A highly efficient, selective, reversible and ultra-sensitive fluorescence "Turn-ON" chemosensor for aluminium ions by a novel Schiff base.

The synthesis of a Schiff base-based chemosensor, denoted as H6L, was accomplished through the condensation reaction of Isophthalohydrazide and 2,6-dihydroxybenzaldehyde in an ethanol solvent. The resulting compound was further characterized using 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, as well as high-resolution mass spectrometry (HRMS). Extensive research has been conducted on several facets of metal sensing phenomena, revealing that the Schiff base H6L demonstrates discerning and expeditious fluorescence sensing characteristics specifically towards Al (III) in acetonitrile. The purported method detects Al (III) can be ascribed to the suppression of photo-induced electron transfer (PET) and the enhanced chelation-induced fluorescence (CHEF). The stoichiometry of metal-ligand complexes (2:1) was determined using Job's plots titrations, HRMS and subsequently confirmed using NMR titration studies. The H6L sensors demonstrated remarkable fluorescence sensing capabilities in acetonitrile, with a low detection limit (LOD) of 0.44 µM. This LOD is suitably low for the detection of Al3+, which is commonly found in many environmental and biological systems. Fluorescence lifetime measurement provides additional evidence of complexation of H6L with Al (III). The reversibility of the sensor was demonstrated through the introduction of pyrophosphate (PPi), which forms a complex with aluminium ions, thereby releasing the chemo sensor for subsequent utilization. The findings suggest that H6L has the potential to serve as a viable probe for the detection and identification of Al3+ ions.

Ultrafast symmetry-breaking charge separation in Perylenemonoimide-embedded multichromophores: impact of regioisomerism.

Symmetry-breaking charge separation (SB-CS) has recently evolved as an emerging concept offering its potential to the latest generation of organic photovoltaics. However there are several concerns that need to be addressed to reach the state-of-the-art in SB-CS chemistry, for instance, the desirable molecular geometry, interchromophoric distance and extent of electronic coupling. To shed light on those features, it is reported herein, that ortho-functionalized perylene monoimide (PMI) constituted regioisomeric dimer and trimer derivatives with varied molecular twisting and electronic conjugation have been synthesized. In steady-state photophysical studies, all the dimers and trimer derivatives exhibit a larger bathochromic shift in the emission spectra and a significant reduction of fluorescence quantum yield in polar DMF. Among the series of multichromophores, ortho- and self-coupled dimers display the strikingly different optical feature of SB-CS with a very fast charge separation rate (τCS = 80.2 ps) upon photoexcitation in DMF, which is unveiled by femtosecond transient absorption (fs-TA) studies. The SB-CS for two dimers is well-supported by the formation of PMI˙+ and PMI˙- bands in the fs-TA spectra. Further analysis of fs-TA data revealed that, among the other multichromophores the trimer also exhibits a clear charge separation, whereas SB-CS signatures are less prominent, but can not be completely disregarded, for the meta- and para-dimers. Additionally, the charge separation dynamics of those above-mentioned PMI derivatives are devoid of a kinetically favorable excimer or triplet formation. The evidence of a profound charge transfer phenomenon in the ortho-dimer is characterized by density functional theory (DFT) calculations on excited state electronic structures. The excitonic communications in the excited state electronic arrangements unravel the key role of dihedral twisting in SB-CS. The thermodynamic feasibility of CS (ΔGCS) and activation barrier (ΔG≠) of the derivatives in DMF are established from the Rehm-Weller equation and Marcus's theory, respectively. This work is an in-depth study of the effect of mutual orientation of PMIs and regioisomerism in determining sustainable guidelines for using SB-CS.

A small-molecule probe to decipher stress-induced ER microenvironments and ER-Golgi communication.

