Small Dye Molecules Research Articles

Constructing chemical stable 4-carboxyl-quinoline linked covalent organic frameworks via Doebner reaction for nanofiltration

Covalent linkages are the key component of covalent organic frameworks (COFs). The development of stable and functional linkages is essential to expand the COFs family and broaden their application prospects. In this work, we report the synthesis of crystalline and chemical stable 4-carboxyl-quinoline linked COFs (QL-COFs) via Doebner reactions in both one-pot (OP) and post-synthetic modification (PSM) methods. Both methods can be universally applied to most of the reported imine COFs family via bottom-up construction or linkage conversion. Owing to the contractive pore size, more hydrophilic structure and better chemical stability than the conventional imine COFs endowed by 4-carboxyl-quinoline linkage, QL-COFs are supposed to possess a wider application range. We further demonstrate the nanofiltration membrane (NFM) based on QL-COF exhibited a desirable separation capacity with high rejection for small dye molecules (> 90%), high water permeance (850 L m−2 h−1 MPa−1) and tolerance of extreme conditions (1 M HCl/NaOH), which were benefitted from the enhanced properties of QL-COFs. Additionally, efficient ion sieving properties were also achieved by QL-COF membrane. We anticipate that this work opens up a way for the construction of robust and functional COFs materials for practical applications.

In Situ Electroporation on PERFECT Filter for High-Efficiency and High-Viability Tumor Cell Labeling.

Labeling-assisted visualization is a powerful strategy to track circulating tumor cells (CTCs) for mechanism study (e.g., tumor metastasis). Due to the rarity of CTCs in the whole blood, efficient simultaneous enrichment and labeling of CTCs are needed. Hereby, novel in situ electroporation on a previously-developed micropore-arrayed filter (PERFECT filter) is proposed. Benefiting from the ultra-small-thickness and high-porosity of the filter plus high precision pore diameter, target rare tumor cells were enriched with less damage and uniform size distribution, contributing to enhanced molecular delivery efficiency and cell viability in the downstream electroporation. Various biomolecules (e.g., small molecule dyes, plasmids, and functional proteins) were used to verify this in situ electroporation system. High labeling efficiency (74.08 ± 2.94%) and high viability (81.15 ± 3.04%, verified via live/dead staining) were achieved by optimizing the parameters of electric field strength and pulse number, ensuring the labeled tumor cells can be used for further culture and down-stream analysis. In addition, high specificity (99.03 ± 1.67%) probing of tumor cells was further achieved by introducing fluorescent dye-conjugated antibodies into target cells. The whole procedure, including cell separation and electroporation, can be finished quickly (<10 min). The proposed in situ electroporation on the PERFECT filter system has great potential to track CTCs for tumor metastasis studies.

Twins of Minimalistic Carbon Dots: Uniform Emitting‐Units and Molecular Level Repeatable Photoluminescence

AbstractUnderstanding the photoluminescence mechanism of carbon dots (C‐dots) is both of fundamental and technical significance. However, it has remained an extreme challenge due to C‐dots’ indeterminate constitution and complicated composition/structure. Herein, a combined processing system, namely extraction and subsequent preparative thin layer chromatography for C‐dots separation is presented. Benefiting from its powerful separation performances, two minimalistic C‐dots with almost identical structure and optical properties (named as “twin” C‐dots) are well separated. Then, by contrastive analysis, a photophysical picture for the C‐dots’ photoluminescence is presented: The C‐dots’ photoluminescence comes from uniform surface polycyclic aromatic hydrocarbon units instead of the whole particles, which is both size‐ and oxygen‐independent. The products not only are highly bright and stable against photobleaching, but possess repeatable photoluminescence with molecular level accuracy. So, the C‐dots favorably integrate the advantages from small molecule dyes to photoluminescent nanomaterials, which is unprecedented and desirable for property exploration and application expansion.

