Search

The blood-brain barrier (BBB) and tight junction (TJ) proteins maintain the homeostasis of the central nervous system (CNS). The dysfunction of BBB allows peripheral T cells infiltration into CNS and contributes to the pathophysiology of multiple sclerosis (MS). Teriflunomide is an approved drug for the treatment of MS by suppressing lymphocytes proliferation. However, whether teriflunomide has a protective effect on BBB in MS is not understood. We found that teriflunomide restored the injured BBB in the EAE model. Furthermore, teriflunomide treatment over 6 months improved BBB permeability and reduced peripheral leakage of CNS proteins in MS patients. Teriflunomide increased human brain microvascular endothelial cell (HBMEC) viability and promoted BBB integrity in an in vitro cell model. The TJ protein claudin-1 was upregulated by teriflunomide and responsible for the protective effect on BBB. Furthermore, RNA sequencing revealed that the Wnt signaling pathway was affected by teriflunomide. The activation of Wnt signaling pathway increased claudin-1 expression and reduced BBB damage in cell model and EAE rats. Our study demonstrated that teriflunomide upregulated the expression of the tight junction protein claudin-1 in endothelial cells and promoted the integrity of BBB through Wnt signaling pathway., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Researchers are increasingly using insights derived from large-scale, electronic healthcare data to inform drug development and provide human validation of novel treatment pathways and aid in drug repurposing/repositioning. The objective of this study was to determine whether treatment of patients with multiple sclerosis with dimethyl fumarate, an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, results in a change in incidence of type 2 diabetes and its complications. This retrospective cohort study used administrative claims data to derive four cohorts of adults with multiple sclerosis initiating dimethyl fumarate, teriflunomide, glatiramer acetate or fingolimod between January 2013 and December 2018. A causal inference frequentist model averaging framework based on machine learning was used to compare the time to first occurrence of a composite endpoint of type 2 diabetes, cardiovascular disease or chronic kidney disease, as well as each individual outcome, across the four treatment cohorts. There was a statistically significantly lower risk of incidence for dimethyl fumarate versus teriflunomide for the composite endpoint (restricted hazard ratio [95% confidence interval] 0.70 [0.55, 0.90]) and type 2 diabetes (0.65 [0.49, 0.98]), myocardial infarction (0.59 [0.35, 0.97]) and chronic kidney disease (0.52 [0.28, 0.86]). No differences for other individual outcomes or for dimethyl fumarate versus the other two cohorts were observed. This study effectively demonstrated the use of an innovative statistical methodology to test a clinical hypothesis using real-world data to perform early target validation for drug discovery. Although there was a trend among patients treated with dimethyl fumarate towards a decreased incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease relative to other disease-modifying therapies-which was statistically significant for the comparison with teriflunomide-this study did not definitively support the hypothesis that Nrf2 activation provided additional metabolic disease benefit in patients with multiple sclerosis., Competing Interests: This work was funded by Eli Lilly and Company and all authors are employees of Eli Lilly and Company. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Alan J.M. Brnabic was involved with the conceptualization, methodology, investigation and formal analysis of the data for the work and contributed to the original draft preparation, review and editing of the manuscript. Sarah E. Curtis was involved with the conceptualization, methodology, investigation and formal analysis of the data for the work and contributed to the review and editing of the manuscript. Joseph A. Johnston was involved with the conceptualization, methodology and investigation of the data for the work, and contributed to the original draft preparation, review and editing of the manuscript. Albert contributed to the review and editing of the manuscript. Anthony J. Zagar was involved with the methodology and investigation of the data for the work and contributed to the original draft preparation of the manuscript. Ilya Lipkovich was involved with the methodology and validation of the data for the work and contributed to the original draft preparation of the manuscript. Zbigniew Kadziola was involved with the formal analysis of the data for the work and contributed to the review and editing of the manuscript. Megan H. Murray was involved with the investigation, methodology and formal analysis of the data for the work and contributed to the original draft preparation of the manuscript. Timothy Ryan was involved with the conceptualization and investigation of the data for the work and contributed to the original draft preparation, review and editing of the manuscript. All authors have participated sufficiently in the work to agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors give final approval of the manuscript to be published., (Copyright: © 2024 Brnabic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Teriflunomide is administered orally to treat relapsing-remitting multiple sclerosis. In this prospective pilot study, the free and total serum concentrations of teriflunomide obtained during routine health care were measured and their relationship with disease activity was evaluated., Methods: Eighty-nine patients were included in this study. Blood samples were collected from April 2021 to February 2022, and free and total teriflunomide serum concentrations were measured. Patient assessment involved monitoring of blood counts and potential adverse effects of teriflunomide., Results: In the steady-state group, total teriflunomide concentrations ranged from 14.7 to 144.2 mg/L, while free concentrations from 31.1 to 389.7 μg/L. In the non-steady-state group, the total concentration ranged from 2.2 to 59.3 mg/L, with free concentrations ranging from 6.8 to 143.5 μg/L. In the steady-state group, a significant inverse correlation was found between absolute peripheral blood lymphocyte count and both total and free teriflunomide serum concentrations., Conclusion: Although all patients were treated with the same dose, up to a 10-fold difference in total and free teriflunomide serum concentrations, and up to a 5-fold difference in steady-state trough concentrations were observed. This vast interindividual variability can potentially lead to toxicity or, conversely, to suboptimal therapeutic concentrations of teriflunomide, with the risk of further worsening of multiple sclerosis compensation., Competing Interests: Declaration of competing interest All authors advise that there are not any actual or potential financial or other conflict of interest related to the submitted manuscript (ownership, equity position, stock options, consulting fees, patent rights, and corporate affiliations) associated with any drug, product, process, or commercial laboratory mentioned in the submitted material., (Copyright © 2023. Published by Elsevier B.V.)

