Chemistry of the phenoxathiins and isosterically related heterocycles. XXXII . The synthesis of 2-azathianthrene and selected analogs

The synthesis of 2-azathianthrene ([1,4]benzodithiino[2,3-c]pyridine), the only remaining monoazathianthrene yet to be reported, is described. Attempts at the direct condensation of disubstituted pyridines with the dianion of 1,2-dimercaptobenzene were generally unsuccessful requiring that the alternative condensation of the dianion with disubstituted pyridine 1-oxides be employed. The title compound was characterized by physical means including ¹³C-nmr spectroscopy. One analog, 4-nitro-2-azathianthrene was also studied by X-ray crystallographic means; the molecule crystallized with two molecules in the asymmetric unit P2₁/n, a = 20.712(3), b = 7.8109(13), c = 13.720(2)Å, β = 107.880(11)°, Z = 8, the data refined to a final R = 0.051 for 3061 reflections. Dihedral angles between the planes of the phenyl rings were 135.00(13) and 132.52(13)° for the two independent molecules contained in the crystal. Close non? bonded S ?O intramolecular contacts were observed in both molecules between the sulfur and nitro-group oxygens. Both nitro groups are twisted out of the plane of the pyridine ring and are oriented at angles of 28.75 and 38.82° respectively.     

Theoretical studies on the metathesis processes, (Tp(PH3)MR(eta 2-H[bond]CH3)]-->[Tp(PH3)M(CH3)(eta 2-H[bond]R)] (M=Fe,Ru, and Os; R=H and CH3)

Theoretical calculations on the metathesis process, [Tp(PH3)MR(eta 2-H[bond]CH3)] --> [Tp(PH3)M(CH3)(eta 2-H[bond]R)] (M=Fe, Ru, and Os; R=H and CH3), have been systematically carried out to study their detailed reaction mechanisms. Other than the one-step mechanism via a four-center transition state and the two-step mechanism through an oxidative addition/reductive elimination pathway, a new one-step mechanism, with a transition state formed under oxidative addition, has been found. Based on the intrinsic reaction coordinate calculations, we found that the trajectories of the transferring hydrogen atom in the metathesis processes studied are similar to each other regardless of the nature of reaction mechanisms.     

Conformational dependence of the intrinsic acidity of the aspartic acid residue sidechain in N-acetyl- -aspartic acid-N′-methylamide

The sidechain conformational potential energy hypersurfaces (PEHS) for the γ_L, β_L, α_L, and α_D backbone conformations of N-acetyl- -aspartate-N′-methylamide were generated. Of the 81 possible conformers initially expected for the aspartate residue, only seven were found after geometric optimizations at the B3LYP/6-31G(d) level of theory. No stable conformers could be located in the δ_L, _L, γ_D, δ_D, and _D backbone conformations. The ‘adiabatic’ deprotonation energies for the endo and exo forms of N-acetyl- -aspartic acid-N′-methylamide were calculated by comparing their optimized relative energies against those found for the seven stable conformers of N-acetyl- -aspartate-N′-methylamide. Sidechain conformational PEHSs were also generated for the estimation of ‘vertical’ deprotonation energies for both endo and exo forms of N-acetyl- -aspartic acid-N′-methylamide. All backbone–sidechain (N–H⁻O–C) and backbone–backbone (N–HO=C) hydrogen bond interactions were analyzed. A total of two backbone–backbone and four backbone–sidechain interactions were found for N-acetyl- -aspartate-N′-methylamide. The deprotonated sidechain of N-acetyl- -aspartate-N′-methylamide may allow the aspartyl residue to form strong hydrogen bond interactions (since it is negatively charged) which may be significant in such processes as protein–ligand recognition and ligand binding. As a primary example, the molecular geometry of the aspartyl residue may be important in peptide folding, such as that in the RGD tripeptide.     

Solid-phase synthesis of pyrazolines and isoxazolines with sodium benzenesulfinate as a traceless linker

[reaction: see text] The preparation of pyrazoline and isoxazoline derivatives with traceless solid-phase sulfone linker strategy is described. Key steps involved in the solid-phase synthetic procedure include (i) sulfinate S-alkylation, (ii) sulfone anion alkylation, (iii) gamma-hydroxy sulfone --> gamma-ketosulfone oxidation, and (iv) traceless product release via elimination-cyclization. A library of 12 pyrazolines and isoxazolines was synthesized.     

Development and validation of a method for determination of residues of 15 pyrethroids and two metabolites of dithiocarbamates in foods by ultra-performance liquid chromatography-tandem mass spectrometry

This paper reports a novel approach for the detection, confirmation, and quantification of 15 selected pyrethroid pesticides, including pyrethins, and two metabolites of dithiocarbamates in foods by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS–MS). The proposed method makes use of a modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure that combines isolation of the pesticides and sample cleanup in a single step. Analysis of pyrethroids and dithiocarbamate metabolites was performed by UPLC–MS–MS operated with electrospray and atmospheric pressure chemical ionization, respectively. Two specific precursor–product ion transitions were acquired per target compound in multiple reaction monitoring (MRM) mode. Such acquisition achieved the minimum number of identification points according to European Commission (EC) document no. SANCO/10684/2009, thus fulfilling the EC point system requirement for identification of contaminants in samples. The method was validated with a variety of food samples. Calibration curves were linear and covered from 1 to 800 μg kg⁻¹ in the sample for all target compounds. Average recoveries, measured at mass fractions of 10 and 100 μg kg⁻¹ for pyrethroids and 5 and 50 μg kg⁻¹ for dithiocarbamate metabolites, were in the range of 70–120% for all target compounds with relative standard deviations below 20%. Method limits of quantification (MLOQ) were 10 μg kg⁻¹ and 5 μg kg⁻¹ for pyrethroids and dithiocarbamate metabolites, respectively. The method has been successfully applied to the analysis of 600 food samples in the course of the first Hong Kong total diet study with pyrethroids and metabolites of dithiocarbamates being the pesticides determined.     

