Major Isomer Research Articles

Computational Modeling of the Ce@C82 Metallofullerene Isomeric Composition

Relative populations of the IPR (isolated-pentagon-rule) isomers of Ce@C82 under the high-temperature synthetic conditions are computed using the Gibbs energy based on characteristics from the density functional theory calculations (B3LYP/3-21G ∼ SDD entropy term, B2PLYPD/6-31G* ∼ SDD energetics). In agreement with observation, Ce@C2v(9)-C82 (major isomer) and Ce@Cs(c; 6)-C82 (minor isomer) endohedrals are the most populated species. Their observed ratio is in the computational modeling reached at a temperature of about 1225 K (under a presumption of the same solubility of the isomers).

Performance of Density-Functional Tight-Binding in Comparison to Ab Initio and First-Principles Methods for Isomer Geometries and Energies of Glucose Epimers in Vacuo and Solution.

Density functional theory (DFT) is a widely used methodology for the computation of molecular and electronic structure, and we confirm that B3LYP and the high-level ab initio G3B3 method are in excellent agreement for the lowest-energy isomers of the 16 glucose epimers. Density-functional tight-binding (DFTB) is an approximate version of DFT with typically comparable accuracy that is 2 to 3 orders of magnitude faster, therefore generally very suitable for processing large numbers of complex structures. Conformational isomerism in sugars is well known to give rise to a large number of isomer structures. On the basis of a comprehensive study of glucose epimers in vacuo and aqueous solution, we found that the performance of DFTB is on par to B3LYP in terms of geometrical parameters excluding hydrogen bonds and isomer energies. However, DFTB underestimates both hydrogen bonding interactions as well as torsional barriers associated with rotations of the hydroxy groups, resulting in a counterintuitive overemphasis of hydrogen bonding in both gas phase as well as in water. Although the associated root mean squared deviation from B3LYP within epimer isomer groups is only on the order of 1 kcal/mol, this deviation affects the correct assignment of major isomer ordering, which span less than 10 kcal/mol. Both second- as well as third-order DFTB methods are exhibiting similar deviations from B3LYP. Even after the inclusion of empirical dispersion corrections in vacuum, these deviations remain for a large majority of isomer energies and geometries when compared to dispersion-corrected B3LYP.

Inositols in Insulin Signaling and Glucose Metabolism.

In the past decades, both the importance of inositol for human health and the complex interaction between glucose and inositol have been the subject of increasing consideration. Glucose has been shown to interfere with cellular transmembrane transport of inositol, inhibiting, among others, its intestinal absorption. Moreover, intracellular glucose is required for de novo biosynthesis of inositol through the inositol-3-phosphate synthase 1 pathway, while a few glucose-related metabolites, like sorbitol, reduce intracellular levels of inositol. Furthermore, inositol, via its major isomers myo-inositol and D-chiro-inositol, and probably some of its phosphate intermediate metabolites and correlated enzymes (like inositol hexakisphosphate kinase) participate in both insulin signaling and glucose metabolism by influencing distinct pathways. Indeed, clinical data support the beneficial effects exerted by inositol by reducing glycaemia levels and hyperinsulinemia and buffering negative effects of sustained insulin stimulation upon the adipose tissue and the endocrine system. Due to these multiple effects, myoIns has become a reliable treatment option, as opposed to hormonal stimulation, for insulin-resistant PCOS patients.

Geometry Change in a Series of Zirconium Compounds during Lactide Ring-Opening Polymerization

A new series of zirconium compounds, (salfen)Zr(OtBu)2 (salfen = N,N′-bis(2,4-di-tert-butylphenoxy)-1,1′-ferrocenediimine), (salfen)Zr(OiPr)2, and (salfen)Zr(OnPr)2, was synthesized and characterized, featuring a cis-β coordination geometry for the major isomer found in solution. An isomerization between the trans and cis-β coordination geometry was observed at ca. 100 °C in solution. This isomerization was also observed in the presence of l-lactide (LA) before its ring-opening polymerization could occur. The isolation of a (salfen)Zr(OnPr)2 lactide intermediate supports the change to the trans coordination geometry necessary before polymerization.

