Sensitive Fluorescence Response Research Articles

Photochemical and electrochemical behavior of a molecular probe: Fluorescence on-off-on response to detect multiple ions (Cu2+, ClO− and CN−) with different rate of reaction

A molecular probe 3 containing phenyl substituted imidazolyl unit and diaminomaleonitrile (DAMN) moiety has been synthesized and characterized. Photophysical and electrochemical behavior probe 3 were studied in partial aqueous medium (ACN/H2O, 9.5:0.5 v/v). Probe 3 upon interaction with different class of ions showed sensitivity for Cu2+, ClO− and CN− ions with different response time and reaction rates due to variation in intramolecular charge transfer (ICT) process. Both Cu2+ and ClO− ions displayed enhanced emission due to hydrolysis of imine bond to form compound 2 in the medium whereas, with CN− fluorescence quenching was observed due to the deprotonation of –OH/–NH2 functions. The kinetic and optical behavior of the probe suggested that interaction occurred in two steps with Cu2+ (complexation and hydrolysis; absk1,2,3(Cu2+) = 1.17, 0.74 and 0.06 s−1) and ClO− (hydrolysis and deprotonation; absk1,2(ClO−) = 3.0 and 0.60 s−1) ions while CN− (absk1,2(CN−) = 2.13 and 1.66 s−1) induces deprotonation in one step. The interaction of probe 3 with ClO− was relatively fast than with Cu2+/CN− ions. Job's plot analysis between probe 3 and ions revealed a 1:1 (Cu2+/ClO−) and 1:2 (CN−) ratio stoichiometry with good limit of detection (nM) and binding affinity (LOD, 17; KCu2+ = 3.23 × 106 M−1; LOD, 18.5; KClO− = 5.23 × 105 M−1 and LOD, 23.2; KCN− = 5.50 × 109 M−2) respectively. Probe 3 displayed a naked–eye sensitive fluorescence response to detect tested ions on test paper strips and good recovery percentage of ions in real water sample analysis.

A novel carbazolyl thiophene-based fluorescent “off-on” probe PCTMF for sequential detection of Cu2+ and cysteine in aqueous

Copper ions and cysteine play a crucial role in pathophysiologic processes in the human body and the environment, so the development of probes with high sensitivity and specificity for continuous detection has become the focus of current research. In the paper, a novel fluorescent compound (named PCTMF) is synthesized with a carbazolyl thiophene group as a fluorescent moiety and formyl hydrazine as a recognition group of Cu2+. In the given DMSO-H2O solvent system, the PCTMF exhibits a highly selective and sensitive turn-off fluorescence response towards Cu2+ with its detection limit (LOD) of 0.14 μM, in the presence of other competing metal ions. The turn-off response mechanism of the probe can be attributed to the formation of complex 2PCTMF-Cu. The 2PCTMF-Cu complex presents good sensing capacity on cysteine (Cys) with a LOD of 52 nM. The molecule designing method provides an “off-on” strategy for sequentially fluorescence detecting metal ions and ligands related.

Construction of a multifunctional paper-based fluorescent material for the detection and adsorption of formaldehyde

Indoor air pollution is one of the significant inducing factors of some diseases, such as leukemia, tumors, respiratory disease, and kidney failure. Among these contaminants, formaldehyde has a long release span and is a great threat to our health. However, methods for formaldehyde elimination and detection are limited. Herein, a new paper-based multifunctional fluorescent material was developed for the simultaneous high-efficiency removal and detection of formaldehyde. The paper-based material was fabricated using polyethyleneimine (PEI) and a highly sensitive ratiometric fluorescent probe (FP). The paper-based material can detect formaldehyde with a significant change in fluorescence: the fluorescence at 450 nm decreased by over 75 %, and the fluorescence of FP in the ratiometric channel increased by over 100-fold. Moreover, the formaldehyde elimination rate is up to 99 %. By combining the porous network structures of paper, the abundant amino groups in PEI, and the highly sensitive fluorescent response of FP, the multifunctional fluorescent paper material can be effectively utilized for formaldehyde removal and detection.

