Visible-Light-Promoted Cascade Radical Cyclization: Synthesis of Chroman-4-ones and Dihydroquinolin-4-ones.

A novel visible-light photoredox catalysis protocol for the effective and efficient synthesis of 3-substituted chroman-4-ones and 2,3-dihydroquinolin-4(1H)-ones via tandem radical addition/cyclization of alkenyl aldehydes has been described. This reaction features a broad substrate scope, mild reaction conditions, and good functional group tolerance character.

The prevalence and incidence of Parkinson's disease in China: a systematic review and meta-analysis.

Parkinson's disease (PD) is a chronic neurodegenerative disorder affecting older individuals. There is inconsistent evidence about the prevalence and incidence of PD in China at present. The aim of the meta-analysis was to estimate the prevalence and incidence of PD and its relation to age, gender, and stage in China. The literature search was conducted using PubMed, EMBASE, Chinese Biological Medical Literature database (CBM), Chinese National Knowledge Infrastructure database (CNKI), Chinese Wanfang and Chongqing VIP database for studies investigating the prevalence and incidence of PD in China from the commencement of the database until August 2012; both English and Chinese publications were included. We estimated the prevalence and incidence of PD using meta-analysis. Thirteen eligible articles were collected. The results showed that the pooled prevalence and incidence of PD were 2 per 100,000 population and 797 per 100,000 person-years. A higher prevalence of PD was found in males than in females (OR 1.29, 95 % CI 1.05-1.57). The prevalence of PD increased with age: the highest was 1,663 per 100,000 in those aged 80 and older. The overall prevalence of PD is lower in China than in developed countries, but the incidence is higher than in some developed countries. Overall, the prevalence of PD appears to increase with age and there are sex differences evident in Chinese individuals.

Brønsted acid-mediated tandem cyclization of triarylphosphines and in situ generated ortho-alkynyl quinone methides: access to heterocyclic quaternary phosphonium salts.

Heterocyclic Quaternary Phosphonium Salts (HQPS) have emerged as promising chemicals for organic synthesis and medicinal chemistry. However, the present synthetic methodology of this type of compound is still limited. Here, we report a deconstructive reorganization strategy based on Brønsted acid-mediated tandem 1,4 addition/intramolecular cyclization of triphenylphosphine derivatives and in situ generated o-AQMs for the first time. This protocol provides a novel approach to heterocyclic quaternary phosphonium salts. The method also features a non-metal catalyst, mild reaction conditions, high efficiency and wide substrate scope. Moreover, a series of obtained heterocyclic phosphonium salts can be converted to isotopically labelled 2-benzofuran compounds directly by simple deuteration reactions.

A Eu(iii) metal-organic framework based on anthracenyl and alkynyl conjugation as a fluorescence probe for the selective monitoring of Fe3+ and TNP.

In this work, a luminescent metal-organic framework (Eu-MOF {[Eu6L6(µ3-OH)8(H2O)3]8·H2O} n ) was constructed by a solvothermal method with a linear organic ligand L (10-[(2-amino-4-carboxyl-phenyl)ethynyl]anthracene-9-carboxylic acid) based on anthracene and alkyne groups and using Eu3+ as the metal center. The MOF exhibits a stable UiO-66 crystal structure, and a six-core cluster twelve-linked secondary structural unit was successfully synthesized using 2-fluorobenzoic acid as a modulator, forming a classical fcu topology. Moreover, it exhibits good chemical stability. Interestingly, Eu-MOF exhibited high selectivity and sensitive fluorescence burst properties towards Fe3+ ions and 2,4,6-trinitrophenol (TNP) in DMF solution. For Fe3+, the K SV value is 5.06 × 105 M-1 and the LOD value is 5.1 × 10-7 M. For TNP, the K SV value is 1.92 × 104 M-1 and the LOD value is 1.93 × 10-6 M. In addition, Eu-MOF showed good anti-interference ability and fast response. This work provides an excellent fluorescent sensor for the detection of Fe3+ and 2,4,6-trinitrophenol (TNP) residues in contaminants.