Spectrophotometric method for the determination of sorbic acid in various food samples with iron(III) and 2-thiobarbituric acid as reagents

A simple, rapid and accurate spectrophotometric method has been developed for the determination of sorbic acid in various food samples based on the oxidation of sorbic acid by iron(III) at 100 degrees C to malonaldehyde, which then reacts with 2-thiobarbituric acid to form a reddish brown product. The optimum experimental conditions for colour development have been assessed. Absorbance measurements were made at 529 nm in the presence of 0.4% m/V citric acid. The calibration graph was linear for 0-6 micrograms ml-1 of sorbic acid with a slope of 0.131 A micrograms-1 ml. The recoveries of sorbic acid at concentrations of 164-557 micrograms ml-1 ranged from 96 to 103%. The relative standard deviations of ten replicate determinations of sorbic acid in a synthetic cream soda sample spiked with 573 micrograms ml-1 of sorbic acid and in an onion juice sample containing 82 micrograms ml-1 of sorbic acid were 1.6 and 1.9%, respectively. Interferences from several common food additives can be minimised by extracting sorbic acid with diethyl ether and then back-extracting the acid with sodium hydrogen carbonate. The method has been applied successfully to the determination of sorbic acid in a wide range of food samples including beverages, cake, cake mate, garlic bread sprinkle, onion juice, oyster flavoured sauce and grenadine syrup.     

A silicone-based stretchable micropost array membrane for monitoring live-cell subcellular cytoskeletal response

External forces are increasingly recognized as major regulators of cellular structure and function, yet the underlying mechanism by which cells sense forces and transduce them into intracellular biochemical signals and behavioral responses ('mechanotransduction') is largely undetermined. To aid in the mechanistic study of mechanotransduction, herein we devised a cell stretching device that allowed for quantitative control and real-time measurement of mechanical stimuli and cellular biomechanical responses. Our strategy involved a microfabricated array of silicone elastomeric microposts integrated onto a stretchable elastomeric membrane. Using a computer-controlled vacuum, this micropost array membrane (mPAM) was activated to apply equibiaxial cell stretching forces to adherent cells attached to the microposts. Using the mPAM, we studied the live-cell subcellular dynamic responses of contractile forces in vascular smooth muscle cells (VSMCs) to a sustained static equibiaxial cell stretch. Our data showed that in response to a sustained cell stretch, VSMCs regulated their cytoskeletal (CSK) contractility in a biphasic manner: they first acutely enhanced their contraction to resist rapid cell deformation ('stiffening') before they allowed slow adaptive inelastic CSK reorganization to release their contractility ('softening'). The contractile response across entire single VSMCs was spatially inhomogeneous and force-dependent. Our mPAM device and live-cell subcellular contractile measurements will help elucidate the mechanotransductive system in VSMCs and thus contribute to our understanding of pressure-induced vascular disease processes.     

Microwave survey of the conformational landscape exhibited by the propeller molecule triethyl amine

Conformational studies with quantum chemical methods yielded for the most stable conformer of triethyl amine a propeller-like structure belonging to the point group C(3), which corresponds to an oblate top. The microwave spectrum of this conformer with (14)N hyperfine splitting of all rotational transitions was assigned and molecular parameters were determined. The rotational constants were found to be A = B = 2.314873978(11) GHz, the (14)N quadrupole coupling constant χ(cc) = -5.2444(07) MHz. The observed spectrum could be reproduced within experimental accuracy. The standard deviation of a global fit with 48 rotational transitions is 1.5 kHz. The propeller-like structure seems to be energetically favorable and therefore also typical for related systems like triethyl phosphine, triisopropyl amine, tri-n-propyl amine, and tri-tert-butyl amine. Furthermore, the rotational transitions of two isotopologues, (13)C(2) and (13)C(5), could be measured in natural abundance and fitted with an excellent standard deviation. The C rotational constants could be determined to be 1.32681(96) GHz and 1.32989(18) GHz for the (13)C(2) and (13)C(5) isotopologues, respectively.     

A vacuum ultraviolet photoionization mass spectrometric study of acetone

The photoionization and dissociative photoionization of acetone have been studied at the photon energy range of 8-20 eV. Photoionization efficiency spectra for ions CH3COCH3+, CH3+, C2H3+, C3H3+, C3H5+, CH(2-)CO+, CH3CO+, C3H4O+, and CH3COCH2+ have been measured. In addition, the energetics of the dissociative photoionization has been examined by ab initio Gaussian-3 (G3) calculations. The computational results are useful in establishing the dissociation channels near the ionization thresholds. With the help of G3 results, the dissociation channels for the formation of the fragment ions CH3CO+, CH2CO+, CH3+, C3H3+, and CH3COCH2+ have been established. The G3 results are in fair to excellent agreement with the experimental data.