C2 Site Research Articles

PH-responsive UV crosslinkable chitosan hydrogel via “thiol-ene” click chemistry for active modulating opposite drug release behaviors

Numbers of UV crosslinkable chitosan hydrogels through chemical modification had drawn increasing attention, however most of these chitosan hydrogels lost the pH-responsive performance because plenty of amino groups (‒NH2) in chitosan were consumed by reacting with other functional groups. To construct a pH-responsive UV-crosslinkable chitosan hydrogel for active modulating drug release with desired behavior, C6-OH selectively modified chitosan via protection/deprotection strategy to amino groups was synthesized, the allyl groups on C6 site and amino groups on C2 site endowed chitosan with UV crosslinking capability and pH responsiveness, respectively. Rapid UV crosslinking gelation (30 s) with low-dose UV irradiation (4 mW/cm2) via “thiol-ene” click chemistry were demonstrated for the patterned microgel and in-situ formed hydrogel in vivo. The swelling and shrinkage of hydrogel could active modulate the opposite release behaviors of doxorubicin (DOX) and bovine serum albumin (BSA) in different pH medium. The smart UV-crosslinkable chitosan hydrogel via click chemistry might provide a new drug carrier for active modulating opposite drug release behaviors.

A theoretical insight into the microstructure and electronic properties of Ho3+-doped potassium gadolinium tungstate

We have systematically studied the structural evolutions of trivalent holmium ion (Ho3+) doped potassium gadolinium tungstate (KGd(WO4)2) crystals by means of the CALYPSO structure search method coupled with first-principles calculations. The unbiased global minimum structure search is successful in reproducing the standardized monoclinic structure with C2/c phase for KGd(WO4)2. For the first time, the lowest energy structure of Ho3+-doped KGd(WO4)2 system is identified, which possesses a significantly different monoclinic configuration with P2 space group. It is found that the impurity Ho3+ ions can substitute the sites of Gd3+ ions, forming the [HoO8]13− local units with C2 site symmetry. Our electronic calculations show that the energy band gap of Ho3+-doped KGd(WO4)2 is equal to 3.03 eV. The impurity of Ho3+ ion remains the insulating character of Ho:KGW system. These results could provide important information for understanding the structural evolution and electronic properties of other rare-earth-doped materials.

Copper(II)-Catalyzed Direct Amination of 1-Naphthylamines at the C8 Site.

A new and simple protocol for C8-H amination of 1-naphthylamine derivatives was developed using copper salt and di-tert-butyl peroxide (DTBP) as the catalyst and oxidant, respectively. This reaction proceeded smoothly under the additive and solvent-free conditions. In addition, this amination showed excellent regioselectivity and could tolerate various functional groups.

Deprotonation of Isoxazole: A Photoelectron Imaging Study.

We report a photoelectron imaging study of gas-phase deprotonation of isoxazole in which spectroscopic data are compared to the results of electronic structure calculations for the anion products corresponding to each of three possible deprotonation sites. The observed photoelectron spectra are assigned to a mixture of the anion isomers. Deprotonation at the most acidic (C5) and the least acidic (C4) positions yields the respective C5- and C4-isoxazolide anions, while the reaction at the intermediate-acidity C3 site leads to a cleavage of the O-N bond and an opening of the ring in the anion. Following photodetachment, the ground states of neutral C5- and C4-isoxazolyl are assigned to be σ radicals (X2A'), while the ground-state neutral derived from the ring-open C3-anion is a π radical (X2A″). The relative intensities of the spectral bands exhibit sensitivity to the ion source conditions, giving evidence of competing and varying contributions of the dominant C5 and C3, as well as possible C4, deprotonation pathways.

Naphthoquinone-Based Meroterpenoids from Marine-Derived Streptomyces sp. B9173.

