollutant, plays a significant role in various biological processes, posing both environmental and health challenges. This comprehensive review delves into the latest advancements in electrochemical methods for detecting formaldehyde, a compound of growing concern due to its widespread use and potential health hazards. This review underscores the inherent advantages of electrochemical techniques, such as high sensitivity, selectivity, and capability for real-time analysis, making them highly effective for formaldehyde monitoring. We explore the fundamental principles, mechanisms, and diverse methodologies employed in electrochemical formaldehyde detection, highlighting the role of innovative sensing materials and electrodes. Special attention is given to recent developments in nanotechnology and sensor design, which significantly enhance the sensitivity and selectivity of these detection systems. Moreover, this review identifies current challenges and discusses future research directions. Our aim is to encourage ongoing research and innovation in this field, ultimately leading to the development of advanced, practical solutions for formaldehyde detection in various environmental and biological contexts.

Biosensors with Metal Ion-Phosphate Chelation Interaction for Molecular Recognition.

Biosensors show promising prospects in the assays of various targets due to their advantages of high sensitivity, good selectivity and rapid response. Molecular recognition is a key event of biosensors, which usually involves the interaction of antigen-antibody, aptamer-target, lectin-sugar, boronic acid-diol, metal chelation and DNA hybridization. Metal ions or complexes can specifically recognize phosphate groups in peptides or proteins, obviating the use of biorecognition elements. In this review, we summarized the design and applications of biosensors with metal ion-phosphate chelation interaction for molecular recognition. The sensing techniques include electrochemistry, fluorescence, colorimetry and so on.

Switch-on Fluorescence Analysis of Protease Activity with the Assistance of a Nickel Ion-Nitrilotriacetic Acid-Conjugated Magnetic Nanoparticle.

Heterogeneous protease biosensors show high sensitivity and selectivity but usually require the immobilization of peptide substrates on a solid interface. Such methods exhibit the disadvantages of complex immobilization steps and low enzymatic efficiency induced by steric hindrance. In this work, we proposed an immobilization-free strategy for protease detection with high simplicity, sensitivity and selectivity. Specifically, a single-labeled peptide with oligohistidine-tag (His-tag) was designed as the protease substrate, which can be captured by a nickel ion-nitrilotriacetic acid (Ni-NTA)-conjugated magnetic nanoparticle (MNP) through the coordination interaction between His-tag and Ni-NTA. When the peptide was digested by protease in a homogeneous solution, the signal-labeled segment was released from the substrate. The unreacted peptide substrates could be removed by Ni-NTA-MNP, and the released segments remained in solution to emit strong fluorescence. The method was used to determine protease of caspase-3 with a low detection limit (4 pg/mL). By changing the peptide sequence and signal reporters, the proposal could be used to develop novel homogeneous biosensors for the detection of other proteases.

All-in-One Luminescent Lanthanide Coordination Polymer Nanoprobe for Facile Detection of Protein Kinase Activity.

This study developed a novel luminescent assay for kinase activity using metal-organic coordination polymer nanoparticles (Tb/ATP-Zn) as the probe. Tb/ATP-Zn, self-assembled by adenosine triphosphate (ATP), Zn2+, and Tb3+, is non-luminescent. Protein kinase A (PKA) can catalyze the transformation of ATP within Tb/ATP-Zn nanoparticles to adenosine diphosphate (ADP), which in turn effectively sensitizes the luminescence of Tb3+. Based on this mechanism, Tb/ATP-Zn can realize the facile luminescent "turn-on" sensing of protein kinase activity without the use of external ATP and substrate peptide. Under optimized conditions, the fluorescence intensities of Tb/ATP-Zn at 550 nm are linear with the PKA activity within a range of 0.3-1.5 U·µL-1. The LOD (S/N = 3) of this method is down to 0.001 U·µL-1. The presented assay also features high selectivity, long-term stability, fast response, and convenient operation. Furthermore, Tb/ATP-Zn was successfully employed for monitoring PKA activity in cell lysis solutions. Probe Tb/ATP-Zn is thus expectable to be a powerful tool for the practical study of PKA in relevant biological events.

Dual-Response Ratiometric Electrochemical Microsensor for Effective Simultaneous Monitoring of Hypochlorous Acid and Ascorbic Acid in Human Body Fluids.

