In vitro incubation of all-trans-retinol (atROL) with kidney homogenate from vitamin A-deficient and retinoic acid-supplemented (VAD−RAS) female rats produces a new retinol metabolite. Reverse-phase (RP) and normal-phase (NP) high-performance liquid chromatography (HPLC) analysis showed that this metabolite coelutes with the unknown all-trans-retinol (atROL) metabolite previously found in the day 10 conceptus and kidneys of vitamin A-deficient rats maintained on all-trans-retinoic acid (VAD−RA) and given 2 μg of [3H]atROL. Normal-phase (NP) HPLC purification of the metabolite collected from a RP HPLC column further separated the radiolabeled material into two components. The two isolated compounds have identical or very similar spectroscopic properties. Their nuclear magnetic resonance (1H NMR) and mass spectra (MS) indicated that they are isomers. Spectroscopic studies of the metabolites and their derivatives showed that they are nine-carbon fragments resulting from an oxidative cleavage of the side chain of atROL. The cleavage occurs at C-9, and the product is then oxidized to a keto group. The primary hydroxy group from atROL is preserved in the metabolite. A sulfide bridge is formed between C-11 and C-14, which interrupts the conjugation. The formation of the new metabolites, possessing a 2,5-dihydrothiophene ring, is catalyzed by an enzyme(s) located in the cytosolic fraction of kidneys. The process represents a new retinol metabolic pathway; however, its biological significance is unknown.
The mechanism for the reaction of pentafulvenone with HNC in singlet and triplet states is studied theoretically at MP2/6-311+G**//B3LYP/6-311+G** level. Eleven singlet and two triplet stable points, 21 singlet and 11 triplet transition states are found. The results show that the reaction has two attacking modes, which are HNC attacking carbon–oxygen and carbon–carbon double bond of pentafulvenone. The reaction is more favourable in singlet state, and the dominant pathway is to form cyclopentadienyl isocyanide P via TS6. The structure of the most stable product is identified. The interconversions between cyclopentadienyl isocyanides and cyclopentadienyl cyanides are thoroughly studied in the singlet state. In aqueous solvent, the reaction of pentafulvenone with HNC are investigated using the PCM-UAHF model at the MP2 (PCM)/6-311+G**//B3LYP (PCM)/6-311+G** and MP2 (PCM)/6-311+G**//B3LYP/6-311+G** levels. The barrier of the transition state in the main pathway is decreased.
The dual-level direct kinetics method has been used to investigate the multichannel reactions of C(2)H(5)I + Cl. Three hydrogen abstraction channels and one displacement process are found for the title reaction. The calculation indicates that the hydrogen abstraction from -CH(2)- group is the dominant reaction channel, and the displacement process may be negligible because of the high barrier. The rate constants for individual reaction channels are calculated by the improved canonical variational transition-state theory with small-curvature tunneling correction over the temperature range of 220-1500 K. Our results show that the tunneling correction plays an important role in the rate constant calculation in the low-temperature range. Agreement between the calculated and experimental data available is good. The Arrhenius expression k(T) = 2.33 x 10(-16) T(1.83) exp(-185.01/T) over a wide temperature range is obtained. Furthermore, the kinetic isotope effects for the reaction C(2)H(5)I + Cl are estimated so as to provide theoretical estimation for future laboratory investigation.
The reaction of H radical with C(2)H(5)CN has been studied using various quantum chemistry methods. The geometries were optimized at the B3LYP/6-311+G(d,p) and B3LYP/6-311++G(2d,2p) levels. The single-point energies were calculated using G3 and BMC-CCSD methods based on B3LYP/6-311++G(2d,2p) geometries. Four mechanisms were investigated, namely, hydrogen abstraction, C-addition/elimination, N-addition/elimination and substitution. The kinetics of this reaction were studied using the transition state theory and multichannel Rice-Ramsperger-Kassel-Marcus methodologies over a wide temperature range of 200-3000 K. The calculated results indicate that C-addition/elimination channel is the most feasible over the whole temperature range. The deactivation of initial adduct C(2)H(5)CHN is dominant at lower temperature with bath gas H(2) of 760 Torr; whereas C(2)H(5)+HCN is the dominant product at higher temperature. Our calculated rate constants are in good agreement with the available experimental data.