Introduction and Objective: The ConcePTION project aims to improve the way medication use during pregnancy is studied. This includes exploring the possibility of developing a distributed data processing and analysis infrastructure using a common data model that could form a foundational platform for future surveillance and research. A prerequisite would be that data from various data access providers (DAPs) can be harmonised according to an agreed set of standard rules concerning the structure and content of the data. To do so, a reference framework of core data elements (CDEs) recommended for primary data studies on drug safety during pregnancy was previously developed. The aim of this study was to assess the ability of several public and private DAPs using different primary data sources focusing on multiple sclerosis, as a pilot, to map their respective data variables and definitions with the CDE recommendations framework., Methods: Four pregnancy registries (Gilenya, Novartis; Aubagio, Sanofi; the Organization of Teratology Information Specialists [OTIS]; Aubagio, Sanofi; the Dutch Pregnancy Drug Register, Lareb), two enhanced pharmacovigilance programmes (Gilenya PRIM, Novartis; MAPLE-MS, Merck Healthcare KGaA) and four Teratology Information Services (UK TIS, Jerusalem TIS, Zerifin TIS, Swiss TIS) participated in the study. The ConcePTION primary data source CDE includes 51 items covering administrative functions, the description of pregnancy, maternal medical history, maternal illnesses arising in pregnancy, delivery details, and pregnancy and infant outcomes. For each variable in the CDE, the DAPs identified whether their variables were: identical to the one mentioned in the CDE; derived; similar but with a divergent definition; or not available., Results: The majority of the DAP data variables were either directly taken (85%, n = 305/357, range 73-94% between DAPs) or derived by combining different variables (12%, n = 42/357, range 0-24% between DAPs) to conform to the CDE variables and definitions. For very few of the DAP variables, alignment with the CDE items was not possible, either because of divergent definitions (1%, n = 3/357, range 0-2% between DAPs) or because the variables were not available (2%, n = 7/357, range 0-4% between DAPs)., Conclusions: Data access providers participating in this study presented a very high proportion of variables matching the CDE items, indicating that alignment of definitions and harmonisation of data analysis by different stakeholders to accelerate and strengthen pregnancy pharmacovigilance safety data analyses could be feasible., (© 2023. The Author(s).)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small honorarium for time spent reviewing the subject work.

