Fluorescent Molecules Research Articles

Declined Singletbut Constant TripletEnergy: Thermally Activated Delayed Fluorescence with Triplet Blocking Effect.

Thermally activated delayed fluorescence (TADF) molecules have been widely investigated in organic light emitting diodes, etc. Small singlet-triplet energy gapand high radiative constantsare desired. The prevalent TADF molecules are via donor-acceptor molecular design, whichis at the expense of reducing radiative constants. Herein, we demonstrated a new singlet-triplet energy gap modulation approach to construct TADF with high radiative constant, based on triplet blocking effect, i.e., the extension of conjugation of a triplet constrainer (IB) leads to a gradually red-shifted singletbut a constant tripletenergy, and therefore reduced singlet-triplet energy gap controlled from monomer (IB), monomer-linker (IB-BF2), to dimer of IB-BF2-IB. The natural transition orbital analysis indicates that singletstate is delocalized while tripletstate is localized as confirmed by time resolved electron paramagnetic resonance spectroscopy. Therefore, the singlet-triplet energy gap is reduced from 0.60 eV, 0.46 eV to 0.25 eV, while keeping faster radiation rate (around 10^8/s) than that of conventional donor-acceptor molecules (10^6 ~ 10^7/s). As a result, the emission mechanisms are regulated from fluorescence for IB, phosphorescence/TADF dual emissions for IB-BF2 to TADF for IB-BF2-IB. This paper proposed a new approach of singlet-triplet energy gap modulation, which is crucial for fundamental photophysics and material science.

A biocompatible fluorescent probe for endogenous hydrogen sulfide detection and imaging.

Hydrogen sulfide (H2S) acts as a messenger molecule and can mediate a variety of physiological functions. Conventional methods are seldom used to detect endogenous H2S and present some difficulties in selective and accurate detection. Reaction-based recognition of endogenous H2S by organic small molecule probes with good specificity and biocompatibility. To address this challenge, we developed a novel H2S fluorescent probe 4-(2-(6-hydroxy-2-naphthyl) ethyl)-1-methylpyridinium (DSNP) that triggers a thiolysis reaction through a strong electron withdrawing group, releasing a fluorescent molecule. The simple probe DSNP not only have good selectivity, large Stokes shifts and biocompatibility, but also demonstrated a detection limit as low as 28.4 nM and reaction times as quick as 30 minutes. Moreover, it has been successfully applied to imaging intracellular H2S in myeloma cells and zebrafish. This study opens new insights to help push this probe forward for its applicability for detailed H2S localization studies in osteosarcoma.

Dual Responsive Emulsions Based on Amphiphilic Elastin-like Polypeptide Bioconjugates.

To achieve the desired therapeutic response, drug delivery systems must ensure the controlled release of the loaded content at the targeted site. One possible strategy relies on the improvement of conventional drug delivery systems. To do so, smart polymers, able to change their behavior upon chemical, physical, or biological stimuli, can be used. In this context, this study aims to evaluate the potential of natural amphiphilic smart elastin-like polypeptides grafted with alkyl chains (ELP-g-Bu) to stabilize conventional oil-in-water emulsions and trigger the release of loaded molecules upon dual stimuli. With butyl pendant chains and methionine residues, the macromolecular surfactant ELP-g-Bu demonstrated a modification of physicochemical properties, looking at critical aggregation concentration, upon both temperature and oxidation stimuli. The macromolecular surfactant was then able to stabilize a paraffin-oil-in-water emulsion. The ELP-g-Bu emulsion presented a droplet size of 9 ± 1 μm and stability for at least a month at 4 and 25 °C. After successful loading of a fluorescent lipophilic molecule used as a drug model, a complete destabilization of the ELP-g-Bu emulsion and burst release of the content was achieved with thermal triggering at 42 °C. In oxidative conditions, a partial release was measured, which can be improved by increasing the number of oxidable thioether groups. Overall, these dually responsive amphiphilic ELP-g-Bu demonstrated their potential for smart-polymer-based drug delivery systems that can be promising for inflammatory disease treatment as increased temperature and radical oxygen species are present in such cases.