Thiophene site activation: Synthesis and structures of Fischer carbene complexes with 3,3′- and 2,3′-bithienyl substituents

Deprotonation of the reactive α-thiophene ring positions of 3,3′-bithiophene and 2,3′-bithiophene afforded, after metalation with group 6 transition metal carbonyls and alkylation, a diverse range of mono- and biscarbene complexes. The bithienyl isomers differ in the number of active α-positions but representative examples of Fischer monocarbene complexes of all possible isomers were obtained. For 3,3′-bithienyl, the carbene fragment is in the electronically favoured C2-positions on the “inside” of the bithienyl and is structurally and electronically significantly different from the carbene substituent in the “outside” C5-positions. In the unsymmetrically substituted 2,3′-bithienyl scaffold, in addition to [M(CO)5{C(OEt)-2′-(2,3′-BT)}] and [M(CO)5{C(OEt)-5′-(2,3′-BT)}], a carbene moiety in the C5-position of the T2-thienyl ring, [M(CO)5{C(OEt)-5-(2,3′-BT)}], was also formed. In the same reaction mixture of the mono(ethoxycarbene) complexes, biscarbene complexes were obtained. In contrast, the major biscarbene complexes display the carbene fragments in the sterically favoured outside C5,C5′-positions. The unexpected formation of the 2,2′-bithienyl biscarbene complex, [{M(CO)5C(OEt)}2-5,5′-(2,2′-BT)] as well as the formation of the biscarbene complexes [{M(CO)5C(OEt)}2-2,5-(3,3′-BT)] and [{M(CO)5C(OEt)}2-2′,5′-(2,3′-BT)] with both carbene moieties on the same thiophene ring, were observed. By a modified method of synthesis, a mixed metal biscarbene complex of chromium and tungsten in the C2,C5-positions on the same thiophene ring could be isolated for both 3,3′-bithienyl and thiophene [{Ma/b(CO)5C(OEt)}2-2,5-(T/3,3′-BT)]. The formation of a monocarbene complex of 2,3′-bithienyl, [W(CO)5C(OEt)-5-(2,3′-BT){C(O)(OEt)}2-2′,5′] betrays the presence of an unstable triscarbene intermediate [{W(CO)5C(OEt)}3-5,2′,5′-(2,3′-BT)]. The molecular structures of most of the major isomers were confirmed by single crystal X-ray studies.

Isomers of conjugated linoleic acid induce insulin resistance through a mechanism involving activation of protein kinase Cε in liver cells

Conjugated linoleic acid (CLA) constitutes a group of isomers derived from linoleic acid. Diverse studies have suggested that these unsaturated fatty acids have beneficial effects on human health. However, it has also been reported that their consumption can generate alterations in hepatic tissue. Thus, in the present study, we evaluated the effect of two of the major isomers of CLA, cis-9, trans-11-CLA and trans-10, cis-12-CLA, in the regulation of insulin signaling in a hepatic cell model, clone 9 (C9). We found that the two isomers decrease insulin-stimulated phosphorylation of the main proteins involved in insulin signaling, such as Akt at Ser473 and Thr308, the insulin receptor at Tyr1158, IRS-1 at Tyr632, and GSK-3 at Ser9/21. Protein expression, however, was unaffected. Interestingly, both isomers of CLA promoted phosphorylation and activation of PKCε. Inhibition of PKCε activity by a dominant-negative form or knockdown of endogenous PKCε prevented the adverse effects of CLA isomers on insulin-induced Akt phosphorylation. Additionally, we also found that both isomers of CLA increase phosphorylation of IRS-1 at Ser612, a mechanism that probably underlies the inhibition of IRS-1 signaling by PKCε. Using confocal microscopy, we found that both isomers of CLA induced lipid accumulation in C9 cells with the presence of spherical cytosolic vesicles, suggesting their identity as neutral lipid droplets. These findings indicate that cis-9, trans-11-CLA and trans-10, cis-12-CLA isomers could have a significant role in the development of insulin resistance in hepatic C9 cells through IRS-1 serine phosphorylation, PKCε activation, and hepatic lipid accumulation.

