An Efficient, Regioselective Pathway to Cationic and Zwitterionic <i>N</i>‑Heterocyclic Cellulose Ionomers

Cationic derivatives of cellulose and other polysaccharides are attractive targets for biomedical applications due to their propensity for electrostatically binding with anionic biomolecules, such as nucleic acids and certain proteins. To date, however, relatively few practical synthetic methods have been described for their preparation. Herein, we report a useful and efficient strategy for cationic cellulose ester salt preparation by the reaction of 6-bromo-6-deoxycellulose acetate with pyridine or 1-methylimidazole. Dimethyl sulfoxide solvent favored this displacement reaction to produce cationic cellulose acetate derivatives, resulting in high degrees of substitution (DS) exclusively at the C-6 position. These cationic cellulose derivatives bearing substantial, permanent positive charge exhibit surprising thermal stability, dissolve readily in water, and bind strongly with a hydrophilic and anionic surface, supporting their potential for a variety of applications such as permeation enhancement, mucoadhesion, and gene or drug delivery. Expanding upon this chemistry, we reacted a 6-imidazolyl-6-deoxycellulose derivative with 1,3-propane sultone to demonstrate the potential for further elaboration to regioselectively substituted zwitterionic cellulose derivatives

Specific Detection of Integrin α_vβ₃ by Light-Up Bioprobe with Aggregation-Induced Emission Characteristics

Specific bioprobes with fluorescence turn-on response are highly desirable for high contrast biosensing and imaging. In this work, we developed a new generation bioprobe by integrating tetraphenylsilole, a fluorogenic unit with aggregation-induced emission (AIE) characteristic, with cyclic arginine–glycine–aspartic acid tripeptide (cRGD), a targeting ligand to integrin α_vβ₃ receptor. Emission of the AIE probe is switched <i>on</i> upon its specific binding to integrin α_vβ₃, which allows quantitative detection of integrin α_vβ₃ in solution and real-time imaging of the binding process between cRGD and integrin α_vβ₃ on cell membrane. The probe can be used for tracking integrin α_vβ₃ and for identifying integrin α_vβ₃-positive cancer cells

Specific Detection of Integrin α_vβ₃ by Light-Up Bioprobe with Aggregation-Induced Emission Characteristics

Specific bioprobes with fluorescence turn-on response are highly desirable for high contrast biosensing and imaging. In this work, we developed a new generation bioprobe by integrating tetraphenylsilole, a fluorogenic unit with aggregation-induced emission (AIE) characteristic, with cyclic arginine–glycine–aspartic acid tripeptide (cRGD), a targeting ligand to integrin α_vβ₃ receptor. Emission of the AIE probe is switched <i>on</i> upon its specific binding to integrin α_vβ₃, which allows quantitative detection of integrin α_vβ₃ in solution and real-time imaging of the binding process between cRGD and integrin α_vβ₃ on cell membrane. The probe can be used for tracking integrin α_vβ₃ and for identifying integrin α_vβ₃-positive cancer cells

Real-Time Monitoring of Cell Apoptosis and Drug Screening Using Fluorescent Light-Up Probe with Aggregation-Induced Emission Characteristics

Real-time monitoring of cell apoptosis could provide valuable insights into early detection of therapy efficiency and evaluation of disease progression. In this work, we designed and synthesized a new live-cell-permeable, fluorescent light-up probe for real-time cell apoptosis imaging. The probe is comprised of a hydrophilic caspase-specific Asp-Glu-Val-Asp (DEVD) peptide and a hydrophobic tetraphenylethene (TPE) unit, a typical fluorogen with aggregation-induced emission characteristics. In aqueous solution, the probe is almost nonfluorescent but displays significant fluorescence enhancement in response to caspase-3/-7, which are activated in the apoptotic process and able to cleave the DEVD moieties. This fluorescence “turn-on” response is ascribed to aggregation of cleaved hydrophobic TPE residues, which restricts the intramolecular rotations of TPE phenyl rings and populates the radiative decay channels. The light-up nature of the probe allows real-time monitoring of caspase-3/-7 activities both in solutions and in living cells with a high signal-to-noise ratio. The probe provides a new opportunity to screen enzyme inhibitors and evaluate the apoptosis-associated drug efficacy

