Measuring aliphatic hydrocarbons in sediments by direct thermal desorption-gas chromatography-mass spectrometry: Matrix effects and quantification challenges.

Direct sample introduction thermal desorption (TD) coupled to GC-MS was investigated for the analysis of paraffinic hydrocarbons (HCs) from polluted sediments. TD-GC-MS is sometimes used for analysing paraffinic HCs from atmospheric particles but rarely for their direct desorption from sediments. So, the new TD methodology, applied to sediments, required development, optimization and validation. A definitive screening experimental design was performed to discriminate the critical factors on TD efficiency, from model sediments containing various organic matter (OM) amounts. Low molecular weight HCs had extraction behaviours markedly different from high molecular ones (HMW-HCs), but a compromise was found using very few sediment amount (5 mg), high temperature rate (55 °C min-1) and final temperature (350 °C). Linear HCs (n-C10 to n-C40) could be quantified using the matrix-matched calibration method, with very low detection limits (3.8-13.4 ng). The amount of the overall paraffinic alkanes was also determined as a sum of unresolved components between predefined equivalent carbon ranges. The developed solventless methodology was compared to an optimized solvent microwave assisted extraction (MAE). Matrix effects could be higher for TD compared to MAE but it depended on sediment matrix. When matrix effect was strong, particularly on HMW-HCs signal depletion, a dilution with pure non-porous sand was favourable for accurate quantification. The sum of resolved and unresolved HCs gave comparable results between MAE and TD extractions, with an exception of alkanes greater than C30 which were less quantitatively extracted via TD. However, TD-GC-MS was more sensitive than MAE-GC-MS. So TD-GC-MS is useful for analyzing sediments containing a great range of paraffinic HCs (C9-C34) and it has the advantages of being fully automated, with few sample preparation and operator intervention, using very low amounts of solvent, and generating few wastes.

Quantifying Global Origin-Diagnostic Features and Patterns in Biotic and Abiotic Acyclic Lipids for Life Detection.

Lipids are a geologically robust class of organics ubiquitous to life as we know it. Lipid-like soluble organics are synthesized abiotically and have been identified in carbonaceous meteorites and on Mars. Ascertaining the origin of lipids on Mars would be a profound astrobiological achievement. We enumerate origin-diagnostic features and patterns in two acyclic lipid classes, fatty acids (i.e., carboxylic acids) and acyclic hydrocarbons, by collecting and analyzing molecular data reported in over 1500 samples from previously published studies of terrestrial and meteoritic organics. We identify 27 combined (15 for fatty acids, 12 for acyclic hydrocarbons) molecular patterns and structural features that can aid in distinguishing biotic from abiotic synthesis. Principal component analysis (PCA) demonstrates that multivariate analyses of molecular features (16 for fatty acids, 14 for acyclic hydrocarbons) can potentially indicate sample origin. Terrestrial lipids are dominated by longer straight-chain molecules (C4-C34 fatty acids, C14-C46 acyclic hydrocarbons), with predominance for specific branched and unsaturated isomers. Lipid-like meteoritic soluble organics are shorter, with random configurations. Organic solvent-extraction techniques are most commonly reported, motivating the design of our novel instrument, the Extractor for Chemical Analysis of Lipid Biomarkers in Regolith (ExCALiBR), which extracts lipids while preserving origin-diagnostic features that can indicate biogenicity.

Isotretinoin-induced arthritis: A rare but feasible diagnosis. Case report

Many medications and vaccines have had implications in the development of musculoskeletal and joint symptoms, and among them the use of retinoids has been associated with the development of musculoskeletal symptoms, as well as axial symptoms suggestive of spondyloarthritis, with sacroiliitis, and to a lesser extent the development of peripheral symptoms. We describe the debut of peripheral inflammatory symptoms with the use of isotretinoin, in a previously healthy patient.

Muchos medicamentos y vacunas han tenido implicaciones en el desarrollo de síntomas osteomusculares y articulares. Entre ellos, el uso de retinoides se ha asociado con el desarrollo de síntomas musculoesqueléticos, así como síntomas axiales sugestivos de espondiloartritis con sacroileítis, y en menor proporción el desarrollo de síntomas periféricos. Describimos el inicio de síntomas inflamatorios periféricos con el uso de isotretinoína en una paciente previamente sana.

Combining In Vivo Data with In Silico Predictions for Modeling Hepatic Steatosis by Using Stratified Bagging and Conformal Prediction.