Naphthoquinone-based meroterpenoids are hybrid polyketide-terpenoid natural products with chemical diversity and a broad range of biological activities. Here, we report the isolation of a group of naphthoquinone-containing compounds from Streptomyces sp. B9173, and their structures were elucidated by using a combination of spectroscopic techniques, including 1D, 2D NMR, and high-resolution mass (HRMS) analysis. Seven flaviogeranin congeners or intermediates, three of which were new, have been derived from common naphthoquinone backbone and subsequent oxidation, methylation, prenylation, and amino group incorporation. Both flaviogeranin B1 (1) and B (2) contain an amino group which was incorporated into the C8 of 1,3,6,8-terhydroxynaphthalene (THN). Flaviogeranin D (3) contains an intact C-geranylgeranyl residue attached to the C2 of THN, while the O-geranylgeranyl group of 2 links with the hydroxyl on the C2 site of THN. Four compounds were selected and tested for antibacterial activity and cytotoxicity, with 3 and flaviogeranin C2 (5) displaying potent activity against selected bacteria and cancer cell lines. In light of the structure features of isolated compounds and the biosynthetic genes, a biosynthetic pathway of naphthoquinone-based flaviogeranins has been proposed. These isolated compounds not only extend the structural diversity but also represent new insights into the biosynthesis of naphthoquinone-based meroterpenoids.

The effect of hydrogen addition on the N2 formation from armchair carbonaceous surface

This work reveals the role of hydrogen in the N2 desorption using DFT calculations at the B3LYP/6-31G(d) level of theory as implemented in Gaussian 16 programme. The addition of one hydrogen on the active site, exothermicity by ≈380 kJ/mol, favors the hydrogenation of nearby active sites (ΔE ≈ 480 kJ/mol) but inhibits the hydrogenation of itself (ΔE ≈ 220 kJ/mol). N1 exposure with the highest barrier of 232.0 kJ/mol is the rate-determining step. By paying attention to this step, the potential roles are clarified: (1) two hydrogen attached to the same site creating a highly hydrogenated environment retards the overall reaction; (2) the attachment of one hydrogen to C2 site inhibits the overall reaction; and (3) the addition of one hydrogen on C1 and C3 sites favors the overall reaction. The proposed mechanism will help to explain various reported findings on the gasification of the carbonaceous surface.

Expanding the chemical space: Discovery of new anticancer 3‐arylbenzofuran derivatives

AbstractA new chemical space was generated via C2‐functionalization of 3‐arylbenzofurans. Mannich reaction of 3‐arylbenzofurans with secondary amines and formaldehyde allowed for installation of aminomethyl unit at C2 position of benzofurans. A formyl group at C2 site introduced as a result of Vilsmeier‐Haack formylation of 3‐arylbenzofurans was employed as a reacting partner for three‐component Kabachnik‐Fields reaction with various amines and triethyl phosphite to give a wide variety of aminomethylphosphonates. Furthermore, several benzo[d]oxazoles and pyrrolo[1,2‐a]quinoxalines were prepared by using the formyl group. Biological screening of the synthesized compounds revealed that the benzofuran bearing a pyrrolo[1,2‐a]quinoxaline moiety (5b) most potently inhibited the viability of human blood cancer cells, but not solid tumor cells. Caspase activity assay, analysis of Annexin V‐positive cells, and Western blot analysis indicated that 5b‐induced death of human lymphoma U937 cells could result from its potential to induce the caspase‐dependent apoptotic death of blood cancer cells with inhibition of ERK activation.

Heatwave effects on gross primary production of northern mid-latitude ecosystems

Heatwave events are expected to become more frequent and intense in the mid-latitudes of the Northern Hemisphere in the future. However, our knowledge of the impacts of these extreme temperature events on ecosystem functions is still limited. We investigated the responses of ecosystem gross primary productivity (GPP) to heatwaves for nine sites encompassing a wide variety of ecosystem types with long-term (i.e., >7 years) flux and meteorological observations at northern mid-latitudes. Our results showed that GPP was depressed during heatwaves for most ecosystems except the C4 sites. The evaporative stress index (ESI) was the primary variable responsible for the changes in GPP during heatwaves across the nine ecosystems. Furthermore, forest ecosystems were more resistant and resilient to heatwaves than other ecosystems. Additionally, the asymmetric diurnal pattern of GPP in forest ecosystems was attributed to xylem refilling and high water storage capacity, indicating that GPP was more sensitive to heatwaves in the afternoon. Interestingly, C4 herbaceous ecosystems could promote canopy stomatal conductance (Gc) for avoiding leaf burn and tissue damage during heatwaves. The herbaceous ecosystems had weaker stomatal control on water loss during heatwaves and were more vulnerable to heatwaves owing to the water stress afterwards. This research highlighted the importance of ecosystem type and plant functional type in determining the responses of photosynthesis to heatwaves. Understanding the post-effect after heatwaves is also vital for comprehensively assessing the impacts of heatwaves on ecosystem functions.