The mechanisms and dynamics studies of the multichannel reactions of CH(2)FCF(2)OCHF(2) + OH (R1) and CH(2)FOCH(2)F + OH (R2) have been carried out theoretically. Three hydrogen abstraction channels and two displacement processes are found for reaction R1, whereas there are two hydrogen abstraction channels and one displacement process for reaction R2. The minimum energy paths are optimized at the B3LYP/6-311G(d,p) level, and the energy profiles are further refined by interpolated single-point energies (ISPE) method at the BMC-QCISD level of theory. By means of canonical variational transition state theory with small-curvature tunneling correction, the rate constants of reactions R1 and R2 are obtained over the temperature range of 220-2000 K. The rate constants are in good agreement with the experimental data for reaction R1 and estimated data for reaction R2. The Arrhenius expression k(1) = 1.62 x 10(-20) T(2.75) exp(-1011/T) for reaction R1 and k(2) = 3.40 x 10(-21) T(3.04) exp(-384/T) for reaction R2 over 220-2000 K are obtained. Furthermore, to further reveal the thermodynamics properties, the enthalpies of formation of reactants CH(2)FCF(2)OCHF(2), CH(2)FOCH(2)F, and the product radicals CHFCF(2)OCHF(2), CH(2)FCF(2)OCF(2), and CHFOCH(2)F are calculated by using isodesmic reactions.
Abstract The detailed reaction mechanism of 1-chloroethyl radical with NO2 is investigated theoretically. The results show that the title reaction is more favourable on the singlet potential energy surface than on the triplet one. For the singlet PES of CH3CHCl + NO2, it is shown that the CH3CHCl radical can react with NO2 to barrierlessly generate adduct a (H3CHClCNO2), b1 (H3CHClCONO-trans), and b2 (H3CHClCONO-cis), respectively. A total of six energetically reaction pathways and ten products are found. However, the most competitive path way is P1 (CH3CHO + ClNO), which can further dissociate to give P6 (CH3CHO + Cl + NO) and P2 (CH3CClO + HNO). The present results can lead to a deep understanding of the mechanism of the title reaction and may be helpful for understanding the halogenated ethyl chemistry. Keywords: reaction mechanismpotential energy surface (PES)1-chloroethyl radical (CH3CHCl)nitric dioxide (NO2) Acknowledgements This work is supported by the Training Fund of NENU's Scientific Innovation Project (NENU-STC07016). We thank the referees for helpful comments.
A dual-level direct dynamic method is employed to study the reaction mechanisms of CF(3)CHFOCF(3) (HFE-227 mc) with the OH radical and Cl atom. The geometries and frequencies of all the stationary points and the minimum energy paths (MEPs) are calculated at the BH&H-LYP/6-311G(d,p) level, and the energetic information along the MEPs is further refined by MC-QCISD theory. The classical energy profile is corrected by the interpolated single-point energies (ISPE) approach, incorporating the small-curvature tunneling effect (SCT) calculated by the variational transition state theory (VTST). The rate constants are in good agreement with the experimental data and are found to be k(1) = 2.87 x 10(-21)T(2.80) exp(-1328.60/T) and k(2) = 3.26 x 10(-16)T(1.65) exp(-4642.76/T) cm(3) molecule(-1) s(-1) over the temperature range 220-2000 K. The standard enthalpies of formation for the reactant CF(3)CHFOCF(3) and product radical CF(3)CFOCF(3) are evaluated via group-balanced isodesmic reactions, and the corresponding values are -454.06 +/- 0.2 and -402.74 +/- 0.2 kcal/mol, respectively, evaluated by MC-QCISD theory based on the BH&H-LYP/6-311G(d, p) geometries. The theoretical studies provide rate constants of the title reactions and the enthalpies of formation of the species, which are important parameters in determining the atmospheric lifetime and the feasible pathways for the loss of HFE-227 mc.