Determination of Three Main Chlorogenic Acids in Water Extracts of Coffee Leaves by Liquid Chromatography Coupled to an Electrochemical Detector.

Coffee is a beverage widely consumed in the world. The coffee species most commercialized worldwide are Arabica (Coffea arabica) and Robusta (Coffea canephora). Roasted coffee beans are the most used, but coffee leaves are also consumed as infusion in several countries for traditional medicinal purposes. They contain several interesting phenolic antioxidant compounds mainly belonging to chlorogenic acids (CGAs). In the present work, a liquid chromatography-electrochemical detection (LC-EC) method was developed for the determination of three main chlorogenic acid isomers, namely 3-, 4-, and 5-caffeoylquinic acids (CQA), in coffee leaves aqueous extracts. Samples from eight coffee species, namely; Coffea arabica, Coffea canephora, Coffea liberica, Coffea humilis, Coffea mannii, Coffea charrieriana, Coffea anthonyi, and Coffea liberica var. liberica, were grown and collected in tropical greenhouses. Linearity of the calibration graphs was observed in the range from the limit of quantification to 1.0 × 10−5 M, with R2 equal to 99.9% in all cases. High sensitivity was achieved with a limit of detection of 1.0 × 10−8 M for 3-CQA and 5-CQA (i.e., 3.5 µg/L) and 2.0 × 10−8 M for 4-CQA (i.e., 7.1 µg/L). The chromatographic profile of the samples harvested for each Coffea species was studied comparatively. Obtained raw data were pretreated for baseline variations and shifts in retention times between the chromatographic profiles. Principal Component Analysis (PCA) was applied to the pretreated data. According to the results, three clusters of Coffea species were found. In the water sample extracts, 5-CQA appeared to be the major isomer, and some species contained a very low amount of CQAs. Fluctuations were observed depending on the Coffea species and harvesting period. Significant differences between January and July were noticed regarding CQAs content. The species with the best CQAs/caffeine ratio was identified. The LC-EC data were validated by liquid chromatography-high resolution mass spectrometry (LC-HRMS).

Green Synthesis and Z/E-Isomerization of Novel Coumarin Enamines Induced by Organic Solvents

An efficient and straightforward synthesis of novel (Z/E)-3-[(heteroarylamino)methylidene]chromane-2,4-dione derivatives via a one-pot three-component condensation of 4-hydroxycoumarin, triethyl orthoformate, and heteroaryl amines in the presence of guanidinium chloride as organocatalyst under solvent-free conditions is described. Investigation of spectroscopy data indicated that coumarin enamines exist in the ketoenamine tautomeric form and undergo Z/E-isomerization in respect to the C=C bond in CDCl3 and DMSO-d6 at room temperature. Furthermore, intramolecular hydrogen bonds have been observed in the synthesized compounds. Also, 1H NMR spectra indicated that E-ketoenamines are the major isomers. High to excellent yields, short reaction times, simple workup, and very easy purification of products by non-chromatographic methods are advantages of this synthetic procedure.

Synthesis directed towards trans-clerodanes employing an exo-selective Diels–Alder reaction as a key-step

A potential intermediate in the synthesis of several trans-clerodane natural products has been constructed employing a Diels–Alder reaction as a key-step. Two epimeric exo-adducts were formed in a 4:3 ratio in an EtAlCl2-mediated cycloaddition of O-silylated 2-vinylcyclohex-2-enol and N-tigloylisoxazolidinone. Both isomers were converted to the trans-clerodane intermediate in four steps; reductive removal of the oxazolidinone, followed by O-benzylation, removal of the silyl protecting group, and, finally, a Dess–Martin oxidation of the deprotected alcohol to the corresponding ketone. It was possible to transform both isomers from the cycloaddition into the final target, but the major isomer was converted at greater yields. An interesting discovery made during the work was that the desilylation demanded significantly different conditions depending on which isomer was deprotected. The fact that the cycloaddition not only resulted in an excellent exo-selectivity, but also that the alkene to a large extent approached from the least hindered side, opens the possibility for enantioselective synthesis of the target compound from (R) or (S) diene starting materials in the future.

