Synthesis,characterization, crystal structure and cytotoxicity of 2,4-bis(selenomethyl)quinazoline

Organoselenium compounds have already been reported to be good anticarcinogenic candidates. A new selenoquinazoline derivative, 2,4-bis(selenomethyl)quinazoline (compound 1), has been synthesized, spectroscopically characterized and its crystal structure has been studied. An intermolecular coupling between C₂ and \( {\text{H}}_{5}^{\prime } \) in the Heteronuclear Multiple Bond Correlation (HMBC) experiment has been observed. Assuming that the head-to-tail overlap of parallel molecules (as identified by X-ray diffraction) remains in solution to give bimolecular entities, the π–π interaction enables heteronuclear coupling between the former atoms with a three-bond distance [C₂···(π–π)···\( {\text{C}}_{5}^{\prime } \)–\( {\text{H}}_{5}^{\prime } \)]. The crystal structure of compound 1 has been solved by X-ray diffraction. It crystallizes in triclinic system, space group P?1. Unit cell parameters are a = 7.4969(7) Å, b = 8.7008(8) Å, c = 10.1666(9) Å, α = 110.215(2)°, β = 90.354(2)°, γ = 115.017(1)°. Linear chains in crystals of compound 1 are generated by C–H···Se and Se···Se bonds between molecules. Furthermore, head-to-tail overlap of parallel molecules, in which π–π interactions can occur, is observed. Compound 1 exhibited a cytotoxic effect in all of the evaluated tumoral cell lines and showed a higher cytotoxic effect in colon and breast cancer cell lines than etoposide, which was used as a reference compound.     

Analysis of chiral amino acids in cerebrospinal fluid samples linked to different stages of Alzheimer disease

Chiral micellar electrokinetic chromatography with laser-induced fluorescence detection (chiral-MEKC-LIF) was used to investigate D- and L-amino acid contents in cerebrospinal fluid (CSF) samples related to different Alzheimer disease (AD) stages. CSF samples were taken from (i) control subjects (S1 pool), (ii) subjects showing a mild cognitive impairment who remained stable (S2 pool), (iii) subjects showing an mild cognitive impairment that progressed to AD (S3 pool) and (iv) subjects diagnosed with AD (S4 pool). The optimized procedure only needed 10 μL of CSF and it included sample cleaning, derivatization with FITC and chiral-MEKC-LIF separation. Eighteen standard amino acids were baseline separated with efficiencies up to 703,000 plates/m, high sensitivity (LODs in the nM range) and good resolution (values ranging from 2.6 to 9.5). Using this method, L-Arg, L-Leu, L-Gln, γ-aminobutyric acid, L-Ser, D-Ser, L-Ala, Gly, L-Lys, L-Glu and L-Asp were detected in all the CSF samples. S3 and S4 samples (i.e. AD subjects) showed significant lower amounts of L-Arg L-Lys, L-Glu and L-Asp compared to the non-AD S1 and S2 samples, showing in the S4 group the lowest amounts of L-Arg L-Lys, L-Glu and L-Asp. Moreover, γ-aminobutyric acid was significantly higher in AD subjects with the highest amount also found for S4. No significant differences were observed for the rest of amino acids including D-Ser. Based on the obtained chiral-MEKC-LIF data, it was possible to correctly classify all the samples into the four groups. These results demonstrate that the use of enantioselective procedures as the one developed in this work can provide some new light on the investigations of AD, including the discovery of new biomarkers related to different stages of AD.     

Chemical, antioxidant and antimicrobial investigations of Pinus cembra L. bark and needles

The chemical constituents and biological activity of Pinus cembra L. (Pinaceae), native to the Central European Alps and the Carpathian Mountains, are not well known. The aim of the present work was to examine the phenolic content, antioxidant and antimicrobial effects of hydromethanolic extracts of Pinus cembra L. bark and needles. Bark extract had higher concentrations of total phenolics (299.3 vs. 78.22 mg gallic acid equivalents/g extract), flavonoids (125.3 vs. 19.84 mg catechin equivalents/g extract) and proanthocyanidins (74.3 vs. 12.7 mg cyanidin equivalents/g extract) than needle extract and was more active as a free radical scavenger, reducing agent and antimicrobial agent. The EC?? values in the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) and reducing power assays were 71.1, 6.3 and 26 mg/mL for bark extract and 186.1, 24 and 104 mg/mL for needle extract, respectively. In addition, needle extract showed ferrous ions chelating effects (EC?? = 1,755 μg/mL). The antimicrobial effects against Staphylococcus aureus, Sarcina lutea, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans were assessed by the agar diffusion method. Both extracts (4 mg/well) were active against all the microorganisms tested; bark extract showed higher inhibition on all strains. These results indicate that Pinus cembra L. bark and needles are good sources of phytochemicals with antioxidant and antimicrobial activities.     