Di-, tri- and tetraphosphine-substituted Fe/Se carbonyls: synthesis, characterization and electrochemical properties.

The active sites of [FeFe]-hydrogenase promoted by Fe/E (E = S, Se) clusters have attracted considerable interest due to their significance in understanding the interconversion of hydrogen with protons and electrons. As an extension of the study on Fe/Se clusters related to H-cluster model compounds of [FeFe]-hydrogenase, a series of tertiary phosphine substituted Fe/Se carbonyls were successfully prepared. The treatment of Fe2(µ-SePh)2(CO)6 (A) and excess PR3 resulted in the ferrous bis(selenolate) carbonyls Fe(SePh)2(CO)2(PR3)2 (PR3 = PPhMe2, 1; PMe3, 2) in moderate yields. In striking contrast, the reaction of Fe2(µ-SeCH2Ph)2(CO)6 (B) with the same PR3 ligand resulted in the PR3-disubstituted models Fe2(µ-SeCH2Ph)2(CO)4(PR3)2 (PR3 = PPhMe2, 3; PMe3, 4) as the principal products. The more interesting finding is that two independent isomers (anti- and syn-) can be isolated according to different reaction temperatures. Further reactions of 3 or 4 with PR3 under UV irradiation afforded the first PR3-trisubstituted 2Fe2Se derivatives Fe2(µ-SeCH2Ph)2(CO)3(PR3)3 (PR3 = PPhMe2, 5; PMe3, 6). 6 could be further converted into the tetrasubstituted product Fe2(µ-SeCH2Ph)2(CO)2(PMe3)4 (7), while no further substitution was observed with 5 and excess of PPhMe2. All the prepared compounds were fully characterized by elemental analysis, various spectroscopic techniques and X-ray crystallography. In addition, some electrochemical properties of these models were studied by cyclic voltammetry (CV) in MeCN. Compounds 4, 6 and 7 were found to be catalysts for the H2 evolution reaction under electrochemical conditions.

Optimal Formula of Angelica sinensis Ameliorates Memory Deficits in ß-amyloid Protein-induced Alzheimer's Disease Rat Model.

OBJECTIVE: Angelica (A.) sinensis is used as a traditional medical herb for the treatment of neurodegeneration, aging, and inflammation in Asia. A. sinensis optimal formula (AOF) is the best combination in A. sinensis that has been screened to rescue the cognitive ability in ß-amyloid peptide (Aß25-35)-treated Alzheimer's disease (AD) rats. The objective of this study was to investigate the effect of AOF on the learning and memory of AD rats as well as to explore the underlying mechanisms. METHODS: Male Wistar rats were infused with Aß25-35 for AD model induction or saline (negative control). Five groups of AD rats were fed on AOF at 20, 40, or 80 mL/kg every day, donepezil at 0.9 mg/kg every day (positive control), or an equal volume of water (AD model) intragastrically once a day for 4 weeks, while the negative control rats were fed on water. The Morris water maze test was used to evaluate the cognitive function of the rats. The Aß accumulation, cholinergic levels, and antioxidative ability were detected by ELISA. Additionally, the candidate mechanism was determined by gene sequencing and quantitative real-time polymerase chain reaction. RESULTS: The results showed that AOF administration significantly ameliorated Aß25-35-induced memory impairment. AOF decreased the levels of amyloid-ß precursor protein and Aß in the hippocampus, rescued the cholinergic levels, increased the activity of superoxide dismutase, and decreased the malondialdehyde level. In addition, AOF inhibited the expression of IL1b, Mpo, and Prkcg in the hippocampus. CONCLUSION: These experimental findings illustrate that AOF prevents the decrease in cognitive function and Aß deposits in Aß25-35-treated rats via modulating neuroinflammation and oxidative stress, thus highlighting a potential therapeutic avenue to promote the co-administration of formulas that act on different nodes to maximize beneficial effects and minimize negative side effects.

Bis(4,6-dimethyl-pyrimidine-2-thiol-ato)dimethyl-tin(IV).