Amelioration of Oxidative Stress in Caco-2 Cells Treated with Pro-inflammatory Proteins by Chlorogenic Acid Isomers via Activation of the Nrf2-Keap1-ARE-Signaling Pathway.

Understanding the potential effects of chlorogenic acid (CGA) isomers on the intestinal epithelium is important because coffee intake exposes consumers to the six major CGA isomers: 3-caffeoylquinic acid (3-CQA), 4-caffeoylquinic acid (4-CQA), 5-caffeoylquinic acid (5-CQA), 3,4-dicaffeoylquinic acid (3,4-diCQA), 3,5-dicaffeoylquinic acid (3,5-diCQA), and 4,5-dicaffeoylquinic acid (4,5-diCQA). The present study determined the relative effects of CGA isomers on the antioxidant status of inflamed Caco-2 intestinal cells by investigating the oxidative-stress-responsive pathway and nuclear-factor-erythroid-derived-2-like 2 (Nrf2) signaling. Differentiated Caco-2 cells were challenged with the inflammatory mediators PMA and IFNγ, as a model of intestinal inflammation in vitro. Significant redox ( p < 0.05) responses to these mediators were assessed by indirect measurement of induced generation of reactive oxygen species (ROS), as well as the expression of reduced (GSH) and oxidized (GSSG) glutathione. This translated to a 40% reduction in the GSH/GSSG ratio. We found that responses in these parameters were associated with increased Nrf2 activation ( p < 0.05). ROS generation and increased IL-8 secretion were found in challenged cells, indicating an association between induced oxidation and inflammatory status. Oxidative stress was ameliorated by CGA isomers, which scavenged intracellular ROS, increased GSH, and activated Nrf2 signaling. diCQA isomers were relatively more effective at reducing IL-8 ( p < 0.05). The observed increase in Nrf2 signaling led to upregulated expression of some Nrf2 target genes ( GPX2, KEAP1, and NFE2L2) in Caco-2 cells and activated the Nrf2-Keap1-ARE-signaling pathway. These findings indicate that CGA isomers present in coffee have bioactivity toward alleviating oxidative stress associated with intestinal inflammation.

Probing Solvation-Induced Structural Changes in Conformationally Flexible Peptides: IR Spectroscopy of Gly3H+·(H2O).

IR predissociation spectroscopy of the Gly3H+(H2O) complex formed inside of a cryogenic ion trap reveals how the flexible model peptide structurally responds to solvation by a single water molecule. The resulting one-laser spectrum is quite congested, and the spectral analyses were assisted by both H2O/D2O substitution and IR-IR double resonance spectroscopy, revealing the presence of two contributing isomers and extensive anharmonic features. Comparisons to structures found via a systematic computational search identified the geometries of these two isomers. The major isomer, with all trans amide bonds and protonation on the terminal amine, represents ∼90% of the overall population. It noticeably differs from the unsolvated Gly3H+, which exists in two isomeric forms: one with a cis amide bond and the other with protonation on an amide C═O. These results indicate that interactions with just one water molecule can induce significant structural changes, i.e., cis- trans amide bond rotation and proton migration, even as the clustering occurs within an 80 K cryogenic ion trap. Calculations of the isomerization pathways further reveal that the binding energy of the water molecule provides sufficient internal energy to overcome the barriers for the observed structural changes, and the minor solvation isomer results from a small fraction of the ions being kinetically trapped along one of the pathways.