A Cell-Based Screening Assay for rRNA-Targeted Drug Discovery.

Worldwide, bacterial antibiotic resistance continues to outpace the level of drug development. One way to counteract this threat to society is to identify novel ways to rapidly screen and identify drug candidates in living cells. Developing fluorescent antibiotics that can enter microorganisms and be displaced by potential antimicrobial compounds is an important but challenging endeavor due to the difficulty in entering bacterial cells. We developed a cell-based assay using a fluorescent aminoglycoside molecule that allows for the rapid and direct characterization of aminoglycoside binding in a population of bacterial cells. The assay involves the accumulation and competitive displacement of a fluorescent aminoglycoside binding probe in Escherichia coli as a Gram-negative bacterial model. The assay was optimized for high signal-to-background ratios, ease of performance for reliable outcomes, and amenability to high-throughput screening. We demonstrate that the fluorescent binding probe shows a decrease in fluorescence with cellular uptake, consistent with RNA binding, and also shows a subsequent increase upon the addition of the positive control neomycin. Fluorescence intensity increase with aminoglycosides was indicative of their relative binding affinities for A-site rRNA, with neomycin having the highest affinity, followed by paromomycin, tobramycin, sisomicin, and netilmicin. Intermediate fluorescence was found with plazomicin, neamine, apramycin, ribostamicin, gentamicin, and amikacin. Weak fluorescence was observed with kanamycin, hygromycin, streptomycin, and spectinomycin. A high degree of sensitivity was observed with aminoglycosides known to be strong binders for the 16S rRNA A-site compared with antibiotics that target other biosynthetic pathways. The quality of the optimized assay was excellent for planktonic cells, with an average Z' factor value of 0.80. In contrast to planktonic cells, established biofilms yielded an average Z' factor of 0.61. The high sensitivity of this cell-based assay in a physiological context demonstrates significant potential for identifying potent new ribosomal binding antibiotics.

Tetraphenylethylene-Derived Tetracarboxylate Featuring AIE Properties for Dual Ion Sensing and Mechanochromic Self-Erasable Writing.

The integration of multiple functions within a single fluorescent molecule provides a promising platform for developing versatile, efficient, and cost-effective materials with enhanced performance across diverse applications. In this study, we introduce TPEC, an aggregation-induced emission (AIE) molecule derived from tetraphenylethylene-based tetracarboxylate, which demonstrates multifunctional capabilities, including metal ion sensing and self-erasable writing. TPEC exhibits amphiphilicity in water, self-assembling into single-layer nanosheets with robust blue fluorescence. Notably, the aqueous solution of TPEC displays a fluorescence colorimetric response to Al3+ ions and fluorescence quenching in the presence of Fe³⁺ ions. Additionally, TPEC powders undergo fluorescence colorimetric changes under mechanical stimulation, enabling self-erasable writing on prepared paper. This study presents a straightforward strategy for the development of multifunctional luminescent materials based on the self-assembly of a single-component fluorophore.

Fluorescence from a single-molecule probe directly attached to a plasmonic STM tip

The scanning tunneling microscope (STM) provides access to atomic-scale properties of a conductive sample. While single-molecule tip functionalization has become a standard procedure, fluorescent molecular probes remained absent from the available tool set. Here, the plasmonic tip of an STM is functionalized with a single fluorescent molecule and is scanned on a plasmonic substrate. The tunneling current flowing through the tip-molecule-substrate junction generates a narrow-line emission of light corresponding to the fluorescence of the negatively charged molecule suspended at the apex of the tip, i.e., the emission of the excited molecular anion. The fluorescence of this molecular probe is recorded for tip-substrate nanocavities featuring different plasmonic resonances, for different tip-substrate distances and applied bias voltages, and on different substrates. We demonstrate that the width of the emission peak can be used as a probe of the exciton-plasmon coupling strength and that the energy of the emitted photons is governed by the molecule interactions with its environment. Additionally, we theoretically elucidate why the direct contact of the suspended molecule with the metallic tip does not totally quench the radiative emission of the molecule.