The asymmetric unit of the title complex, [Sn(CH(3))(2)(C(6)H(7)N(2)S)(2)], contains two independent mol-ecules with similar configurations. In each, the Sn(IV) cation is coordinated by two methyl and two 4,6-dimethyl-pyrimidine-2-thiol-ate anions in a distorted SnS(2)C(2) tetra-hedral geometry. In the two mol-ecules, the S-Sn-S bond angles are 87.70 (5) and 88.93 (4)°, while the C-Sn-C bond angles are 125.7 (3) and 125.9 (2)°. Weak C-H⋯N hydrogen bonding is present in the crystal structure.

Novel triorganotin complexes based on phosphonic acid ligands: Syntheses, structures and in vitro cytostatic activity.

Six novel organotin phosphonate complexes, [(Me3Sn)4(HL1)4]n1, [(Me3Sn)2(HL2)2]n2, [(Me3Sn)2L3(H2O)]n3, [(Ph3Sn)(HL1)]64, [(Ph3Sn)2L2]n5 and [(Ph3Sn)2L3]66, derived from phosphonic acid ligands [NaHL1 = 1-C10H7OPO2(OH)Na, H2L2 = 1-C10H7PO(OH)2, H2L3 = 2-C10H7PO(OH)2], have been synthesized and characterized by elemental analysis, FT-IR, NMR (1H, 13C, 31P and 119Sn) spectroscopy and X-ray crystallography. The structural analysis reveals that complexes 1 and 5 display 1D infinite zig-zag chain structures, and complex 2 shows 1D right-handed helical chain structure, while complex 3 displays 1D left-handed helical chain structure. Complexes 4 and 6 are 24-membered macrocyclic rings interconnected by P, O and Sn atoms. Additionally, the molecules of complexes 1 and 3 are further linked through intermolecular π···π and O-H···O interaction into supramolecular structures, respectively. Furthermore, we preliminarily estimated in vitro cytostatic activity of complexes 1-6 against the human cervix tumor cells (HeLa), human hepatocellular carcinoma cells (HepG-2) and human normal breast cells (HBL-100). Importantly, the anti-proliferative properties and possible pathway of complex 6 are investigated, and the results demonstrate that complex 6 could induce apoptotic cell death via an overload of intracellular reactive oxygen species (ROS) levels and the dysfunctional depolarization of mitochondrial membranes.

catena-Poly[[(3-methyl-sulfanyl-1,2,4-thia-diazole-5-thiol-ato)sodium]di-µ-aqua-κO:O].

The crystal structure of the title compound, [Na(C(3)H(3)N(2)S(3))(H(2)O)(2)](n), features polymeric chains made up of O⋯O edge-shared NaSN(H(2)O)(4) units running along the b axis. The Na(+) ion and all non-H atoms of the thia-diazole ligand lie on a mirror plane.

Lewis Base-Catalyzed [4 + 3] Annulation of ortho-Quinone Methides and MBH Carbonates: Synthesis of Functionalized Benzo[ b]oxepines Bearing Oxindole Scaffolds.

A novel Lewis base-catalyzed [4 + 3] annulation process for the construction of benzo[ b]oxepine scaffolds has been developed. 1,4-Diazabicyclo[2.2.2]octane (DABCO) promotes the union of o-QMs and Morita-Baylis-Hillman carbonates in reasonable to excellent yields and good stereoselectivities (dr > 20:1). This straightforward, catalytic approach offers access to a variety of synthetically useful benzo[ b]oxepine derivatives bearing oxindole scaffolds containing all-carbon spiro-quaternary stereocenters.

Lewis Acid Catalyzed Tandem 1,4-Conjugate Addition/Cyclization of in Situ Generated Alkynyl o-Quinone Methides and Electron-Rich Phenols: Synthesis of Dioxabicyclo[3.3.1]nonane Skeletons.

A versatile Lewis acid catalyzed tandem cyclization of in situ generated alkynyl o-quinone methides ( o-AQMs) with electron-rich phenols has been developed on the basis of the mode involving an intermolecular 1,4-conjugate addition/6-endo cyclization/1,3-aryl shift/intramolecular 1,4-conjugate addition cascade. This reaction provides a new method for expeditious assembly of synthetically and biologically interesting tetracyclic bridged dioxabicyclo[3.3.1]nonane skeletons featuring a congested bridgehead oxa-quaternary stereocenter.