Cellular stress is a crucial factor in regulating and maintaining both organismal and microenvironmental homeostasis. It induces a response that also affects the micropolarity of specific cellular compartments, which is essential for early disease diagnosis. In this contribution, we present a quantitative study of micropolarity changes inside the endoplasmic reticulum (ER) during the G1/S and G2/M phases, using a biocompatible small-molecule fluorophore called ER-Oct. This probe is selectively driven to the ER by its hydrophobicity, and it has the fastest diffusion properties among a series of analogous probes. We found that induced ER stress caused cell cycle arrests leading to an increase in ER micropolarity which is well supported by lambda scanning experiments and fluorescence lifetime imaging microscopy (FLIM) as well. ER-Oct is a versatile staining agent that could effectively stain the ER in various living/fixed mammalian cells, isolated ER, Caenorhabditis elegans, and mice tissues. Furthermore, we used this probe to visualize a well-known biological event, ER to Golgi transport, by live-cell fluorescence microscopy. Our exhaustive investigation of micropolarity using ER-staining dye provides a new way to study ER stress, which could provide a deeper understanding of proteostasis in model systems and even in fixed patient samples.

Review of NIR-responsive ''Smart'' carriers for photothermal chemotherapy.

This review focuses on the versatile applications of near-infrared (NIR)-responsive smart carriers in biomedical applications, particularly drug delivery and photothermal chemotherapy. These carriers demonstrate multi-responsive theranostics capabilities, including pH-dependent drug release, targeted delivery of chemotherapeutics, heat-mediated drug release, and photothermal tumor damage. Biological samples are transparent to NIR light with a suitable wavelength, and therefore, NIR light is advantageous for deep-tissue penetration. It also generates sufficient heat in tissue samples, which is beneficial for on-demand NIR-responsive drug delivery in vivo systems. The development of biocompatible materials with sufficient NIR light absorption properties and drug-carrying functionality has shown tremendous growth in the last five years. Thus, this review offers insights into the current research development of NIR-responsive materials with therapeutic potential and prospects aimed at overcoming challenges to improve the therapeutic efficacy and safety in the dynamic field of NIR-responsive drug delivery.

Review on Lysosomal Metal Ion Detection Using Fluorescent Probes.

Metal ions are indispensable and play an important role in living systems. Metal ions coordinated to metalloenzymes pocket activate the bound substrate and labile metal ions maintaining the ionic balance. The amount of metal ions present in various subcellular compartments of the cells is highly regulated for maintaining cellular homeostasis. An imbalance in the metal ion concentration is related to several diseases and results in serious pathological conditions. Mostly the internalized metal ions are processed in the lysosomal compartment of the cell. A delicate regulation of metal ions in the lysosomal compartment can modulate the lysosomal pH and inhibit hydrolytic enzymes, which ultimately causes lysosomal storage disorders. In the past decade, the understanding and regulation of lysosomal metal ions based on fluorometric methods have gained significant attention. In this review, we have comprehensively summarized the development of various fluorescent reporters over the past five years for a selective and sensitive estimation of lysosomal metal ion concentration. We believe this consolidated and timely review will help researchers working in the areas associated with lysosomal metal ions.

Dual role far red fluorescent molecular rotor for decoding the plasma membrane and mitochondrial viscosity.

The dysfunctions in the mitochondria are associated with various pathological conditions like neurodegeneration, metabolic disorder, and cancer, leading to dysregulated cell death. Here, we have designed and synthesized a julolidine-based molecular rotor (JMT) to target mitochondria with far-red emission accounting for mitochondrial dysfunction. JMT showed viscosity sensitivity with 160-fold enhancement in fluorescence intensity. The origin of the dark state in a lower viscous environment was investigated through density functional calculations. We have employed JMT to monitor mitochondrial dysfunction induced by nystatin using confocal and fluorescence lifetime imaging microscopy. Further, we investigated mitochondrial abnormalities under inflammatory conditions triggered by lipopolysaccharide in live HeLa cells. The cellular uptake mechanisms of JMT were studied using various endocytosis inhibitors. Moreover, we reported tracking small fluorescent molecule switching from mitochondria to the plasma membrane upon introducing mitochondrial depolarizer in cells. On treating the mitochondria potential uncoupler, JMT relocates to the cell membrane and can be utilized for understanding the interplay between mitochondria and cell membranes. Moreover, JMT was applied to stain the RBC plasma membrane isolated from human blood.

A perylenemonoimide-based fluorescent probe: ultrasensitive and selective tracing of endogenous peroxynitrite in living cells.

