Electrochemical Radical Tandem Difluoroethylation/Cyclization of Unsaturated Amides to Access MeCF2-Featured Indolo/Benzoimidazo [2,1-a]Isoquinolin-6(5H)-ones.

A metal-free electrochemical oxidative difluoroethylation of 2-arylbenzimidazoles was accomplished, which provided an efficient strategy for the synthesis of MeCF2-containing benzo[4,5]imidazo[2,1-a]-isoquinolin-6(5H)-ones. In addition, the method also enabled the efficient construction of various difluoroethylated indolo[2,1-a]isoquinolin-6(5H)-ones. Notably, this electrochemical synthesis protocol proceeded well under mild conditions without metal catalysts or exogenous additives/oxidants added.

B(C6 F5 )3 -Catalyzed [2+3]-Cyclative o,m-diC-H Functionalization of Phenols.

Metal-free catalytic C-H functionalization is highly desired for the construction of C-C bonds. We herein report a highly chemoselective consecutive C-H [2+3]-cyclative functionalization for the simultaneous formation of two C-C bonds with construction of polycyclic phenols catalyzed by commercially available and low-cost B(C6 F5 )3 . This catalytic system tolerates a wide range of substrate scope, providing a series of 2,6,7,8-tetrahydroacenaphthylen-3-ol-type polycyclic compounds efficiently. Several derivatizations of the catalytic products have also been conducted to show the potential application of this method in synthesis of polycyclic compounds.

Small Molecule EGFR Inhibitors as Anti-Cancer Agents: Discovery, Mechanisms of Action, and Opportunities.

Epidermal growth factor receptors (EGFRs) are a class of receptor tyrosine kinase that are also called ErbB1 and HER1. EGFR tyrosine kinase activity inhibition is considered a promising therapeutic strategy for the treatment of cancer. Many small-molecule inhibitors of EGFR tyrosine kinase (EGFR-TK), from medicinally privileged molecules to commercial drugs, have been overviewed. Particular attention has been paid to the structure of the molecule and its mechanism of action if reported. Subsequent classification of the molecules under discussion has been carried out. Both natural and synthetic and reversible and irreversible EGFR-tyrosine kinase inhibitors have been discussed. Various types of cancers that are caused by overexpression of the EGFR gene, their possible molecular origins, and their natures have also been counted in this article. Because the EGFR signaling pathway controls the proliferation, growth, survival, and differentiation of cells, and the mutated EGFR gene overproduces EGFR protein, which ultimately causes several types of cancer, proper understanding of the molecular dynamics between the protein structure and its inhibitors will lead to more effective and selective EGFR-TKIs, which in turn will be able to save more lives in the battle against cancer.

Improved Breakdown Strength of Polypropylene Film by Polycyclic Compounds Addition for Power Capacitors.

In this paper, an improved method for the electric performance of polypropylene (PP) film was proposed to promote the safety and stability of power capacitors. Modified PP films containing three different polycyclic compounds were prepared, which showed good thermal properties and decreased DC conductivity. The DC breakdown strength of the modified PP films under both positive and negative voltage is increased compared with that of the original film. The deep traps introduced by polycyclic compounds and the decreased carrier mobility give an explanation of the decreased DC conductivity. A quantum chemistry calculation was further performed to clarify the mechanism for improving electrical performance, presenting that polycyclic compounds with a high electron affinity and low ionization energy can capture high-energy electrons, protecting the PP molecular chain from attack, and then increase the breakdown strength. It is concluded that the modified PP films by polycyclic compounds have great potential in improving the insulating properties of power capacitors.

Dodecacyclic-Fused Electron Acceptors with Multiple Electron-Deficient Units for Efficient Organic Solar Cells.

Fused aromatic cores in non-fullerene electron acceptors (NFEAs) play a significant role in determining their optoelectronic properties and photovoltaic performance. In this work, a dodecacyclic-fused core with three electron-deficient units is synthesized through a double intramolecular Cadogan reduction cyclization. Terminal groups with different halogen substitution (F or Cl) are grafted onto the dodecacyclic-fused core to afford MS-4F and MS-4Cl, both of which showed strong and broad absorption, narrow bandgaps around 1.40 eV, and variable molecular packing model in pristine and blend films. Photovoltaic performance of solar cells containing MS-4F and MS-4Cl as NFEAs were investigated with resultant power conversion efficiencies (PCEs) of 11.75 % and 11.79 %, respectively. The mechanism study indicates that both of PBDB-T : MS-4F- and PBDB-T : MS-4Cl-based devices displayed high hole and electron mobility values, efficient charge transfer, and low charge recombination etc. These results indicate that designing multiple-fused aromatic cores with multiple electron-deficient units is a promising strategy to obtain high-performance NFEAs.