Real-time blood gas analysis using pH, PO2 and PCO2 multifunctional fluorescent capillary sensing system

Real-time blood gas analysis is of great significance in disease diagnosis and treatment. Here we have developed a pH, PO2 and PCO2 multifunctional fluorescent capillary sensing system. The pH, O2 and CO2 fluorescent indicators with same excitation wavelength are fixed into a single capillary tube. The sensing system possesses sensitive fluorescence response to pH, O2 and CO2, and the changes of pH, O2 and CO2 in buffer, in vitro, and in vivo can be detected simultaneously by measuring the fluorescence signals of sensor probe. The PO2, PCO2 and pH of rabbits in four disease models were assessed efficiently by the sensing system, exhibiting similar variation trend with the results by blood gas analyzer. Studies in living rabbit display the reasonable and favorable feasibility of capillary sensing system in real-time arterial blood gas analysis. Overall, the multifunctional fluorescent capillary sensing system exhibits significant potential in real-time arterial blood gas analysis and clinical application of disease diagnosis.

Highly selective and sensitive fluorescent probes for nitrofurazone and Hg2+ by two Zn (II)‐based coordination polymers

The self‐assembly of the π‐conjugated 1,4‐di(1H‐imidazol‐1‐yl)benzene (dib) and 4,4′‐di(1H‐imidazol‐1‐yl)‐1,1′‐biphenyl (dibp) ligands together with 4′‐(3,4‐ dicarboxylphenyloxy)‐4‐biphenylcarboxylic acid (H3L) reacts with metal Zn (II) salts to construct two new coordination polymers (CPs), namely [Zn (dib)(HL)(H2O)] (1) and [Zn (dibp)(HL)] (2). Fluorescence measurements reveal that 1 and 2 could display a highly sensitive fluorescence response toward Hg2+ and nitrofurazone (NFZ). Fluorescence investigations suggest that 1 and 2 are promising multi‐responsive sensing materials for detecting Hg2+ and NFZ through fluorescence quenching (turn‐off). The limits of detection toward Hg2+ ions are 0.221 μM and 0.124 μM, while the limits of detection toward NFZ are 0.757 μM and 0.960 for 1 and 2, respectively. Interestingly, these Hg2+ and NFZ selective sensing processes can even be completed by the reusable CPs detected by the naked eyes. Hirshfeld surfaces and fingerprint plots are extensively used to investigate intermolecular interactions, which play a crucial role in creating diverse supramolecular designs that can be compared.

Novel Schiff base embedded in nanostructured molecularly imprinted polymers as OFF–ON fluorescent sensor for highly selective detection of rutin residues in fruit juice

This study aimed to create a fluorescent novel Schiff base polymer (SBP) sensor for the detection of rutin (RT) flavonoid based on nanostructured molecularly imprinted polymer (SBM), precisely designed template molecules, and site-specific post-imprinting modifications. The fabricated SBM sensor was characterized in detail, and the prepared SBM exhibited stable and sensitive reproducible fluorescence response and highly selective recognition capability for detecting trace amounts of RT. Besides, the influential factors, such as pH and incubation time were performed in the optimal extraction conditions. The calibration curve yields a linear range for the detection of RT under optimal conditions. The linear fluorescence response of SBM to RT was obtained in the concentration range of 1–200 μg L− 1 (R2 = 0.9988) with a limit of detection (LOD) of 0.024 μg L−1. The SBM presented satisfying recoveries with a relative standard deviation of less than 3.0 % (n = 7) in spiked samples. The sensor shows broad prospects in the quality evaluation and grading of functional foods, as it can rapidly identify and quantify RT in red raspberry and green tea samples.

A simple yet effective H2S‐activated fluorogenic probe for precise imaging of hepatitis and arthritis in situ

AbstractHepatitis and arthritis are prevalent inflammatory diseases, and the utilization of fluorogenic probes incorporating hydrogen sulfide (H2S) as a crucial mediator of inflammation presents significant opportunities for early detection. However, the poor in vivo biodistribution and limited targeted efficacy of molecule probes for inflammation imaging severely impede their ability to differentiate the extent of inflammation and provide real‐time monitoring of inflammatory levels. Therefore, we developed a highly efficient H2S‐activated near‐infrared (NIR) fluorogenic probe (hCy‐DNP) for real‐time tracking and capturing fluctuations in H2S levels within inflammatory lesions. hCy‐DNP demonstrates an exceptionally sensitive fluorescence response to H2S expression, enabling specific differentiation between various levels of lipopolysaccharide (LPS) ‐stimulated early hepatitis models in situ, while also facilitating visual monitoring for diagnosis and efficacy evaluation of arthritis. Therefore, hCy‐DNP offers an innovative tool for exploring early diagnosis and evaluating treatment effectiveness across diverse inflammatory diseases.