6‐(Hetero)arylindolizino[1,2‐c]quinolines as highly fluorescent chemical space: Synthesis and photophysical properties

AbstractA highly fluorescent indolizino[1,2‐c]quinoline with a substituent at the C6 position was designed and synthesized as a new indolizine‐quinoline hybrid structure via a tetracyclic lactam. Various (hetero)aryl groups were introduced at the C6 site of this basic skeleton to display intriguing photophysical properties.

Kramers doublets, phonons, crystal-field excitations, and their coupling in Nd2ZnIrO6

We report comprehensive Raman-scattering measurements on a single crystal of double-perovskite Nd2ZnIrO6 in temperature range of 4-330 K, and spanning a broad spectral range from 20 cm-1 to 5500 cm-1. The paper focuses on lattice vibrations and electronic transitions involving Kramers doublets of the rare-earth Nd3+ ion with local C1 site symmetry. Temperature evolution of these quasi-particle excitations have allowed us to ascertain the intricate coupling between lattice and electronic degrees of freedom in Nd2ZnIrO6. Strong coupling between phonons and crystal-field excitation is observed via renormalization of the self-energy parameter of the phonons i.e. peak frequency and line-width. The phonon frequency shows abrupt hardening and line-width narrowing below ~ 100 K for the majority of the observed first-order phonons. We observed splitting of the lowest Kramers doublets of ground state (4I9/2) multiplets i.e. lifting of the Kramers degeneracy, prominently at low-temperature (below ~ 100 K), attributed to the Nd-Nd/Ir exchange interactions and the intricate coupling with the lattice degrees of freedom. The observed splitting is of the order of ~ 2-3 meV and is consistent with the estimated value. We also observed a large number of high-energy modes, 46 in total, attributed to the intra-configurational transitions between 4f3 levels of Nd3+ coupled to the phonons reflected in their anomalous temperature evolution.

Fibrinogen interaction with complement C3: a potential therapeutic target to reduce thrombosis risk.

Complement C3 binds fibrinogen and compromises fibrin clot lysis, thereby enhancing the risk of thrombosis. We investigated the role of the fibrinogen-C3 interaction as a novel therapeutic target to reduce thrombosis risk by analyzing: (i) consistency in the fibrinolytic properties of C3; (ii) binding sites between fibrinogen and C3; and (iii) modulation of fibrin clot lysis by manipulating fibrinogen-C3 interactions. Purified fibrinogen and C3 from the same individuals (n=24) were used to assess inter-individual variability in the anti-fibrinolytic effects of C3. Microarray screening and molecular modeling evaluated C3 and fibrinogen interaction sites. Novel synthetic conformational proteins, termed affimers, were used to modulate the C3-fibrinogen interaction and fibrinolysis. C3 purified from patients with type 1 diabetes showed enhanced prolongation of fibrinolysis compared with healthy control protein (195±105 and 522±166 s, respectively; P=0.04), with consistent effects but a wider range (5-51% and 5-18% lysis prolongation, respectively). Peptide microarray screening identified two potential C3-fibrinogen interaction sites within the fibrinogen β chain (residues 424-433 and 435-445). One fibrinogen-binding affimer that was isolated displayed sequence identity with C3 in an exposed area of the protein. This affimer abolished C3- induced prolongation of fibrinolysis (728±25.1 s to 632±23.7 s; P=0.005) and showed binding to fibrinogen in the same region that is involved in C3-fibrinogen interactions. Moreover, it shortened plasma clot lysis of patients with diabetes, cardiovascular disease or controls by 7-11%. C3 binds fibrinogen -chain and disruption of the fibrinogen-C3 interaction using affimer proteins enhances fibrinolysis, which represents a potential novel tool to reduce thrombosis in high-risk individuals.

