Design and Construction of Carbon-Coated Fe3 O4 /Cr2 O3 Heterostructures Nanoparticles as High-Performance Anodes for Lithium Storage.

Transition metal oxides, highly motivated anodes for lithium-ion batteries due to high theoretical capacity, typically afflict by inferior conductivity and significant volume variation. Architecting heterogeneous structures with distinctive interfacial features can effectively regulate the electronic structure to favor electrochemical properties. Herein, an engineered carbon-coated nanosized Fe3 O4 /Cr2 O3 heterostructure with multiple interfaces is synthesized by a facile sol-gel method and subsequent heat treatment. Such ingenious components and structural design deliver rapid Li+ migration and facilitate charge transfer at the heterogeneous interface. Simultaneously, the strong coupling synergistic interactions between Fe3 O4 , Cr2 O3 , and carbon layers establish multiple interface structures and built-in electric fields, which accelerate ion/electron transport and effectively eliminate volume expansion. As a result, the multi-interface heterostructure, as a lithium-ion battery anode, exhibits superior cycling stability maintaining a reversible capacity of 651.2 mAh g-1 for 600 cycles at 2 C. The density functionaltheory calculations not only unravel the electronic structure of the modulation but also illustrate favorable lithium-ion adsorption kinetics. This multi-interface heterostructure strategy offers a pathway for the development of advanced alkali metal-ion batteries.

Longipetalol A: A Highly Modified Triterpenoid from Dichapetalum longipetalum.

Longipetalol A (1) is an unprecedented highly modified triterpenoid with a unique 1,2-seco-3-(2-oxo-phenylethyl)-17α-13,30-cyclodammarane skeleton, featuring an acetal-lactone fragment. It was isolated from Dichapetalum longipetalum along with two additional derivatives, namely, longipetalols B (2) and C (3). Their structures were elucidated using spectroscopic analyses combined with single-crystal X-ray diffraction. Compounds 1, 2, and 3 exhibited inhibitory effects on nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophages.

Intracellular delivery of liposome-encapsulated Finland trityl radicals for EPR oximetry.

Tetrathiatriarylmethyl (TAM, trityl) radicals have found wide applications in electron paramagnetic resonance (EPR) oximetry. However, the biomedical applications of TAM radicals were exclusively limited to an extracellular region owing to their negatively charged nature. The intracellular delivery of TAM radicals still remains a challenge. In the present work, we report a liposome-based method to encapsulate the water-soluble Finland trityl radical CT-03 for its intracellular delivery. Using the thin lipid film hydration method, CT-03-loaded liposomes were prepared from DSPC/cholesterol/DOTAP with a mean size of 167.5 ± 2.4 nm and a zeta potential of 27.8 ± 0.8 mV. EPR results showed that CT-03 was entrapped into the liposomes and still exhibited good oxygen (O2) sensitivity. Moreover, CT-03 was successfully delivered into HepG2 cells and HUVECs using the CT-03-loaded liposomes. Importantly, the combination of the liposome-encapsulated radical CT-03 and the other TAM radical CT02-H enabled simultaneous measurements of the intracellular and extracellular O2 concentrations and O2 consumption rates in HepG2 cells. Our present study provides a new approach for intracellular delivery of TAM radicals and could significantly expand their biomedical applications.

Synthesis of difluoroalkylated 2-azaspiro[4.5]decane derivatives via copper-catalyzed difluoroalkylation/dearomatization of N-benzylacrylamides.

An efficient method for the synthesis of difluoroalkylated 2-azaspiro[4.5]decanes via copper-catalyzed difluoroalkylation of N-benzylacrylamides with ethyl bromodifluoroacetate has been established. The reaction experienced a tandem radical addition and dearomatizing cyclization process. In addition, the resultant products can be smoothly converted into a difluoroalkylated quinolinone and saturated spirocyclohexanone scaffold.

Photoactive NO hybrids with pseudo-zero-order release kinetics for antimicrobial applications.

Bacterial infection is a major threat to the health and life of humans due to the development of drug resistance, which is related to biofilm formation. Nitric oxide (NO) has emerged as an important factor in regulating biofilm formation. In order to harness the potential benefits of NO and develop effective antibacterial agents, we designed and synthesized a new class of NO hybrids in which the active scaffold benzothienoazepine was tagged with a nitroso group and further conjugated with quaternary ammoniums or phosphoniums. The temporal release of NO from these hybrids can be achieved by photoactivation. Interestingly, the NO release follows a pseudo-zero-order kinetics, which is easily determined by measuring the fluorescent benzothienoazepine or NO. Compared to the positive control ciprofloxacin, the NO hybrid with triphenyl phosphonium (TPP) exhibited more effective activity against S. aureus biofilm in darkness. Irradiation of the NO hybrid led to higher inhibition against S. aureus biofilm compared to the parental NO hybrid in darkness or the corresponding NO-released product, indicating the combined effect of NO and the NO-released product. Therefore, this new class of NO hybrids includes very promising antimicrobial agents and this work provides a new way for the design of highly effective antimicrobial agents.

