Visible-Light-Induced, Graphene Oxide-Promoted C3-Chalcogenylation of Indoles Strategy under Transition-Metal-Free Conditions.

An efficient and general method for the synthesis of 3-sulfenylindoles and 3-selenylindoles employing visible-light irradiation with graphene oxide as a promoter at room temperature has been achieved. The reaction features are high yields, simple operation, metal-free and iodine-free conditions, an easy-to-handle oxidant, and gram-scalable synthesis. This simple protocol allows one to access a wide range of 3-arylthioindoles, 3-arylselenylindoles, and even 3-thiocyanatoindoles with good to excellent yields.

Photoinitiated Multicomponent Anti-Markovnikov Alkoxylation over Graphene Oxide.

The development of graphene oxide-based heterogeneous materials with an economical and environmentally-friendly manner has the potential to facilitate many important organic transformations but proves to have few relevant reported reactions. Herein, we explore the synergistic role of catalytic systems driven by graphene oxide and visible light that form nucleophilic alkoxyl radical intermediates, which enable an anti-Markovnikov addition exclusively to the terminal alkenes, and then the produced benzyl radicals are subsequently added with N-methylquinoxalones. This photoinduced cascade radical difunctionalization of olefins offers a concise and applicable protocol for constructing alkoxyl-substituted N-methylquinoxalones.

Consistency and applicability of different brief screen instrument of cognitive function in elderly population.

BACKGROUND: Screening for cognitive impairment (CI) is often hampered by lack of consensus as to which screening instrument to use. The aim is to assess the consistence and applicability of different CI screening tools. METHOD: In a cross-sectional study from October 2017 to September 2018 in 7 communities in Shanghai, China, elder (≧60) residential volunteers with no history of major cardiovascular diseases, cancers and other comorbidities known to affect cognitive functions were recruited. The participants underwent tests with 7 cognitive function screening instruments. Multivariate linear regressions were performed to test correlations between demographic characteristics, including gender, age, education, and marital status, with cognitive test scores. Mini-Mental State Examination (MMSE) score adjusted according to the correlation coefficients was used to detect CI with a cutoff of 24. Other cognitive function scores were compared between participants with and without CI. In addition, Pearson's correlation test was used to detect association between different test scores. RESULTS: 172 participants with relatively low education levels were included. Age and education showed significant association with cognitive test scores. Using adjusted MMSE, 39.6% of participants were identified with CI, while the percentage was 87.2% when adjusted Montreal Cognitive Assessment (MoCA) with cutoff of 26 was used. Analysis of "abnormal" test scores showed that MMSE had the highest percentage of valid data (98.8%). MoCA and Isaacs test of Verbal Fluency (VF) score had correlation with most the other scores, while MMSE only significantly associated with VF and MoCA. CONCLUSIONS: MMSE may still present the most applicable tools for quick screen of cognitive functions, especially when environmental conditions may interfere with participants' attention.

Graphene oxide-catalyzed trifluoromethylation of alkynes with quinoxalinones and Langlois' reagent.

The direct C-H trifluoromethylation of alkynes and quinoxalinones has been achieved using a graphene oxide/Langlois' reagent system. This multi-component tandem reaction using graphene oxide as the catalyst and Langlois' reagent as the robust CF3 radical source results in the formation of olefinic C-CF3 to access a series of 3-trifluoroalkylated quinoxalin-2(1H)-ones.

ATAS Acupuncture Reduces Chemotherapy Induced Fatigue in Breast Cancer Through Regulating ADROA1 Expression: A Randomized Sham-Controlled Pilot Trial.

OBJECTIVE: To investigate the feasibility and effectiveness of ATAS acupuncture (Acupoints-Time-Space Acupuncture) as a non-pharmacological intervention to prevent or relieve chemotherapy-induced fatigue in breast cancer patients undergoing taxane chemotherapy. METHODS: A pilot study in Kunming center with the aim of evaluating 40 patients randomized to 3 groups: ATAS, sham and non-acupuncture with an unequal randomization of 2:1:1. Participants with stage I-III breast cancer were scheduled to receive adjuvant EC4P4 chemotherapy. Participants in the ATAS and sham acupuncture arms received 20 sessions of acupuncture over 20 weeks, non-acupuncture arm received usual care. Evaluation scales, including VAS-F, MFI-20, HDAS, ISI, and blood samples were collected at four timepoints (T1-T4). mRNA sequencing was performed to detect the mechanism of acupuncture. RESULTS: A total of 581 sessions of acupuncture were performed on patients in the acupuncture group. There was no difference between the three groups in terms of clinical characteristics. Patients randomized to ATAS acupuncture had improved symptoms including fatigue, anxiety and insomnia during the whole process of chemotherapy compared with the other two groups. The VAS-F score of ATAS acupuncture group was decreased compared with non-acupuncture group (P=0.004). The score of MFI-20 in ATAS acupuncture group was kept at low level, while the other two groups' scores kept climbing during chemotherapy (P=0.016; P=0.028, respectively). The mechanism of ATAS acupuncture which reduced fatigue and depression may be related to ADROA1, by regulating cGMP/PKG pathway. CONCLUSION: This pilot study has demonstrated that ATAS acupuncture can significantly reduce fatigue induced by chemotherapy. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR-IPR-17,013,652, registered Dec 3, 2017. http://www.chictr.org.cn/. PROTOCOL VERSION: Version 3.2 dated from 2018/04/20.