Triphenylamine-based conjugated microporous polymers as dye adsorbents and supercapacitors

Background: Conjugated microporous polymers CMPs have unique position among porous materials thus they are studied widely. Realistically, triphenylamine (TPA) derivatives generally possess high aromaticity, redox capabilities, high charge motilities, and outstanding electronic features, therefore designing CMPs based on TPA derivatives could result in fantastic properties.Methods: We performed one-pot coupling and polycondensation of a boronated triphenylamine derivative (TPA-3Bor) with bromobenzene (Bz-4Br) and bromopyrene (Py-4Br) derivatives to obtain two new TPA-based conjugated microporous polymers (TPA-Bz and TPA-Py CMPs, respectively). The successful synthesis of two TPA CMPs and their features were examined via Fourier transform infrared (FTIR) and 13C solid state NMR spectroscopies.Significant Findings: These two CMPs displayed attractive adsorptive properties toward the small dye molecule rhodamine B (RhB) from an aqueous solution. Outstanding adsorption performance, rapid kinetics, and good reusability suggest that our CMPs could function as effective adsorbents for RhB and, perhaps, other pollutants from wastewater. Moreover, our TPA-based CMPs displayed effective and stable performance when introduced as electrodes for supercapacitors, with capacitances as high as 78 F g–1 at a current density of 1 A g–1 as well as high stability. This study emphasizes the importance of conjugation and planarity in the future design of such materials.

Construction of solvent resistance O‐PASS@UiO‐66‐NH2/O‐PASS composite membrane for methylene blue removal

AbstractThe purification of dye wastewater plays a critical role in water pollution treatment. Adsorption is a cheap and effective separation technology but is limited by the reuse of adsorption materials. Ultrafiltration membranes have a relatively high flux but their pores are too large to reject small dye molecules. In this study, negatively charged oxidized poly (arylene sulfide sulfone) (O‐PASS) membrane, NMP pretreatment oxidized O‐PASS (N‐O‐PASS) membrane, and O‐PASS@UiO‐66‐NH2/O‐PASS composite membranes were fabricated to retain cationic methylene blue (MB) from wastewater by combining ultrafiltration and adsorption techniques. The increased porosity of the N‐O‐PASS membrane provides more available adsorption sites for an equilibrium MB adsorption amount of 22.5 (mg g−1) and 100% rejection in the first 10 min during ultrafiltration with a pure water flux of 162.32 (L m−2 h−1 bar−1). Due to the enhanced hydrophilicity and separating property by deposited UiO‐66‐NH2 particles and PASS resin, O‐PASS@UiO‐66‐NH2/O‐PASS composite membrane shows a flux of 170.32 (L m−2 h−1 bar−1) and a 100% MB rejection in 60 min with great reusability. The O‐PASS@UiO‐66‐NH2/O‐PASS composite membrane is a new promising membrane for the removal of dyes from wastewater. Meanwhile, the superior solvent resistance endows it great adaptability in wide applications, especially in harsh conditions.

Preparation of the Biodegradable Lymphatic Targeting Imaging Agent Based on the Indocyanine Green Mesoporous Silicon System.

The lymphatic system plays a crucial role in the immune system’s recognition and response to disease. Therefore, the imaging of the lymphatic system, especially lymphatic vessels, has emerged as a valuable tool for the diagnosis of metastasis. FDA-approved small-molecule dyes, namely, indocyanine green (ICG), have been widely applied to lymphatic vessels imaging. However, due to the small physical size, such molecule-based agents show no selectivity, and rapid clearance from lymph nodes. Herein, a biodegradable lymphatic targeting imaging agent based on the ICG-mesoporous silicon system (ICG@HMONs-HA) was obtained, which not only could target lymph vessels but also had a long residence time. The reported work provides a practical way for lymph vessel fluorescence imaging and paves the way for clinical translation of nanomaterial-based tracers.