Inside Front Cover: Robust Sandwich‐Structured Thermally Activated Delayed Fluorescence Molecules Utilizing 11,12‐Dihydroindolo[2,3‐a]carbazole as Bridge

Inside Front Cover: Robust Sandwich‐Structured Thermally Activated Delayed Fluorescence Molecules Utilizing 11,12‐Dihydroindolo[2,3‐a]carbazole as Bridge

Inside Front Cover: Robust Sandwich‐Structured Thermally Activated Delayed Fluorescence Molecules Utilizing 11,12‐Dihydroindolo[2,3‐a]carbazole as Bridge

Inside Front Cover: Robust Sandwich‐Structured Thermally Activated Delayed Fluorescence Molecules Utilizing 11,12‐Dihydroindolo[2,3‐a]carbazole as Bridge

A photocurable and thermocurable composite hydrogel and the application in a contraction resistant full-thickness skin model.

Three-dimensional (3D) organotypic skin in vitro has attracted increasing attention for drug development, cosmetics evaluation, and even clinical applications. However, the severe contraction of these models restricts their application, especially in the analyses based on barrier functions such as percutaneous penetration. For the full-thickness skin equivalents, the mechanical properties of the dermis scaffold plays an important role in the contraction resistance. In this investigation, we optimized a hydrogel composed of gelatine methacrylamide (GelMA), hyaluronic acid methacrylate (HAMA), and type I collagen (Col I), adjusted the elastic moduli to 2.27±0.08 kPa to fit the skin cells growth and resist contraction as well. This optimized hydrogel exhibited a swelling ratio of 23.25 ± 0.94% and demonstrated satisfactory cell viability in fibroblasts cultures. Then, we mixed this hydrogel with fibroblasts of liquid-liquid culture to construct the dermis, on which seeded keratinocytes were seeded for another 14 days of air-liquid culture to form cornified epidermis, and a commercialized hydrogel Ava-FT-Skin was used as control. This optimized skin model could maintained its integrity for a prolonged period of 28 days. Differentiated epidermis presented basal, spinous, granular, and cornified layers, meanwhile, epidermis markers like keratin-10, keratin-14, involucrin, loricrin, filaggrin, and dermis markers vimentin were expressed distinctly in the right distribution. Furthermore, penetration of a 607 Da Cascade blue-labelled dextran was calculated and compared to the Avatarget skin model, both of which could prevent more than 99% of the fluorescent molecule. We consider that this full-thickness skin model could be widely used in pharmaceutical and cosmetic industries, especially in penetration detection, contributing to the excellent contraction resistance.

The Throttle Effect in Metal-Organic Frameworks for Distinguishing Water Isotopes.

Metal-organic frameworks (MOFs) have been widely used for separation, but amplifying subtle differences between similar molecules to achieve effective separation remains a great challenge. In this study, we utilize the fluorescent molecule uranine (Ura) to modulate the pores of zeolitic-imidazolate framework 8 (ZIF8), creating an unusual throttle effect. By monitoring fluorescence intensity changes in Ura, the transport diffusion process could be quantified to reveal the diffusion constant of solvents. When we pushed the Ura occupancy to its limit (from 59% to 76% and 98%), the diffusion rate decreases by 2 orders of magnitude. Most importantly, there is a significant dissymmetry between the two-way exchange rates of solvents, and the rates of H2O and D2O became distinguishable. Such unusual throttle effects disappear at low Ura occupancy of 59% and 76%. We believe that the throttle effect with small-molecule loading could provide a universal design principle for MOF-based applications, especially for isotope separation.