Alkaline hydrolysis pathway of 2,4-dinitroanisole verified by 18O tracer experiment

The environmental fate of insensitive munitions compounds, such as 2,4-dinitroanisole (DNAN), has drawn increasing attention because of their growing use in military activities. One of the main attenuation mechanisms of DNAN degradation in aqueous environments is alkaline hydrolysis. We investigated the pathway for alkaline hydrolysis of DNAN at pH 12 by a combined approach of experiment and theory. An experiment using 18O-labeled water was performed to verify the reaction pathway. Calculated free energies for two putative reaction pathways by density-functional theory optimized at the SMD(Pauling)/M06-2X/6-311++G(2d,2p) level including explicit solvation of DNAN by 10 H2O molecules and one OH− ion gave a prediction in agreement with the experimental result. The verified reaction pathway for alkaline hydrolysis of DNAN is a SN2Ar nucleophilic aromatic substitution with a methoxy leaving group (OCH3) at the C1 site.

Microwave assisted preparation and characterization of a chitosan based flocculant for the application and evaluation of sludge flocculation and dewatering

In this study, a new type of graft modified flocculant (CS-g-PAD) was copolymerized of AM, DAC and chitosan (CS) by microwave assisted initiation and used for sludge conditioning and dewatering. The effect of reaction conditions on microwave assisted copolymerization was investigated and their optimal values were obtained by orthogonal experiments. The structure and chemical properties of CS-g-PAD were characterized and the results indicated that microwave assisted polymerization can cause the generated side polymer chain of PAD to react with the –NH2 active group in CS. Thus, the graft copolymerization occurred at amino group connected with C2 site. Compared with CCPAM, PAD and CS, the synthesized CS-g-PAD exhibits superior sludge dewatering performance (FCMC: 72.1%, SRF: 4.5 × 1012 m/kg, d50: 679.556 μm, Df: 1.72, floc sedimentation rate: 5.72 cm/min) in a wide pH range (pH = 3.5–9.5). Because CS-g-PAD contains a large amount of cationic DAC and positively charged CS as well as many functional groups on CS, it increases the charge neutralization, electrical patching and adsorption capability. Additionally, the grafting PAD on CS has a good extension in solution to increase its adsorption bridging effect. The new grafted CS-g-PAD is promising and has great practical application value in sludge dewatering and condition.

Binding and Metabolism of Brominated Flame Retardant β-1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane in Human Microsomal P450 Enzymes: Insights from Computational Studies.

The emerging brominated flame retardant, 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH), has recently attracted strong interest due to its extensive detection in the environment and potential toxicological effects on humans. Previous in vitro experiments have shown that the technical mixture of TBECH and the pure β-isomer (β-TBECH) can be metabolized by cytochrome P450 enzymes (CYPs) into multiple metabolites, but the specific CYP isoforms involved in TBECH metabolism and the relevant metabolic regioselectivity remain unknown. Here, we, for the first time, investigated the binding patterns and affinities of β-TBECH in human CYPs 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4, through molecular dynamics (MD) simulations. The binding affinities of β-TBECH in CYPs, which are estimated by the calculated binding free energies, follow the order of 2A6 > 2C9 > 2B6 > 2E1 > 3A4 ≈ 2C19 ≈ 1A2 > 2D6. Although all CYPs are important β-TBECH receptors, only 2A6, 2C19, 2E1, and 3A4 are responsible for metabolizing β-TBECH. Specially, 2A6 and 2E1 may selectively hydroxylate the C1 and C7 sites of β-TBECH, while 2C19 and 3A4 show metabolic preference for C7- and C8-hydroxylations, respectively. The three hydroxylation routes proposed by the further density functional theory (DFT) calculations generate C1-, C7-, and C8-hydroxylated metabolites, while the latter two may further undergo debromination to yield the respective ketone and aldehyde as additional metabolites. The results provide meaningful insight into the binding and metabolism of β-TBECH by human CYPs, which is helpful for understanding the metabolic fate and toxicity mechanism of this chemical.