Abstract Background : Pulmonary fibrosis (PF) is a chronic progressive disease whose pathogenesis is thought to be associated with activation of the immune system and consequent metabolic changes. Recent studies suggested that gut microbes are closely related with host's immune response and metabolic changes in fibrotic hosts. However, the dynamic changes of the gut microbiome and the interaction profiles with host metabolism during the development of pulmonary fibrosis remain inconclusive. Results : We collected serum and fecal samples from bleomycin-induced fibrotic mice at 0, 7, 14, and 28 days and performed UPLC-MS analysis on serum metabolites and metagenomic sequencing on fecal samples. It is found that the serum metabolic profile and gut microbiome were significantly altered in mice during the progression of fibrosis. Among the serum metabolites, the levels of three major types of lipids, i.e ., glycerolipids, glycerophospholipids, and fatty acids exhibit significant time-dependent changes. The glycerolipid TG and multiple glycerophospholipids (3 PG, 6 PE, and 1 PC) decreased in the early stage of fibrosis and increased in the late stage. The other two types of glycerolipids MG and DG and the fatty acids Cartinine and Punicic acid decreased through the development of fibrosis. In the meantime, we detected significantly elevated abundance of gut microbiome taxa, including Prevotella sp. from Bacteroidetes , Lactobacillus from Firmicutes, and Bifidobacterium from Actinobacteria in mice with pulmonary fibrosis. When compared to the dynamic profiles of serum metabolites, the abundances of gut microbiome show a high level of correlation with that of serum metabolites. The taxa from Bacteroides , such as Butyricimonas_synergistica and Muribaculaceae, show positive correlation with the cluster of glycerophospholipids, while taxa from Firmicutes , such as Clostridioides difficile and Enterococcus faecium exhibit negative correlation. Further functional classification suggested that those taxa are involved in multiple functional modules, such as Transporters, Secretion system, and Metabolism. Conclusions : The results reveal the synergistic changes between the gut microbiome and host metabolism and the dynamic responses of gut microbiome to host fibrosis during the progression of fibrosis.
In this study, the mechanistic and kinetic analysis for reactions of CF3OCH(CF3)2 and CF3OCF2CF2H with OH radicals and Cl atoms have been performed at the CCSD(T)//B3LYP/6-311++G(d,p) level. Kinetic isotope effects for reactions CF3OCH(CF3)2/CF3OCD(CF3)2 and CF3OCF2CF2H/CF3OCF2CF2D with OH and Cl were estimated so as to provide the theoretical estimation for future laboratory investigation. All rate constants, computed by canonical variational transition state theory (CVT) with the small-curvature tunneling correction (SCT), are in reasonable agreement with the limited experimental data. Standard enthalpies of formation for the species were also calculated. Atmospheric lifetime and global warming potentials (GWPs) of the reaction species were estimated, the large lifetimes and GWPs show that the environmental impact of them cannot be ignored. The organic nitrates can be produced by the further oxidation of CF3OC(•)(CF3)2 and CF3OCF2CF2• in the presence of O2 and NO. The subsequent decomposition pathways of CF3OC(O•)(CF3)2 and CF3OCF2CF2O• radicals were studied in detail. The derived Arrhenius expressions for the rate coefficients over 230-350 K are: k T(1) = 5.00 × 10-24T3.57 exp(-849.73/T), k T(2) = 1.79 × 10-24T4.84 exp(-4262.65/T), kT(3) = 1.94 × 10-24 T4.18 exp(-884.26/T), and k T(4) = 9.44 × 10-28T5.25 exp(-913.45/T) cm3 molecule-1 s-1.
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