Peroxynitrite (ONOO-), a highly reactive species, plays a key role in various physiological and pathological processes. Herein, a red-emitting fluorescent reporter perylenemonoimide-boronate ester (PMI-BE) was synthesized and utilized for ultrasensitive detection of ONOO-. The unique feature of PMI-BE is its nanomolar sensitivity with high selectivity towards ONOO-. Moreover, PMI-BE also detects endogenously generated ONOO- in live cells.

Perylene-Based Smart Fluoroprobe with Dual Function: Ratiometric Response toward Hazardous Organic Peroxides and Pure White Light Generation via Self-Assembly.

In this report, we have designed and synthesized a perylene-based smart fluoroprobe (PBE) in which the perylene core has been functionalized with the boronate group at the peri-position. PBE shows a very fast and ratiometric response toward harmful organic peroxides (OPs) generated in old ethereal solvents via auto-oxidation. The response toward OPs takes place with a visible color change from green to yellow, which could be easily observed with the naked eye. The reaction between PBE and OPs involves the cleavage of the boronate group and its consequent conversion into the -OH group. The response of PBE toward OPs was monitored using UV-vis absorption, fluorescence emission, IR spectroscopy, and mass spectrometry. Additionally, we have also explored the self-assembly of PBE in an organic-aqueous solvent mixture, which shows pure white light emission (WLE) with the CIE coordinates (0.33, 0.33) in a 50% dimethyl sulfoxide-water mixture. This work clearly reveals that PBE fluoroprobe can be employed for sensitive detection of hazardous OPs present in old ethereal solvents. Moreover, the ability of PBE to generate the perfect pure WLE makes it a potential candidate for application in organic light-emitting devices.

Trivalent metal ion sensor enabled bioimaging and quantification of vaccine-deposited Al3+ in lysosomes.

Extracellular metallic debris is deposited into the well-known 'recycle bins' of the cells named lysosomes. The accumulation of unwanted metal ions can cause dysfunction of hydrolyzing enzymes and membrane rupturing. Thus, herein, we synthesized rhodamine-acetophenone/benzaldehyde derivatives for the detection of trivalent metal ions in aqueous media. In solution, the synthesized probes exhibited a 'turn-on' colorimetric and fluorometric response upon complexation with trivalent metal ions (M3+). Mechanistically, M3+ chelation enables the appearance of a new emission band at approximately 550 nm, which verifies the disruption of the closed ring and the restoration of conjugation on the xanthene core in rhodamine 6G derivatives. Exclusive localization of the biocompatible probes at the lysosomal compartment favored the quantification of deposited Al3+. Moreover, the novelty of the work lies in the detection of Al3+ deposited in the lysosome that originated from hepatitis B vaccines, which shows their efficiency for near future in vivo applications.

Mitochondria-Directing Fluorogenic Probe: An Efficient Amyloid Marker for Imaging Lipid Metabolite-Induced Protein Aggregation in Live Cells and Caenorhabditis elegans.

The design and development of optical probes for sensing neurotoxic amyloid fibrils are active and important areas of research and are undergoing continuous advancements. In this paper, we have synthesized a red emissive styryl chromone-based fluorophore (SC1) for fluorescence-based detection of amyloid fibrils. SC1 records exceptional modulation in its photophysical properties in the presence of amyloid fibrils, which has been attributed to the extreme sensitivity of its photophysical properties toward the immediate microenvironment of the probe in the fibrillar matrix. SC1 also shows very high selectivity toward the amyloid-aggregated form of the protein as compared to its native form. The probe is also able to monitor the kinetic progression of the fibrillation process, with comparable efficiency as that of the most popular amyloid probe, Thioflavin-T. Moreover, the performance of SC1 is least sensitive to the ionic strength of the medium, which is an advantage over Thioflavin-T. In addition, the molecular level interaction forces between the probe and the fibrillar matrix have been interrogated by molecular docking calculations which suggest the binding of the probe to the exterior channel of the fibrils. The probe has also been demonstrated to sense protein aggregates from the Aß-40 protein, which is known to be responsible for Alzheimer's disease. Moreover, SC1 exhibited excellent biocompatibility and exclusive accumulation at mitochondria which allowed us to successfully demonstrate the applicability of this probe to detect mitochondrial-aggregated protein induced by an oxidative stress indicator molecule 4-hydroxy-2-nonenal (4-HNE) in A549 cell lines as well as in a simple animal model like Caenorhabditis elegans. Overall, the styryl chromone-based probe presents a potentially exciting alternative for the sensing of neurotoxic protein aggregation species both in vitro as well as in vivo.