Small molecule diffusion in poly-(olygo ethylene glycol methacrylate) based hydrogels studied by fluorescence correlation spectroscopy

Understanding just how solutes such as small molecules, polymers or proteins diffuse in “smart” hydrogels is a key factor in developing potential applications. In this work, we used fluorescence correlation spectroscopy (FCS) to study how structural parameters (length of side groups, network density) influence the diffusion of small dye molecules in poly (oligo (ethylene glycol) methyl ether methacrylates) (POEGMAs) hydrogels. Two diffusion components were found and attributed to (i) Fickian-like diffusion slowed only by steric effects, and (ii) diffusion slowed by interactions with the polymer. The relationship between the diffusion component (i) and the polymer concentration showed two regimes with different slopes in both hydrogels and solutions of non-crosslinked polymers, additionally studied for reference. The threshold between these regimes depended on the polymer hydrophilicity/hydrophobicity and the presence of cross-links. The release time of the model drug (ibuprofen) proved to be shorter in the case of denser hydrogel networks than for looser ones. This means that the drug affinity to the polymer network is the crucial parameter determining release processes, while the diffusion factor is of secondary and minor importance.

Exploring the structural dynamics of DNA using fluorescence polarization microscopy and optical tweezers

DNA structural transitions facilitate genomic processes, mediate drug-DNA interactions, and inform the development of emerging DNA-based biotechnology. Here, we use concurrent fluorescence polarization imaging and DNA manipulation experiments to probe the structure of DNA conformations that form under high tension and topological constraints. First, we employ polarization imaging of DNA intercalators (small dye molecules that slide between the DNA base-pairs) to probe the structure of S-DNA, an elongated conformation that can be accessed by mechanical overstretching of (relaxed) B-DNA.

The Mechanochemical Synthesis and Activation of Carbon-Rich π-Conjugated Materials.

Mechanochemistry uses mechanical force to break, form, and manipulate chemical bonds to achieve functional transformations and syntheses. Over the last years, many innovative applications of mechanochemistry have been developed. Specifically for the synthesis and activation of carbon‐rich π‐conjugated materials, mechanochemistry offers reaction pathways that either are inaccessible with other stimuli, such as light and heat, or improve reaction yields, energy consumption, and substrate scope. Therefore, this review summarizes the recent advances in this research field combining the viewpoints of polymer and trituration mechanochemistry. The highlighted mechanochemical transformations include π‐conjugated materials as optical force probes, the force‐induced release of small dye molecules, and the mechanochemical synthesis of polyacetylene, carbon allotropes, and other π‐conjugated materials.

Use of High-Refractive Index Hydrogels and Tissue Clearing for Large Biological Sample Imaging.

Recent advances in tissue clearing and light sheet fluorescence microscopy have improved insights into and understanding of tissue morphology and disease pathology by imaging large samples without the requirement of histological sectioning. However, sample handling and conservation of sample integrity during lengthy staining and acquisition protocols remains a challenge. This study overcomes these challenges with acrylamide hydrogels synthesised to match the refractive index of solutions typically utilised in aqueous tissue clearing protocols. These hydrogels have a high-water content (82.0 ± 3.7% by weight). The gels are stable over time and FITC-IgG readily permeated into and effluxed out of them. Whilst the gels deformed and/or swelled over time in some commonly used solutions, this was overcome by using a previously described custom refractive index matched solution. To validate their use, CUBIC cleared mouse tissues and whole embryos were embedded in hydrogels, stained using fluorescent small molecule dyes, labels and antibodies and successfully imaged using light sheet fluorescence microscopy. In conclusion, the high water content, high refractive index hydrogels described in this study have broad applicability to research that delves into pathophysiological processes by stabilising and protecting large and fragile samples.

Progress in the past five years of small organic molecule dyes for tumor microenvironment imaging.