Aim: Comparative effectiveness research using real-world data often involves pairwise propensity score matching to adjust for confounding bias. We show that corresponding treatment effect estimates may have limited external validity, and propose two visualization tools to clarify the target estimand. Materials & methods: We conduct a simulation study to demonstrate, with bivariate ellipses and joy plots, that differences in covariate distributions across treatment groups may affect the external validity of treatment effect estimates. We showcase how these visualization tools can facilitate the interpretation of target estimands in a case study comparing the effectiveness of teriflunomide (TERI), dimethyl fumarate (DMF) and natalizumab (NAT) on manual dexterity in patients with multiple sclerosis. Results: In the simulation study, estimates of the treatment effect greatly differed depending on the target population. For example, when comparing treatment B with C, the estimated treatment effect (and respective standard error) varied from -0.27 (0.03) to -0.37 (0.04) in the type of patients initially receiving treatment B and C, respectively. Visualization of the matched samples revealed that covariate distributions vary for each comparison and cannot be used to target one common treatment effect for the three treatment comparisons. In the case study, the bivariate distribution of age and disease duration varied across the population of patients receiving TERI, DMF or NAT. Although results suggest that DMF and NAT improve manual dexterity at 1 year compared with TERI, the effectiveness of DMF versus NAT differs depending on which target estimand is used. Conclusion: Visualization tools may help to clarify the target population in comparative effectiveness studies and resolve ambiguity about the interpretation of estimated treatment effects.

Using the bacterial proton-activated pentameric receptor-channel Gloeobacter violaceus ligand-gated ion channel (GLIC): (1) We characterize saturated, mono-carboxylates as negative modulators of GLIC (as previously shown for crotonate; Alqazzaz et al., Biochemistry, 2016, 55, 5947). Butyrate and crotonate have indistinguishable properties regarding negative modulation of wt GLIC. (2) We identify a locus in the pre-β5 strand (Loop Ω) whose mutation inverses the effect of the mono-carboxylate crotonate from negative to positive modulation of the allosteric transitions, suggesting an involvement of the pre-β5 strand in coupling the extracellular orthotopic receptor to pore gating. (3) As an extension to the previously proposed "in series" mechanism, we suggest that a orthotopic/orthosteric site-vestibular site-Loop Ω-β5-β6 "sandwich"-Pro-Loop/Cys-Loop series may be an essential component of orthotopic/orthosteric compound-elicited gating control in this pentameric ligand-gated ion channel, on top of which compounds targeting the vestibular site may provide modulation., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Purpose: Leflunomide is an immunosuppressive drug indicated for the treatment of rheumatoid arthritis (RA). While the pharmacokinetics (PK) of its active metabolite A771726 reportedly show large interindividual variability, no efficient dose individualization strategy is currently available. The goal of this work was to develop a population PK model for A771726 and propose an optimal individualized dosing strategy., Methods: A771726 plasma concentration data were collected from 50 healthy male volunteers participating in two leflunomide PK studies given a single oral dose of 40 mg. Concentrations were elevated in low body weight (WT) subjects and showed multiple peaks. Thus, A771726 PK modeling was conducted incorporating allometry scaling and enterohepatic circulation (EHC). For dose optimization, simulating a set of 1000 virtual subjects from the developed model and dividing the subjects into 5 groups with WT of 50, 60, 70, 80, 90 kg, respectively, the optimal dose was explored that achieves the drug concentration most similar to the target, which was defined as the concentration for the 70 kg subject treated with the current standard dosage regimen (the loading dose of 100 mg QD for 3 days, followed by the maintenance dose of 20 mg QD)., Results: The data were best described by a two compartment model with first order absorption incorporating EHC with the bile released into the intestine. None of the covariates tested was found to be significant other than WT used in allometry. Simulation showed that the optimal loading dose increased by 15 mg for every 10 kg increment in WT while the optimal maintenance dose was 15 and 25 mg for 50 and 90 kg groups, respectively, and the same (= 20 mg) for the others. Large concentration differences from the target observed in low and high WT groups disappeared when optimal doses were given., Conclusions: This work demonstrates the importance of a population PK model-based dose optimization approach in maintaining drug therapeutic concentrations in leflunomide treatment., Competing Interests: Declaration of Competing Interest The authors declared no conflict of interest, (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The solventless synthesis of an amide was performed in a twin-screw extruder in the presence of a coupling agent, providing a high yielding and productive method. The reaction conditions were optimized to prepare APIs, teriflunomide and moclobemide.