Hepatic steatosis (fatty liver) is a severe liver disease induced by the excessive accumulation of fatty acids in hepatocytes. In this study, we developed reliable in silico models for predicting hepatic steatosis on the basis of an in vivo data set of 1041 compounds measured in rodent studies with repeated oral exposure. The imbalanced nature of the data set (1:8, with the "steatotic" compounds belonging to the minority class) required the use of meta-classifiers-bagging with stratified under-sampling and Mondrian conformal prediction-on top of the base classifier random forest. One major goal was the investigation of the influence of different descriptor combinations on model performance (tested by predicting an external validation set): physicochemical descriptors (RDKit), ToxPrint features, as well as predictions from in silico nuclear receptor and transporter models. All models based upon descriptor combinations including physicochemical features led to reasonable balanced accuracies (BAs between 0.65 and 0.69 for the respective models). Combining physicochemical features with transporter predictions and further with ToxPrint features gave the best performing model (BAs up to 0.7 and efficiencies of 0.82). Whereas both meta-classifiers proved useful for this highly imbalanced toxicity data set, the conformal prediction framework also guarantees the error level and thus might be favored for future studies in the field of predictive toxicology.

Mountain pine beetle (Dendroctonus ponderosae) CYP4Gs convert long and short chain alcohols and aldehydes to hydrocarbons.

Hydrocarbon biosynthesis in insects involves the elongation of fatty acyl-CoAs to very-long chain fatty acyl-CoAs that are then reduced and converted to hydrocarbon, with the last step involving the oxidative decarbonylation of an aldehyde to hydrocarbon and carbon dioxide. Cytochromes P450 in the 4G family decarbonylate aldehydes to hydrocarbon. All insect acyl-CoA reductases studied to date reduce fatty acyl-CoAs to alcohols. The results of the work reported herein demonstrate that CYP4G55 and CYP4G56 from the mountain pine beetle, Dendroctonus ponderosae, expressed as fusion proteins with house fly cytochrome P450 reductase (CPR), convert both long chain aldehydes and long chain alcohols to hydrocarbons. CYP4G55 and CYP4G56 appear to prefer primary alcohols to aldehydes as substrates. These data strongly suggest that hydrocarbon biosynthesis in insects occurs by the two-step reduction of very long chain fatty acyl-CoAs to alcohols, which are then oxidized to aldehydes and then oxidatively decarbonylated to hydrocarbon by CYP4G enzymes. In addition, both CYP4G55 and CYP4G56 fusion proteins convert C10 alcohols and aldehydes to hydrocarbons, including the conversion of (Z)-7-decenal, a putative intermediate in the exo-brevicomin pheromone biosynthetic pathway, to (Z)-3-nonene. These data demonstrate that the highly conserved CYP4G enzymes accept a broad range of carbon chain lengths, including C10 and C18, and have evolved to function in cuticular hydrocarbon biosynthesis and pheromone production.

Catalytic Enantioselective Synthesis of Acyclic Quaternary Centers: Palladium-Catalyzed Decarboxylative Allylic Alkylation of Fully Substituted Acyclic Enol Carbonates.

The first enantioselective palladium-catalyzed decarboxylative allylic alkylation of fully substituted acyclic enol carbonates providing linear α-quaternary ketones is reported. Investigation into the reaction revealed that the use of an electron-deficient phosphinooxazoline ligand renders the enolate geometry of the starting material inconsequential, with the same enantiomer of product obtained in the same level of selectivity regardless of the starting ratio of enolates. As a result, a general method toward acyclic all-carbon quaternary stereocenters has been developed.

Recent progress of C-glycosylation methods in the total synthesis of natural products and pharmaceuticals.

Chemical C-glycosylation has been well developed to improve stereoselectivity in recent years. Due to its high efficiency to build C-glycosides or O-cyclic compounds, C-glycosylation has found widespread use in the synthesis of biologically active molecules. This review highlights the C-glycosylation methods that have been practised in the total synthesis of natural products and pharmaceuticals in the past decade.

Biodegradation and detoxification of aliphatic and aromatic hydrocarbons by new yeast strains.