Discriminative Detection of Biothiols by Electron Paramagnetic Resonance Spectroscopy using a Methanethiosulfonate Trityl Probe.

Biothiols, such as glutathione (GSH), homocysteine (Hcy), and cysteine (Cys), coexist in biological systems with diverse biological roles. Thus, analytical techniques that can detect, quantify, and distinguish between multiple biothiols are desirable but challenging. Herein, we demonstrate the simultaneous detection and quantitation of multiple biothiols, including up to three different biothiols in a single sample, using electron paramagnetic resonance (EPR) spectroscopy and a trityl-radical-based probe (MTST). We term this technique EPR thiol-trapping. MTST could trap thiols through its methanethiosulfonate group to form the corresponding disulfide conjugate with an EPR spectrum characteristic of the trapped thiol. MTST was used to investigate effects of l-buthionine sulfoximine (BSO) and pyrrolidine dithiocarbamate (PDTC) on the efflux of GSH and Cys from HepG2 cells.

Synthesis and Characterization of Hydrophilic Trityl Radical TFO for Biomedical and Biophysical Applications.

Tetrathiatriarylmethyl (TAM, trityl) radicals have found wide applications as spin probes/labels for EPR spectroscopy and imaging, and as polarizing agents for dynamic nuclear polarization. The high hydrophilicity of TAM radicals is essential for their biomedical applications. However, the synthesis of hydrophilic TAM radicals (e.g., OX063) is extremely challenging and has only been reported in the patent literature, to date. Herein, an efficient synthesis of a highly water-soluble TAM radical bis(8-carboxyl-2,2,6,6-tetramethylbenzo[1,2-d:4,5-d']bis([1,3]dithiol-4-yl)-mono-(8-carboxyl-2,2,6,6-tetrakis(2-hydroxyethyl)benzo[1,2-d:4,5-d']bis([1,3]dithiol-4-yl)methyl (TFO), which contains four additional hydroxylethyl groups, relative to the Finland trityl radical CT-03, is reported. Similar to OX063, TFO exhibits excellent properties, including high water solubility in phosphate buffer, low log P, low pKa , long relaxation times, and negligible binding with bovine serum albumin. On the other hand, TFO has a sharper EPR line and higher O2 sensitivity than those of OX063. Therefore, in combination with its facile synthesis, TFO should find wide applications in magnetic resonance related fields and this synthetic approach would shed new light on the synthesis of other hydrophilic TAM radicals.

Synthesis of Central Chirality-Containing Triarylmethanols and Triarylmethyl Radicals with Extraordinarily Stable Configurations.

Triarylmethanol adopts a propeller-shaped conformation with either right-handed (P) or left-handed (M) configuration. Herein, new triarylmethanols with two chiral centers were obtained via introduction of two cis-hydroxyl groups on the side chains, affording four stereoisomers. These four stereoisomers were easily separated by silica gel column chromatography into two pairs of propeller-shaped enantiomers, as shown by NMR and X-ray crystallographic studies. High-performance liquid chromatography (HPLC) studies showed that the configurations of the hydroxyl-bearing triarylmethanols are much more stable than those of the bulky tert-butyldimethylsilyl-protected precursors, inconsistent with the general strategy in which the steric repulsion is largely responsible for the configurational stability. Similarly, two hydroxyl-bearing tetrathiatriarylmethyl (TAM) radicals also exhibit excellent configurational stability and are thus separable by CS-HPLC into four stereoisomers. Interestingly, both helical chirality from triaryl group (M or P) and central chirality (R and S) on the side chain have little effect on their electron paramagnetic resonance properties. Our present study provides a new strategy to construct configurationally stable triaryl compounds and demonstrates that the side chain on TAM radicals is a new site for their structural modifications.

Design, synthesis, and biological activity evaluation of (-)-6-O-desmethylantofine analogues as potent anti-cancer agents.