[Exploration on professor ZHU Mian-sheng's space-time acupuncture of the eightfold method of the sacred tortoise].

The space-time acupuncture is a new needling method, summarized by professor ZHU Mian-sheng on the base of the inheritance of four time-acupuncture method in ancient time and the absorption of the European medical culture idea, aiming to the application of the combination of time acupoints and space acupoints. Through constructing the internal and external qi field, the field effect of human body self-healing function is mobilized. The space-time acupuncture of the eightfold method of the sacred tortoise is one of the four methods, on the base of the acquired Wenwang eight diagrams and the night numbers of Luoshu diagrams, and in match with the eight confluent points. It is a special structure of "number, diagram and acupoint". The authors explain systematically the space-time acupuncture of the eightfold method of the sacred tortoise in the aspects of the opening of time acupoints and composition of space acupoints as well as the characteristics of its clinical operation so as to elaborate the essential composition and the feature of clinical application of such method. Moreover, professor ZHU Mian-sheng's innovation is introduced besides inheriting the ancient experience and the theoretic connotation is explored on the spatial acupoint corresponding to the time acupuncture of ancient eightfold method of the sacred tortoise.

CoCl2-promoted TEMPO oxidative homocoupling of indoles: access to tryptanthrin derivatives.

A novel TEMPO/CoCl2-promoted aerobic oxidation of indoles was developed. The reaction provided one-step access to tryptanthrin derivatives in moderate to good yields and excellent regioselectivity via a cascade process. The reactions could be carried out under mild reaction conditions with varying functional group tolerance, especially halogen functional groups. Mechanistic studies disclosed that the oxygen atom in the desired product originated from molecular dioxygen.

Tuning the activity of the inert MoS2 surface via graphene oxide support doping towards chemical functionalization and hydrogen evolution: a density functional study.

The basal plane of MoS2 provides a promising platform for chemical functionalization and the hydrogen evolution reaction (HER); however, its practical utilization remains challenging due to the lack of active sites and its low conductivity. Herein, using first principles simulations, we first proposed a novel and effective strategy for significantly enhancing the activity of the inert MoS2 surface using a graphene oxide (GO) support (MoS2/GOs). The chemical bonding of the functional groups (CH3 and NH2) on the MoS2-GO hybrid is stronger than that in freestanding MoS2 or MoS2-graphene. Upon increasing the oxygen group concentration or introducing N heteroatoms into the GO support, the stability of the chemically functionalized MoS2 is improved. Furthermore, use of GOs to support pristine and defective MoS2 with a S vacancy (S-MoS2) can greatly promote the HER activity of the basal plane. The catalytic activity of S-MoS2 is further enhanced by doping N into GOs; this results in a hydrogen adsorption free energy of almost zero (ΔGH = ∼-0.014 eV). The coupling interaction with the GO substrate reduces the p-type Schottky barrier heights (SBH) of S-MoS2 and modifies its electronic properties, which facilitate charge transfer between them. Our calculated results are consistent with the experimental observations. Thus, the present results open new avenues for the chemical functionalization of MoS2-based nanosheets and HER catalysts.

Regioselective synthesis of 2,3'-biindoles mediated by an NBS-induced homo-coupling of indoles.

Mild conditions have been developed to achieve NBS-induced homodimerization of indole derivatives with excellent regioselectivity at 15 °C in high efficiency. This method provides a simple route to a 2,3'-linked biindolyl scaffold from the electron-rich to moderately electron-poor indoles. In addition, [3,2-a]carbazole derivatives can also be prepared through this method.

Diels-Alder reactions of graphene oxides: greatly enhanced chemical reactivity by oxygen-containing groups.