Bidirectional transfer of a small membrane-impermeable molecule between the C. elegans intestine and germline

The extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) is a positive regulator of cell proliferation often upregulated in cancer. Its C. elegans ortholog MPK-1 stimulates germline stem cell (GSC) proliferation non-autonomously, from the intestine or somatic gonad. How MPK-1 can perform this task from either of these two tissues however remains unclear. We reasoned that somatic MPK-1 activity could lead to the generation of pro-proliferative small molecules that could transfer from the intestine and/or somatic gonad to the germline. Here, in support of this hypothesis, we demonstrate that a significant fraction of the small membrane-impermeable fluorescent molecule, 5-carboxyfluorescein (5-CF), transfers to the germline after its microinjection in the animal’s intestine. The larger part of this transfer targets oocytes and requires the germline RME-2 yolk receptor. A minor quantity of the dye is however distributed independently from RME-2 and more widely in the animal, including the distal germline, gonadal sheath, coelomocytes and hypodermis. We further show that the intestine-to-germline transfer efficiency of this RME-2 independent fraction does not vary together with GSC proliferation rates or MPK-1 activity. Therefore, if germline proliferation was influenced by small membrane-impermeable molecules generated in the intestine, it is unlikely that proliferation would be regulated at the level of molecule transfer rate. Finally, we show that conversely, a similar fraction of germline injected 5-CF transfers to the intestine, demonstrating transfer bidirectionality. Altogether, our results establish the possibility of an intestine-to-germline signaling axis mediated by small membrane-impermeable molecules that could promote GSC proliferation cell non-autonomously downstream of MPK-1 activity.

Fast and simple fluorometric measurement of phloem loading exposes auxin-dependent regulation of Arabidopsis sucrose transporter AtSUC2.

The rate of sucrose export from leaves is a major factor in balancing whole-plant carbon and energy partitioning. A comprehensive study of its dynamics and relationship to photosynthesis, sink demand, and other relevant processes is hampered by the shortcomings of current methods for measuring sucrose phloem loading. We utilize the ability of sucrose transporter proteins, known as SUCs or SUTs, to specifically transport the fluorescent molecule esculin in a novel assay to measure phloem loading rates. Esculin was administered to source leaves and its fluorescence in the leaf extract was measured after 1 or 2 h. Dicot plants with an active phloem loading strategy showed an export-dependent reduction of esculin fluorescence. Relative leaf esculin export rates correlated with leaf export rates of isotopic carbon and phloem exudate sucrose levels. We used esculin experiments to examine the effects of phytohormones on phloem loading in Arabidopsis, showing, for example, that auxin induces phloem loading while cytokinin reduces it. Transcriptional regulation of AtSUC2 by AUXIN RESPONSE FACTOR1 (ARF1) corroborated the link between auxin signaling and phloem loading. Unlike established methods, the esculin assay is rapid and does not require specialized equipment. Potential applications and limitations of the esculin assay are discussed.

Nanodomain-Enhanced Stable and Multifunctional Probes with Near 100% Quantum Yield for Versatile Biosensing.

The preparation of high quantum yield, stable, and multifunctional fluorescent probes is of great significance in the fields of biomedicine and photoelectric sensing. Here, a triphenylamine-based D-π-A fluorescent molecule (TPA-CN) was designed and prepared, demonstrating a fluorescence quantum yield of 88.84%. With a polystyrene nanosphere as the carrier, TPA-CN was encapsulated inside the nanosphere to form intra-nanosphere confining domains. These nanodomain-enhanced fluorescent nanospheres exhibited a fluorescence quantum yield of 98.21%. Using antigen-antibody specificity and the selective catalytic activity of a bioenzyme, with chloramphenicol as a model target, a dual-signal readout biosensor (in fluorescence and colorimetric modes) was designed for ultrasensitive and instrument-free determination. The detection limit was 24 pg/mL within 30 min in fluorescence mode, 38-fold more sensitive and 10-fold faster than that of enzyme linked immunosorbent assays. The nanodomain-enhanced fluorescent probes and dynamic biosensor provide a robust and versatile solution for public health and environmental monitoring needs.

Review of contemporary fluorescence correlation spectroscopy method in diverse solution studies.

