Proton dynamics in the hydrogen bond. Inelastic neutron scattering by single crystals of CsH2PO4 at 20 K

Inelastic neutron scattering spectra (INS) of the powder and of oriented single crystals of cesium dihydrogen phosphate (CsH₂PO₄, or CDP) at 20 K have been investigated. For single crystals the incident neutron beam was perpendicular to either the [100] or [001] crystal planes in order to distinguish between the short and long hydrogen bonds. The proposed assignments are based on previous infrared and Raman data and on the INS band intensities and polarisation. The optical and INS OH stretching band profiles are compared. Their shapes are described in terms of mechanical and electrical coupling of the two stretching modes of a O---H…O hydrogen bond. For the longer bond a Fermi resonance of the OH stretching mode with an overtone of the bending mode is observed. Finally, a broad central mode observed in the INS at very low frequency has been tentatively assigned to the relaxation of the proton transfer along the hydrogen bond.     

Practical synthesis of the new carbapenem antibiotic ertapenem sodium

[reaction: see text] A practical synthesis for the large-scale production of the new carbapenem antibiotic, [4R,5S,6S]-3-[[(3S,5S)-5-[[(3-Carboxyphenyl)amino]carbonyl]-3-pyrrolidinyl]thio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monosodium salt (ertapenem sodium, 1), has been developed. The synthesis features the novel use of 1,1,3,3-tetramethylguanidine as base for the low-temperature reaction of a thiol, derived from trans-4-hydroxy-L-proline, with the carbapenem nucleus activated as the enol phosphate. Hydrogenolysis of a p-nitrobenzyl ester is effected using a palladium on carbon catalyst to give an overall yield for the two steps of 90%. The use of bicarbonate in the hydrogenolysis was key in providing protection of the pyrrolidine amine as the sodium carbamate improving both the performance of the reaction and the stability of the product. This discovery made processing at manufacturing scale possible. Experimental evidence for the formation of the sodium carbamate is provided. A remarkably expedient process for the simultaneous purification and concentration of the aqueous product stream relies on ion-pairing extraction for the removal of the water-soluble 1,1,3,3-tetramethylguanidine. Crystallization then affords 59-64% overall yield of the monosodium salt form of the product.     

Essential oil composition and antioxidant activity of Stachys sylvatica L. (Lamiaceae) from different wild populations in Kosovo

Leaves and inflorescences of Stachys sylvatica L. (Lamiaceae) were collected from three different wild populations in Kosovo to study the natural variation of the chemical composition of essential oils, total flavonoids, total phenolics and the antioxidant activity. Essential oils were obtained by steam distillation and analysed by GC-FID and GC-MS, whereas total flavonoids, total phenolics and antioxidant activities were determined by spectrophotometric methods. Yields of essential oils ranged from 0.001% to 0.007% (v per dry weight). Twenty-eight volatile constituents were identified. The main constituents were α-pinene, β-pinene and germacrene-D. Total phenolics ranged from 39.3 to 70.8?mg?g?1 dry mass, whereas total flavonoid content ranged from 30.44 to 70.63?mg?g?1 dm. The antioxidant activity, as measured by the DPPH method, exhibited a rather high degree of activity ranging from 25.5% to 57.2%, whereas the FRAP antioxidant activity showed a lower variability and ranged from 93 to 133.4?mg?g?1 dm.     

Magnetic Mn and Co complexes with a large polycyclic aromatic substituted nitronylnitroxide

2-(1'-Pyrenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (PyrNN) was reacted with M(hfac)(2) (M = Mn(II) and Co(II), hfac = hexafluoracetylacetonate) to give two isostructural ML(2) stoichiometry M(hfac)(2)(PyrNN)(2) complexes and a ML stoichiometry one-dimensional (1-D) polymer chain complex [Mn(hfac)(2)(PyrNN)]. The ML(2) complexes have similar crystal structures with monoclinic unit cells, in which one NO unit from each PyrNN ligand is bonded to the transition metal on cis vertices of a distorted octahedron. The major magnetic interactions are intracomplex metal-to-radical exchange (J), and intermolecular exchange across a close contact between the uncoordinated NO units (J'). For M = Mn(II) an approximate chain model fit gives g = 2.0, J = (-)125 cm(-1) and J' = (-)49 cm(-1); for M = Co(II), g = 2.4, J = (-)180 cm(-1), and J' = (-)70 cm(-1). Hybrid density functional theory (DFT) computations modeling the intermolecular exchange by using only the radical units across the close contact are in good accord with the estimated values of J'. The chain type complex structure shows solvent incorporation for overall structure [Mn(hfac)(2)(PyrNN)](n)·0.5(CHCl(3))·0.5(C(7)H(16)). Both NO groups of the PyrNN ligand are complexed to form helical chains, with very strong metal to radical antiferromagnetic exchange that gives overall ferrimagnetic behavior.     

Composition and antimicrobial activities of Lippia multiflora Moldenke, Mentha x piperita L. and Ocimum basilicum L. essential oils and their major monoterpene alcohols alone and in combination

Essential oils from leaves of Lippia multiflora, Mentha x piperita and Ocimum basilicum from Burkina Faso were analysed by GC-FID and GC-MS. Major components were p-cymene, thymol, b-caryophyllene, carvacrol and carvone for L. multiflora, menthol and iso-menthone for M. x piperita and, linalool and eugenol for O. basilicum. The essential oils and their major monoterpene alcohols were tested against nine bacterial strains using the disc diffusion and broth microdilution methods. The essential oils with high phenolic contents were the most effective antimicrobials. The checkerboard method was used to quantify the efficacy of paired combinations of essential oils and their major components. The best synergetic effects among essential oils and major components were obtained with combinations involving O. basilicum essential oil and eugenol, respectively. As phenolic components are characterized by a strong spicy aroma, this study suggests that the selection of certain combinations of EOs could help to reduce the amount of essential oils and consequently reduce any adverse sensory impact in food.     