Redox homeostasis between hypochlorous acid (HClO/ClO-) and ascorbic acid (AA) significantly impacts many physiological and pathological processes. Herein, we report a new electrochemical sensor for the simultaneous determination of HClO and AA in body fluids. We first coated a carbon fiber microelectrode (CFME) with a three-dimensional nanocomposite consisting of graphene oxide (GO) and carbon nanotubes (CNTs) to fabricate the CFME/GO-CNT electrode. After the electrochemical reduction of GO (ERGO), we integrated a latent 1-(3,7-bis(dimethylamino)-10H-phenothiazin-10-yl)-2-methylpropan-1-one (MBS) electrochemical molecular recognition probe to monitor HClO and employed anthraquinone (AQ) as an internal reference. The compact CFME/ERGO-CNT/AQ + MBS sensor enabled the accurate and simultaneous measurement of HClO and AA with excellent selectivity and sensitivity. Measurements were highly reproducible, and the sensor was stable and exceptionally biocompatible. We successfully detected changes in the redox cycles of HClO and AA in human body fluids. This sensor is a significant advance for the investigation of reactions involved in cellular redox regulation. More importantly, we have devised a strategy for the design and construction of ratiometric electrochemical biosensors for the simultaneous determination of various bioactive species.

Recent Progress in the Development of Fluorescent Probes for Thiophenol.

Thiophenol (PhSH) belongs to a class of highly reactive and toxic aromatic thiols with widespread applications in the chemical industry for preparing pesticides, polymers, and pharmaceuticals. In this review, we comprehensively summarize recent progress in the development of fluorescent probes for detecting and imaging PhSH. These probes are classified according to recognition moieties and are detailed on the basis of their structures and sensing performances. In addition, prospects for future research are also discussed.

A Green-emitting Fluorescent Probe Based on a Benzothiazole Derivative for Imaging Biothiols in Living Cells.

A new green-emitting fluorescent probe 1 was developed for biothiol detection. The sensing mechanism was considered to be biothiol-induced cleavage of the 2,4-dinitrobenzene- sulfonate group in probe 1 and resulting inhibition of the probe's photoinduced electron transfer (PET) process. Probe 1 exhibited favorable properties such as excellent selectivity, highly sensitive (0.12 µM), large Stokes shift (117 nm) and a remarkable turn-on fluorescence signal (148-fold). Furthermore, confocal fluorescence imaging indicated that probe 1 was membrane-permeable and suitable for visualization of biothiols in living A549 cells.

Lanthanide Functionalized Metal-Organic Coordination Polymer: Toward Novel Turn-On Fluorescent Sensing of Amyloid ß-Peptide.

Metal-organic coordination polymers (MOCPs) have been emerging as very attractive nanomaterials due to their tunable nature and diverse applications. Herein, using Tb3+ as the luminescence center, 1,3,5-benzenetricarboxylate (BTC) as building block and Cu2+ as the signal modulator as well as a recognition unit, we propose a novel and effective lanthanide functionalized MOCP (LMOCP) fluorescent sensor (Cu-BTC/Tb) for amyloid ß-peptide (Aß) monomer, a biomarker for Alzheimer disease (AD). Specifically, Cu-BTC/Tb, created by postsynthesis modification strategy under room temperature, is almost nonemissive due to the quenching effect of Cu2+ in the MOCP, exhilaratingly, the presence of Aß1-40 triggered a significant emission enhancement of Cu-BTC/Tb assay due to the high binding affinity of Aß1-40 for Cu2+ and the subsequent suppression of the quenching effect. In the assay, this LMOCP sensor shows high sensitivity with detection limit of 0.3 nM. Due to its capability to eliminate autofluorescence, Cu-BTC/Tb was also applied to the time-gated detection of Aß1-40 in human plasma with promising results. This work presents a novel strategy for the construction of functional luminescent LMOCP for sensitively turn-on fluorescent sensing of Aß1-40. We believe the proposed strategy would inspire the development of various LMOCP-based fluorescent assays or medical imaging platforms for advanced biological implementations.

Recent progress in the development of fluorescent probes for hydrazine.

Hydrazine (N2 H4 ) is an important and commonly used chemical reagent for the preparation of textile dyes, pharmaceuticals, pesticides and so on. Despite its widespread industrial applications, hydrazine is highly toxic and exposure to this chemical can cause many symptoms and severe damage to the liver, kidneys, and central nervous system. As a consequence, many efforts have been devoted to the development of fluorescent probes for the selective sensing and/or imaging of N2 H4 . Although great efforts have been devoted in this area, the large number of important recent studies have not yet been systematically discussed in a review format so far. In this review, we have summarized the recently reported fluorescent N2 H4 probes, which are classified into several categories on the basis of the recognition moieties. Moreover, the sensing mechanism and probes designing strategy are also comprehensively discussed on aspects of the unique chemical characteristics of N2 H4 and the structures and spectral properties of fluorophores.