Graphene oxides (GOs) or reduced GOs (rGOs) may offer extraordinary potential for chemical functionalization of graphene due to their unique electronic and structural properties. By means of dispersion-corrected density functional theory computations, we systematically investigated the Diels-Alder (DA) chemistry of GOs. Our computations showed that the dual nature of GOs as both a diene and a dienophile is stronger than that of pristine graphene. Interestingly, the interior bonds of a graphene surface modified by oxygen-containing groups could be functionalized by maleic anhydride (MA) and 2,3-dimethoxybutadiene (DMBD) through cycloaddition reactions, and the cycloaddition products of MA and DMBD are more favorable than the non-covalent complexes between these reagents and the GO surface. The feasibility of covalent functionalization of GOs as a diene and a dienophile strongly depends on the local structural environment of the oxygen groups, including the atomic arrangement and the number of these groups surrounding the reaction site. The exothermicities for (4+2) adducts of DMBD with GO are far larger than those of MA, which indicates that the dienophile character of the GO surface is stronger than its behavior as a diene.

Recent Advances in the Synthesis of Antischistosomal Drugs and Agents.

Schistosomiasis is a notable neglected tropical disease caused by trematodes that infect mainly the intestines, bladder, and liver. Because of the unavailability of a schistosomiasis vaccine, control of the disease depends mainly on chemotherapy. Praziquantel (PZQ), which is active against all schistosome species (Among the five major species of human schistosomes-S. mansoni, S. haematobium, S. japonicum, S. intercalatum, and S. mekongi, S. mansoni is the most prevalent) as well as probably their hybrids and the recommended drug by the World Health Organization for schistosomiasis treatment at either the community or individual level, has become the exclusive drug because of its low cost and efficacy against the adult form of all schistosome species. In view of rapid re-infection following treatment and concern about the development of tolerance and/or resistance to praziquantel, there is an urgent need for research and development of novel drugs for the prevention and treatment of schistosomiasis. This comprehensive review shall attempt to briefly review the recent advances in the synthesis of antischistosomal drugs and agents in the literature from 1990s to now, particularly focusing on the context of potential development of antischistosomal agents. It shall be of interest for the pharmacologist.

A multifunctionalized strategy of indoles to C2-quaternary indolin-3-ones via a TEMPO/Pd-catalyzed cascade process.

A method for combinative oxidative homo dimerization and cyanomethylation of free indole derivatives catalysed by TEMPO and Pd(OAc)2 was demonstrated for the first time. This new methodology is both atom and step efficient and is applicable to a broad scope of substrates, allowing the synthesis of a range of synthetically valuable 2-(2-(1H-indol-3-yl)-3-oxoindolin-2-yl)acetonitriles in moderate to excellent yields.

Oxygen-Molecule Adsorption and Dissociation on BCN Graphene: A First-Principles Study.

Boron and nitrogen co-doped (BCN) graphene is an attractive material for use as a metal-free oxygen reduction reaction electrocatalyst and as other catalysts due to its unique structure and electronic properties. Reported here is the structure, determined by using density functional theory, of the active O2 -dissociation site of BCN graphene containing different types of BN cluster. The results show that the edge termination and shape of substitutional BN clusters are two important factors that determine the catalytic activity of BCN graphene for the dissociation of molecular oxygen. N-Terminated triangular BN (t-BN) cluster doping can reduce the energy barrier more effectively compared to a t-BN with a B edge or quadrangular BN cluster. Interestingly, the B atom neighboring the N edge, only in the case of N-terminated t-BN doping, is determined to be the most active site for O2 dissociation due to the barrier being as low as 0.08 eV. The electronic structure calculations reveal that in addition to the large positive charge densities, the catalytic activity of graphene enhanced by B,N doping is also attributed to the increased density of states of the π* states of the active site around the Fermi level.

Recent Advances in Antischistosomal Drugs and Agents.

Schistosomiasis is a notable neglected tropical disease caused by trematodes that inflame mainly the intestines, bladder, and liver. Because of the unavailability of a schistosomiasis vaccine, control of the disease depends mainly on chemotherapy. Praziquantel (PZQ), which is active against all schistosome species and the recommended drug by the World Health Organization for schistosomiasis treatment at either the community or individual level, has become the exclusive drug because of its low cost and efficacy against the adult form of all schistosome species. In view of rapid re-infection following treatment and concern about the development of tolerance and/or resistance to praziquantel, there is an urgent need for research and development of novel drugs for the prevention and treatment of schistosomiasis. This comprehensive review shall attempt to briefly review the recent advances in the chemotherapy of schistosomiasis in the literature from 1990s to now, particularly focusing on the context of potential development of antischistosomal agents. Their antischistosomal properties, advantages, and disadvantages as well as structure-activity relationships are reviewed in a simple manner. It shall be of interest for both the synthetic chemist as well as the pharmacologist.

Anion Effects on Lanthanide(III) Tetrazole-1-acetate Dinuclear Complexes Showing Slow Magnetic Relaxation and Photofluorescent Emission.