Inactivation of horseradish peroxidase (HRP) treatment is a conventional preference to stripping for sequential detections of different proteins of chemiluminescent western blotting (WB). However, little evidence exists on whether other chemical substances treatment can affects the biological activity of HRP during stripping and re-probing of WB blots. Here, we successfully develop 20% crotonic acid (CA) as an alternative to stripping to inhibit HRP used for sequential chemiluminescent WB on polyvinylidene difluoride (PVDF) and Nitrocellulose (NC) membrane. Moreover, NC blots incubation in CA (40 °C, 30min) allow us to perform three round HRP inhibition in sequential detections without losing transferred proteins and damaging membrane. Hence, the method will help us save time and valuable samples without the need to rerun gels., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Fluorine ( 19 F) magnetic resonance imaging (MRI) is severely limited by a low signal-to noise ratio (SNR), and tapping it for 19 F drug detection in vivo still poses a significant challenge. However, it bears the potential for label-free theranostic imaging. Recently, we detected the fluorinated dihydroorotate dehydrogenase (DHODH) inhibitor teriflunomide (TF) noninvasively in an animal model of multiple sclerosis (MS) using 19 F MR spectroscopy (MRS). In the present study, we probed distinct modifications to the CF 3 group of TF to improve its SNR. This revealed SF 5 as a superior alternative to the CF 3 group. The value of the SF 5 bioisostere as a 19 F MRI reporter group within a biological or pharmacological context is by far underexplored. Here, we compared the biological and pharmacological activities of different TF derivatives and their 19 F MR properties (chemical shift and relaxation times). The 19 F MR SNR efficiency of three MRI methods revealed that SF 5 -substituted TF has the highest 19 F MR SNR efficiency in combination with an ultrashort echo-time (UTE) MRI method. Chemical modifications did not reduce pharmacological or biological activity as shown in the in vitro dihydroorotate dehydrogenase enzyme and T cell proliferation assays. Instead, SF 5 -substituted TF showed an improved capacity to inhibit T cell proliferation, indicating better anti-inflammatory activity and its suitability as a viable bioisostere in this context. This study proposes SF 5 as a novel superior 19 F MR reporter group for the MS drug teriflunomide.

The problem of how rubber is synthesized in the plant has been divided into two portions: (i) the nature of the monomer used and how this monomer is synthesized, and (ii) the nature of the polymerization reaction by which the monomer is transformed to rubber. With respect to the first, the monomer appears to be the 5-carbon branched-chain compound beta-methylcrotonic acid or a derivative thereof. This substance is synthesized in the plant from acetyl-coA. With respect to the second, no information is available, since polymerization of the 5-carbon monomer units to polymers has not yet been achieved outside the living plant.

Law, John H. (Harvard University, Cambridge, Mass.) and Ralph A. Splepecky. Assay of poly-beta-hydroxybutyric acid. J. Bacteriol. 82:33-36. 1961-A convenient spectrophotometric assay of bacterial poly-beta-hydroxybutyric acid has been devised. Quantitative conversion of poly-beta-hydroxybutyric acid to crotonic acid by heating in concentrated sulfuric acid and determination of the ultraviolet absorption of the produce permits an accurate determination of this material in quantities down to 5 mug. This method has been used to follow the production of poly-beta-hydroxybutyric acid by Bacillus megaterium strain KM.