A Stable Antiaromatic 5,20‐Dibenzoyl [28]Hexaphyrin(1.1.1.1.1.1): Core AuIII Metalation and Subsequent Peripheral BIII Metalation

5,20-Dibenzoyl [28]hexaphyrin(1.1.1.1.1.1) was synthesized as the first hexaphyrin bearing meso-aroyl substituents. The meso-dibenzoyl substituents are hydrogen-bonded with the pyrrolic protons to stabilize an antiaromatic dumbbell conformer. Core metalation of this hexaphyrin with AuIII afforded rectangular and aromatic [26]hexaphyrin bis-AuIII complexes, the major isomer of which was reduced with NaBH4 to give its antiaromatic 28π bis-AuIII complex. This complex allowed facile peripheral metalation with BIII owing to the peripheral benzoyl substituents.

A Stable Antiaromatic 5,20‐Dibenzoyl [28]Hexaphyrin(1.1.1.1.1.1): Core AuIII Metalation and Subsequent Peripheral BIII Metalation

Abstract5,20‐Dibenzoyl [28]hexaphyrin(1.1.1.1.1.1) was synthesized as the first hexaphyrin bearing meso‐aroyl substituents. The meso‐dibenzoyl substituents are hydrogen‐bonded with the pyrrolic protons to stabilize an antiaromatic dumbbell conformer. Core metalation of this hexaphyrin with AuIII afforded rectangular and aromatic [26]hexaphyrin bis‐AuIII complexes, the major isomer of which was reduced with NaBH4 to give its antiaromatic 28π bis‐AuIII complex. This complex allowed facile peripheral metalation with BIII owing to the peripheral benzoyl substituents.

The carotenoids of shrimps (Decapoda: Caridea and Dendrobranchiata) cultured in China

We compared the carotenoids in tissues of various organs from four shrimps cultured in China, Penaeus monodon Fabricius, 1978, Fenneropenaeus chinensis Osbeck, 1765, Litopenaeus vannamei Boone, 1931, and Exopalaemon carinicauda Holthuis, 1950. The carotenoid levels vary greatly depending on the species and the tissues sampled, with the highest levels found in the cephalothorax of L. vannamei (295.20 mg kg(-1)), and the lowest in the abdominal muscle of L. vannamei (2.12 mg kg(-1)). Astaxanthin, mainly esterified (47.69-95.56%), but also unesterified (4.445-2.31%), was the predominant carotenoid and contributed 66.64-95.26% of the total carotenoids in all species. beta-carotene, echinenone, canthaxanthin, astacene, zeaxanthin, and some unidentified carotenoids were also detected. All-trans-astaxanthin was the predominant geometrical isomer and 9-cis and 13-cis were the major cis isomers. Two other isomers, 15-cis and di-cis-astaxanthin, were also detected. The stereoisomers (3S, 3'S) and (3S, 3'R)-astaxanthin were only observed in E. carinicauda, where (3'S, 3'S)-astaxanthin contributed more than 96% to the total astaxanthin content. In contrast, all three possible stereoisomers were detected in P. monodon, F. chinensis, and L. vannamei and the relative levels of these stereoisomers were similar, 25.37-39.11% of (3S, 3'S)-astaxanthin, 38.85-52.01% of (3S, 3'R)-astaxanthin, and 14.07-29.89 % of (3R, 3'R)-astaxanthin. The astaxanthin-enriched waste, particularly the cephalothorax generated from L. vannamei, is suggested as a good source of natural astaxanthin available by further processing. These results provide some valuable information on carotenoid characteristics of cultured shrimps, especially the specific configurations of astaxanthin.