Three types of lanthanide complexes based on the tetrazole-1-acetic acid ligand and the 2,2'-bipyridine coligand were prepared and characterized by single-crystal X-ray diffraction, IR spectroscopy, and elemental analyses; the formulas of these complexes are [Ln2(1-tza)4(NO3)2(2,2'-bipy)2] (Ln = Sm (1), Eu (2), Gd (3), Tb (4), Dy (5)), [Dy2(1-tza)4Cl2(2,2'-bipy)2] (6), and [Yb2(1-tza)4(NO3)2(2,2'-bipy)2] (7) (1-tza = tetrazole-1-acetate and 2,2'-bipy = 2,2'-bipyridine). They are dinuclear complexes possessing similar structures but different lanthanide(III) ion coordination geometries because of the distinction of peripheral anions (such as NO3(-) and Cl(-)) and the effect of lanthanide contraction. The variable-temperature magnetic susceptibilities of 1-6 were measured. Both Dy(III) complexes (5 and 6) display field-induced single-molecule magnet behaviors. Ab initio calculations revealed that the Dy(III) complex 6 possesses a more anisotropic Dy(III) ion in comparison to that in 5. The room-temperature photoluminescence spectra of Sm(III) (1), Eu(III) (2), Tb(III) (4), and Dy(III) (5 and 6) complexes exhibit strong characteristic emissions in the visible region, whereas the Yb(III) (7) complex shows near-infrared (NIR) luminescence.

Synthesis and pharmacological evaluation of novel bisindole derivatives bearing oximes moiety: identification of novel proapoptotic agents.

In an effort to develop potent anti-cancer chemopreventive agents, a novel series of bisindole derivatives bearing oxime moiety were synthesized. Structures of all compounds were characterized by NMR and HRMS. Anti-proliferative activities for all of these compounds were investigated by the method of MTT assay on 7 human cancer lines and the normal cell lines (HUVEC). Most of them showed a noteworthy anti-cancer activity in vitro, the half maximal inhibitory concentration (IC50) value is 4.31 µM of 4e against T24. The results from Hoechst 33258 and acridine orange/propidium iodide staining as well as annexinV-FITC assays provided evidence for an apoptotic cell death. The further mechanisms of compound 4e-induced apoptosis in T24 cells demonstrated that compound 4e induced the productions of ROS, and altered anti- and pro-apoptotic proteins, leading to mitochondrial dysfunction and activations of caspase-9 and caspase-3 for causing cell apoptosis. Moreover, the cell cycle analysis and western-blot analysis indicated that compound 4e effectively arrested T24 cells in G1 stage and possibly has an effect on cell cycle regulatory proteins particularly cyclin D1.

NiSO4-catalyzed C-H activation/C-S cross-coupling of 1,2,3-triazole N-oxides with thiols.

An efficient nickel-catalyzed protocol for C-S cross-coupling through the direct functionalization of 2-aryl-1,2,3-triazole N-oxide C-H bonds with aryl or alkyl thiols, or diphenyl disulfide has been developed. The targeted N(+)-O(-) bond cleavage can be observed during the reaction, and thus obviates the need to use an additional deoxygenation step. This new protocol for the preparation of thiolated 2-aryl-1,2,3-triazoles appears to offer good yields with high regioselectivity, mild conditions, and a wide substrate scope.

Metal-free (Boc)2O-mediated C4-selective direct indolation of pyridines using TEMPO.

Direct metal-free C-4-selective indolation of pyridines is achieved for the first time using TEMPO and (Boc)2O. A variety of substituents on both indoles and pyridines are tolerated to give 3-(pyridin-4-yl)-1H-indole derivatives in moderate to excellent yields. This finding provides a novel approach for developing metal-free C-H functionalization of pyridines.

Transition-metal-free semihydrogenation of diarylalkynes: highly stereoselective synthesis of trans-alkenes using Na2S·9H2O.

A highly stereoselective and efficient transition-metal-free semihydrogenation of internal alkynes to E-alkenes using cheap and green water as hydrogen donor is described. The reactions are conducted under convenient conditions and provide products in good to excellent yields, with broad substrate scope, including a variety of diarylalkynes.

The four-step total synthesis of (-)-chaetominine.

The total synthesis of the alkaloid (-)-chaetominine (1) has been achieved in four steps with an overall yield of 33.4%. Key features of our strategy include a one-pot cascade indole epoxidation - epoxide ring-opening cyclization - lactamization reaction sequence, and the use of a nitro group as a latent amino group for the one-pot construction of the quinazolinone ring. This constitutes a step economical, redox economical and protecting group-free total synthesis.