Metal-Free One-Pot Synthesis of 3-Phosphinoylbenzofurans via Phospha-Michael Addition/Cyclization of H-Phosphine Oxides and in Situ Generated ortho-Quinone Methides.

A novel metal-free one-pot protocol for the effective and efficient synthesis of 3-phosphinoylbenzofurans via a phospha-Michael addition/cyclization of H-phosphine oxides and in situ generated ortho-quinone methides is described. Based on the expeditious construction of C(sp2)-P bonds, asymmetric synthesis of optically pure 3-phosphinoylbenzofurans containing chiral P-stereogenic center has also been probed by using chiral RP-(-)-menthyl phenylphosphine oxide.

A novel octa-nuclear 32-membered zirconocene macrocycle based on the aromatic selenite.

A novel macrocyclic zirconocene(iv) aromatic selenite [(CpZr)8L16]·2(Cp4Zr2(µ-O)Cl2) (complex 1) (Cp = cyclopentadienyl anion; L = 4-fluorobenzeneseleninic acid) was prepared by the reaction of bis(cyclopentadienyl)zirconium dichloride with 4-fluorobenzeneseleninic acid and characterized by elemental analysis, infrared spectroscopy, 1H, 13C NMR spectroscopy, ESI-MS, XRD and X-ray diffraction. The structure analysis shows that complex 1 is a centrosymmetric 32-membered macrocycle containing an eight-nuclear zirconocene. In this complex, the 4-fluorobenzeneseleninic acid ligands adopt bidentate mode in coordinating to zirconium, which play a bridging role in the formation of a macrocycle. The title compound is a rare example of aromatic selenic acid-based zirconocene derivatives. Furthermore, the preliminary in vitro anti-tumor activity of complex 1 has also been studied toward breast cancer cell lines (MDA-MB-231) and human cervix cell lines (HeLa). The results indicate that complex 1 shows higher activity compared with the ligand and bis(cyclopentadienyl)zirconium dichloride.

Syntheses, structures and anti-tumor activity of four new organotin(iv) carboxylates based on 2-thienylselenoacetic acid.

With the 2-thienylselenoacetic acid ligand, four new organotin complexes, [Me3Sn(O2CCH2SeC4H3S-o)]n (), [(Ph3Sn)6(O2CCH2SeC4H3S-o)6] (), [(Me2Sn)4(µ3-O)2(O2CCH2SeC4H3S-o)4] (), and [(PhSn)6(µ3-O)6(O2CCH2SeC4H3S-o)6] (), have been synthesized and characterized by X-ray crystallography, elemental analysis, FT-IR and NMR ((1)H, (13)C, and (119)Sn) spectroscopy. The structure analysis indicates that complex adopts a 1D infinite zig-zag chain structure, while complex shows a centrosymmetric hexanuclear 24-membered macrocycle. In contrast, complex and complex display ladder and drum structures, respectively. Examination of the non-covalent intermolecular contacts in complex reveals the existence of the C-HO and C-Hπ interactions, which play an important function in the supramolecular construction. These compounds are rare examples of selenium carboxylic acid-based organotin derivatives. Furthermore, the anti-tumor activity of complexes has also been studied. Importantly, the anti-proliferative properties and possible mechanism of complex are preliminarily investigated. The results demonstrate that complex could induce apoptotic cell death via accumulation of ROS and collapse of the mitochondrial membrane permeabilization (MMP).

Heparanase mRNA and Protein Expression Correlates with Clinicopathologic Features of Gastric Cancer Patients: a Meta- analysis.