The tumor microenvironment (TME) is the survival environment for tumor cell proliferation and metastasis in deep tissues. Prognostic factors, such as growth, invasion and metastasis of malignant tumors, are closely related to changes in physiological parameters, including hypoxia, enzymes, low extracellular pH, and reduction conditions. Therefore, it is of great clinical significance to study tumor microenvironment markers to evaluate tumor progression and predict therapeutic effects. Organic fluorescent dyes are popular because of their small size, easy modification, adjustable luminescence and simple elucidation of their mechanism, and are widely used in tumor diagnosis and treatment. This paper reviews recent progress in fluorescent probes based on small organic molecules for imaging TME markers. Firstly, the design mechanism of a fluorescent probe is discussed, and then the application of pH, hypoxia, and reactive oxygen species, and a reduction-condition-responsive fluorescent probe in tumor imaging is discussed in detail. Finally, the prospects for the application of small-molecule fluorescent probes for imaging a tumor microenvironment in vivo are explored, but the potential application of small-molecule fluorescent probes in the early diagnosis of cancer as well as in the clinical laboratory for differentiating cancers, and further use in image-guided tumor surgery still face great challenges.

A hypoxia-responsive supramolecular formulation for imaging-guided photothermal therapy.

Photothermal agents (PTAs) based on organic small-molecule dyes emerge as promising theranostic strategy in imaging and photothermal therapy (PTT). However, hydrophobicity, photodegradation, and low signal-to-noise ratio impede their transformation from bench to bedside. In this study, a novel supramolecular PTT formulation by a stimuli-responsive macrocyclic host is prepared to overcome these obstacles of organic small-molecule PTAs.Methods: Sulfonated azocalix[4]arene (SAC4A) was synthesized as a hypoxia-responsive macrocyclic host. Taking IR780 as an example, the supramolecular nanoformulation IR780@SAC4A was constructed by grinding method, and its solubility, photostability, and photothermal conversion were evaluated. The hypoxia tumor-selective imaging and supramolecular PTT of IR780@SAC4A were further evaluated in vitro and in vivo.Results: IR780@SAC4A is capable of enhancing the solubility, photostability, and photothermal conversion of IR780 significantly, which achieve this supramolecular formulation with good imaging-guided PTT efficacy in vitro and in vivo.Conclusions: This study demonstrates that the supramolecular PTT strategy is a promising cancer theranostic method. Moreover, this supramolecular approach is applicative to construct kinds of supramolecular PTAs, opening a general avenue for extending smart PTT formulations.

Development of Mitochondria-Targeted Small-Molecule Dyes for Myocardial PET and Fluorescence Bimodal Imaging

Mitochondria-targeting positron emission tomography (PET) and fluorescent dual-modal probes are rarely reported. As one of the most promising lipophilic cations, F16 and its derivatives (F16s) have never been used for myocardial imaging. In this work, 14 F16s are synthesized and evaluated for cardiac imaging. In vitro cell fluorescence imaging revealed that the lead probe 5MEF is precisely localized in the mitochondria of cardiomyocytes. In addition, it shows excellent ex vivo fluorescence imaging quality with the heart-to-muscle and heart-to-liver ratios up to ∼2. Furthermore, the radiofluorinated probe 18F-5MEF is successfully prepared and shows a high initial heart uptake of 8.66 ± 0.34 % ID/g at 5 min post injection. It displays a high heart imaging performance, a long retention time in the heart, and a low background in the most normal tissues as revealed by PET. To our knowledge, this is the first time novel F16 analogues are designed and developed for myocardial dual-modal imaging.

“Gold Inlaid with Hair”: Permanent Fluorescent Hair Dyeing Using Fast Protein-Assisted Biomineralization of Gold Nanoclusters

Permanent fluorescent hair dyeing is one of the modern coloration modes to meet the increasing demands of personality and fashion statements. However, the limited durability and narrow Stokes shift of small molecule dyes hinder the permanent performance and distinguished use of fluorescent hair dyes from conventional hair coloration. Here, fluorescent metal nanomaterials, gold nanoclusters, have been utilized as hair dyes and embedded inside hair through a fast protein-assisted biomineralization approach under heating and alkaline conditions. Heat and alkalinity not only ensure that the scales of hair fully open and the dye precursor is deeply pervasive but also largely promote the reducibility of hair protein. The introduction of gold nanocluster bestows a broad range of new photophysical, much enhanced antistatic, mechanical, durable, and biocompatible properties to hair, largely improving the comfort experience and cosmetic performance.