Acanthifoliosides, minor steroidal saponins from the Caribbean sponge Pandaros acanthifolium

Seven novel steroid glycosides, acanthifoliosides A-F (1-6), and the methyl ester of 6 (7), were isolated from the marine sponge Pandaros acanthifolium as minor components. Acanthifoliosides are characterized by a rare C-15 and C-16 oxidized D ring, which was previously found in saponins produced by starfishes. Very uncommon is the presence of additional sugar residues at C-15 or C-16. Their structures were determined on the basis of extensive spectroscopic analyses, including two-dimensional NMR and HRESIMS data. The absolute configurations of the aglycones were assigned by comparison between experimental and TDDFT calculated CD spectra of 1, whereas the absolute configurations of the monosaccharide units were determined by chiral GC analyses of the acid methanolysates. Some of the acanthifoliosides exhibit moderate antiprotozoal activity but to a lesser extent than the most potent pandarosides.     

Rapid wide-scope screening of drugs of abuse, prescription drugs with potential for abuse and their metabolites in influent and effluent urban wastewater by ultrahigh pressure liquid chromatography-quadrupole-time-of-flight-mass spectrometry

In the present work, a rapid method with little sample handling has been developed for determination of 23 selected volatile organic compounds in environmental and wastewater samples. The method is based on headspace solid-phase microextraction (SPME) followed by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) determination using triple quadrupole analyzer (QqQ) in electron ionization mode. The best conditions for extraction were optimised with a factorial design taking into account the interaction between different parameters and not only individual effects of variables. In the optimized procedure, 4 mL of water sample were extracted using a 10 mL vial and adding 0.4 g NaCl (final NaCl content of 10%). An SPME extraction with carboxen/polydimethylsiloxane 75 μm fiber for 30 min at 50°C (with 5 min of previous equilibration time) with magnetic stirring was applied. Chromatographic determination was carried out by GC-MS/MS working in Selected Reaction Monitoring (SRM) mode. For most analytes, two MS/MS transitions were acquired, although for a few compounds it was difficult to obtain characteristic abundant fragments. In those cases, a pseudo selected reaction monitoring (pseudo-SRM) with three ions was used instead. The intensity ratio between quantitation (Q) and confirmation (q) signals was used as a confirmatory parameter. The method was validated by means of recovery experiments (n=6) spiking mineral water samples at three concentration levels (0.1, 5 and 50 μg L(-1)). Recoveries between 70% and 120% were generally obtained with relative standard deviations (RSDs) lower than 20%. The developed method was applied to surface water and wastewater from a wastewater treatment plant and from a municipal solid-waste treatment plant. Several compounds, like chloroform, benzene, trichloroethylene, toluene, tetrachloroethylene, dibromochloromethane, xylenes and bromoform were detected and confirmed in all the samples analyzed.     

Two flavors of PEPPSI-IPr: activation and diffusion control in a single NHC-ligated Pd catalyst?

Abnormal reactivity has been observed in Negishi, Suzuki-Miyaura, and Kumada-Tamao-Corriu cross-couplings in which PEPPSI-IPr (where PEPPSI stands for pyridine enhanced precatalyst preparation, stabilization, and initiation and IPr refers to the NHC ligand) is employed, implicating the presence of two distinct Pd(0) species in the catalytic cycle. Polybrominated arenes and organometallic reagents react selectively to give the product of exhaustive polysubstitution regardless of the initial reaction stoichiometry. Competition experiments suggest that, after an initial activation controlled oxidative addition, reductive elimination produces an ultrareactive Pd(0) species which consumes all remaining C-Br bonds in the molecule under diffusion control.     

Building an empirical mass spectra library for screening of organic pollutants by ultra-high-pressure liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry

Hybrid quadrupole time-of-flight mass spectrometry (QTOF MS) has gained wide acceptance in many fields of chemistry, for example, proteomics, metabolomics and small molecule analysis. This has been due to the numerous technological advances made to this mass analyser in recent years. In the environmental field, the instrument has proven to be one of the most powerful approaches for the screening of organic pollutants in different matrices due to its high sensitivity in full acquisition mode and mass accuracy measurements. In the work presented here, the optimum experimental conditions for the creation of an empirical TOF MS spectra library have been evaluated. For this model we have used a QTOF Premier mass spectrometer and investigated its functionalities to obtain the best MS data, mainly in terms of mass accuracy, dynamic range and sensitivity. Different parameters that can affect mass accuracy, such as lock mass, ion abundance, spectral resolution, instrument calibration or matrix effect, have also been carefully evaluated using test compounds (mainly pesticides and antibiotics). The role of ultra-high-pressure liquid chromatography (UHPLC), especially when dealing with complex matrices, has also been tested. In addition to the mass accuracy measurements, this analyser allows the simultaneous acquisition of low and high collision energy spectra. This acquisition mode greatly enhances the reliable identification of detected compounds due to the useful (de)protonated molecule and fragment ion accurate mass information obtained when working in this mode. An in-house empirical spectral library was built for approximately 230 organic pollutants making use of QTOF MS in MS(E) mode. All the information reported in this paper is made available to the readers to facilitate screening and identification of relevant organic pollutants by QTOF MS.     

Water-dispersible ultrathin Au nanowires prepared using a lamellar template of a long-chain amidoamine derivative

Straight ultrathin Au nanowires (NWs) with diameters less than 2 nm were synthesized using the lamellar structure of C18AA in an organogel and its selective adsorption for specific gold surfaces. In addition, the potential to form a bilayer structure with interdigitated hydrocarbon chains enabled the production of water-dispersible Au NWs without morphological change.