Fluorescence correlation spectroscopy (FCS) is a well-known and established non-invasive method for quantification of physical parameters that preside over molecular mechanisms and dynamics. It combines maximum sensitivity and statistical confidence for the analysis of speed, size, and number of fluorescent molecules and interactions with surrounding molecules by time-averaging fluctuation analysis in a well-defined volume element. The narrow compass of this study is to acquaint the basic principle of diffusion and the FCS method in general regarding variable magnitudes and standardization adjustment. In this review, we give a theoretical introduction, examples of experimental applications, and utensils in solution systems with future perspectives.

Iodine‐DMSO Catalyzed β‐carboline Derivative Chemoselective Fluorescent Molecule for Detection of Fluoride and Cyanide Anion

AbstractIn this work, a simple and highly sensitive fluorescent receptor 1‐(p‐tolyl)‐4,9‐dihydro‐3H‐pyrido[3,4‐b]indole (receptor 1), has been synthesized for the detection of fluoride and cyanide ions. The receptor 1 was very selective towards fluoride and cyanide anions over other anions such as Cl−, Br−, I−, HSO4−, NO3−, HPO42−, and OAc−. Synthesized receptor 1 shows low detection limits 3.29 × 10−8 M for fluoride ion, which was determined by UV–vis absorption. While LOD for cyanide was observed to be 61.5 nM. Importantly, while, receptor 1 produced binding constant for fluoride and cyanide in DMSO‐H2O (1:9, v/v) was found to be 5 × 10−4M−1 and 3.28 × 10−5 M−1, respectively. The variation in the optical and fluorescence spectroscopy confirms the formation of N─H⋯F− and N─H⋯CN− hydrogen bond of the pyrrolic proton The sensing mechanism displayed by receptor 1 for fluoride and cyanide ions was confirmed by 1H‐NMR and FT‐IR spectroscopic along with density functional theory (DFT) calculations. Solution with the fluoride and cyanide ions in DMSO‐H2O (1:9, v/v) shows a color change from light yellow to blue under UV light and yellow to colorless in visible light.

Ferrocenyl β-Diketonate Compounds: Extended Ring Systems for Improved Anticancer Activity.

A library of ferrocenyl β-diketonate compounds with varying degrees of aromatic functionality have been synthesized and fully characterized. This includes cyclic voltammetry and the analysis of four new structures by single crystal X-ray diffraction. The compounds cytotoxic potential has been determined by MTT screening against pancreatic carcinoma (MIA PaCa-2), ovarian adenocarcinoma (A2780), breast adenocarcinomas (MDA-MB-231 and MCF-7) and normal epithelial retinal (ARPE-19). The compounds show a general trend, where increasing the number of aromatic rings in the molecule yields an increase in cytotoxicity and follows the trend anthracenyl > naphthyl > phenyl > methyl. The compounds are particularly sensitive to the triple negative cancer cell line MDA-MB-231, and the potential modes of action have been studied by production of reactive oxygen species using fluorescence microscopy and cell morphology using Scanning Electron Microscopy. All assays highlight the ferrocenyl β-diketonate with an anthracenyl substituent to be the lead compound in this library. The decomposition was also observed within cells, to give a cytotoxic fluorescent molecule, which has been visualized by confocal microscopy.

Coumarin-Based ACQ-AIE Conversion Photosensitizer for Mitochondrial Imaging and Synergistic Cancer Therapy.

Most of the traditional fluorescent molecules have the advantages of high fluorescence quantum yield, good stability, and excellent structural adjustability, but they exhibit the characteristics of fluorescence quenching caused by aggregation, which restricts their application in aqueous solutions or solids. The excellent luminescence properties and photosensitive potential of aggregation-induced emission (AIE) materials in a condensed state have made them widely concerned in the scientific research field, so it is very challenging to regulate the transformation of traditional aggregation-caused quenching (ACQ) fluorophores into AIE fluorophores. In this study, the traditional coumarin fluorophore was used as a matrix. After conjugating the triphenylamine AIE group, the triphenylphosphine cation was linked through the alkyl chain to obtain a molecular probe NCTPP with excellent AIE characteristic, water solubility, mitochondrial green light imaging, chemotherapy and photodynamic therapy capabilities. As far as we know, it was the first time that the photosensitivity of coumarin fluorescent molecules was imparted by the ACQ-AIE conversion method.