Real-Time Monitoring of Cell Apoptosis and Drug Screening Using Fluorescent Light-Up Probe with Aggregation-Induced Emission Characteristics

Real-time monitoring of cell apoptosis could provide valuable insights into early detection of therapy efficiency and evaluation of disease progression. In this work, we designed and synthesized a new live-cell-permeable, fluorescent light-up probe for real-time cell apoptosis imaging. The probe is comprised of a hydrophilic caspase-specific Asp-Glu-Val-Asp (DEVD) peptide and a hydrophobic tetraphenylethene (TPE) unit, a typical fluorogen with aggregation-induced emission characteristics. In aqueous solution, the probe is almost nonfluorescent but displays significant fluorescence enhancement in response to caspase-3/-7, which are activated in the apoptotic process and able to cleave the DEVD moieties. This fluorescence “turn-on” response is ascribed to aggregation of cleaved hydrophobic TPE residues, which restricts the intramolecular rotations of TPE phenyl rings and populates the radiative decay channels. The light-up nature of the probe allows real-time monitoring of caspase-3/-7 activities both in solutions and in living cells with a high signal-to-noise ratio. The probe provides a new opportunity to screen enzyme inhibitors and evaluate the apoptosis-associated drug efficacy

Construction of Functional Macromolecules with Well-Defined Structures by Indium-Catalyzed Three-Component Polycoupling of Alkynes, Aldehydes, and Amines

We present here a new programmable polymerization route for the synthesis of new conjugated polymers via one-pot reaction route. The three-component polycoupling reactions of terephthalaldehyde and dibenzylamine with 4,4′-diethynyl-1,1′-biphenyl, bis­(4-ethynylphenyl)­dimethylsilane, 1,2-bis­(4-ethynylphenyl)-1,2-diphenylethene, <i>N</i>,<i>N</i>-bis­(4-ethynylphenyl)­aniline, or 2,5-bis­(4-ethynylphenyl)-1,1-dimethyl-3,4-diphenylsilole are catalyzed by indium­(III) chloride in <i>o</i>-xylene at 140 °C, affording soluble polymers with well-defined structures and high molecular weights (<i>M</i>_w up to 51 200) in high yields (up to 96.9%). Model reaction was carried out to elucidate the chemical structures of the polymers. The resulting polymers are processable and enjoy high thermal stability. The polymers carrying tetraphenylethene and silole units are weakly emissive in solutions but become strong emitters when aggregated in poor solvents or fabricated as thin films in the solid state, displaying a phenomenon of aggregation-enhanced emission characteristic. Thin films of the polymers show high refractive indices (<i>n</i> = 1.7529–1.6041) in a wide wavelength region of 400–1600 nm with low optical dispersions (<i>D</i>′ down to 0.005). The polymers are readily metallified by complexation of their triple bonds with cobalt octacarbonyls. Pyrolysis of the resulting organometallic polymers at high temperature under inert atmosphere generates nanostructured ceramics with high magnetic susceptibility (<i>M</i>_s up to 80.7 emu/g) and near-zero coercivity (<i>H</i>_c down to 0.19 kOe)

Direct Visualization of Surface-Assisted Two-Dimensional Diyne Polycyclotrimerization

Cyclotrimerization of alkynes to aromatics represents a promising approach to two-dimensional conjugated networks due to its single-reactant and atom-economy attributes, in comparison with other multicomponent coupling reactions. However, the reaction mechanism of alkyne cyclotrimerization has not yet been well understood due to characterization challenges. In this work, we take a surface reaction approach to study fundamental polymerization mechanism by using a diyne monomer named 4,4′-diethynyl-1,1′-biphenyl as a test bed. We have succeeded in directly characterizing reactants, intermediates, and their reaction products with the aid of scanning tunneling microscope, which allows us to gain mechanistic insights into the reaction pathways. By combining with density functional theory calculation, our result has revealed for the first time that the polycyclotrimerization is a two-step [2+2+2] cyclization reaction. This work provides an in-depth understanding of polycyclotrimerization process at the atomic level, offering a new avenue to design and construct of single-atom-thick conjugated networks