Luminescent carbon dots-rooted polysaccharide crosslinked hydrogel adsorbent for sensitive determination and efficient removal of Cu2+

In this study, a novel luminescent carbon dot-rooted polysaccharide hydrogel (CDs@CCP hydrogel) was prepared by crosslinking cellulose, chitosan (CS), and polyvinyl alcohol (PVA) for simultaneous fluorescent sensing and adsorption of Cu2+. The crosslinking of these low-cost, polysaccharide polymers greatly enhance the mechanical strength of the composite hydrogel while making the polysaccharide-based adsorbent easy to reuse. This composite hydrogel exhibited an excellent adsorption capacity (124.7 mg∙g−1) for residual Cu2+ in water, as well as a sensitive and selective fluorescence response towards Cu2+ with a good linear relationship (R2 > 0.97) and a low detection limit (LOD) of 0.02 μM. The adsorption isotherms, adsorption kinetics, and thermodynamics studies were also conducted to investigate the adsorption mechanism. This composite hydrogel offers an efficient tool for simultaneous monitoring and treatment of Cu2+ from wastewater.

Modulation of Heterotypic and Homotypic Interactions to Visualize the Evolution of Organic Aggregates in a Fluorescence Turn-on Manner.

The abnormal evolution of membrane-less organelles into amyloid fibrils is a causative factor in many neurodegenerative diseases. Fundamental research on evolving organic aggregates is thus instructive for understanding the root causes of these diseases. In-situ monitoring of evolving molecular aggregates with built-in fluorescence properties is a reliable approach to reflect their subtle structural variation. To increase the sensitivity of real-time monitoring, we presented organic aggregates assembled by TPAN-2MeO, which is a triphenyl acrylonitrile derivative. TPAN-2MeO showed a morphological evolution with distinct turn-on emission. Upon rapid nanoaggregation, it formed non-emissive spherical aggregates in the kinetically metastable state. Experimental and simulation results revealed that the weak homotypic interactions between the TPAN-2MeO molecules liberated their molecular motion for efficient non-radiative decay, and the strong heterotypic interactions between TPAN-2MeO and water stabilized the molecular geometry favorable for the non-fluorescent state. After ultrasonication, the decreased heterotypic interactions and increased homotypic interactions acted synergistically to allow access to the emissive thermodynamic equilibrium state with a decent photoluminescence quantum yield (PLQY). The spherical aggregates were eventually transformed into micrometer-sized blocklike particles. Under mechanical stirring, the co-assembly of TPAN-2MeO and Pluronic F-127 formed uniform fluorescent platelets, inducing a significant enhancement in PLQY. These results decipher the stimuli-triggered structural variation of organic aggregates with concurrent sensitive fluorescence response and pave the way for a deep understanding of the evolutionary events of biogenic aggregates.

2-Aminopurine-based quencher-free DNA tweezers with fluorescence properties well tuned by surrounding bases.

Reversible structural changes in DNA nanomachines have great potential in the field of bioanalysis. Here, we demonstrate an assembly strategy for quencher-free and tunable DNA tweezers based on 2-aminopurine (2-AP), avoiding the tedious fluorescence labelling step. The conformational state of the tweezers could be controlled by specific oligonucleotides (fuel or anti-fuel). Taking advantage of the local environmental sensitivity of 2-AP, the structural changes of the tweezers were easily tracked, and multiple cyclic switching of the tweezers between the open and closed states was achieved. In addition, the influence of oligonucleotide structure on the fluorescence properties of 2-AP was deeply explored. We figured out that the fluorescence of 2-AP was highly quenched by the base-stacking of natural bases in DNA oligonucleotides. Moreover, by comprehensively regulating the type of bases surrounding the inserted 2-AP site, a sensitive fluorescence response towards dynamic change can be obtained. This principle of quencher-free nanodevices based on 2-AP provides a convenient method for monitoring the structural changes of DNA nanomachines.

A ratiometric fluorescent probe revealing the abnormality of acetylated tau by visualizing polarity in Alzheimer's disease.

