A sensitive, rapid and specific determination of midazolam in human plasma and saliva by liquid chromatography/electrospray mass spectrometry

A rapid, sensitive and selective liquid chromatography/electrospray mass spectrometry (LC/ES-MS) method was developed for the quantitative determination of the anaesthetic benzodiazepine midazolam (MID) in human saliva and plasma from patients undergoing anesthesia procedures. Biological samples spiked with diazepam-d5, the internal standard, were extracted into diethyl ether. Compounds were separated on a Xterra RP18 column using a mobile phase of acetonitrile/formic acid 0.1% at a flow rate of 0.25 mL/min under a linear gradient. Column effluents were analyzed using MS with an ES source in the positive ionization mode. Calibration curves were linear in the concentration ranges of 1-250 and 0.2-25 ng/mL in plasma and saliva, respectively. The limits of detection were 0.5 ng/mL in plasma and 0.1 ng/mL in saliva, using a 0.5-mL sample volume. The recoveries of the spiked samples were above 65%. The method was applied to ten real samples from patients undergoing midazolam treatment.     

A new catalytic method for the synthesis of selectively substituted biphenyls containing an oxoalkyl chain

A novel reaction sequence leading to the synthesis of substituted biphenyls containing a carbonyl group in an aliphatic chain has been achieved in one-pot reaction starting from iodoarenes and allylic alcohols under the catalytic action of palladium and norbornene. The latter is temporarily incorporated into a palladacycle, which directs the reaction towards the selective formation of an arylaryl bond. Norbornene spontaneously deinserts to allow the biphenylylpalladium bond thus formed to react in its turn with the allylic alcohol.     

Transition metal-catalysed organic reactions promoted by chelating or metallacycle-forming substrates

Chelating or metallacycle-forming substrates are very useful for directing organometallic reactions. This review covers the more recent research that has been carried out in the authors' laboratory. Rhodium(I)- and (III)-catalysed reactions of C---C coupling of butadiene with N-allylamides or N-alkylbutenamides are described. These reactions are controlled by the size and strength of the chelate ring formed by double-bond insertion into the crotyl-rhodium bond (formed from butadiene) and their regioselectivity can change with the oxidation state of the metal. Rhodium(I)-catalysed reactions of butadiene with enamides are also chelation controlled and lead to different products, depending on the substituents at nitrogen. Cobalt(II) metallacycles have been utilized for promoting some organic reactions. It has been shown that alkenes can be catalytically incorporated into cobaltacyclopentadiene rings, that spirocycles can be obtained from diynes, carbon monoxide and acrylic esters and that a Pauson-Khand-type reaction can be combined with a Michael-type reaction to prepare catalytically new cyclopentenones. The use of palladacycles, derived from norbornene insertion into aryl-palladium bonds, followed by cyclization, has allowed the selective functionalization of either end of the metallacycle and the formation of condensed rings. Conversion of a palladium(II) into a palladium(IV) metallacycle, and catalytic processes involving these intermediates, have been achieved. The formation of alkylaromatic palladacycles has also been exploited for the selective meta functionalization of the aromatic moiety by means of alkyl groups, accompanied by expulsion of the norbornene molecule.     

Comparison of low-order multireference many-body perturbation theories

Tests have been made to benchmark and assess the relative accuracies of low-order multireference perturbation theories as compared to coupled cluster (CC) and full configuration interaction (FCI) methods. Test calculations include the ground and some excited states of the Be, H(2), BeH(2), CH(2), and SiH(2) systems. Comparisons with FCI and CC calculations show that in most cases the effective valence shell Hamiltonian (H(v)) method is more accurate than other low-order multireference perturbation theories, although none of the perturbative methods is as accurate as the CC approximations. We also briefly discuss some of the basic differences among the multireference perturbation theories considered in this work.     

Stabilization of γ‘ phase in Bi<Subscript>4</Subscript>V<Subscript>2-x</Subscript>Fe<Subscript>x</Subscript><Superscript>II</Superscript>O<Subscript>11-1.5x</Subscript> series

Summary This work reports the room-temperature stabilization of the Bi₄V_2-xFe_x^IIO_11-1.5x γ ‘ phase, a promising ionic conductive material that finds application in solid oxide fuel cell and oxygen sensor devices. The Fe(II) cation proved to be a better stabilizer than Fe(III), which was previously used, since a lower substitution degree of V⁵⁺ is needed for the former. Powder X-ray diffraction, Fourier-transform infrared spectroscopy and differential scanning calorimetry were used in these experiments.     

Two Intercalation Mechanisms of Oxazole Yellow Dimer (YOYO-1) into DNA

The oxazole yellow dye, YOYO-1 (a symmetric homodimer), is a commonly used molecule for staining DNA. We applied the brightness analysis to study the intercalation of YOYO-1 into the DNA. We distinguished two binding modes of the dye to dsDNA: mono-intercalation and bis-intercalation. Bis-intercalation consists of two consecutive mono-intercalation steps, characterised by two distinct equilibrium constants (with the average number of base pair per binding site equals 3.5): K1=3.36±0.43×107M−1 and K2=1.90±0.61×105M−1, respectively. Mono-intercalation dominates at high concentrations of YOYO-1. Bis-intercalation occurs at low concentrations.     