Tracking endoplasmic reticulum viscosity during ferroptosis and autophagy using a molecular rotor probe.

Ferroptosis is a unique non-apoptotic cell death process associated with endoplasmic reticulum (ER) stress-related diseases. We have designed and synthesized a far-red emitting and ER targetable viscosity-sensitive fluorophore to track ER-phagy. Furthermore, the ER viscosity alteration during the ferroptosis process was investigated via intensity and lifetime-based spectroscopy and microscopy.

Bioimaging of labile lysosomal iron through naphthalimide-based fluorescent probe.

Lysosomal labile iron detection is immensely important as it is related to various diseases like Alzheimer's disease, Huntington's disease, Parkinson's disease, and cell apoptosis like ferroptosis. The fluorescent-based detection methods are preferred due to their sensitive, non-invasive, and spatial-temporal detection in biological samples. However, this remains a great challenge due to the lysosomal compartment being acidic alters the photophysical properties of the probe. Herein, we have rationally designed and synthesized multi-component naphthalimide-based fluorescent marker with preferred optical properties and bio-compatibility for selective detection of labile iron present in the lysosomal compartment. The synthesized probe was characterized structurally and optically by NMR, mass spectrometry, UV-visible, and fluorescence spectroscopy. The developed probe with an appropriate linking strategy turns out to be tolerant to fluorescence alternation in lysosomal pH. The probe exhibits great selectivity and high sensitivity for Fe(III) with limit of detection of 0.44 µM and is also able to detect Fenton-type reactions. Further, the probe has been successfully applied for lysosomal imaging and detecting labile Fe(III) present in the lysosomal lumen of the live cells.

Multi-action of a Fluorophore in the Sight of Light: Release of NO, Emergence of FONs, and Organelle Switching.

Light, as an external stimulus, has begun to engage a phenomenal role in the diverse field of science. Encouraged by recent progress from biology to materials chemistry, various light-responsive fluorescent probes have been developed. Herein, we present a 1,8-naphthalimide-based probe NIT-NO2 capable of releasing nitric oxide (NO) along with the formation of fluorescent organic nanoparticles (FONs) upon exposure to near-visible UV light. By synthesizing the photoproduct NIT-OH, we unveiled that initially NIT-NO2 released NO and converted to NIT-OH, while prolonged irradiation led to the formation of FONs that is corroborated by the red-edge excitation shift as well as microscopic investigation. Finally, we have successfully applied NIT-NO2 and NIT-OH for specific labeling of lipid droplets and plasma membranes, respectively, and demonstrated the switching from lipid droplets to plasma membranes by using light as a stimulus. These two probes show unique imaging applications inside the cells depending on the polarity and hydrophobicity of the environment. This work paves a fascinating way for the generation of excitation-dependent FONs from a small organic fluorophore and highlights its potency as an exclusive imaging tool.

Construing the metaxin-2 mediated simultaneous localization between mitochondria and nucleolus using molecular viscometry.

Fluorescent probes for specific inter-organelle communication are of massive significance as such communication is essential for a diverse range of cellular events. Here, we present the microviscosity-sensitive fluorescence marker, Quinaldine Red (QR), and its dual organelle targeting light-up response in live cells. This biocompatible probe was able to localize in mitochondria and nucleolus simultaneously. While QR was able to sense the viscosity change inside these compartments under the induced effect of an ionophore and ROS-rich microenvironment, the probe's ability to stain mitochondria remained unperturbed even after protonophore-induced depolarization. Consequently, a systematic quantification was performed to understand the alteration of microviscosity. Similar behavior in two distinct organelles implied that QR binds to metaxin-2 protein, common to mitochondrial and nucleolar proteomes. We believe this is the first of its kind investigation that identifies the inter-organelle communications marker and opens up a new dimension in this field.

Intracellular Physical Properties with Small Organic Fluorescent Probes: Recent Advances and Future Perspectives.