Changes of the chlorogenic acid, caffeine, gama-aminobutyric acid (GABA) and antioxdant activities during germination of coffee bean (Coffea arabica)

This study was carried out to identify changes in functional materials during the germination of coffee seeds. Chlorogenic acid (CGA), caffeine, and g-aminobutyric acid (GABA) was assayed by HPLC method while germinating coffee beans for 20 days. The contents of total phenolic compounds and total flavonoid compounds were measured by colorimetric method. Antioxidant activity was measured by both 2,2-diphenyl-2-pycryl hydrazyl (DPPH) radical scavenging activity assay and 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+) assay method. It was found that CGAs (5-caffeoylquinic acid (CQA), 4-CQA, 3-CQA), caffeine, and GABA increased and then decreased during germination. There were no significant changes in total phenolics, total flavonoids and antioxidant activities. Especially, all of the major isomers of CGA increased to the highest value at 10 days of germination, and GABA also increased significantly at the early stage of germination. This study showed that coffee beans changed into more functional food materials by germination and showed maximum functionality in appropriate germination conditions.

Chlorinated organic compounds in liquid wastes (DNAPL) from lindane production dumped in landfills in Sabiñanigo (Spain)

α, β and γ-hexachlorocyclohexane (HCH) are persistent and bioaccumulative pollutants and they were included in the Stockholm Convention on Persistent Organic Pollutants (POPs). Old lindane factories generated high amounts of wastes with HCH and other Chlorinated Organic Compounds (COCS). These were often dumped in the surroundings of the production sites, polluting soil and groundwaters with the associated risk of surface pollution. This is the case of the Sardas and Bailin landfills, located in Sabiñánigo (Huesca, Spain). Among the waste from lindane production, a liquid residue was detected in the landfill subsurfaces, forming a dense non-aqueous phase liquid (DNAPL) composed of HCH isomers, benzene and chlorobenzenes, with a high impact on groundwater pollution. In this study, six DNAPL samples obtained from the Bailin and Sardas landfills were analyzed by GC/MSD and GC/FID/ECD. Compounds were identified using mass spectra and the retention index from pure standards and literature information. Pure positional isomers of dichlorobenzene (DCB), trichlorobenzene (TCB), tetrachlorobenzene (TetraCB), HCH and pentachlorocyclohexene (PentaCX) were distinguished and quantified. In addition, heptachlorocyclohexane (HeptaCH) isomers, precursors of hexacholorocylohexene (HexaCX), were also identified and quantified in the DNAPL samples, although the corresponding isomers could not be discriminated. Information about PentaCX, HexaCx and HeptaCH identification is very limited in the literature. HCH contents in the DNAPL ranged from 22% to 30% in weight, the major isomers being lindane and δ-HCH, followed by α-HCH. The β isomer was the least abundant. HeptaCH contents were present in the same order of magnitude as HCHs in the DNAPL. PentaCXs and HexaCXs could have appeared as dehydrochlorination derivatives of HCHs and HeptaCHs, respectively. Two of the DNAPLs analyzed showed a higher content of TCBs and TetraCBs, associated with lower HCH and HeptaCH contents. Variations of these compounds in the DNAPL could be related to an alkaline dehydrochlorination in the landfill conditions.

Stereoselective accumulations of hexachlorocyclohexanes (HCHs) are correlated with Sphingomonas spp. in agricultural soils across China

The wide usage of hexachlorocyclohexanes (HCHs) as pesticides has caused soil pollution and adverse health effects through direct contact or bioaccumulation in the food chain. This study quantified major HCH isomers in farmland topsoils across China, and evaluated their correlations with microbial community structure, function, and abiotic variables (e.g., moisture, pH, and temperature). Recalcitrant β-HCH was more abundant than α-, γ-, and δ-HCHs, and α-HCH enantiomeric fractions (EF) were larger than 0.5, indicating preferential degradation of (−)-α-HCH. Sphingomonas was not only a predominant population (especially in samples collected in the south), but also a promising biomarker indicating total- and β-HCH residuals, and EF values of α-HCH. Soil moisture and temperature were among the most influential factors that structured the diversity and function of soil microbial communities. The results suggested that increasing soil moisture (in the range of 5–45%) would benefit the growth of HCH-degrading populations and the enrichment of HCH-degradation related pathways. Revealing the site-specific relationships between topsoil physical, chemical, and microbial properties will benefit the in situ bioremediation of farmlands with relatively low HCH residuals across the world.