Data_Sheet_1_Metagenomic evidence of suppressed methanogenic pathways along soil profile after wetland conversion to cropland.docx

Wetland conversion to cropland substantially suppresses methane (CH4) emissions due to the strong suppression of methanogenesis, which consists of various pathways. In this study, we evaluated the cultivation impacts on four predominant CH4 production pathways, including acetate, carbon dioxide (CO2), methylamines, and methanol, in a wetland and cultivated cropland in northeastern China. The results showed significant suppression of CH4 production potential and the abundance of genes for all four methanogenic pathways in cropland. The consistency between CH4 production and methanogenesis genes indicates the robustness of genomic genes in analyzing methanogenesis. The suppression effects varied across seasons and along soil profiles, most evident in spring and 0 to 30 cm layers. The acetate pathway accounted for 55% in wetland vs. 70% in the cropland of all functional genes for CH4 production; while the other three pathways were stronger in response to cultivation, which presented as stronger suppressions in both abundance of functional genes (declines are 52% of CO2 pathway, 68% of methanol pathway, and 62% of methylamines pathway, vs. 19% of acetate pathway) and their percentages in four pathways (from 20 to 15% for CO2, 15 to 9% for methylamines, and 10 to 6% for methanol pathway vs. 55 to 70% for acetate pathway). The structural equation models showed that substrate availability was most correlated with CH4 production potential in the wetland, while the positive correlations of acetate, CO2, and methylamine pathways with CH4 production potential were significant in the cropland. The quantitative responses of four CH4 production pathways to land conversion reported in this study provide benchmark information for validating the CH4 model in simulating CH4 cycling under land use and land cover change.</p

Full-Range Intracellular pH Sensing by an Aggregation-Induced Emission-Active Two-Channel Ratiometric Fluorogen

Intracellular pH (pH_i) is an important parameter associated with cellular behaviors and pathological conditions. Sensing pH_i and monitoring its changes in live cells are essential but challenging due to the lack of effective probes. We herein report a pH-sensitive fluorogen for pH_i sensing and tracking. The dye is a tetraphenyl­ethene–cyanine adduct (TPE-Cy). It is biocompatible and cell-permeable. Upon diffusing into cells, it responds sensitively to pH_i in the entire physiological range, visualizing the acidic and basic compartments with intense red and blue emissions, respectively. The ratiometric signal of the red and blue channels can thus serve as an indicator for local proton concentration. The utility of TPE-Cy in pH_i imaging and monitoring is demonstrated with the use of confocal microscopy, ratiometric analysis, and flow cytometry

<i>N</i>⁶‑Allyladenosine: A New Small Molecule for RNA Labeling Identified by Mutation Assay

RNA labeling is crucial for the study of RNA structure and metabolism. Herein we report <i>N</i>⁶-allyladenosine (a⁶A) as a new small molecule for RNA labeling through both metabolic and enzyme-assisted manners. a⁶A behaves like A and can be metabolically incorporated into newly synthesized RNAs inside mammalian cells. We also show that human RNA <i>N</i>⁶-methyladenosine (m⁶A) methyltransferases METTL3/METTL14 can work with a synthetic cofactor, namely allyl-SAM (<i>S</i>-adenosyl methionine with methyl replaced by allyl) in order to site-specifically install an allyl group to the <i>N</i>⁶-position of A within specific sequence to generate a⁶A-labeled RNAs. The iodination of <i>N</i>⁶-allyl group of a⁶A under mild buffer conditions spontaneously induces the formation of <i>N</i>¹,<i>N</i>⁶-cyclized adenosine and creates mutations at its opposite site during complementary DNA synthesis of reverse transcription. The existing m⁶A in RNA is inert to methyltransferase-assisted allyl labeling, which offers a chance to differentiate m⁶A from A at individual RNA sites. Our work demonstrates a new method for RNA labeling, which could find applications in developing sequencing methods for nascent RNAs and RNA modifications