New complex polycyclic compounds: Synthesis, antiproliferative activity and mechanism of action.

Polycyclic or O-glycoconiugate polycyclic compounds 1a-g were previously tested for their in vitro antiproliferative activity. In this series of compounds, activity increases as log P decreases. Specifically, compounds 1d and 1g showed lower log P values together with the best antiproliferative profiles. With the aim of extending our understanding of the structure-activity relationship (SAR) of this class of compounds, we prepared new polycyclic derivatives 2a-c, which bear on each of the two phenyl rings hydrophilic substituents (OH, SO2NH2 or NHCOCH3). These substituents are able to form hydrogen bonds and to decrease the partition coefficient value as compared with compound 1d. Compound 2a was slightly more active than 1d, while 2b and 2c had antiproliferative activity comparable to that of 1d. Finally, the role of the two phenyl groups of polycycle derivatives 1 was also investigated. The analog 3, which bears two methyls instead of the two phenyls had a lower log P value (2.94 ± 1.22) than all the other compounds, but it had negligible antiproliferative activity at 10 µM. The analysis of the most active derivative 2a revealed a significant antiproliferative activity against the triple-negative breast cancer cell line MDA-MB231. After a 24 h treatment, an autophagic process was activated, as demonstrated by an increase in monodansylcadaverine-positive cells as well as by the appearance of the autophagic markers Beclin and LC3II. Prolonging the treatment to 48 h, 2a caused cytotoxicity through the activation of caspase-dependent apoptosis.

Association between polycyclic aromatic hydrocarbons and rheumatoid arthritis / 中华老年医学杂志

Objective To analyze the association between polycyclic aromatic hydrocarbons(PAHs)exposure and rheumatoid arthritis (RA)based on large sample data.Methods The RA patients(RA group)and non-RA patients(non-RA group)with complete data were selected from the National Health and Nutrition Survey Database in the United States(NHANES)(2005-2014).The logistic regression model was used to analyze the association between 8 monohydroxylated(OH-)PAH metabolites in the urine and RA.Results A total of 357 RA patients and 5,256 non-RA participants were included.After adjusting the confounding factors by logistic analysis,the level of OH-PAHs mixture at the highest quartile(Q4)was associated with increased risk of RA compared with that at the lowest quartile(Q1) (OR =1.60,95 ％ CI:1.16 2.23).For a single kind of OH-PAHs,the Q4 levels of 1-hydroxynaphthalene (OR =1.59,95 ％ CI.1.14-2.23),2-hydroxynaphthalene (OR =1.66,95 ％ CI:1.19-2.32),2-hydroxyfluorene(OR =1.61,95 ％ CI:1.17-2.22),3-hydroxyfluorene(OR =1.64,95％ CI:1.18-2.27) and 1-hydroxyphenanthrene (OR =1.38,95 ％ CI:1.00-1.94) were all associated with significantly increased risk of RA compared with the Q1 level(all P＜0.05).However,the Q2 level of 1-hydroxypyrene(OR =0.60,95％ CI:0.43-0.83) was related to a decreased incidence of RA (P＜0.01).Conclusions OH-PAHs mixed exposure is a risk factor for RA.The association between the level of individual OH-PAH and the rate of RA is bidirectional and is depended on the type and concentration of OH-PAHs.

Association between polycyclic aromatic hydrocarbons and rheumatoid arthritis / 中华老年医学杂志