Seeking new efficient hydrocarbon-degrading yeast stains was the main goal of this study. Because microorganisms are greatly affected by the environmental factors, the biodegradation potentiality of the microorganisms varies from climatic area to another. This induces research to develop and optimize the endemic organisms in bioremediation technology. In this study, 67 yeast strains were tested for their growth potentiality on both aliphatic and aromatic hydrocarbons. The most efficient six strains were identified using sequence analysis of the variable D1/D2 domain of the large subunit 26S ribosomal DNA. The identity of these strains was confirmed as Yamadazyma mexicana KKUY-0160, Rhodotorula taiwanensis KKUY-0162, Pichia kluyveri KKUY-0163, Rhodotorula ingeniosa KKUY-0170, Candida pseudointermedia KKUY-0192 and Meyerozyma guilliermondii KKUY-0214. These species are approved for their ability to degrade both aliphatic and aromatic hydrocarbons for the first time in this study. Although, all of them were able to utilize and grow on both hydrocarbons, Rhodotorula taiwanensis KKUY-0162 emerged as the best degrader of octane, and Rhodotorula ingeniosa KKUY-170 was the best degrader of pyrene. GC-MS analysis approved the presence of many chemical compounds that could be transitional or secondary metabolites during the utilization of the hydrocarbons. Our results recommend the application of these yeast species on large scale to approve their efficiency in bioremediation of oil-contamination of the environment. Using these yeasts, either individually or in consortia, could offer a practical solution for aquatic or soil contamination with the crude oil and its derivatives in situ.

Dependence between LD50 for Rodents and LC50 for Adult Fish and Fish Embryos.

We revealed empirical dependences between common logarithm of a ratio of rat oral LD50 to LCa50 for adult fish and lgP for 50 different chemicals; and common logarithm of a ratio of the oral LD50 in rodents to LCe50 for fish embryos and lgP for 30 different chemicals. The dependences were obtained by constructing a trend line between experimental points and calculation of Pearson's R correlation coefficient as a measure of regression significance. These dependences can show the influence of substance lipophilicity on its toxicity for aquatic organisms comparing to mammals.

Cationic lipids bearing succinic-based, acyclic and macrocyclic hydrophobic domains: Synthetic studies and in vitro gene transfer.

In this communication we describe the construction of four succinic-based cationic lipids, their formulation with plasmid DNA (pDNA), and an evaluation of their in vitro gene delivery into Chinese hamster ovarian (CHO-K1) cells. The cationic lipids employed in this work possess either a dimethylamine or trimethylamine headgroup, and a macrocyclic or an acyclic hydrophobic domain composed of, or derived from two 16-atom, succinic-based acyl chains. The synthesized lipids and a co-lipid of neutral charge, either cholesterol or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), were formulated in an overall 3:2 cationic-to-neutral lipid molar ratio, then complexed with plasmid DNA (pDNA). The relative transfection performance was evaluated via a comparison between matched versus mismatched formulations defined by the rigidity relationship between the lipids employed. Gel electrophoresis was used to characterize the binding of the lipid formulations with plasmid DNA and the relative degree of plasmid degradation using a DNase I degradation assay. Small angle X-ray diffraction (SAXD) was employed to characterize the packing morphology of the lipid-DNA complexes. In general, the succinic unit embedded within the hydrophobic domain of the cationic lipids was found to improve lipid hydration. The transfection assays revealed a general trend in which mismatched formulations that employed a rigid lipid combined with a non-rigid (or flexible) lipid, outperformed the matched formulations. The results from this work suggest that the design of the cationic lipid structure and the composition of the lipoplex formulation play key roles in governing the transfection performance of nonviral gene delivery agents.

[TOXICOMETABOLOMICS: DETERMINATION OF MARKERS OF CHRONIC EXPOSURE TO LOW DOSES OF ALIPHATIC HYDROCARBONS].

The metabolic profile of plasma of white non-linear rats was investigated under normal conditions and after chronic inhalational exposure to low doses of aliphatic hydrocarbons with the number of carbon atoms from 6 to 10. Metabolic profile was determined with combination of gas chromatography-mass spectrometry and high performance, high resolution liquid chromatography-mass spectrometry with subsequent use of chemometrical methods for data treatment and presentation. It was shown that continuous 90-day exposure to a mixture of C6-C10 saturated hydrocarbons at concentration of 160 ± 20.5 mg/m³ results in various impairments of metabolic processes in liver and kidneys. Exposure to hydrocarbons at doses of 31.4 ± 5.6 mg/m³ and 5.2 ± 1.8 mg/m³ evoked significantly smaller changes. Novel metabolic markers of the toxic effect of low concentrations of C6-C10 aliphatic hydrocarbons were revealed. The ratio of concentrations of pyrophosphoric and oxalic acids in rat blood plasma was found to be the most sensitive marker called <>. A hypothesis is put forward about the redox balance violation as the leading pathogenetic mechanism of neuropathies and concomitant pathologies associated with hydrocarbon chronic intoxication.