The intracellular physical parameters i. e., polarity, viscosity, fluidity, tension, potential, and temperature of a live cell are the hallmark of cellular health and have garnered immense interest over the past decade. In this context, small molecule organic fluorophores exhibit prominent useful properties including easy functionalizability, environmental sensitivity, biocompatibility, and fast yet efficient cellular uptakability which has made them a popular tool to understand intra-cellular micro-environmental properties. Throughout this discussion, we have outlined the basic design strategies of small molecules for specific organelle targeting and quantification of physical properties. The values of these parameters are indicative of cellular homeostasis and subtle alteration may be considered as the onset of disease. We believe this comprehensive review will facilitate the development of potential future probes for superior insight into the physical parameters that are yet to be quantified.

Rationally designed far-red emitting styryl chromones and a magnetic nanoconjugate for strip-based 'on-site' detection of metabolic markers.

The global burden of liver damage and renal failure necessitates technology-aided evolution towards point-of-care (POC) testing of metabolic markers. Hence in the prevalence of current health conditions, achieving on-site detection and quantifying serum albumin (SA) can contribute significantly to halting the increased mortality and morbidity rate. Herein, we have rationally designed and synthesized far-red emitting, solvatofluorochromic styryl chromone (SC) derivatives SC1 and SC2, and SC2-conjugated fluorescent magnetic nanoparticles (SCNPs) for sensing SA with a fluorogenic response via interacting at an atypical drug binding site. In solution, the highly sensitive and selective fluorogenic response was evaluated by the prominent amplification and blue-shift in the emission maxima of the probes from deep red to dark yellow through an intermediate orange emission. The transformation of the fluorogen into a fluorophore was manifested through spectroscopic measurements. The stabilization of the probes at protein pockets was ascribed to the non-covalent interactions, such as H-bonding, cation-π, and hydrophobic interactions, as unveiled by docking studies. The practical applications revealed the novelty of SC derivatives through (a) the capability to detect SA isolated from real blood samples via a turn-on fluorescence response; (b) the design of a simple, cheap, and portable test-strip using a glass-slide loaded with solid-state emissive SC2, which provided differential emission color of the SC2-HSA complex in solution and the solid-state with increasing concentration of HSA. Moreover, a smartphone-based color analysis application was employed to obtain the ratio of green and red (G/R) channels, which was utilized for quantitative detection of HSA; (c) the biocompatibility of the SC1 was ascertained through confocal laser scanning microscopic imaging (CLSM). Detailed investigation showed that SC1 could entirely localize in the mitochondria and evolve as a promising biomarker for distinguishing cancer cells from normal cells. Additionally, the validation of uncommon binding of SC1 and SC2 between domains I and III was determined using competition experiments with a known site-specific binder and molecular docking studies. This unique property of the probes can be further exploited to understand the cellular intake of HSA-drug complexes in the multifaceted biological system. These results find the utility of SC derivatives as small molecule-based chemosensors for at-home SA detection and as a biomarker for cancer.

Red to NIR-emissive anthracene-conjugated PMI dyes with dual functions: singlet-oxygen response and lipid-droplet imaging.

The rich chemistry of solution-processable red and near-infrared (NIR) organic emitters has emerged as an attractive and progressive research field because of their particular applications in organic optoelectronics and bioimaging. Also, one can see that the research area of perylene monoimide-based red and NIR-emissive fluorophores is underexplored, which prompted us to design and synthesize three anthracene-conjugated PMI dyes exhibiting strong emission in the red and NIR window in solution. Three PMI-based fluorophores were synthesized via conjoining anthracene and donor moieties (-Ph, -N,N-PhNMe2) with a PMI core via an acetylene linkage at the peri-position, which helped to attain extensive electronic conjugation, which was reflected in red and NIR-emission in solution. The key molecular features to be highlighted here are: all three dyes are strongly emissive in solution, as unveiled by the excellent absolute fluorescence QYs; and they possess tuneable emission properties, guided by the donor strength and a profound Stokes shift (100-200 nm). The three fluorescent dyes demonstrated appreciable singlet-oxygen (1O2) sensitivity when photoirradiated with methylene blue (MB) in solution, showing a substantial blue-shift in emission in a ratiometric manner. Further, the treatment of dye-MB solution with α-tocopherol (1O2 scavenger) validated the presence of 1O2 as the only oxidizing species generated by MB in solution. Computational investigations gave insight into the twisting of donor moieties in their ground-state optimized geometries, the modulation of the FMO energy gap, and the thermodynamic feasibility of the 1O2 reaction. Finally, via taking advantage of the red and NIR-emission, we successfully utilized one of the fluorophores as a lipid-droplet marker for bioimaging in HepG2 cells.

