Carbocyclic Acids Research Articles

Microbiome-derived metabolites in early to mid-pregnancy and risk of gestational diabetes: a metabolome-wide association study

BackgroundPre-diagnostic disturbances in the microbiome-derived metabolome have been associated with an increased risk of diabetes in non-pregnant populations. However, the roles of microbiome-derived metabolites, the end-products of microbial metabolism, in gestational diabetes (GDM) remain understudied. We examined the prospective association of microbiome-derived metabolites in early to mid-pregnancy with GDM risk in a diverse population.MethodsWe conducted a prospective discovery and validation study, including a case–control sample of 91 GDM and 180 non-GDM individuals within the multi-racial/ethnic The Pregnancy Environment and Lifestyle Study (PETALS) as the discovery set, a random sample from the PETALS (42 GDM, 372 non-GDM) as validation set 1, and a case–control sample (35 GDM, 70 non-GDM) from the Gestational Weight Gain and Optimal Wellness randomized controlled trial as validation set 2. We measured untargeted fasting serum metabolomics at gestational weeks (GW) 10–13 and 16–19 by gas chromatography/time-of-flight mass spectrometry (TOF–MS), liquid chromatography (LC)/quadrupole TOF–MS, and hydrophilic interaction LC/quadrupole TOF–MS. GDM was diagnosed using the 3-h, 100-g oral glucose tolerance test according to the Carpenter-Coustan criteria around GW 24–28.ResultsAmong 1362 annotated compounds, we identified 140 of gut microbiome metabolism origin. Multivariate enrichment analysis illustrated that carbocyclic acids and branched-chain amino acid clusters at GW 10–13 and the unsaturated fatty acids cluster at GW 16–19 were positively associated with GDM risk (FDR < 0.05). At GW 10–13, the prediction model that combined conventional risk factors and LASSO-selected microbiome-derived metabolites significantly outperformed the model with only conventional risk factors including fasting glucose (discovery AUC: 0.884 vs. 0.691; validation 1: 0.945 vs. 0.731; validation 2: 0.987 vs. 0.717; all P < 0.01). At GW 16–19, similar results were observed (discovery AUC: 0.802 vs. 0.691, P < 0.01; validation 1: 0.826 vs. 0.780; P = 0.10).ConclusionsDysbiosis in microbiome-derived metabolites is present early in pregnancy among individuals progressing to GDM.

A C-H functionalization approach to diverse nitrogenous scaffolds through conjugate addition of catalytic allyliron nucleophiles.

Cyclopentadienyliron(ii) dicarbonyl complexes capable of coordinating to and enhancing the acidity of a range of unsaturated substrates have emerged as a new class of base-metal derived catalysts for C-H functionalization. In this manuscript, the iron-catalyzed C-H functionalization of allylic C(sp3)-H bonds using nitrogen containing α,β-unsaturated carbonyl compounds as coupling partners is reported. Employing a cationic cyclopentadienyliron dicarbonyl complex, this redox neutral process converts simple alkenes into allylic anion equivalents for 1,4-addition into maleimides, acyclic α,β-unsaturated imides, and vinylogous amides. The judicious pairing of pyridine and alkylamine bases with Lewis acid additives allowed each of these classes of substrates to be successfully employed, allowing for the formation of a diverse collection of cyclic and acyclic nitrogen-containing compounds featuring C-C unsaturation. The resulting Michael adducts can be further transformed into a variety of useful scaffolds such as allylated pyrroles, pyrrolidines, and carbocyclic acids.

Improvement of two-phased closed thermosyphon thermal performance by deploying nanofluids of metal nanoparticles decorated on CNT

In this investigation, nanofluids including CNT, milled CNT, and decorated Ag/CNT and Cu/CNT have been applied to enhance the thermal performance of a two-phase closed thermosyphon (TPCT). For better dispersing of carbon nanotube (CNT) in water and producing stable nanofluid, CNTs have been functionalized with hydrophilic groups such as carbocyclic acid and hydroxyl. A reducing agent and calcareous process are effective methods for decoration of CNT with NPs. Nanofluids were prepared in different weight concentrations (0.175%, 0.350%, 0.525% and 0.700%). Also, different input powers (40 W, 80 W, 120 W, 160 W, and 200 W) were applied to the evaporator section. According to the experimental results, it can be deduced that the effect of nanotubes functionalization on the thermal performance of thermosyphon decreases by increasing CNT concentration. Moreover, the transmission electron microscopy (TEM) images showed that functional group disjoins CNTs from each other and result in the formation of uniform silver and copper clusters that have been decorated on the surface of CNT. The results demonstrated that in the presence of nanoparticles (NPs), the thermal performance of thermosyphon improved through a reduction in thermal resistance by 34% (at 0.700 wt% for Ag), 36% (at 0.700 wt% for Cu), and 16% (for milled CNT). Furthermore, the decoration of CNTs improved the thermosyphon performance, especially at low input power.