Abnormal neuronal polarity leads to early deficits in Alzheimer's disease (AD) by affecting the function of axons. Precise and rapid evaluation of polarity changes is very important for the early prevention and diagnosis of AD. However, due to the limitations of existing detection methods, the mechanism related to how neuronal polarity changes in AD is unclear. Herein, we reported a ratiometric fluorescent probe characterized by neutral molecule to disclose the polarity changes in nerve cells and the brain of APP/PS1 mice. Cy7-K showed a sensitive and selective ratiometric fluorescence response to polarity. Remarkably, unlike conventional intramolecular charge transfer fluorescent probes, the fluorescence quantum yield of Cy7-K in highly polar solvents is higher than that in low polar solvents due to the transition of neutral quinones to aromatic zwitterions. Using the ratiometric fluorescence imaging, we found that beta-amyloid protein (Aβ) inhibits the expression of histone deacetylase 6, thereby increasing the amount of acetylated Tau protein (AC-Tau) and ultimately enhancing cell polarity. There was a high correlation between polarity and AC-Tau. Furthermore, Cy7-K penetrated the blood-brain barrier to image the polarity of different brain regions and confirmed that APP/PS1 mice had higher polarity than Wild-type mice. The probe Cy7-K will be a promising tool for assessing the progression of AD development by monitoring polarity.

High-purity C3N quantum dots for enhancing fluorescence detection of metal ions.

A new type of two-dimensional layered material, namely C3N, has been fabricated by polymerization and recommended to have great potential in various applications such as the development of electronic devices or photo-detectors, due to its enhanced conductivity, electronegativity, and unique optical properties. Actually, most of the present research on C3N is limited in the scope of theoretical calculation, while experimental research is blocked by inefficient synthesis with low purity and homogeneity. Here, we report an optimized efficient synthesis method of high-purity C3N QDs in aqueous solution by polymerization of DAP with combined centrifugation and filtration of products, with the synthesis yield up to 33.1 ± 3.1%. Subsequently, the C3N QDs have been used as novel metal ion probes exhibiting a sensitive fluorescent response to various metal ions including monovalent alkaline metals (Li+, Na+, and K+), divalent alkaline-earth metals (Mg2+, Ca2+, and Sr2+), and multivalent transition metals (Cu2+, Co2+, Ni2+, and Au3+, Fe3+, Cr3+) due to the high electronegativity of the C3N surface. Particularly, the fluorescent quenching response of Al3+, Ga3+, In3+, and Sc3+ ions is significantly different from the fluorescent enhanced response of most other carbon-based QDs, which is promising for enriching the detection methods of these metal ions and beneficial to improve the accuracy of ion recognition.

Combined detection of hepatitis B virus surface antigen and hepatitis B virus DNA using a DNA sensor.

Hepatitis B virus (HBV) infection is associated with the progression of liver disease. Occult HBV infection (OBI) is defined as the existence of detectable HBV DNA in HBV surface antigen negative individuals. However, HBV DNA is negative in serum while HBV surface antigen remains positive in incompletely cured chronic HBV infection. Hence, combined detection of HBV surface antigen and HBV DNA is essential for the accurate detection and rehabilitation of HBV infection. Therefore, a multiplex detection strategy based on branched DNA nanostructures was developed. The single-stranded segment of a branched DNA nanostructure (segments of S4 and S2) assembled by four single-stranded DNA was hybridized with the aptamer of HBV surface antigen and DNA hairpin to construct a DNA nanosensor, which can achieve high specificity identification and highly sensitive fluorescence responses to the targets. The detection limits of the developed nanosensor for HBV and HBV DNA are 50 pM and 5 nM, respectively. The combined detection of HBV surface antigen and HBV DNA provides a new insight for more thorough diagnostic evaluation of HBV infection and rehabilitation.

Synthesis and characterization of 2-(anthracene-9-yl)-4,5-diphenyl-1H-imidazole derivatives as environmentally sensitive fluorophores.

2-(Anthracene-9-yl)-4,5-diphenyl-1H-imidazole (ADPI) provides an intriguing molecular platform for developing organic fluorophores with diverse properties and fluorescence performances. However, derivatives of ADPI have not yet been well explored and extensive studies are warranted. To shed more light on this, we have synthesized a series of π-extended ADPIs through a concise synthetic route involving an efficient cross-condensation reaction followed by Pd-catalyzed Suzuki cross-coupling. The obtained compounds were subjected to X-ray single crystallographic analysis to understand their molecular conformational and solid-state packing properties. Furthermore, UV-Vis absorption and fluorescence spectroscopic analyses were conducted. Our experimental results have disclosed interesting solvatofluorochromic properties of these compounds which are useful for solvent polarity-sensitive applications. The presence of an amphoteric imidazolyl group in the ADPI derivatives also renders them sensitive fluorescence responses to strong protic acids (e.g., trifluoroacetic acid) as well as fluoride anion. It transpires that the fluorescence changes are dependent on the functional groups attached to the ADPI core, suggesting a bottom-up molecular tuning approach for development of fluorophores and chemosensors with diverse functions.