Unraveling the Hydrolysis of Merocyanine-Based Probes in Biological Assay.

Merocyanine dyes, owing to their unique photochemical properties, are widely used to fabricate probes for the detection of biologically active small molecules and bioimaging. In this paper, merocyanine-based probes were proved of undergoing unwanted hydrolysis. To explore the strategies toward avoiding the hydrolysis, the detailed hydrolysis mechanism was first investigated, which was also confirmed by density functional theory (DFT) calculation. Then a series of merocyanine dyes were rationally designed. Influences of molecular structures of the probes, the analytical media such as pH and components of the solution on the hydrolysis were systematically studied. The experimental results suggest that merocyanine based probes with low electron density are more likely to suffer the hydrolysis, which could be exacerbated by the well-accepted strategy for constructing type-II probes. It is worth noting that chemical surroundings could also exert distinctive influence on the hydrolysis. The hydrolysis could be obviously aggravated when fetal calf serum or DMSO was deployed. Our findings will definitely provide an effective and reliable approach for guiding the rational design of highly robust merocyanine-based probes and the optimization of the analytical media, which is helpful in terms of avoiding the hydrolysis of the probes and hydrolysis caused analytical errors.

Dyes and Redox Couples with Matched Energy Levels: Elimination of the Dye-Regeneration Energy Loss in Dye-Sensitized Solar Cells.

In dye-sensitized solar cells (DSSCs), a significant dye-regeneration force (ΔG(reg)(0)≥0.5 eV) is usually required for effective dye regeneration, which results in a major energy loss and limits the energy-conversion efficiency of state-of-art DSSCs. We demonstrate that when dye molecules and redox couples that possess similar conjugated ligands are used, efficient dye regeneration occurs with zero or close-to-zero driving force. By using Ru(dcbpy)(bpy)2(2+) as the dye and Ru(bpy)2(MeIm)2(3+//2+) as the redox couple, a short-circuit current (J(sc)) of 4 mA cm(-2) and an open-circuit voltage (V(oc)) of 0.9 V were obtained with a ΔG(reg)(0) of 0.07 eV. The same was observed for the N3 dye and Ru(bpy)2(SCN)2(1+/0) (ΔG(reg)(0)=0.0 eV), which produced an J(sc) of 2.5 mA cm(-2) and V(oc) of 0.6 V. Charge recombination occurs at pinholes, limiting the performance of the cells. This proof-of-concept study demonstrates that high V(oc) values can be attained by significantly curtailing the dye-regeneration force.

The elevated copper binding strength of amyloid-ß aggregates allows the sequestration of copper from albumin: a pathway to accumulation of copper in senile plaques.

Copper coexists with amyloid-ß (Aß) peptides at a high concentration in the senile plaques of Alzheimer's disease (AD) patients and has been linked to oxidative damage associated with AD pathology. However, the origin of copper and the driving force behind its accumulation are unknown. We designed a sensitive fluorescent probe, Aß(1-16)(Y10W), by substituting the tyrosine residue at position 10 in the hydrophilic domain of Aß(1-42) with tryptophan. Upon mixing Cu(II), Aß(1-16)(Y10W), and aliquots of Aß(1-42) taken from samples incubated for different lengths of time, we found that the Cu(II) binding strength of aggregated Aß(1-42) has been elevated by more than 2 orders of magnitude with respect to that of monomeric Aß(1-42). Electron paramagnetic spectroscopic measurements revealed that the Aß(1-42) aggregates, unlike their monomeric form, can seize copper from human serum albumin, an abundant copper-containing protein in brain and cerebrospinal fluid. The significantly elevated binding strength of the Aß(1-42) aggregates can be rationalized by a Cu(II) coordination sphere constituted by three histidines from two adjacent Aß(1-42) molecules. Our work demonstrates that the copper binding affinity of Aß(1-42) is dependent on its aggregation state and provides new insight into how and why senile plaques accumulate copper in vivo.

Sensitive and continuous screening of inhibitors of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) at single SPR chips.

