Density Functional Theory Study on the Mechanism of Nickel-Catalyzed 3,3-Dialkynylation of 2‑Aryl Acrylamides Via Double Vinylic C–H Bond Activation

The mechanisms of Ni-catalyzed 3,3-dialkynylation of 2-aryl acrylamide have been investigated by using density functional theory calculations. The result shows that this reaction includes double alkynylation, which involves sequential key steps of vinylic C–H bond activation, successive oxidative addition, and reductive elimination, with the second C–H bond activation being the rate-determining step. C–H and N–H bond activation occurs via the concerted metalation-deprotonation mechanism. The calculations show that no transition state exists in the first reductive elimination process, and a negative free energy barrier in the second reductive elimination process though a transition state is identified, indicating that the nickel-catalyzed vinylic C(sp2)–C(sp) bond formation does not require activation energy. Z–E isomerization is the prerequisite for the second alkynylation. In addition, our spin-flip TDDFT (SF-TDDFT) computational result discloses that the actual process of Z–E isomerization occurs on the potential energy surface of the first excited singlet state S1

Density Functional Theory Study of the Mechanism of Ni-Catalyzed Carboxylation of Aryl C(sp²)–S Bonds with CO₂: Computational Evidence for the Multifaceted Role of Additive Zn

The mechanism of Ni-catalyzed carboxylation of aryl C(sp2)–S bonds with CO2 was studied for the first time by density functional theory calculations. We first proposed another possible reaction pathway in which CO2 insertion occurs prior to reduction. Then, we performed calculations on all proposed reaction pathways, and our calculation results show that the pathway in which reduction occurs prior to CO2 insertion is the favored pathway for this reaction. Additionally, our calculations disclose that additive Zn0 acts in multifaceted roles. (1) Zn0 acts as a reductant to reduce the NiI and NiII intermediates. (2) The simultaneously formed ZnIIBr2 can undergo transmetalation with NiI or NiII intermediates to produce an aryl reservoir by forming arylzinc species. (3) ZnIIBr2 can also coordinate to the CO2 to lower the energy barrier of the CO2 insertion step. Moreover, the calculation results suggest that CO2 insertion is the rate-determining step of the reaction, and CO2 is easier to insert into the NiI–Ph bond rather than into the NiII–Ph bond. These calculation results can improve our understanding of the mechanism of the carboxylation process and the multifaceted roles of metal additive Zn0 and provide theoretical guidance for improving the carboxylation reaction

Confirmation miRNA level by RT-qPCR.

<p>RT-qPCR analysis confirmed microarray data. After normalization to U6 RNA, data were presented as mean ± SD (n = 30) and obtained average value for each miRNA was used for statistics. MiR-19b-2* was underexpressed while miR-3179 and miR-147 were overexpressed in TB sputum compared with controls. The experiment was conducted in triplicate. ^#<i>P</i><0.05 versus control.</p

Overexpressed miRNAs in TB sputum.

<p>Column “Name” contained the name of miRNA; Column “TB patients versus control” contained level ratio of TB/control; Column “Chromosome” meant distribution of each miRNA on chromosome.</p><p>Each miRNA spot was replicated for four times on the same slide and two microarray chips were used for each group. After normalization, obtained average values for each miRNA spot were used for statistics. The <i>P</i> values for these miRNAs were less than 0.05 in TB group compared with controls.</p

Oligonucleotides used in this study.

<p>Oligonucleotides used in this study.</p

Underexpressed miRNAs in TB sputum.

<p>Column “Name” contained the name of miRNA; Column “TB patients versus control” contained level ratio of TB/control; Column “Chromosome” meant distribution of each miRNA on chromosome.</p><p>Each miRNA spot was replicated for four times on the same slide and two microarray chips were used for each group. After normalization, obtained average values for each miRNA spot were used for statistics. The <i>P</i> values for these miRNAs were less than 0.05 in TB group compared with controls.</p

Hierarchical clustering of miRNA in sputum samples.

<p>Samples were clustered according to the signature profile of 97 differentially expressed miRNAs. Data from each miRNA were median centered. Samples were in columns and miRNAs in rows. Red and green indicated high relative level and low relative level, respectively. The <i>P</i> values for these miRNAs were less than 0.05 in TB group compared with controls.</p

Characteristics of participants.

<p>All patients had clinical signs and symptoms of active pulmonary TB; comprising, 79.3% cough, 72.4% fever, 67.2% weight loss, 55.2% night sweats, and 46.6% hemoptysis. Healthy controls involved in the study, were free of active TB infection, latent TB infection and any clinical symptoms of any infectious disease. Both TB patients and healthy controls were non-smokers.</p

Additional file 1: Table S1. of An obesity-associated gut microbiome reprograms the intestinal epigenome and leads to altered colonic gene expression

This file contains Table S1 which provides detailed descriptions of the components of the diets used in this study. (XLSX 9 kb

L'Avenir de Luchon : journal scientifique, littéraire, annonces et réclames : guide général des baigneurs et des touristes aux eaux thermales, bains de mer de la France et de l'étranger

09 mai 19201920/05/09 (N40)-1920/05/09.Appartient à l’ensemble documentaire : MidiPyren