Anthraquinone-based Schiff base fluorescent probe for the sequential sensing of Al3+ and pyrophosphate in a near-perfect aqueous solution and bioimaging

A new anthraquinone derivative fluorescent probe (DPHA) was designed and synthesized for sequentially detecting aluminum ions and pyrophosphate (PPi) in a near-perfect aqueous medium with 0.4 % DMSO as a co-solvent. The DPHA probe displayed “turn-on” fluorescence sensing of Al3+ at 575 nm, overcoming the interference of the other common cations through an apparent color variation from purple to light pink. Anthraquinone-derived conjugated skeleton and Schiff base-mediated multiple binding sites were responsible for the sensitive fluorescence response and selective recognition, respectively, thus producing a chelation-enhanced fluorescence effect. Furthermore, Job's plot analysis and high-resolution mass spectrometry (HRMS) studies supported the formation of a 1:1 ligand/metal complex for Al3+. The plausible binding mechanism was recognized by both experimentally and theoretically. The succeeding addition of PPi regenerated the original spectrum of DPHA and thus the strong affinity of Al3+ to PPi. The in-situ formed DPHA-Al3+ complex for selective identification of PPi by electrostatic interaction by drawing out Al3+ and releasing the DPHA probe. Except for specific recognition of Al3+ and PPi with corresponding low detection limits of 42.2 nM and 65.2 nM (S/N = 3). Owing to its good biocompatibility, DPHA also applied as a visual probe for monitoring Al3+ ions and PPi in living cells and zebrafish, demonstrating its outstanding potential in biological work.

Magnetically driven nanorobots based on peptides nanodots with tunable photoluminescence for rapid scavenging reactive α-dicarbonyl species and effective blocking of advanced glycation end products.

The present work constructed magnetically driven nanorobots by conjugating the photoluminescent β-alanine-histidine (β-AH) nanodots to superparamagnetic nanoparticles (SPNPs) for simultaneously sensitive determination and fast trapping RDS in food processing, achieving efficient regulation of advanced glycation end products (AGEs) risk. Bio-derivative β-AH nanodots with orderly self-assembly nanostructure and tunable photoluminescent properties served as both biorecognition elements to effectively bind and scavenge the reactive α-dicarbonyl species (RDS), as well as the indicator with sensitive fluorescence response in the food matrix. The magnetically driven nanorobots with excellent biosafety of endogenous dipeptides displayed a high binding capacity of 80.12mgg-1 with ultrafast equilibrium time. Furthermore, the magnetically driven nanorobots achieved rapid removal of the RDS with the manipulation of the external magnetic field, which enabled intercepting AGEs generation without byproducts residual as well as ease-of-operation. This work provided a promising strategy with biosafety and versatility for both accurate determination and efficient removal of hazards.

A large Stokes shift and emission shift ratiometric mitochondria-targeted fluorescent probe for sensing HClO with an ESIPT-ICT integrated platform

Hypochlorous acid (HClO) is regarded as a significant oxidative stress marker and plays key factor in various pathological and physiological processes. However, the overexpression of HClO is relation to variety of diseases due to cellular damage and oxidative stress. Studies have described that the HClO level in mitochondria is crucial to maintain the normal function of mitochondrial. Herein, we presented a simple mitochondria-targeted fluorescent probe (BA-MR), which consists of the benzothiazole dye as the fluorescent signaling unit, the methyl thioether as the HClO recognition group, and the imine pyridinium salt moiety as the mitochondria targeting group. The free probe BA-MR possessed a super large Stokes shift (260 nm) and displayed a red fluorescent at 600 nm. Upon addition of HClO, the methyl thioether of BA-MR was oxidezed exclusively into a sulfoxide group, thereby leading to the generation of compound BAO-MR with a prominent blueshift of emission at 450 nm. As expected,the probe displayed highly sensitive and selective fluorescence response to HClO with fast response (120 s) and a low detection limit (86 nM). Importantly, the newly-synthesized probe was displayed to have low cytotoxicity, and could be successfully used to imaging HClO in mitochondria, which demonstrated the probe BA-MR can act as an effective tool for researching HClO-related physiological and pathological processes.