The development of new methods that meet the demand of high-throughput, high-fidelity screening of hit compounds is important to researching modalities of important diseases such as neurological disorders, HIV, and cancer. A surface plasmon resonance- (SPR-) based method capable of continuously screening enzyme inhibitors at a single chip with antibody-amplified signal enhancement has been developed. The proof of concept is demonstrated by monitoring the cleavage of chip-confined peptide substrates [a segment of the amyloid precursor protein (APP) with the Swiss mutation] by ß-site APP-cleaving enzyme 1 (BACE1). In the presence of a noninhibitor, BACE1 clips the peptide substrate at the cleavage site, detaching a fragment that is homologous to the N-terminus of the amyloid beta (Aß) peptide. Consequently, a subsequent injection of the Aß antibody does not lead to any molecular recognition or SPR signal change at the chip. In contrast, suppression of the BACE1 activity by a strong inhibitor leaves the peptide substrate intact, and the subsequent antibody attachment produces an easily detectable SPR signal. Compared to the widely used FRET (fluorescence resonance energy transfer) assay, the method reported here is more cost-effective, as unlabeled peptide is used as the BACE1 substrate. Furthermore, the assay is faster (each screening cycle lasts for ca. 1.5 h) and can be continuously carried out at a single, regenerable SPR chip for more than 30 h. Consequently, excellent reproducibility (RSD < 5%) and throughput can be attained. Two inhibitors were screened, and their half-maximal inhibitory concentrations (IC50) determined by the SPR method were in excellent agreement with values deduced from ELISA and mass spectrometry.

Kinetic studies of inhibition of the amyloid beta (1-42) aggregation using a ferrocene-tagged ß-sheet breaker peptide.

The aggregation of amyloidogenic proteins/peptides has been closely linked to the neuropathology of several important neurological disorders. In Alzheimer's disease, amyloid beta (Aß) peptides and their aggregation are believed to be at least partially responsible for the etiology of Alzheimer's disease. The aggregate-inflicted cellular toxicity can be inhibited by short peptides whose sequences are homologous to segments of the Aß(1-42) peptide responsible for ß-sheet stacking (referred to as the ß-sheet breaker peptides). Here, a water-soluble ferrocene (Fc)-tagged ß-sheet breaker peptide, Fc-KLVFFK(6), was used as an electrochemical probe for kinetic studies of the inhibition of the Aß(1-42) fibrillation process and for determination of the optimal concentration of ß-sheet breaker peptide for efficient inhibition. Our results demonstrate that Fc-KLVFFK(6) interacts with the Aß aggregates instantaneously in solution, and a sub-stoichiometric amount of Fc-KLVFFK(6) is sufficient to inhibit the formation of the Aß oligomers and fibrils and to reduce the toxicity of Aß(1-42). The interaction between Fc-KLVFFK(6) and Aß(1-42) follows a pseudo-first-order reaction, with a rate constant of 1.89 ± 0.05 × 10(-4) s(-1). Tagging ß-sheet breaker peptides with a redox label facilitates design, screening, and rational use of peptidic inhibitors for impeding/altering Aß aggregation.

Ferrocene tripeptide Gly-Pro-Arg conjugates: synthesis and inhibitory effects on Alzheimer's Aß(1-42) fibrillogenesis and Aß-induced cytotoxicity in vitro.

Alzheimer's disease (AD) is the most common cause of dementia, and currently there is no clinical treatment to cure it or to halt its progression. Aggregation and fibril formation of ß-amyloid peptides (Aß) are central events in the pathogenesis of AD. Many efforts have been spent on the development of effective inhibitors to prevent Aß fibrillogenesis and cause disaggregation of preformed Aß fibrils. In this study, the conjugates of ferrocene and Gly-Pro-Arg (GPR) tripeptide, Boc-Gly-Pro-Arg(NO(2))-Fca-OMe (4, GPR-Fca) and Fc-Gly-Pro-Arg-OMe (7, Fc-GPR) (Fc: ferrocene; Fca: ferrocene amino acid) were synthesized by HOBT/HBTU protocol in solution. These ferrocene GPR conjugates were employed to inhibit Aß(1-42) fibrillogenesis and to disaggregate preformed Aß fibrils. The inhibitory properties of ferrocene GPR conjugates on Aß(1-42) fibrillogenesis were evaluated by thioflavin T (ThT) fluorescence assay, and confirmed by atomic force microscopy (AFM) analysis. The interaction between the ferrocene GPR conjugates and Aß(1-42) was monitored by electrochemical means. Our results showed that both GPR and GPR-Fca can significantly inhibit the fibril formation of Aß(1-42), and cause disaggregation of the preformed fibrils. As expected, GPR-Fca shows stronger inhibitory effect on Aß(1-42) fibrillogenesis than that of its parent peptide GPR. In contrast, Fc-GPR shows no inhibitory effect on fibrillogenesis of Aß(1-42). Furthermore, GPR-Fca demonstrates significantly protection against Aß-induced cytotoxicity and exhibits high resistance to proteolysis and good lipophilicity.