Phenanthroindolizidine alkaloids that possess profound anti-proliferative activity and unique mode of action have recently attracted much attention as potential anti-cancer drug candidates. To intensively study the structure-activity-relationship, we designed, synthesized, and evaluated a series of derivatives of 6-desmethylantofine at C-6 position. Most of the derivatives exhibited potent anti-proliferative activity in BEL-7402 and HL60cells. Compound R-12, the cyanomethyl ether of 6-desmethylantofine, exhibited significant anti-cancer activity and inhibited the proliferation of a panel of 30 cancer cell lines including 2 multi-drug-resistant cell lines with an average IC50 value of 18.7 nM, which suggests that R-12 is a promising new anti-cancer agent. Our studies suggest that R-12 displayed potent inhibitory effect on cell growth and colony formation, which is associated with delaying S phase progression by inhibiting DNA synthesis in human hepatoma cancer BEL-7402, SMMC-7721 and ZIP-177 cells.

[Protective effect of Wuzi Yanzong recipe on testicular DNA damage and apoptosis in natural ageing rats].

To study the protective effect of Wuzi Yanzong recipe on testicular DNA damage and apoptosis in natural ageing rats, SPF grade 16-month-old SD male rats were randomly divided into three groups: ageing model group, low and high dose Wuzi Yanzong recipe groups (WZ, 1， 4 g·kg⁻¹). In addition, 2-month-old SD rats were used as adult control group (10 rats in each group). The ageing model group and the adult control group were fed with normal diet for 4 months. Wuzi Yanzong groups received medicated feed for 4 months. After fasting for 12 hours, the rats were sacrificed. Then testis tissues were taken and weighed to calculate the testis index. The change of testicular tissue morphology was observed by HE staining. Expression and localization of DNA damage-associated protein ATR were observed by immunofluorescence. The expressions of DNA damage-related proteins γ-H2AX, Chk1, p-p53 and apoptosis-related proteins Bcl-2 and Bax in testes were detected by Western blot. The apoptosis of testis tissue in rats was detected by using TUNEL. The results showed that as compared with the youth control group, the protein expression levels of γ-H2AX, Chk1, p-p53 and Bax were significantly increased while Bcl-2 protein expression level was significantly decreased intestis tissues of ageing model group. Wuzi Yanzong recipe significantly decreased protein expression levels of γ-H2AX, Chk1, p-p53 and Bax and increased Bcl-2 protein expression level as well as Bcl-2/Bax ratio. Immunofluorescence results showed that Wuzi Yanzong recipe could significantly decrease the ageing-induced ATR, increase in testis tissues. TUNEL results showed that Wuzi Yanzong recipe could significantly attenuate the germ cell apoptosis in testicular tissues. All the above results suggest that Wuzi Yanzong recipe could protect the germ cell in testicular tissues of natural ageing rates from DNA damage and apoptosis, and the mechanism may be associated with regulating p53 signaling pathway.

Synthesis and Characterization of PEGylated Trityl Radicals: Effect of PEGylation on Physicochemical Properties.

Tetrathiatriarylmethyl (TAM, trityl) radicals have attracted considerable attention as spin probes for biological electron paramagnetic resonance (EPR) spectroscopy and imaging owing to their sharp EPR singlet signals and high biostability. However, their in vivo applications were limited by the short blood circulation lifetimes and strong binding with albumins. Our previous results showed that PEGylation is a feasible method to overcome the issues facing in vivo applications of TAM radicals. In the present study, we synthesized a series of new PEGylated TAM radicals (TTP1, TPP2, TNP1, TNP2, d-TNP1, and d-TNP3) containing various lengths and numbers of mPEG chains. Our results found that the pattern of PEGylation exerts an important effect on physicochemical properties of the resulting TAM radicals. Dendritic PEGylated TAM radicals, TNP1 and TNP2, have higher water solubility and lower susceptibility for self-aggregation than their linear analogues TPP1 and TPP2. Furthermore, dendritic PEGylated TAM radicals exhibit extremely high stability toward various biological oxidoreductants as well as in rat whole blood, liver homogenate, and following in vivo intravenous administration in mice. Importantly, the deuterated derivatives, especially d-TNP3, exhibit excellent properties including the sharp and O2-sensitive EPR singlet signal, good biocompatibility, and prolonged kinetics with half-life time of ≥10 h in mice. These PEGylated TAM radicals should be suitable for a wide range of applications in in vivo EPR spectroscopy and imaging.

Design, synthesis, and anti-tobacco mosaic virus (TMV) activity of glycoconjugates of phenanthroindolizidines alkaloids.