Objective@#To analyze the association between polycyclic aromatic hydrocarbons(PAHs)exposure and rheumatoid arthritis(RA)based on large sample data.@*Methods@#The RA patients(RA group)and non-RA patients(non-RA group)with complete data were selected from the National Health and Nutrition Survey Database in the United States(NHANES)(2005—2014). The logistic regression model was used to analyze the association between 8 monohydroxylated(OH-)PAH metabolites in the urine and RA.@*Results@#A total of 357 RA patients and 5, 256 non-RA participants were included.After adjusting the confounding factors by logistic analysis, the level of OH-PAHs mixture at the highest quartile(Q4)was associated with increased risk of RA compared with that at the lowest quartile(Q1)(OR=1.60, 95%CI: 1.16-2.23). For a single kind of OH-PAHs, the Q4 levels of 1-hydroxynaphthalene(OR=1.59, 95%CI: 1.14-2.23), 2-hydroxynaphthalene(OR=1.66, 95%CI: 1.19-2.32), 2-hydroxyfluorene(OR=1.61, 95%CI: 1.17-2.22), 3-hydroxyfluorene(OR=1.64, 95%CI: 1.18-2.27)and 1-hydroxyphenanthrene(OR=1.38, 95%CI: 1.00-1.94)were all associated with significantly increased risk of RA compared with the Q1 level(all P<0.05). However, the Q2 level of 1-hydroxypyrene(OR=0.60, 95%CI: 0.43-0.83)was related to a decreased incidence of RA(P<0.01).@*Conclusions@#OH-PAHs mixed exposure is a risk factor for RA.The association between the level of individual OH-PAH and the rate of RA is bidirectional and is depended on the type and concentration of OH-PAHs.

DNA-damaging activities of twenty-four structurally diverse unsubstituted and substituted cyclic compounds in embryo-fetal chicken livers.

DNA-damaging activities of twenty-four structurally diverse unsubstituted and substituted cyclic compounds were assessed in embryo-fetal chicken livers. Formation of DNA adducts and strand breaks were measured using the nucleotide 32P-postlabelling (NPL) and comet assays, respectively. Unsubstituted monocyclic benzene, polycyclic fused ring compound naphthalene, covalently connected polycyclic ring compound biphenyl, and heterocyclic ring compound fluorene did not produce DNA damage. Amino-substituted monocyclic compounds, aniline and p-phenylenediamine, as well as polycyclic 1-naphthylamine were also negative. In contrast, carcinogenic monocyclic methyl-substituted anilines: o-toluidine, 2,6-xylidine, 3,4-dimethylaniline, 4-chloro-o-toluidine; 2 methoxy-substituted methylaniline: p-cresidine; 2,4 and 2,6 diamino- or dinitro- substituted toluenes all produced DNA damage. Genotoxic polycyclic amino-substituted 2-naphthylamine, 4-aminobiphenyl, benzidine, methyl-substituted 3,2'-dimethyl-4-aminobiphenyl and 4-dimethylaminoazobenzene as well as amino- and nitro- fluorenes substituted at the 1 or 2 positions also were positive in at least one of the assays. Overall, the DNA damaging activity of cyclic compounds in embryo-fetal chicken livers reflected the type and position of the substitution on the aromatic ring. Additionally, substituted polycyclic compounds exhibited higher DNA-damaging potency compared to monocyclic chemicals. These results are congruent with in vivo findings in other species, establishing chicken eggs as a reliable system for structure-activity assessment of members of groups of related chemicals.

New Rigid Polycyclic Bis(phosphane) for Asymmetric Catalysis.

A simple, highly efficient synthesis of a series of novel chiral non-racemic rigid tetracyclic phosphorus ligands, applicable in important chemical asymmetric transformations, was performed. In a tandem cross-coupling/C-H bond activation reaction, a well-recognised and readily available ligand (R,R)-NORPHOS was used as the starting material. The palladium complexes of new ligands were obtained and characterised on the example of a crystalline dichloropalladium complex of [(1R,2R,9S,10S,11R,12R)-4-phenyltetracyclo[8.2.1.02,9.03,8]trideca-3,5,7-triene-11,12-diyl]bis(diphenylphosphane). A notably high activity and stereoselectivity of the palladium catalysts based on the new ligands were confirmed in a model asymmetric allylic substitution reaction. Herein, we discuss the geometry of the palladium complexes formed and its impact on the efficiency of the catalysts. A comparison of their geometric features with other bis(phosphane) ligand complexes found in the Cambridge Structural Database and built density functional theory (DFT) commutated models is also presented and rationalised.

C-Halogenated 9,10-Diboraanthracenes: How the Halogen Load and Distribution Influences Key Optoelectronic Properties.

9,10-Dihydro-9,10-diboraanthracenes (DBAs) have low-energy LUMOs and narrow HOMO-LUMO gaps and are thus attractive electron-transporting and light-emitting materials in optoelectronic devices. A systematic series of ten C-halogenated 9,10-(Mes)2 -DBAs was synthesized and studied by cyclic voltammetry, UV/Vis absorption and emission spectroscopy, and quantum-chemical calculations (Mes=mesityl). We probed the influence of the nature of the halogen atoms and the halogen substitution patterns on key optoelectronic properties of the DBAs. All 9,10-(Mes)2 derivatives can be reversibly reduced at the DBA cores and at electrode potentials between E1/2 Red1 =-1.84 and -1.26 V (vs. FcH/FcH+ ). The most bathochromic UV/Vis absorption and the fluorescence emission of each DBA correspond to an ICT transition between the Mes rings and the DBA core. Br substituents lower the DBA LUMO energy and narrow the energy gap to the highest degree along the series F

Facile synthesis and antiproliferative activity of 7H-benzo[7,8]chromeno[2,3-d]pyrimidin-8-amines.