Water-soluble optical sensors: keys to detect aluminium in biological environment.

Metal ion plays a critical role from enzyme catalysis to cellular health and functions. The concentration of metal ions in a living system is highly regulated. Among the biologically relevant metal ions, the role and toxicity of aluminium in specific biological functions have been getting significant attention in recent years. The interaction of aluminium and the living system is unavoidable due to its high earth crust abundance, and the long-term exposure to aluminium can be fatal for life. The adverse Al3+ toxicity effects in humans result in various diseases ranging from cancers to neurogenetic disorders. Several Al3+ ions sensors have been developed over the past decades using the optical responses of synthesized molecules. However, only limited numbers of water-soluble optical sensors have been reported so far. In this review, we have confined our discussion to water-soluble Al3+ ions detection using optical methods and their utility for live-cell imaging and real-life application.

A Fluorogenic Far Red-Emitting Molecular Viscometer for Ascertaining Lysosomal Stress in Live Cells and Caenorhabditis elegans.

The cellular physiochemical properties such as polarity, viscosity, and pH play a critical role in cellular homeostasis. The dynamic change of lysosomal viscosity in live cells associated with different environmental stress remains enigmatic and needs to be explored. We have developed a new class of Julolidine-based molecular viscometers with an extended π-conjugation to probe the lysosomal viscosity in live cells. High biocompatibility, pH tolerance, and the fluorogenic response with far red-emission (>600 nm) properties make these molecular viscometers suitable for live-cell fluorescence imaging in Caenorhabditis elegans. Among these probes, JIND-Mor is specifically designed to target lysosomes via simple modification. The real-time monitoring of lysosomal viscosity change under cellular stress was achieved. We believe that such a class of molecule viscometers has the potential to monitor lysosomal health in pathogenic conditions.

Janus -faced oxidant and antioxidant profiles of organo diselenides.

To date, organoseleniums are pre-eminent for peroxide decomposition and radical quenching antioxidant activities. On the contrary, here, a series of Janus-faced aminophenolic diselenides have been prepared from substituted 2-iodoaniline and selenium powder using copper-catalyzed methodology. Subsequently, condensation with substituted salicylaldehyde afforded the Schiff base, which on reduction, yielded the desired substituted aminophenolic diselenides in 72%-88% yields. The generation of reactive oxygen species (ROS) from oxygen gas by the synthesized aminophenolic diselenides was studied by analyzing the oxidation of dichlorofluorescein diacetate (DCFDA) dye and para-nitro-thiophenol by fluorescence and UV-Visible spectroscopic methods. Furthermore, density functional theory calculations and crystal structure analysis revealed the role of functional amine and hydroxyl sites present in the Janus-faced organoselenium catalyst for the activation of molecular oxygen, where NH and phenolic groups bring the oxygen molecule close to the catalyst by N-H⋯O and O-H⋯O intermolecular interactions. Additionally, these functionalities stabilize the selenium-centered radical in the formed transition states. Antioxidant activities of the synthesized diselenides have been explored as the catalyst for the decomposition of hydrogen peroxide using benzenethiol sacrificial co-reductant by a well-established thiol assay. Radical quenching antioxidant activity was studied by the quenching of DPPH radicals at 516 nm by UV-Visible spectroscopy. The structure activity correlation suggests that the electron-rich phenol and electron-rich and sterically hindered selenium center enhance the oxidizing property of the aminophenolic diselenides. Janus-faced diselenides were also evaluated for their cytotoxic effect on HeLa cancer cells via MTT assay, which suggests that the compounds are effective at 15-18 µM concentration against cancer cells. Moreover, the combination with therapeutic anticancer drugs Erlotinib and Doxorubicin showed promising cytotoxicity at the nanomolar concentration (8-28 nM), which is sufficient to suppress the growth of the cancer cells.