A Smartphone-Based Sensing for Portable and Sensitive Visual Detection of Hg (II) via Nitrogen Doped Carbon Quantum Dots Modified Paper Strip.

The development of portable and cost-effective sensing system for Hg2+ quantitation is highly demanded for environmental monitoring. Herein, an on-site, rapid and portable smartphone readout device based Hg2+ sensing system integrating nitrogen-doped carbon quantum dots (NCDs) modified paper strip was proposed, and the physicochemical properties of NCDs were characterized by high resolution TEM, FTIR, UV-vis absorption spectrum and fluorescence spectral analysis. The modified paper strip was prepared via "ink-jet" printing technology and exhibits sensitive fluorescence response to Hg2+ with fluorescence color of bright blue (at the excitation/emission wavelength of 365/440nm). This portable smartphone-based sensing platform is highly selective and sensitive to Hg2+ with the limit of detection (LOD) of 10.6nM and the concentration range of 0-130nM. In addition, the recoveries of tap water and local lake water were in the range of 89.4% to 109%. The cost-effective sensing system based on smartphone shows a great potential for trace amounts of Hg2+ monitoring in environmental water samples.

The Synergistic Mechanisms of AIE, ESIPT and ICT in the α-cyanostilbene-based Derivative: A Red-fluorescence Probe With a Large Stokes' Shift for Copper (II) Ion Determination and Reversible Response to Amine/acid Vapor.

Herein, α-cyanostilbene-based luminogen with an electron donor-π-electron acceptor (D-π-A) architecture was formylated into the salicylaldehyde-analogue luminogen, followed by the Schiff base reaction with phenylamine, a red-emitting luminogen was elaborately designed and successfully synthesized in a high yield of 89%. Its well-defined structure was confirmed by FT-IR, MALDI-TOF-MS, HR-MS and 1H/13C NMR technologies. Based on the synergistic mechanisms of aggregation-induced emission (AIE), excited-state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT), it enjoyed a red-fluorescence emission at 627 nm in THF/water mixtures (fw = 95%) and was used as a probe. Moreover, the TLC-based test strips loaded with the probe not only exhibited the reversible fluorescence response to amine/acid vapor but also showed sensitive and selective fluorescence response towards Cu2+. Furthermore, the fluorescence titration experiment between the probe and Cu2+ in THF/water mixtures (fw = 95%, pH = 7.4) revealed that the detection limit was 1.18 × 10-7 M and the binding constant was 1.59 × 105. Job's plot experiment and HR-MS analysis revealed the 2:1 binding stoichiometry of the probe with Cu2+. The method enabled real-time assessment for Cu2+ in real water samples. This study could offer insightful opinions on the development of long-wavelength emissive luminogens based on α-cyanostilbene.

In Situ Fluorescence Imaging Reveals Contribution of Cerebral Hydroxyl Radicals in Hyperhomocysteinemia-Induced Alzheimer-like Dementia.

Elevated plasma level of homocysteine, also termed as hyperhomocysteinemia, is acknowledged as a significant and independent risk factor of Alzheimer's disease. However, the mechanistic insight has not been thoroughly elucidated yet. In this work, 3,5-dihydroxybenzyloxy was explored as the unique reaction trigger and integrated into the naphthalimide fluorophore via a carbamate linker to afford a new probe for •OH imaging. •OH treatment induced aromatic hydroxylation and subsequent elimination reaction to release the caged fluorophore, accompanied with a highly specific and sensitive turn-on fluorescence response. Cell imaging results revealed that excess homocysteine triggered overwhelming •OH production, which was mediated by N-methyl-d-aspartate receptor and NADPH oxidase, and the resultant •OH stress further initiated neuronal ferroptosis, also confirmed by western blot analyses. Additionally, hyperhomocysteinemic mouse models were established, and Alzheimer-like dementia of the mice was observed from behavioral tests. Most importantly, with this probe, cerebral •OH fluctuation was in situ visualized in live mice, which positively correlated with the severity of Alzheimer-like dementia induced by hyperhomocysteinemia. These results reveal that cerebral •OH stress may be the critical nexus linking hyperhomocysteinemia and Alzheimer's disease. This work provides a robust fluorescence probe for in situ visualizing the cerebral •OH fluctuations and illuminating critical insights into •OH contributions in brain disorders.