MOF-Zn-NHC as an efficient N-heterocyclic carbene catalyst for aerobic oxidation of aldehydes to their corresponding carboxylic acids via a cooperative geminal anomeric based oxidation.

As an efficient heterogenous N-heterocyclic carbene (NHC) catalyst, MOF-Zn-NHC was used in the aerobic oxidation of aryl aldehydes to their corresponding carbocyclic acids via an anomeric based oxidation. Features such as mild reaction conditions and no need for a co-catalyst or oxidative reagent can be considered as the major advantages of the presented method in this study.

GLP‐1 Induces a Shift in Primary Carbon Metabolites in Late‐fasted Northern Elephant Seals

Insulin resistance has been suggested to be an adaptive response to food deprivation since it promotes the preservation of glucose and oxidation of fat. However, the insulin resistance‐like conditions that fasting mammals experience may result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin. Glucagon‐like peptide 1 (GLP‐1) is a gastrointestinal hormone that enhances postprandial glucose‐stimulated insulin secretion. To better assess the effects of GLP‐1 on the metabolism of primary carbon metabolites associated with late‐fasting induced insulin resistance, we dose‐dependently infused late‐fasted seals (naturally adapted to prolonged fasting) with low (10 pM/kg; n=3) or high (100 pM/kg; n=4) GLP‐1 immediately following a glucose bolus (0.5g/kg), using glucose without GLP‐1 as control (n=5). The plasma metabolome was measured from samples collected at 5 time points just prior to and during the infusions and areas under the curve (AUC) were calculated.The median AUC fold changes between the GLP‐1‐treated (low and high doses combined) and control group were analyzed using ChemRICH which is a chemical similarity enrichment analysis software for metabolomics datasets that uses medical subject headings and Tanimoto substructure chemical similarity coefficients to cluster metabolites into non‐overlapping chemical groups. Statistically significant p‐values for clusters were obtained by self‐contained Kolmogorov–Smirnov tests. ChemRich mapped 149 of the identified metabolites to 23 nonoverlapping chemical classes, of which 2 were found to be significantly different between the GLP‐1‐treated and control group (false discovery rate adjusted P value &lt; 0.05). Treatment with GLP‐1 infusions was associated with altered Kreb Cycle activity represented by increased levels of tricarboxylic acids, and reduced levels of carbocyclic acids (benzoic acid being a key compound). Hence, GLP‐1 infusion induced a shift in primary carbon metabolites in a model of fasting‐induced insulin resistance.Support or Funding InformationThis work was supported by grants: NIH NHLBI HL091767, NIH NHLBI HL091767‐S1, NIH NHLBI K02HL103787, NIH NHLBI R01HL09176, and NIH U24 DK097154.

Conversion of amine groups on chitosan-coated SPIONs into carbocyclic acid and investigation of its interaction with BSA in drug delivery systems

Recent studies have indicated that protein adsorption onto NPs affects strongly their functions in biological mediums. In this research, a quantitative modification of superparamagnetic iron oxide nanoparticles (SPIONs), which coated with chitosan (Ch-SPIONs), was applied to examine interactions of bovine serum albumin (BSA). SPIONs were at first synthesized via co-precipitation method in alkali medium and under sonication. They were coated with chitosan in acetic acid solution for 12 h and then, an abundance of primary amine was measured by Orange-II and UV-Vis spectroscopy. After that, they reacted with succinic anhydride in different concentrations to obtain NPs with different amounts of carboxylic acid groups. Investigation of NPs interaction with BSA showed that increment of the numbers of carboxylic acid functional groups reduced BSA adsorption on the NPs. In other words, increasing carboxylic acid groups caused to enhance negative zeta potential and therefore, caused to increase the repulsive interaction with BSA.

Chemical Composition of Lipids from Peat-Forming Leafy Mosses of Eutrophic Swamps of Western Siberia and Altai

The molecular composition of lipids in three samples of leafy mosses (Aulacomnium palustre, Warnstorfia fluitans, and Calliergon giganteum) has been determined. The revealed acyclic compounds included normal and isoprenoid alkanes, isoprenoid alkenes, normal and isoprenoid ketones, carboxylic acids and their esters, alcohols, and aldehydes. Among cyclic compounds, bi-, tri- and tetracyclic polycycloaromatic hydrocarbons (PAHs), bicyclic and pentacyclic terpenoids, steroids and tocopherols have been observed. The identified organic compounds consisted mainly of carbocyclic acids and n-alkanes with the prevalence of C27 homologues. A. palustre is characterized by a reduced content of isoprenoid compounds, alcohols, and ketones, while the content of unsaturated acids, pentacyclic terpenoids, and aldehydes is rather heightened. A. palustre differs from W. fluitans and C. giganteum in the steroid composition and contains eremophylene, a sesquiterpenoid, which is absent in the mosses of the family Amblystegiaceae. Compared to C. giganteum, W. fluitans has a higher content of lycopadiene, carboxylic acids, n-alkanes, phyt-2-ene, aldehydes, esters, squalene, diploptene, α-tocopherol, and triphenyl phosphates.