BACKGROUND: Heparanase is believed to be involved in gastric carcinogenesis. However, the clinicopathologic features of gastric cancer with high heparanase expression remain unclear. AIM: The purpose of this study was to comprehensively and quantitatively summarize available evidence for the use of heparanase mRNA and protein expression to evaluate the clinicopathological associations in gastric cancer in Asian patients by meta-analysis. MATERIALS AND METHODS: Relevant articles listed in MEDLINE, CNKI and the Cochrane Library databases up to MARCH 2015 were searched by use of several keywords in electronic databases. A meta-analysis was performed to clarify the impact of heparanase mRNA and protein on clinicopathological parameters in gastric cancer. Combined ORs with 95%CIs were calculated by Revman 5.0, and publication bias testing was performed by stata12.0. RESULTS: A total of 27 studies which included 3,891 gastric cancer patients were combined in the final analysis. When stratifying the studies by the pathological variables of heparanase mRNA expression, the depth of invasion (633 patients) (OR=4.96; 95% CI=2.38-1.37; P<0.0001), lymph node metastasis (639 patients) (OR=6.22; 95%CI=2.70-14.34, P<0.0001), and lymph node metastasis (383 patients) (OR=6.85; 95% CI=2.04-23.04; P=0.002) were all significant. When stratifying the studies by the pathological variables of heparanase protein expression, this was the case for depth of invasion (1250 patients) (OR=2.76; 95% CI=1.52-5.03; P=0.0009), lymph node metastasis (1178 patients) (OR=4.79 ; 95% CI=3.37-6.80, P<0.00001), tumor size (727 patients) (OR=2.06 ; 95% CI=1.31-3.23; P=0.002) (OR=2.61; 95% CI=2.09-3.27; P=0.000), and TNM stage (1233 patients) (OR=6.85; 95% CI=2.04-23.04; P=0.002). Egger's tests suggested publication bias for depth of invasion, lymph node metastasis, lymph node metastasis and tumor size of heparanase mRNA and protein expression. CONCLUSIONS: This meta- analysis suggests that higher heparanase expression in gastric cancer is associated with clinicopathologic features of depth of invasion, lymph node metastasis and TNM stage at mRNA and protein levels, and of tumor size only at the protein level. Egger's tests suggested publication bias for these clinicopathologic features of heparanase mRNA and protein expression, and which may be caused by shortage of relevant studies. As a result, although abundant reports showed heparanase may be associated with clinicopathologic features in gastric cancer, this meta-analysis indicates that more strict studies were needed to evaluate its clinicopathologic significance.

Human herpesvirus-6-specific interleukin 10-producing CD4+ T cells suppress the CD4+ T-cell response in infected individuals.

Human herpesvirus-6 (HHV-6) infection normally persists for the lifetime of the host and may reactivate with immunosuppression. The mechanism behind HHV-6 latent infection is still not fully understood. In this study, we observed that decreased proliferation of CD4+ T cells and PBMCs but not CD8+ T cells from HHV-6-infected individuals was stimulated with HHV-6-infected cell lysates. Moreover, HHV-6-stimulated CD4+ T cells from HHV-6-infected individuals have suppressive activity on naïve CD4+ T and CD8+ T cells from HHV-6-uninfected individuals. However, no increased proportion of CD4+ CD25+ Treg cells from HHV-6-infected individuals contributed to the suppressive activity of the HHV-6-stimulated CD4+ T cells from HHV-6-infected individuals. Transwell experiments, ELISA and anti-IL-10 antibody blocking experiment demonstrated that IL-10 may be the suppressive cytokine required for suppressive activity of CD4+ T cells from HHV-6-infected individuals. Results of intracellular interleukin (IL)-10 and IL-4 further implicated the HHV-6-specific IL-10-producing CD4+ T cells in the suppressive activity of CD4+ T cells from HHV-6-infected individuals. Results of intracellular interferon (IFN)-gamma demonstrated a decreased frequency of HHV-6-specific IFN-gamma-producing CD4+ T, but not CD8+ T cells in HHV-6-infected individuals, indicating that it was the CD4+ Th1 responses in HHV-6-infected individuals that were selectively impaired. Our findings indicated that HHV-6-specific IL-10-producing CD4+ T cells from HHV-6-infected individuals possess T regulatory type 1 cell activity: immunosuppression, high levels of IL-10 production, with a few cells expressing IFN-gamma, but none expressing IL-4. These cells may play an important role in latent HHV-6 infection.