DEAD-box proteins are an essential class of enzymes involved in all stages of RNA metabolism. The study of DEAD-box proteins is challenging in a native setting since they are structurally similar, often essential and display dosage sensitivity. Pharmacological inhibition would be an ideal tool to probe the function of these enzymes. In this work, we describe a chemical genetic strategy for the specific inactivation of individual DEAD-box proteins with small molecule inhibitors using covalent complementarity. We identify a residue of low conservation within the P-loop of the nucleotide-binding site of DEAD-box proteins and show that it can be mutated to cysteine without a substantial loss of enzyme function to generate electrophile-sensitive mutants. We then present a series of small molecules that rapidly and specifically bind and inhibit electrophile-sensitive DEAD-box proteins with high selectivity over the wild-type enzyme. Thus, this approach can be used to systematically generate small molecule-sensitive alleles of DEAD-box proteins, allowing for pharmacological inhibition and functional characterization of members of this enzyme family.

Osteoclasts are unique bone remodeling cells derived from multinucleated myeloid progenitor cells. They play homeostatic vital roles in skeletal modeling and remodeling but also destroy bone masses in many pathological conditions such as osteoporosis and rheumatoid arthritis. Receptor activation of NF-κB ligand (RANKL) is essential to osteoclastogenesis. In this study, we investigated the effects of bromo-honaucin A (Br-H A) isolated from Leptolyngbya crossbyana (cyanobacterium). To investigate the mechanism of the inhibitory effect of Br-H A on osteoclastogenesis, we employed Br-H Ain RANKL-treated murine monocyte/macrophage RAW 264.7 cells for osteoclastic differentiation in-vitro. The inhibitory effects on in-vitro osteoclastogenesis was evaluated by counting the number of Tartarate resistant acid phospatase (TRAP) positive multinucleated cells and by measuring the expression level of osteoclast-specific genes like matrix metalloproteinase 9 (MMP9), cathepsin K (CATH K), GRB2-associated-binding protein 2 (GAB2), c-terminal myc kinase (C-MYC), C-terminal Src kinase (C-SRC) and Microphthalmia-associated transcription factor (MITF). Moreover, Br-H A blocked the resorbing capacity of RAW 264.7 cells on calcium phosphate-coated plates. Finally, Br-H A clearly decreased the expression of Akt and also decreased the activation of ERK. Thus, the study identifies Br-H A as potent inhibitor potentialin the treatment of diseases involving abnormal bone lysis such as osteoporosis, rheumatoid arthritis, and periodontal bone degradation.

Odor representations are initially formed in the olfactory bulb, which contains a topographic glomerular map of odor molecular features. The bulb transmits sensory information directly to piriform cortex, where it is encoded by distributed ensembles of pyramidal cells without spatial order. Intriguingly, piriform cortex pyramidal cells project back to the bulb, but the information contained in this feedback projection is unknown. Here, we use imaging in awake mice to directly monitor activity in the presynaptic boutons of cortical feedback fibers. We show that the cortex provides the bulb with a rich array of information for any individual odor and that cortical feedback is dependent on brain state. In contrast to the stereotyped, spatial arrangement of olfactory bulb glomeruli, cortical inputs tuned to different odors commingle and indiscriminately target individual glomerular channels. Thus, the cortex modulates early odor representations by broadcasting sensory information diffusely onto spatially ordered bulbar circuits.