A natural cuttlefish melanin nanoprobe for preoperative and intraoperative mapping of lymph nodes

Lymphatic metastasis plays an important role in malignant tumor invasion. Efficient identification of sentinel lymph node (SLN) is extremely significant for designing therapeutic strategies and assessing prognosis. In this work, we developed a natural cuttlefish melanin nanoprobe for the preoperative and intraoperative evaluation of lymphatic metastasis. The cuttlefish melanin nanoparticle could improve the water-solubility and biocompatibility of the near-infrared-II (NIR-II) dye, and extend the retention time of small molecule dye. The NIR-II imaging results verified that the nanoparticles have a high accumulation, high sensitivity, and high signal-to-noise ratio in the lymphatic system. Moreover, the nanoparticles have obvious naked-eye identification potential due to their natural brownish-black color. Additionally, the nanoparticles can combine with Gd ions to achieve preoperative lymphatic magnetic resonance imaging (MRI). The results of this study provide a unique approach to effectively identify and accurately remove lymph nodes before operation and during surgery, exhibiting tremendous potential in clinical translation.

Controlled Nanoconfinement of Polyimide Networks in Mesoporous γ-Alumina Membranes for the Molecular Separation of Organic Dyes

Polyimide networks are key in the development of stable, resilient, and efficient membranes for separation applications under demanding conditions. To this aim, the controlled design of the network’s nanostructure and its properties are needed. However, such control remains a challenge with currently available synthesis methods. Here, we present a simple nanofabrication approach that allows the controlled nanoconfinement, growth, and covalent attachment of polyimide (PI) networks inside the mesopores of γ-alumina layers. The attachment of the PI network on the γ-alumina layer was initiated via different prefunctionalization steps that play a pivotal role in inducing the in situ polymerization reaction at the pore entrance and/or at the inner pore surface. The nanoconfinement was found to be limited to the 1.5 μm-thick γ-alumina supporting layer at maximum, and the resulting hybrid PI/ceramic membranes showed stable performance in a variety of solvents. These PI/ceramic membranes were found to be very efficient in the challenging separation of small organic dye molecules such as Rhodamine B (479 g mol–1) from toxic solvents such as dimethylformamide or dioxane. Therefore, this technique opens up possibilities for a multitude of separations. Moreover, the PI synthesis approach can be applied to other applications that also rely on porosity and stability control, such as for advanced insulation and anticorrosion.

Removal of crystal violet from water by poly acrylonitrile-co-sodium methallyl sulfonate (AN69) and poly acrylic acid (PAA) synthetic membranes

Abstract The current investigation is focused on the removal of crystal violet (CV) from water by adsorption process (bach method). To achieve this purpose, specific membranes were prepared from poly acrylonitrile-co-sodium methallyl sulfonate (AN69) and poly acrylic acid (PAA) blends. The adsorption of CV onto AN69/PAA membranes was studied under various conditions: membrane composition, pH, contact time, initial concentration and temperature. To understand the effect of membrane morphology on adsorption process, scanning electronic microscopy (SEM) was employed to determine the features of section and membrane’s surface. From isotherm results, it was found that: the maximum adsorption capacity Q m was 1250 mg g−1, the Langmuir separation factor R L was lying between 0.33 and 0.76, the Freundlich intensity was higher than Unit (n = 1.25) and the adsorption process follows preferentially the Langmuir model (correlation constant R 2 = 0.99). The mechanism of adsorption is perfectly fitted by pseudo second order. The obtained results tend to confirm that the removal of dye molecules is due to the establishment of strong electrostatic interactions between cationic dye molecules and anionic membrane groups. The high adsorption capacity (1250 mg g−1) for the small dye molecules may open wide opportunities to apply these membranes in the removal of various hazardous pollutants commonly present in water.