Glycoconjugates of phenanthroindolizidine alkaloids targeting tobacco mosaic virus (TMV) RNA were designed, synthesized, and evaluated for their antiviral activity against TMV for the first time. The glycoconjugation of (S)-6-O-desmethylantofine (2) and 14-hydroxyltylophorines (3-6) was accomplished in three ways (O-glycosylation manner, using carbamoyloxy as linker arm, and using 1,2,3-triazole as linker arm) with three different sugar units (glucose, galactose, and mannose). The glycoconjugates showed improved water solubility and molecule polarity compared with phenanthroindolizidine alkaloids. The bioassay results showed that C6 was a suitable position for glycoconjugation and O-glycosylation can increase the antiviral activity of phenanthroindolizidine alkaloids indicating that the introduction of sugar units can improve the antiviral activity profile of glycoconjugates. Two O-glycosides of (S)-6-O-desmethylantofine, (13aS)-6-O-ß-D-galactopyranosyl-2,3-dimethoxyphenanthro [9,10-b]-11-indolizidinone (10) and (13aS)-6-O-ß-D-mannopyranosyl-2,3-dimethoxyphenanthro [9,10-b]-11-indolizidinone (11) displayed significant higher activity than commercial ningnanmycin, and thus could be considered for novel therapy against plant virus infection.

Co and Fe doping effect on negative temperature coefficient characteristics of nano-grained NiMn2O4 thick films fabricated by aerosol-deposition.

Spinel structured highly dense NiMn2O4-based (NMO) negative temperature coefficient (NTC) thermistor thick films were fabricated by aerosol-deposition at room temperature. To enhance the thermistor B constant, which represents the temperature sensitivity of the NMO thermistor material, Co and Co-Fe doping was applied. In the case of single element doping of Co, 5 mol% doped NMO showed a high B constant of over 5000 K, while undoped NMO showed -4000 K. By doping Fe to the 5 mol% Co doped NMO, the B constant was more enhanced at over 5600 K. The aging effect on the NTC characteristics of Co doped and Fe-Co co-doped NMO thick film showed very stable resistivity-time characteristics because of the highly dense microstructure.

Preparation of Bi2O3-YSZ and YSB-YSZ Composite Powders by a Microemulsion Method and Their Performance as Electrolytes in a Solid Oxide Fuel Cell.

Bi2O3 is a promising sintering additive for YSZ that not only decreases its sintering temperature but also increases its ionic conductivity. However, Bi2O3 preferably grows into large-sized rods. Moreover, the addition of Bi2O3 induces phase instability of YSZ and the precipitation of monoclinic ZrO2, which is unfavorable for the electrical property. In order to precisely control the morphology and size of Bi2O3, a microemulsion method was introduced. Spherical Bi2O3 nanoparticles were obtained from the formation of microemulsion bubbles at the water-oil interface due to the interaction between the two surfactants. Nanosized Bi2O3-YSZ composite powders with good mixing uniformity dramatically decreased the sintering temperature of YSZ to 1000 °C. Y2O3-stabilized Bi2O3 (YSB)-YSZ composite powders were also fabricated, which did not affect the phase of YSZ but decreased its sintering temperature. Meanwhile, the oxygen vacancy concentration further increased to 64.9% of the total oxygen with the addition of 5 mol% YSB. In addition, its ionic conductivity reached 0.027 S·cm-1 at 800 °C, one order of magnitude higher than that of YSZ. This work provides a new strategy to simultaneously decrease the sintering temperature, stabilize the phase and increase the conductivity of YSZ electrolytes.

Targeted delivery of Nitric Oxide triggered by α-Glucosidase to Ameliorate NSAIDs-induced Enteropathy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) increase risks of severe small intestinal injuries. Development of effective therapeutic strategies to overcome this issue remains challenging. Nitric oxide (NO) as a gaseous mediator plays a protective role in small intestinal injuries. However, small intestine-specific delivery systems for NO have not been reported yet. In this study, we reported a small intestine-targeted polymeric NO donor (CS-NO) which was synthesized by covalent grafting of α-glucosidase-activated NO donor onto chitosan. In vitro and in vivo experiments demonstrated that CS-NO could be activated by intestinal α-glucosidase to release NO in the small intestine. Pre-treatment of mice with CS-NO significantly alleviated small intestinal damage induced by indomethacin, as demonstrated by down-regulation of the levels of pro-inflammatory cytokines and chemokines CXCL1/KC. Moreover, CS-NO also attenuated indomethacin-induced gut barrier dysfunction as evidenced by up-regulation of the levels of tight junction proteins and restoration of the levels of goblet cells and MUC2 production. Meanwhile, CS-NO effectively restored the defense function of Paneth cells against pathogens in small intestine. Our present study paves the way to develop NO-based therapeutic strategy for NSAIDs-induced small intestinal injuries.