Abstract Frustrated Lewis pairs (FLPs) of Lewis acid (LA) B(C 6 F 5) 3 and Lewis base hydrosilane [SiH] have been utilized to promote controlled polymerization of a challenging β -substituted Michael acceptor, methyl crotonate (MC), devoid of chain transfer side reactions. Mechanistic studies show that chain initiation involves LA-catalyzed 1,4-hydrosilylation of MC with [SiH] via FLP-type activation, generating a silyl ketene acetal nucleophile that participates in chain propagation via classic LA activation of monomer and a bimolecular conjugate addition mechanism. The role of the LA is conflicting in the two different catalytic cycles: the FLP activation in chain initiation requires LA-substrate (monomer) dissociation (or weak interaction) while the classic LA activation in chain propagation demands LA-monomer association (or strong interaction). Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

The enantiomerically pure 5,6‐dihydropyran‐2‐ones play a crucial role as the building blocks in the synthesis of various bioactive compounds. A new straightforward protocol toward enantiomerically pure 5,6‐dihydropyran‐2‐ones based on enzymatic dynamic kinetic resolution (DKR) resulted in non‐racemic homoallylic crotonates, sequentially combined with ring‐closing metathesis (RCM) was designed. The influence of the reaction conditions on the catalytic behavior of selected hydrolases in the synthesis of non‐racemic homoallylic crotonates was investigated. Under optimized conditions for enzymatic DKR desired homoallylic esters were obtained with high yields and enantiomeric excesses exceeding 99 %. Finally, established enzymatic DKR was successfully combined as a two‐steps sequential procedure with RCM affording target 5,6‐dihydropyran‐2‐ones with high yields up to 75 % and enantiomeric excesses exceeding 99 %. Chemoenzymatic protocol combining dynamic kinetic resolution with ring closing metathesis in sequential procedure was developed and applied successfully in the synthesis of the enantiomerically pure 5,6‐dihydropyran‐2‐ones. [ABSTRACT FROM AUTHOR]

A strategy of enhancing the reactivity of lignin molecule towards thermally initiated free radical polymerization was examined. Technical lignin samples were reacted with selected esterification agents (butyric and crotonic anhydrides) leading to extensive conversion of the available hydroxyl groups. The esterified lignins were then subjected to thermal processing in the presence or absence of dicumyl peroxide (DCP). The rheological and viscoelasticity behavior during this process were examined by in-situ rheology and dynamic mechanical analysis (DMA). The functionality and glass transition temperature (T g ) of samples before and after modification were assessed for evaluating the validity of modification. After crotonylation, the lignin derivatives were susceptible to thermally initiated free radical polymerization, especially in the presence of DCP. Upon heating, the lignin crotonate showed a significant increase in storage modulus (E′) from around 200 °C to 260 °C. The T g of lignin crotonate increased by about 20 °C after thermal treatment in the presence of DCP. Fourier transform infrared spectroscopy (FTIR) analysis of samples that were collected from rheological test confirmed the reaction of C C took place. Vanillyl alcohol as a lignin model compound was subjected to the same modification procedure with lignin to uncover the mechanism by FTIR and nuclear magnetic resonance (NMR) analysis, indicating there are three potential reaction sites: C C, C O and CH 2 -, among which C C is likely to form a cross-linked network. The conclusions from this study may provide the foundations for a rational design of technical lignin-based polymeric materials, by providing the double bonds to anchor the lignin molecules in the resin or copolymers. [ABSTRACT FROM AUTHOR]

An efficient and regioselective synthesis of functionalized benzenes via the cascade reactions of 1,2-allenic ketones with 4-sulfonyl crotonates under mild reaction conditions has been established. Mechanistically, the formation of the title compounds involves a cascade procedure consisting of an intermolecular regioselective Michael addition followed by an intramolecular condensation and aromatization. Compared with those of α,β-unsaturated aldehydes/ketones, the reactions of 1,2-allenic ketones with 4-sulfonyl crotonates demonstrated contrary regio-selectivity and distinct reaction conditions. Moreover, the functionalized benzene products obtained herein were found to be ready intermediates for the synthesis of fluorenone and anthracenone derivatives. [ABSTRACT FROM AUTHOR]