Tailored pore size and microporosity of covalent organic framework (COF) membranes for improved molecular separation

Three crystalline truxene-based β-ketoenamine COF membranes (TFP-HETTA, TFP-HBTTA and TFP-HHTTA) are fabricated via a de novo monomer design approach to understand the fundamental correlations between pore structure and molecular separation performance. By introducing bulky alkyl groups into the truxene framework, the pore size of TFP-HETTA, TFP-HBTTA, and TFP-HHTTA are systematically tuned from 1.08 to 0.72 nm. Accordingly, the TFP-HETTA showed good water permeance of 47 L m−2h−1 bar−1 along with a prominent rejection rate of Reactive Blue (RB, 800 Da) but less than 10% rejection rate of inorganic salts. In contrast, the TFP-HHTTA membrane with pore size of 0.72 nm can reject small dye molecules such as Safranin O (SO, 350 Da) and trivalent salts but with a moderate water permeance of 19 L m−2h−1 bar−1. The pore-flow model rooted from the viscous flow could well fit the observed organic solvent nanofiltration results of all three COF membranes.

Ras inhibitor farnesylthiosalicylic acid conjugated with IR783 dye exhibits improved tumor-targeting and altered anti-breast cancer mechanisms in mice.

Ras has long been viewed as a promising target for cancer therapy. Farnesylthiosalicylic acid (FTS), as the only Ras inhibitor has ever entered phase II clinical trials, has yielded disappointing results due to its strong hydrophobicity, poor tumor-targeting capacity, and low therapeutic efficiency. Thus, enhancing hydrophilicity and tumor-targeting capacity of FTS for improving its therapeutic efficacy is of great significance. In this study we conjugated FTS with a cancer-targeting small molecule dye IR783 and characterized the anticancer properties of theconjugate FTS-IR783. We showed that IR783 conjugation greatly improved the hydrophilicity, tumor-targeting and therapeutic potential of FTS. After a single oral administration in Balb/c mice, the relative bioavailability of FTS-IR783 was increased by 90.7% compared with FTS. We demonstrated that organic anion transporting polypeptide (OATP) and endocytosis synergistically drove the uptake of the FTS-IR783 conjugate in breast cancer MDA-MB-231 cells, resulting in superior tumor-targeting ability of the conjugate both in vitro and in vivo. We further revealed that FTS-IR783 conjugate could bind with and directly activate AMPK rather than affecting Ras, and subsequently regulate the TSC2/mTOR signaling pathway, thus achieving 2-10-fold increased anti-cancer therapeutic efficacy against 6 human breast cancer cell lines compared to FTS both in vivo and in vitro. Overall, our data highlights a promising approach for the modification of the anti-tumor drug FTS using IR783 and makes itpossible to return FTS back to the clinic with a better efficacy.

Development of a Dual Fluorescent and Magnetic Resonance False Neurotransmitter That Reports Accumulation and Release from Dopaminergic Synaptic Vesicles.

Myriad neuropsychiatric disorders are due to dopamine dysfunction. However, understanding these disorders is limited by our ability to measure dopamine storage and release. Fluorescent false neurotransmitters (FFNs), small-molecule dyes that co-transit through the synaptic vesicle cycle, have allowed us to image dopamine in cell culture and acute brain slice, but in vivo microscopy is constrained by the biopenetrance of light. Here, we adapt FFNs into magnetic resonance false neurotransmitters (MFNs). The design principles guiding MFNs are (1) the molecule is a valid false neurotransmitter and (2) it has a 19F-substituent near a pH-sensing functional group, which (3) has pKa close to 6 so that the probe within vesicles is protonated. We demonstrate that MFN103 meets these criteria. While a magnetic resonance spectroscopy (MRS) signal was too low for measurement in vivo with the current technology, in principle, MFNs can quantify neurotransmitters within and without synaptic vesicles, which may underlie noninvasive in vivo analysis of dopamine neurotransmission.