(η2,η2-Cycloocta-1,5-diene)[2-(diphenylphosphanylmethyl)pyridine-κ2N,P]rhodium(I) tetrafluoridoborate 1,2-dichloroethane monosolvate

The title compound, [Rh(C8H12)(C18H16NP)]BF4has been prepared as a precatalyst for applications in rhodium-catalysed additions of carbocyclic acids to terminal alkynes leading toanti-MarkovnikovZ-enol esters. Here the triclinic pseudopolymorph of the title compound is presented. In contrast to the earlier reported pseudopolymorph (orthorhombic space group) [Weiet al.(2013).Chem. Eur. J.19, 12067–12076], the triclinic polymorph contains half a molecule of dichloromethane as solvent in the asymmetric unit. The rhodium(I) atom exhibits a square-planar coordination. The estimated diffraction contribution of the disordered solvent (a half molecule of dichloroethane per asymmetric unit) was subtracted from the observed diffraction data using the SQUEEZE [Spek (2015).Acta Cryst.C71, 9–16] routine inPLATON. The given chemical formula and other crystal data do not take the solvent into account.

ChemInform Abstract: Catalytic Chemical Amide Synthesis at Room Temperature: One More Step Toward Peptide Synthesis.

AbstractA direct amide bond synthesis between carbocyclic acids and amines is achieved in the presence of a highly active bench‐stable catalyst.

Synthesis and receptor docking studies of N-substituted indole-2-carboxylic acid esters as a search for COX-2 selective enzyme inhibitors

A series of N-substituted indole-2-carboxylic acid esters have been prepared by replacing the benzoyl group of indomethacin with a benzyl and a phenyl group. The carbocyclic acid side chain was extended via creating an ester structure by using several dialkylaminoalkyl groups. The receptor docking studies were performed to investigate the docking mode of each compound by using dock 4.0. All the compounds were shown to be docked at the site where intact flurbiprofen was embedded for COX-1 and s-58 (1-phenylsulphonamide-3-trifluoromethyl-5- para-bromophenylpyrazole) for COX-2. It was predicted that N-phenyl-indole-2-carboxylic acid piperazine ester 22 can be a fairly strong COX-2 selective compound which was compared to the others. Other predicted COX-2 selective compounds included are NH indole-2-carboxylic acid diethyl 30 and piperazine 34 esters. In view of these findings, compounds 22, 30 and 34 were chosen for the in vitro biological assays.

Highly regioselective intramolecular hydroxymethylation of α,β-unsaturated carboxylic acids

A convenient synthesis of hydroxy esters 7 and lactones 8 by starting from easily available α,β-unsaturated carbocyclic acids 4 is described. The key step of this transformation is a hitherto unknown radical cyclization of silyl esters, which exhibits a high degree of regioselectivity through steric and orbital control.

ChemInform Abstract: Salts of Carbocyclic Acid Halides and 3,5‐Di‐tert‐butyl‐4‐hydroxy‐N,N‐ dimethylbenzylamine in Benzylation Reactions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

New steroid haptens for radioimmunoassay: Synthesis of steroids substituted with thioether or ester linkages at the 2α-position

Haptens with bridge at the 2-position have not yet heen explored. Radioimmunoassays with antibodies directed against 2α-alkyl bridged steroid haptens are expected to he highly specific due to greater topographical exposure and similarity in conformation to the native steroid. The 2α-alkyl bridged haptens were synthesized by first adding a cyclopropane ring to 2-methylene-4-en-3-one. Selective opening of the three-membered ring with trimethyl silyl iodide and transformation of the iodo group gave a carbocyclic acid, the desired analog for conjugation with protein.

Carbocyclic prostaglandin analogs. 1. Steroid carboxylic acids.

Certain structural similarities between prostaglandins with close-packed side chains and the perhydrocyclopentanophenanthrene nucleus of steroids prompted the synthesis and biological evaluation of 6beta, 17 beta-dihydroxy-5alpha-androstane-2alpha-carboxylic acid (30), its 6-deoxy derivative 28, and the corresponding 6-deoxy-2beta derivative 29 in an attempt to evaluate carbocyclic acids as potential prostaglandin analogs. Preliminary in vitro studies on isolated guinea pig ileum have shown weakly specific, prostaglandin-stimulated smooth muscle antagonism for 28 when compared with antagonism of bradykinin- and acetylcholine-induced contractions. Complete dose-response curves for 28 on prostaglandin-stimulated guinea pig ileum have shown a reduction in the maxium response and a decrease in the slope of the curve, indicating a noncompetitive type of inhibition for this type of derivative.