Discovery of small-molecule nonpeptide antagonists of nociceptin/orphanin FQ receptor: The studies of design, synthesis, and structure-activity relationships for (4-arylpiperidine substituted-methyl)-[bicyclic (hetero)cycloalkanobenzene] derivatives.

Nociceptin/orphanin FQ (N/OFQ) and N/OFQ peptide (NOP) receptor are expressed and distributed in various regions such as central nervous system (CNS), peripheral nervous system, immune system, and peripheral tissues. N/OFQ and NOP receptor have important roles on a variety of physiological, pathophysiological, regulatory, and dysregulatory mechanisms in the living body. Both activation and blockade of NOP receptor function have displayed clinical potential of NOP receptor agonists and antagonists for the treatment of various diseases or pathophysiological conditions, respectively. Potent and selective NOP receptor agonists/antagonists are also useful tools to investigate the various mechanisms mediated by NOP receptor-N/OFQ system. As the present study, a series of (4-arylpiperidine substituted-methyl)-[bicyclic (hetero)cycloalkanobenzene] analogs was designed, synthesized, and biologically evaluated in vitro to seek and identify potent and selective, small-molecules of nonpeptide NOP receptor antagonists, which resulted in the discovery of novel potent small-molecule 15 with high human NOP receptor selectivity over human µ receptor. The structure-activity relationship (SAR) of the potency and selectivity, structure-metabolic stability relationship (SMR), and SAR of hERG (human ether-a-go-go related gene) potassium ion channel binding affinity for the analogs in the present studies in vitro provided or suggested significant and/or useful structural determinants and insights for the respective purposes. The superior profiles of compound 15 are discussed with a viewpoint of multisite interactions between ligand and NOP receptor, together with the results of previous NOP receptor agonist/antagonist studies.

Metal-free N-arylation of secondary amides at room temperature.

The arylation of secondary acyclic amides has been achieved with diaryliodonium salts under mild and metal-free conditions. The methodology has a wide scope, allows synthesis of tertiary amides with highly congested aryl moieties, and avoids the regioselectivity problems observed in reactions with (diacetoxyiodo)benzene.

First acyclic diene metathesis polymerization under biphasic conditions using a dicationic ruthenium alkylidene: access to high-molecular-weight polymers with very low ruthenium contamination.

The acyclic diene metathesis (ADMET) polymerization of 6-hydroxy-1,10-undecadiene (M1) and 6-acetoxy-1,10-undecadiene (M2) by the action of two different catalysts, i.e., the second-generation Grubbs-Hoveyda system ([RuCl2(IMesH2)(CH-2-(2-PrO-C6H4)]) (1) and the dicationic ruthenium alkylidene [Ru(DMF)3(IMesH2)(CH-2-(2-PrO-C6H4)] (2, IMesH2 = 1,3-dimesitylimidazolin-2-ylidene) is reported. Biphasic conditions using 1-butyl-2,3-dimethylimidazolium tetrafluoroborate ([BDMIM(+)BF4(-)]) and 1,2,4-trichlorobenzene (TCB) are applied. Under the chosen conditions (T = 75 °C, 20 mbar), the use of catalyst 1 results only in the formation of low-molecular-weight polymers (Mn ≤ 10,000 g mol(-1)), while catalyst 2 allows for the high yield synthesis of high-molecular-weight polymers (Mn ≤ 40,000 g mol(-1), yields ≤ 99%). Irrespective of the catalyst used, all polymers display a high trans-content (>95%). Notably, Ru-contamination of the target polymers without any additional purification is as low as 1.2 ppm with catalyst 2. Together with the high yields and high molecular weights, the low Ru-contaminations clearly illustrate the advantages of the biphasic setup.

Silicon carbide coated with TiO2 with enhanced cobalt active phase dispersion for Fischer-Tropsch synthesis.

The introduction of a thin layer of TiO2 on ß-SiC allows a significant improvement of the cobalt dispersion. This catalyst exhibits an excellent and stable catalytic activity for the Fischer-Tropsch synthesis (FTS) with high C5+ selectivity, which contributes to the development of a new active catalyst family in the gas-to-liquid process.