A series of 7H-benzo[7,8]chromeno[2,3-d]pyrimidin-8-amines 6a-t were synthesized as new potential antiproliferative agents. The in vitro antiproliferative activity evaluation of title compounds using MTT assay revealed that most compounds showed significant activity against tested cancer cell lines (A549, MOLT-4, and HeLa). The 2-fluoro-aniline derivatives 6e and 6l were the most active compounds against A549 and MOLT-4 cells, respectively. The benzylamine analog 6h showed superior activity against HeLa cells. However, compound 6l with IC50 values of 5.2-6.9 µM had the best profile of activity against all tested cell lines. The morphological and flow cytometric analyses showed that compound 6l can induce apoptosis in the MOLT-4 cells.

The First Modular Route to Core-Chiral Bispidine Ligands and Their Application in Enantioselective Copper(II)-Catalyzed Henry Reactions.

The first modular and flexible synthesis of core-chiral bispidines was achieved by using an "inside-out" strategy. The key intermediate, a NBoc-activated bispidine lactam, was constructed in enantiomerically pure form from a chirally modified ß-amino acid and 2-(acetoxymethyl)acrylonitrile in just five steps and good 48% yield. A simple addition-reduction protocol permitted a highly endo-selective introduction of substituents and, thus, a fast and variable access to 2-endo-substituted and 2-endo,N-fused bi- and tricyclic bispidines. The new diamines were evaluated as the chiral ligands in asymmetric Henry reactions. Excellent enantioselectivities of up to 99% ee and good diastereomeric ratios of up to 86:14 were reached with a copper(II) complex modified by a 2-endo,N-(3,3-dimethylpyrrolidine)-annelated bispidine. Its performance is superior to that of the well-known bispidines (-)-sparteine and the (+)-sparteine surrogate.

Synthesis of cyclopropyl-substituted furans by brønsted Acid promoted cascade reactions.

Chloroacetic acid promotes an efficient and diastereoselective intramolecular cascade reaction of electron-deficient ynenones to deliver products featuring a 2,3,5-trisubstituted furan bearing a fused cyclopropyl substituent at the 5-position. Synthetically relevant polycyclic building blocks featuring rings of various sizes and heteroatoms have been synthesized in high yield using this mild acid-catalyzed reaction.

Efecto genotóxico de las mezclas complejas de hidrocarburos en trabajadores de estaciones de servicio de gasolina / Genotoxiceffect of complex hydrocarbon mixtures in workers gasoline service stations

Objetivo: Evaluar el efecto genotóxico de las mezclas complejas de hidrocarburos en los trabajadores de estaciones de servicio de gasolina en Barranquilla (Atlántico, Colombia) a través de la prueba Cometa(CA) alcalina. Materiales y métodos: Se realizó un estudio transversal, prospectivo inferencial de casos y controles. El grupo control estuvo conformado por 15 personas no expuestas laboralmente a hidrocarburos y el expuesto por 38 personas que trabajaron al menos 1 año como despachador de combustible. Se realizó un ensayo cometa alcalino en sangre venosa. Se determinó el efecto genotóxico utilizando el porcentaje de ADN n la cola y por Unidades Arbitrarias de daño. La comparación entre grupos se realizó por la prueba t-student o W-Wilcoxon. Los datos fueron modelados con una regresión simple ajustada. Los análisis de datos fueron realizados con el paquete estadístico R. Resultados: Las edades de los grupos control y experimental fueron de 33±9 y 38±10 años, respectivamente; no hubo diferencia estadísticamente significativa para esta variable (t = -1.82; p-valor > 0,05; a = 95%). Hubo asociación entre Edad y Tiempo de Exposición (x² = 24.9; p-valor < 0,05; a = 95%). El %ADN en la cola para el grupo control fue de 20,67±25,79, mientras que para el grupo expuesto fue 53,35±40,28. El modelo de degradación de ADN es «y=√l(512,687+733,899√1(t))¼. Conclusiones: Las mezclas complejas de heterocíclicos son potencialmente genotóxicas. El daño progresivo se encuentra al 80 % después de 6 años de exposición, siendo igual a los 9 años de exposición que a los 15.