Advancements in Biosensors Based on the Assembles of Small Organic Molecules and Peptides.

Over the past few decades, molecular self-assembly has witnessed tremendous progress in a variety of biosensing and biomedical applications. In particular, self-assembled nanostructures of small organic molecules and peptides with intriguing characteristics (e.g., structure tailoring, facile processability, and excellent biocompatibility) have shown outstanding potential in the development of various biosensors. In this review, we introduced the unique properties of self-assembled nanostructures with small organic molecules and peptides for biosensing applications. We first discussed the applications of such nanostructures in electrochemical biosensors as electrode supports for enzymes and cells and as signal labels with a large number of electroactive units for signal amplification. Secondly, the utilization of fluorescent nanomaterials by self-assembled dyes or peptides was introduced. Thereinto, typical examples based on target-responsive aggregation-induced emission and decomposition-induced fluorescent enhancement were discussed. Finally, the applications of self-assembled nanomaterials in the colorimetric assays were summarized. We also briefly addressed the challenges and future prospects of biosensors based on self-assembled nanostructures.

A near-infrared ratiometric fluorescent probe for hydrazine and its application for gaseous sensing and cell imaging.

Hydrazine (N2H4) is a widely used raw material in the chemical industry, but at the same time hydrazine has extremely high toxicity. Therefore, the development of efficient detection methods is crucial for monitoring hydrazine in the environment and evaluating the biological toxicity of hydrazine. This study reports a near-infrared ratiometric fluorescent probe (DCPBCl2-Hz) for the detection of hydrazine by coupling a chlorine-substituted D-π-A fluorophore (DCPBCl2) to the recognition group acetyl. Due to the halogen effect of chlorine substitution, the fluorophore has an elevated fluorescence efficiency and a lowered pKa value and is suitable for physiological pH conditions. Hydrazine can specifically react with the acetyl group of the fluorescent probe to release the fluorophore DCPBCl2, so the fluorescence emission of the probe system significantly shifted from 490 nm to 660 nm. The fluorescent probe has many advantages, such as good selectivity, high sensitivity, large Stokes shift, and wide applicable pH range. The probe-loaded silica plates can realize convenient sensing gaseous hydrazine with content down to 1 ppm (mg/m3). Subsequently, DCPBCl2-Hz was successfully applied to detect hydrazine in soils. In addition, the probe can also penetrate living cells and allow the visualization of intracellular hydrazine. It can be anticipated that probe DCPBCl2-Hz will be a useful tool for sensing hydrazine in biological and environmental applications.

Target-Induced In Situ Formation of Organic Photosensitizer: A New Strategy for Photoelectrochemical Sensing.

Small-molecule photosensitizers have great application prospects in photoelectrochemical (PEC) sensing due to their defined composition, diversified structure, and adjustable photophysical properties. Herein, we propose a new strategy for PEC analysis based on the target-induced in situ formation of the organic photosensitizer. Taking thiophenol (PhSH) as a model analyte, we designed and synthesized a 2,4-dinitrophenyl (DNP)-caged coumarin precursor (Dye-PhSH), which was then covalently coupled onto the TiO2 nanoarray substrate to obtain the working photoanode. Due to the intramolecular photoinduced electron transfer process, Dye-PhSH has only a very weak photoelectric response. Upon reacting with the target, Dye-PhSH undergoes a tandem reaction of the detachment of the DNP moiety and the intramolecular cyclization process, which leads to a coumarin dye with a pronounced photoelectric effect, thus achieving a highly selective turn-on PEC response to PhSH. For the first time, this study was to construct a PEC sensor by exploiting specific organic reactions for the in situ generation of small molecule-based photoactive material. It can be anticipated that the proposed strategy will expand the paradigm of PEC sensing and holds great potential for detecting various other analytes.