Charge Transfer and π to π* Transitions in the Visible Spectra of Sulfheme Met Isomeric Structures.

Since the 1863 discovery of a new green hemoglobin derivative called "sulfhemoglobin", the nature of the characteristic 618 nm absorption band has been the subject of several hypotheses. The experimental spectra are a function of the observation time and interplay between two major sulfheme isomer concentrations (a three- and five-membered ring adduct), with the latter being the dominant isomer at longer times. Thus, time-dependent density functional theory (TDDFT) was used to calculate the sulfheme excited states and visualize the highest occupied molecular orbitals (HOMOs) and lowest unoccupied MOs (LUMOs) of both isomers in order to interpret the transitions between them. These two isomers have distinguishable a1u and a2u HOMO energies. Formation of the three-membered ring SA isomeric structure decreases the energy of the HOMO a1u and a2u orbitals compared to the unmodified heme due to the electron-withdrawing, sulfur-containing, three-membered ring. Conversely, formation of the SC isomeric structure decreases the energy of the HOMO a1u and a2u orbitals due to the electron-withdrawing, sulfur-containing, five-membered ring. The calculations reveal that the absorption spectrum within the 700 nm region arises from a mixture of MOs but can be characterized as π to π* transitions, while the 600 nm region is characterized by π to dπ (d yz, d xz) transitions having components of a deoxy-like derivative.

КРЕМНИЙ-НИОБИЕВЫЕ БЛОКИ ДЛЯ КОНСТРУИРОВАНИЯ НАНОСТРУКТУРИРОВАННЫХ МАТЕРИАЛОВ

Представлены результаты компьютерного моделирования пространственной структуры анионных кремний-ниобиевых кластеров из 10, 12, 14 и 16 атомов кремния. Для каждого кластера представлен ряд стабильных изомеров с качественно различной структурой, которые могут служить элементарными блоками для построения более крупных наноструктурированных объектов – нанопроволок, нанопроводов, нанокристаллов.&#x0D; Для представленных расчетов были использованы вычислительные ресурсы Суперкомпьютерного центра Воронежского государственного университета.

Catalytic activities of mammalian epoxide hydrolases with cis and trans fatty acid epoxides relevant to skin barrier function

Lipoxygenase (LOX)-catalyzed oxidation of the essential fatty acid, linoleate, represents a vital step in construction of the mammalian epidermal permeability barrier. Analysis of epidermal lipids indicates that linoleate is converted to a trihydroxy derivative by hydrolysis of an epoxy-hydroxy precursor. We evaluated different epoxide hydrolase (EH) enzymes in the hydrolysis of skin-relevant fatty acid epoxides and compared the products to those of acid-catalyzed hydrolysis. In the absence of enzyme, exposure to pH 5 or pH 6 at 37°C for 30 min hydrolyzed fatty acid allylic epoxyalcohols to four trihydroxy products. By contrast, human soluble EH [sEH (EPHX2)] and human or murine epoxide hydrolase-3 [EH3 (EPHX3)] hydrolyzed cis or trans allylic epoxides to single diastereomers, identical to the major isomers detected in epidermis. Microsomal EH [mEH (EPHX1)] was inactive with these substrates. At low substrate concentrations (<10 μM), EPHX2 hydrolyzed 14,15-epoxyeicosatrienoic acid (EET) at twice the rate of the epidermal epoxyalcohol, 9R,10R-trans-epoxy-11E-13R-hydroxy-octadecenoic acid, whereas human or murine EPHX3 hydrolyzed the allylic epoxyalcohol at 31-fold and 39-fold higher rates, respectively. These data implicate the activities of EPHX2 and EPHX3 in production of the linoleate triols detected as end products of the 12R-LOX pathway in the epidermis and implicate their functioning in formation of the mammalian water permeability barrier.