Objective: To evaluate the genotoxic effects of complex mixtures of hydrocarbons in gasoline stations's workers in Barranquilla (Atlántico, Colombia) using the alkaline Comet Assay (CA). Materials and methods: Study was transversal, prospective inferential of case and control. The controls were 15 persons without occupationally exposed to hydrocarbons and the exposed were 38 persons that were working at least one year as fuel dispenser. The alkaline Comet Assay was performed on venous blood. Genotoxic effects was determined throug DNA percentage in tail and damage Arbitrary Units. The comparison between groups was performed by t-student or W-Wilcoxon test. The data were modeled with a simple regression adjusted. The data analyses were performed with the statistical package R. Results: Age of control and experimental groups were 33±9 and 38±10 years respectively, there was no statistically significant difference for this variable (t = -1.82; p-value > 0.05; a = 95 %). There was an association between Age and Exposure Time (x² = 24.9; p-value < 0.05, a = 95%). The %DNA tail for the control group was 20.67 ± 25.79, while for the exposed group was 53.35± 40.28. The DNA degradation model is «y=√ (512.687+733,899√ (t))¼. Conclusions: The complex mixtures of heterocyclic are potentially genotoxic. As the progressive damage is 80 % after 6 years of exposure, being equal damage to the 9 to 15 years of exposure.

Antibacterial activity of novel benzopolycyclic amines.

Staphylococcus aureus, especially strains resistant to multiple antibiotics, is a major pathogen for humans and animals. In this paper we have synthesized and evaluated the antibacterial activity of a new series of benzopolycyclic amines. Some of them exhibited µM MIC values against Staphylococcus aureus and other bacteria, including methicillin-resistant S. aureus MRSA. Compound 8 that displayed a good selectivity index, showed to be active in eliminating bacterial cells forming a preexisting biofilm.

3,10,14,21-Tetra-kis(4-meth-oxy-phen-yl)penta-cyclo-[11.8.0.0(2,11).0(4,9).0(15,20)]henicosa-1(21),2,4(9),5,7,10,13,15(20),16,18-decaen-12-one chloro-form monosolvate.

The asymmetric unit of the title compound, C49H36O6·CHCl3, contains half an organic mol-ecule, the complete mol-ecule being generated by the operation of a crystallographic twofold rotation axis, and half a highly disordered chloro-form mol-ecule. The contribution to the diffraction pattern of the latter was removed using the program SQUEEZE in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148-155]; the unit-cell characteristics take into account the presence of CHCl3. The dihedral angles between the planes of the naphthalene ring system and the meth-oxy-benzene rings are 71.05 (7) (syn to the central C=O group) and 57.27 (6)° (anti to the central C=O group). In the crystal, mol-ecules are linked by C-H⋯O inter-actions, generating C(12) chains running parallel to the b axis.

Novel benzopolycyclic amines with NMDA receptor antagonist activity.

A new series of benzopolycyclic amines active as NMDA receptor antagonists were synthesized. Most of them exhibited increased activity compared with related analogues previously published. All the tested compounds were more potent than clinically approved amantadine and one of them displayed a lower IC50 value than memantine, an anti-Alzheimer's approved drug.

Antiproliferative and antiviral activity of three libraries of adamantane derivatives.

Three libraries of adamantane derivatives were synthesized and evaluated for antiviral and antiproliferative activities against a broad variety of DNA and RNA viruses. Whereas none of the compounds exhibit antiviral activity at subtoxic concentrations, antiproliferative activity was found against murine leukemia cells (L1210), human T-lymphocyte cells (CEM), and cervix carcinoma cells (HeLa) for 4, 8, and 10.

Tris(tetraceno)triquinacenes: synthesis and photophysical properties of threefold linearly extended tribenzotriquinacenes.

The linear extension of the rigid, C(3v)-symmetrical carbon framework of tribenzotriquinacene (TBTQ) along its three wings is reported. The key step of the extension procedure consists of a Diels-Alder reaction of three ortho-quinodimethane units generated in situ at the triquinacene core. The use of 1,4-naphthoquinone provides a facile and particularly efficient access to tris(tetraceno)-annellated triquinacenes. The steady-state photophysical properties of these new oligotetracenes bearing three mutually orthogonal chomophores are determined and analyzed by DFT calculations.