Low-Complexity Alternatives to the Optimal Linear Coding Scheme for Transmitting ARMA Sources

In the era of the Internet of Things, there are many applications where numerous devices are deployed to acquire information and send it to analyse the data and make informed decisions. In these applications, the power consumption and price of the devices are often an issue. In this work, analog coding schemes are considered, so that an ADC is not needed, allowing the size and power consumption of the devices to be reduced. In addition, linear and DFT-based transmission schemes are proposed, so that the complexity of the operations involved is lowered, thus reducing the requirements in terms of processing capacity and the price of the hardware. The proposed schemes are proved to be asymptotically optimal among the linear ones for WSS, MA, AR and ARMA sources.     

Metabolic Profile of Agropyron repens (L.) P. Beauv. Rhizome Herbal Tea by HPLC-PDA-ESI-MS/MS Analysis

Agropyron repens (L.) P. Beauv. (couch grass) is a world-wide infesting rhizomatous plant with pharmacological applications. Chemical research is focused on its allelopathic and anti-inflammatory components, which are mainly present in the essential oil. Conversely, the aqueous extracts have been sparingly investigated, although the herbal tea is by far the most used formulation. To fill the gap, the metabolic profile of Agropyron repens rhizome herbal tea was investigated by electrospray ionization (ESI) tandem–mass spectrometry (MS/MS); the phenolic profile was investigated by HPLC-PDA-ESI-MS/MS. ESI-MS fingerprinting was provided, evidencing diagnostic ions for saccharides, organic acids and amino acids. The HPLC-PDA-ESI-MS/MS analysis evidenced at least 20 characteristic phenolic compounds, the most representative being caffeoyl and feruloyl quinic esters, followed by coumaric, caffeic and ferulic acids, and hesperidin among flavonoids. In addition, the essential amino acid tryptophan was identified for the first time. The results suggest new perspectives of applications for Agropyron repens rhizome.     

The Genus Cetraria s. str.—A Review of Its Botany,Phytochemistry, Traditional Uses and Pharmacology

The genus Cetraria s. str. (Parmeliaceae family, Cetrarioid clade) consists of 15 species of mostly erect brown or greenish yellow fruticose or subfoliose thallus. These Cetraria species have a cosmopolitan distribution, being primarily located in the Northern Hemisphere, in North America and in the Eurasia area. Phytochemical analysis has demonstrated the presence of dibenzofuran derivatives (usnic acid), depsidones (fumarprotocetraric and protocetraric acids) and fatty acids (lichesterinic and protolichesterinic acids). The species of Cetraria, and more particularly Cetraria islandica, has been widely employed in folk medicine for the treatment of digestive and respiratory diseases as decoctions, tinctures, aqueous extract, and infusions. Moreover, Cetraria islandica has had an important nutritional and cosmetic value. These traditional uses have been validated in in vitro and in vivo pharmacological studies. Additionally, new therapeutic activities are being investigated, such as antioxidant, immunomodulatory, cytotoxic, genotoxic and antigenotoxic. Among all Cetraria species, the most investigated by far has been Cetraria islandica, followed by Cetraria pinastri and Cetraria aculeata. The aim of the current review is to update all the knowledge about the genus Cetraria covering aspects that include taxonomy and phylogeny, morphology and distribution, ecological and environmental interest, phytochemistry, traditional uses and pharmacological properties.     

Biochemical and Molecular Investigation of the Effect of Saponins and Terpenoids Derived from Leaves of Ilex aquifolium on Lipid Metabolism of Obese Zucker Rats

Ilex paraguariensis, the holly tree, is a plant with recognized biological properties, whose aqueous infusions are known as “Yerba mate”, that regulate lipid metabolism, reduce obesity, and improve brain stimulation. In the present study, the effect of standardized saponin and terpenoid fractions of a European taxon, Ilex aquifolium, on blood biochemical parameters in a rat model of metabolic disorder, (fa/fa) Zucker, are presented. The profiles of the volatile fractions of two species and six European varieties of Ilex were investigated. After selecting the best variety, the saponin and terpenoid fractions were isolated and standardized, and animals were fed 10 mg kg⁻¹ b.w. for 8 weeks. A statistically significant decrease in liver adiposity was observed, confirmed by histology and quantitative identification (gas chromatography–mass spectrometry analyses of hepatic lipids. RT-qPCR analysis of gene expression in the aorta revealed that the administration of the terpenoid fraction downregulated LOX-1, suggesting a reduction in atherosclerotic stimuli. In addition, a statistically significant reduction (p < 0.05) in PPARγ for the saponin fraction was observed in the liver. The expression of the ACAT-1 gene in the liver, responsible for the formation of cholesterol esters, increased significantly in the group receiving the terpenoid fraction compared to the control, which was also confirmed by the analysis of individual blood biochemical parameters. The opposite effect was observed for saponins. Taking the above into account, it is shown for the first time that Ilex aquifolium can be a source of compounds that positively influence lipid metabolism.