Copper-Catalyzed Hydrodifluoroalkylation of N-benzylacrylamides via Intramolecular 1,4-Hydrogen Atom Transfer: Reaction Development and Mechanistic Insights.

A one-pot protocol for Cu(I)-catalyzed hydrodifluoroalkylation of benzyl-protected acrylamides to construct difluoropentanedioate compounds in moderate to excellent yields has been achieved by using the benzyl group as a traceless redox-active hydrogen donor. The mechanistic studies confirmed that the reaction proceeds by adding a difluoroalkyl radical to acrylamide, followed by unexpected intramolecular 1,4-hydrogen atom transfer (HAT) and SET oxidation reaction. DFT calculations demonstrate that the destabilizing steric repulsion is the key factor controlling the chemoselectivity, which switches from 1,4-HAT to 5-exo spirocyclization. This work provides an important basis for the 1,4-HAT reaction in theoretical and practical synthesis applications.

Effect of NiZnFeO4 content on PZT-pZN + NiZnFeO4 magnetoelectric composite.

We fabricated and characterized the magnetoelectric (ME) properties of 3-0 ME composite materials comprised of the high piezoelectric voltage coefficient material, 0.9Pb(Zr0.52Ti0.48)O3-0.1 Pb(Zn1/3Nb2/3)O3 + 0.005Mn (PZT-PZN), and the magnetostrictive material, Ni0.8Zn0.2Fe2O4 (NZF). As the ME effect is generated by the product coupling between the piezoelectric properties and the magnetostrictive properties, the NZF content should be optimized for a higher ME coefficient. The dielectric constant and spontaneous polarization (P) were decreased with increasing NZF content before the percolation of the NZF particulates. However, as the NZF content exceeded the percolation content, the dielectric loss was dramatically increased due to the low resistivity of NZF. While the piezoelectric constant was decreased with increasing NZF content, the maximum magnetization was linearly increased. When we combined the piezoelectric and magnetostrictive effects, the ME composite sintered at 1200 degrees C with 20% NZF showed a maximum dE/dH of 27 mV/cm x Oe at a magnetic bias of 1240 Oe.

Copper-Catalyzed Trifluoromethylation of Ynones Coupled with Dearomatizing Spirocyclization of Indoles: Access to CF3-Containing Spiro[cyclopentane-1,3'-indole].

A one-pot protocol for the Cu(I)-catalyzed difunctionalization of indolyl ynones has been achieved via trifluoromethylation of alkyne followed by dearomatizing spirocyclization of indoles. This cascade process enables constructing diverse CF3-containing spiro[cyclopentane-1,3'-indole] scaffolds in moderate to excellent yields which have challenging quaternary spirocyclic carbon and tetrasubstituted alkenes.

A mitochondria-targeted nitric oxide donor triggered by superoxide radical to alleviate myocardial ischemia/reperfusion injury.

A novel mitochondria-targeted superoxide-responsive nitric oxide donor was developed by incorporation of diphenylphosphinyl and triphenylphosphonium groups into diazeniumdiolate, enabling remarkable protection against ischemia/reperfusion injury in H9c2 cells and isolated rat hearts.

Cesium Oleate Passivation for Stable Perovskite Photovoltaics.

Despite their emergence as promising materials for low-cost and efficient energy power generation technology, the instability of hybrid organic-inorganic lead-halide perovskites toward moisture and heat stress remains a serious obstacle that needs to be tackled for commercialization. Here, we show improved moisture and thermal stability through the use of cesium oleate to modify the perovskite/hole transporting material interface. Passivation using cesium oleate does not induce the formation of any low-dimensional perovskites, suggesting that the organic species only passivate the perovskite's surface and grain boundaries. As a result, enhanced hydrophobic character of the perovskite film is realized upon passivation, evidenced by a large water contact angle of 107.4° and improved stability at ambient conditions (a relative humidity of ∼70%, room temperature). Concomitantly, the proposed passivation strategy leads to an increased amount of cesium concentration within the films, resulting in beneficial enhanced thermal stability of the film at 85 °C. By maintaining the three-dimensional (3D) structure of the solar absorber while concurrently passivating the interfacial defects and vacancies, improved open-circuit voltage (Voc) and unsacrificed short-circuit current density (Jsc) were obtained from the treated devices, leading to power conversion efficiencies of more than 18%. When stored in a humid environment (a relative humidity of ∼55%), devices with cesium oleate passivation maintain 88% of their initial power conversion efficiency after 720 h, degrading two times slower than those of the control. This work offers a strategy of coating 3D perovskites with a unique combination of inorganic cations and long-chain organics to provide hydrophobicity and moisture stability to the solar absorber layer while maintaining good device performances.