2′-O-Lysylaminohexyladenosine modified oligonucleotides

Abstract  

Development of therapeutically active oligonucleotides for sequence-specific gene knockdown relies on chemical modifications that confer high stability and target affinity and ideally enable cellular uptake. 2′-O-Lysylaminohexyluridine-containing antisense and siRNA oligonucleotides have been shown to be well suited for gene knockdown. They are highly resistant to enzymatic degradation while having good affinity for the targeted RNA strand and efficiently down-regulate their target in cell culture tumor models. The 2′-O-lysylaminohexyl modification was expanded to adenosine nucleosides. The corresponding phosphoramidite building block was prepared in a straightforward procedure comprising six steps starting from adenosine. After 2′-O-alkylation with N-(6-bromohexyl)phthalimide and removal of the N-protecting group, the protected lysine was specifically attached to the alkylamino group. Incorporation of 2′-O-lysylaminohexyladenosine nucleotides in a test sequence confirmed that the cationic chains lead only to minor duplex destabilization and do not disturb the duplex structure. Results further emphasize the advantageous properties of 2′-O-lysylaminohexyl modified oligonucleotides for therapeutic applications.     

Dinuclear copper(II) complexes of a novel 3-(aminomethyl)naphthoquinone Mannich base: Synthesis,structural, magnetic and electrochemical studies

A novel versatile tridentate 3-(aminomethyl)naphthoquinone proligand, 3-[N-(2-pyridylmethyl)aminobenzyl]-2-hydroxy-1,4-naphthoquinone (HL), was obtained from the Mannich reaction of 2-hydroxy-1,4-naphthoquinone (Lawsone) with 2-aminomethylpyridine (amp) and benzaldehyde. The reactions of HL with CuCl₂·2H₂O yielded two novel dinuclear copper(II) complexes, [Cu(L)(H₂O)(μ-Cl)Cu(L)Cl] (1b), [CuCl(L)(μ-Cl)Cu(amp)Cl] (2) and a polymeric compound, [Cu(L)Cl)]_n (1a), whose relative yields were sensitive to temperature, reagents concentration and presence of base. The crystalline structures of 1b and 2 were determined by X-ray diffraction studies. The two copper atoms in complex 1b are connected by a single chloro bridge with a Cu?Cu separation of 4.1342(8) Å and Cu(1)–Cl(1)–Cu(2) angle of 109.31(4)°. In complex 2 the two copper atoms are held together by a chloro and a naphthalen-2-olate bridges [Cu(1)–Cl(2)–Cu(2) and Cu(1)–O(1)–Cu(2) angles being 83.31(3) and 109.70(9)°, respectively, and the Cu?Cu separation, 3.3476(9) Å]. As expected, variable-temperature magnetic susceptibility measurements of complex 1b showed weak antiferromagnetic intramolecular coupling between the copper(II) centers, with J = −5.7 cm⁻¹, and evidenced for complex 2 strong antiferromagnetic coupling, with J ∼ −120 cm⁻¹. Furthermore, the magnetic behaviour of compound 1a suggested an infinite 1D coordination polymeric structure in which the copper(II) centers are connected by Cl–Cu–Cl bridges. Solution data (UV–Vis spectroscopy and cyclic voltammetry) indicated structural changes of 2 and 1a in CH₃CN, and evidenced conversion of polymer 1a into dimer 1b.     

Azlactone Synthesis. 2-Phenyl-2-Oxazolin-5-One

Abstract

2-Phenyl-2-oxazolin-5-one (3) has been used as an intermediate in the synthesis of α-amino acids¹, derivatives of α-amino acids,² and peptides.³ Procedures for the dehydration/cyclization of hippuric acid (1) leading to the isolation of azlactone 3, have been reported using acetic anhydride,⁴ phosphorus trihalides⁵, and N, N′-dicyclohexylcarbodiimide.⁶ We report herein an alternative, high yield procedure utilizing a water soluble carbodiimide.     

Measurement of Stevioside by Square‐Wave Polarography

Steviol glycosides are electroactive compounds and can be detected by mercury electrode. The maxima of square‐wave polarograms of steviol and stevioside appear at ?1.3 V vs. Ag/AgCl in 1 M NaCl at approximately pH 11. The responses are quasireversible and probably caused by electroreduction of carboxyl, or ester groups, respectively. The net peak current is linearly proportional to steviol concentration between 1×10^?6 mol/L and 3.5×10^?5 mol/L. This calibration plot can be used for the determination of the concentration of stevioside in extracts of stevia (Stevia rebaudiana Bertoni) leaves. The proposed method is applicable for routine analysis of stevioside in commercial products.     

Synthesis,Crystal Structure and Magnetic Properties of a Novel Heterobimetallic Rhenium(IV)–Dysprosium(III) Chain

The use of the mononuclear rhenium(IV) precursor [ReBr₅(H₂pydc)]^? (H₂pydc=3,5‐pyridinedicarboxylic acid) as a metalloligand towards dysprosium(III) afforded the first heterobimetallic Re^IV–Dy^III complex. Crystal structures and static and dynamic magnetic properties of both rhenium‐containing species are reported herein. The 5d–4f compound shows an extended 1D structure and the AC magnetic measurements reveal frequency dependence at low temperature suggesting slow relaxation of the magnetization.