A conceptually new synthesis of pyridine rings by a [C4 + CN] assembly has been developed by applying a vinylogous version of the classic Blaise reaction. The zinc-mediated reaction of (het)aryl or alkyl nitriles with ethyl-4-bromocrotonate provided a variety of C(6)-substituted pyridin-2-ones in a single-step. [ABSTRACT FROM AUTHOR]

Summary: 1‐Hexadecene‐contaminated wastewater is produced in oil refineries and can be treated in methanogenic bioreactors, although generally at low conversion rates. In this study, a microbial culture able to degrade 1‐hexadecene was enriched, and different stimulation strategies were tested for enhancing 1‐hexadecene conversion to methane. Seven and three times faster methane production was obtained in cultures stimulated with yeast extract or lactate, respectively, while cultures amended with crotonate lost the ability to degrade 1‐hexadecene. Methane production from 1‐hexadecene was not enhanced by the addition of extra hydrogenotrophic methanogens. Bacteria closely related to Syntrophus and Smithella were detected in 1‐hexadecene‐degrading cultures, but not in the ones amended with crotonate, which suggests the involvement of these bacteria in 1‐hexadecene degradation. Genes coding for alkylsuccinate synthase alpha‐subunit were detected in cultures degrading 1‐hexadecene, indicating that hydrocarbon activation may occur by fumarate addition. These findings are novel and show that methane production from 1‐hexadecene is improved by the addition of yeast extract or lactate. These extra electron donors may be considered as a potential bioremediation strategy of oil‐contaminated sites with bioenergy generation through methane production. [ABSTRACT FROM AUTHOR]

Two compounds with unusual architectures of uranyl complexes were synthesized and then studied by single‐crystal X‐ray diffraction and FTIR spectroscopy. Compound Ba2[UO2(C3H5COO)3]4·2C3H5COOH·7H2O (I) is constructed of neutral hexanuclear clusters {Ba2[UO2(C3H5COO)3]4(C3H5COOH)2(H2O)4} containing crotonate ions. Compound Sr(H2O)6{Na[UO2(i‐C3H7COO)3]3} (II) is constructed of anionic tetranuclear clusters {Na[UO2(i‐C3H7COO)3]3}2– containing isobutyrate ions. These and other examples of heteronuclear clusters imply that the alkali and alkaline‐earth metal atoms in these structures are not just charge‐balancing ions, but truly drive the formation of polynuclear units. The analysis of the coordination modes of crotonate, butyrate, and valerate ions in the crystal structures of all coordination compounds from the Cambridge Structural Database (CSD) allowed the identification of the structural role of these ligands. The results of the analysis show that the bridging function is in fact the most common function for crotonate, butyrate, and valerate ions in known crystal structures. Information on the possible and preferred coordination modes of ligands is extremely important for crystal structure prediction and crystal engineering. [ABSTRACT FROM AUTHOR]

In order to examine in detail the effect of C C bond on the combustion chemistry of biodiesel fuels, two C4 fatty acid methyl esters (FAMEs) were investigated, namely methyl butanoate (MB) and methyl crotonate (MC). Pyrolysis experiments of these two FAMEs at 30, 150 and 780 Torr were conducted in a flow reactor over the temperature range of 773–1323 K, using gas chromatography-mass spectrometry. A number of pyrolysis species including C1 to C4 hydrocarbons, oxygenated products, esters and aromatics were observed and identified. A comprehensive kinetic model for MB and MC combustion was developed, and applied to validate against the new experimental data. In this work, peak mole fraction of benzene, as well as other unsaturated hydrocarbons in MC pyrolysis, was found to be in slightly higher amounts in comparison with that of MB. Kinetic modeling analysis revealed that the dominant formation pathway of benzene was the self-combination reaction of propargyl radical. Furthermore, the model was also validated against the previous experimental data on MB and MC combustion, including oxidation in jet stirred reactor, pyrolysis in shock tube and laminar premixed flame. This study suggests that the effect of C   C double bond in FAMEs might give rise to a growing tendency of initial PAH and soot precursors in the whole thermal decomposition process. [ABSTRACT FROM AUTHOR]