Iridium/Acid Cocatalyzed Direct Access to Fused Indoles via Transfer Hydrogenative Annulation of Quinolines and 1,2-Diketones.

Herein, we present an unprecedented iridium/acid cocatalyzed construction of fused indoles via transfer hydrogenative annulation of nonactivated quinolines and 1,2-diketones. The products are assembled via initial reduction followed by selective coupling of 1,2-diketones with the N and C8 sites of the quinolyl skeleton. The developed synthetic method features operational simplicity, readily available feedstocks, applicability for streamline synthesis of functional molecules, high step and atom efficiency, and generation of water as the byproduct.

Preparation of a graft modified flocculant based on chitosan by ultrasonic initiation and its synergistic effect with kaolin for the improvement of acid blue 83 (AB 83) removal

The chitosan (CTS) characterized with many functional amino and hydroxyl groups has been the research focus on flocculants preparation and synthesis because of the facile grafting and modification to enhance and enlarge its original functions. In this study, a new type of graft modified flocculant CTS-g-PAA and its combination with kaolin have been developed for the treatment of acid blue 83 (AB 83). The CTS-g-PAA prepared by ultrasonic initiation of acrylamide (AM), 3-Acrylamide propyltrimethylammonium chloride (AATPAC) and CTS. The factors affecting CTS-g-PAA molecular weight and CTS graft ratio were examined to have a better understanding and comprehending of the ultrasonic initiated polymerization. The structure and morphological characteristics of CTS-g-PAA were investigated and analyzed by infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (1H NMR), differential thermal/thermogravimetric (TG/DSC), scanning electron microscopy (SEM) and X-Ray Diffraction (XRD), respectively. The results indicated that the CTS cyclic structure was broken by ultrasonic initiation and the grafting occurred at amino group with C2 site of CTS. Meanwhile, the CTS-g-PAA coupled with kaolin exhibited superior flocculation performance better than the single removal effect, and the optimum removal rate for AB 83 could achieve 91.9%. The flocculation mechanism was discussed and summarized based on the conduction of zeta potential, FTIR of floc particles and the adsorption ability of the formed kaolin flocs. During the AB 83 flocculation, the CTS-g-PAA adsorption and flocculation contributed much to the AB 83 removal. The added kaolin particles played a crucial role in the enhancement of AB 83 adsorption and flocculation. The kaolin particles and the formed kaolin floc showed an adsorption effect for AB 83, and the kaolin particles also worked as the bridging between the CTS-g-PAA filled with AB 83 to strengthen the flocculation performance. As a result, the flocculation performance for AB 83 removal was greatly improved.

Study on Structure Activity Relationship of Natural Flavonoids against Thrombin by Molecular Docking Virtual Screening Combined with Activity Evaluation In Vitro.

Thrombin, a key enzyme of the serine protease superfamily, plays an integral role in the blood coagulation cascade and thrombotic diseases. In view of this, it is worthwhile to establish a method to screen thrombin inhibitors (such as natural flavonoid-type inhibitors) as well as investigate their structure activity relationships. Virtual screening using molecular docking technique was used to screen 103 flavonoids. Out of this number, 42 target compounds were selected, and their inhibitory effects on thrombin assayed by chromogenic substrate method. The results indicated that the carbon-carbon double bond group at the C2, C3 sites and the carbonyl group at the C4 sites of flavones were essential for thrombin inhibition, whereas the methoxy and O-glycosyl groups reduced thrombin inhibition. Noteworthy, introduction of OH groups at different positions on flavonoids either decreased or increased anti-thrombin potential. Myricetin exhibited the highest inhibitory potential against thrombin with an IC50 value of 56 μM. Purposively, the established molecular docking virtual screening method is not limited to exploring flavonoid structure activity relationships to anti-thrombin activity but also usefully discovering other natural active constituents.