Robust Sandwich‐Structured Thermally Activated Delayed Fluorescence Molecules Utilizing 11,12‐Dihydroindolo[2,3‐a]carbazole as Bridge

AbstractConstructing folded molecular structures is emerging as a promising strategy to develop efficient thermally activated delayed fluorescence (TADF) materials. Most folded TADF materials have V‐shaped configurations formed by donors and acceptors linked on carbazole or fluorene bridges. In this work, a facile molecular design strategy is proposed for exploring sandwich‐structured molecules, and a series of novel and robust TADF materials with regular U‐shaped sandwich conformations are constructed by using 11,12‐dihydroindolo[2,3‐a]carbazole as bridge, xanthone as acceptor, and dibenzothiophene, dibenzofuran, 9‐phenylcarbazole and indolo[3,2,1‐JK]carbazole as donors. They hold outstanding thermal stability with ultrahigh decomposition temperatures (556–563 °C), and exhibit fast delayed fluorescence and excellent photoluminescence quantum efficiencies (86 %–97 %). The regular and close stacking of acceptor and donors results in rigidified molecular structures with efficient through‐space interaction, which are conducive to suppressing intramolecular motion and reducing reorganized excited‐state energy. The organic light‐emitting diodes (OLEDs) using them as emitters exhibit excellent electroluminescence performances, with maximum external quantum efficiencies of up to 30.6 %, which is a leading value for the OLEDs based on folded TADF emitters. These results demonstrate the proposed strategy of employing 11,12‐dihydroindolo[2,3‐a]carbazole as bridge for planar donors and acceptors to construct efficient folded TADF materials is applicable.

Effects of functional groups on ESIPT and antioxidant activity of apigenin: A non-existent enol* state fluorescein

The development and enhancement of antioxidant drugs, which are aimed at mitigating DNA damage, mutations, and cancer, are of paramount significance in the biomedical sphere. In recent years, antioxidant drug molecules with photoluminescence have sprung up like mushrooms. Apigenin (AP), characterized by its distinctive property of excited state intramolecular proton transfer (ESIPT), plays a pivotal role in mediating antioxidant and anticancer activities. Despite being a representative molecule of the non-existent enol form (E*) state with ESIPT nature, there is a notable lack of theoretical investigations into its antioxidant properties. Herein, density functional theory (DFT) and time-dependent DFT methodologies were utilized to explore the effects of various functional groups on AP molecules in a methanol solvent. Studies have demonstrated that for the non-existent E* state fluorescence molecule AP, the ESIPT process can significantly enhance the antioxidant potency of AP and its derivatives. However, the introduction of electron-withdrawing groups significantly accelerated the ESIPT process while simultaneously suppressing the antioxidant activity of AP-CN. Conversely, the incorporation of electron-donating groups effectively inhibited the ESIPT process, yet markedly enhanced the antioxidant activity of AP-NH2. This investigation furnishes vital perspectives and sources of reference for the conception and advancement of groundbreaking antioxidant medications that aim to tackle non-existent E* state molecules.

Synthesis of a Multi-Stimulus Responsive RGB Fluorescent Organic Molecule Based on Dark Through-Bond Energy Transfer Mechanism.

In this study, a novel multi-stimulus responsive RGB fluorescent organic molecule, RTPE-NH2, was designed and synthesized based on the combination of aggregation-induced emission tetraphenylethylene (TPE) luminophore and acid-responsive fluorescent molecular switch Rhodamine B. RTPE-NH2 exhibits aggregation-induced emission behavior, as well as UV irradiation-stimulus and acid-stimulus responsive fluorescence properties. It could emit orange-red (R), green(G), and blue(B) light in both solution and PMMA film under 365 nm excitation. The dark through-bond energy transfer (DTBET) mechanism was proposed and supported by control experiments and TD-DFT calculations. The synthesis and application of RTPE-NH2 could accelerate the development of organic smart materials with high sensitivity and excellent optical properties.