Comparative study of the luminescence properties of Ca2+xLa8-x(SiO4)6-x(PO4)xO2:Eu3+ (x = 0, 2) red phosphors

A series of Ca2La8(SiO4)6O2:Eu3+ (CLSO:Eu3+) and Ca4La6(SiO4)4(PO4)2O2:Eu3+ (CLSPO:Eu3+) oxyapatite phosphors have been prepared via traditional solid-state reaction process. The phase composition of phosphors was analyzed by X-ray powder diffraction (XRD), and the morphology was evaluated by scanning electron microscopy (SEM). The characteristic photoluminescence properties were evaluated by analysis of photoluminescence excitation (PLE) and emission (PL) spectra. In addition, the luminescence decay times and emission-temperature relationship were also characterized. The results indicated that the phosphors could be efficiently excited by the near ultraviolet (NUV) light and blue light, and they exhibited red light emission. Meanwhile, the average particle sizes of CLSO and CLSPO hosts are about 2∼8 μm. Moreover, the low symmetry C3 or Cs sites appropriate for Eu3+ in the CLSO and CLSPO hosts are benefit to 5D0 → 7F2 electric dipole transition, which leads to greater R/O values of CLSO:yEu3+ than those of CLSPO:yEu3+. All the obtained results suggested that the prepared phosphors have a potential for application in white light emitting diodes (WLEDs).

An Exploratory Study Using Electroencephalography (EEG) to Measure the Smartphone User Experience in the Short Term

ABSTRACT UX (User experience) can influence important user behaviors, including user preference, purchasing decisions, and customer loyalty. The ability to assess UX during the product trial has practical significance for design and improvement of products. In this article, two smartphones with different UX were selected through a focus group. In the EEG (electroencephalography) experiment, we explored the brain signal of users when using two smartphones to complete three tasks. The brain signal of each participant was recorded through Curry Neuroimaging Suite software (Version 7.0, Compumedics Limited, Abbotsford, Australia) when they were using the smartphones. Then results from behavioral, subjective and neural responses were analyzed. The behavioral results showed that participants completed the three tasks faster by using a smartphone with a higher score of UX. The subjective results showed a significant difference between the two smartphones. The patterns of cortical activity were obtained in the five principal frequency bands, Delta (1–4 Hz), Theta (4–8 Hz), Alpha (8–13 Hz), Beta (13–30 Hz) and Gamma (30–45 Hz). The results indicated that a smartphone with higher scores of UX could evoke stronger relative power of Alpha (fronto-central, parietal and partieto-occipital regions), Delta (frontal region) and Gamma rhythms (C3 site), but weaker relative power of Beta (left central region) and Theta rhythms (frontal and parieto-occipital regions). Also, the correlation analysis showed that there was no significant relationship between EEG and behavioral results. User’s subjective experience had a significant positive correlation with the relative power of Gamma band, but a negative correlation with Beta and Theta bands (approximately significant with p = .078 and p = .071). There were also significant correlations between EEG results and sub-items of UX. Our findings suggest that the difference in EEG may be taken as an evaluating indicator of user perception when using products without interruption.

Flipped regiospecificity in L434F mutant of 8-lipoxygenase.

Lipoxygenases are non-heme iron containing enzymes that catalyze oxygenation of poly-unsaturated fatty acids in different animal and plant species with extremely high regio- and stereospecificity. Nature employs 8-lipoxygenase to produce 8R-hydroperoxide from the oxygenation of arachidonic acid. A single-point L434F mutation of 8-lipoxygenase alters the regio- and stereospecificity of the final products, with a product ratio of 66 : 34 for 8R- and 12S-hydroperoxide, respectively. A molecular level explanation of this flipped regiospecificity is presented in this work on the basis of molecular dynamics simulations and transition network analysis of oxygen migration in the protein matrix. Phe434 is shown to exist in two conformations, the so-called open and closed conformations. In the closed conformation, the phenyl group of Phe434 shields the C8 site of the substrate, thereby preventing access of the oxygen molecule to this site, which leads to a quenching of the 8R-product. On the other hand, both closed and open conformations of Phe434 allow the oxygen molecule to approach the pro-S face of the C12 site of the substrate, which enhances the propensity of the 12S-hydroperoxide.