Density functional theory (DFT) calculations were performed to gain an in-depth mechanistic understanding of the Rh(I)-catalyzed transannulation of 1,2,3-thiadiazoles with alkenes, alkynes, and nitriles. Computational results indicate that the denitrogenation...

The construction of C­(sp3)–N bonds via direct radical–radical cross-coupling under benign conditions is a desirable but challenging approach. Herein, the cross-coupling of alkyl and amidyl radicals to build aliphatic C–N bonds in a concise, mild, and oxidant-free manner is implemented by nickel/photoredox dual catalysis. In this protocol, the single electron transfer strategy is successfully employed to generate N- and C-centered radicals from sulfonyl azides/azidoformates and alkyltrifluoroborates, respectively. The photocatalyst-induced triplet–triplet energy-transfer mechanism, however, might not be applicable to this reaction. The oxidative quenching pathway of the excited photocatalyst (RuII/*RuII/RuIII/RuII) combined with a possible NiI/NiII/NiIII/NiI catalytic cycle is proposed to account for the nickel/photoredox dual-catalyzed C­(sp3)–N bond formation based on synergistic experimental and computational studies.

Photosynthesis and the biosynthesis of many important metabolites occur in chloroplasts. In these semi-autonomous organelles, the chloroplast genome encodes approximately 100 proteins. The remaining chloroplast proteins, close to 3000, are encoded by nuclear genes whose products are translated in the cytosol and imported into chloroplasts. However, there is still no consensus on the composition of the protein import machinery including its motor proteins and on how newly imported chloroplast proteins are refolded. In this study, we have examined the function of orf2971, the largest chloroplast gene of Chlamydomonas reinhardtii. Depletion of Orf2971 causes accumulation of protein precursors, partial proteolysis and aggregation of proteins, increased expression of chaperones and proteases, and autophagy. Orf2971 interacts with the TIC complex, catalyzes ATP hydrolysis and associates with chaperones and chaperonins. We propose that Orf2971 is intimately connected to the protein import machinery and plays an important role in chloroplast protein quality control.

The Pd­(0)-catalyzed coupling cyclization of 1,2-allenyl ketones with aryl halides to construct multisubstituted furan derivatives has been developed. Nevertheless, the detailed mechanism of this reaction, proceeding via either the Pd­(II)-carbenoid or the π-allyl-Pd­(II) intermediate, still remains debatable. Herein, computational studies were performed to provide mechanistic insights into the reactions, and substituent-dependent mechanistic pathways were revealed. Computational results suggest that the substituents, R1–R3 attached to 1,2-allenyl ketones and R4 attached to the aryl moiety of aryl halides, could play significant roles in the variation of the mechanistic pathway. It would be favorable to form the Pd­(II)-carbenoid intermediate when R1 is an aryl/alkyl group or steric hindrance is present between R2 and R3. For the substrate of aryl halide, the aryl moiety bearing electron-donating group (R4) at the para position is more ready to undergo migratory insertion to form the π-allyl-Pd­(II) intermediate than that with electron-withdrawing group. The factors responsible for the formation of both Pd­(II)-carbenoid and π-allyl-Pd­(II) intermediates are discussed.

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Density functional theory calculations were performed to reveal the mechanisms of Pd‐catalyzed cascade carbocyclization‐borylation and arylation reactions. The computational results indicate that the reactions start with allylic C−H cleavage through concerted metalation‐deprotonation and an intramolecular exo‐type allene insertion to form a six‐membered carbocycle intermediate. The regioselectivity of insertion could be explained by frontier molecular orbital theory and natural population analysis calculation. In the absence of extra nucleophiles, η1/η3‐isomerization followed by acetate‐assisted deprotonation could yield polyene product. When nucleophile was added to the reaction system, transmetalation and subsequent reductive elimination could give the exo‐substituted triene as major product. Meanwhile, η1/η3‐isomerization, transmetalation, and reductive elimination could afford the endo‐isomer as side product. The regioselectivity of further functionalization is controlled by the competition of transmetalation and η1/η3‐isomerization. The computational results show that both exo‐ and endo‐boronation product could be observed when bis(pinacolato)diboron is added as nucleophile. However, only exo‐phenylation product is observed when phenylboronic acid is used as nucleophile because of the high free‐energy barrier for reductive elimination from aryl η3‐allylic palladium.

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Basal cell carcinoma (BCC) is the most common malignancy worldwide, with increasing incidence. BCCs present low mortality but high morbidity, and its pathogenesis remains unclear. Eph receptors have been implicated in tumorigenesis. EphA7 plays a role as a tumor suppressor in certain cancers. We checked EphA7 expression levels and methylation status in a set of BCCs, benign skin diseases, and compound nevus tissue samples using immunohistochemistry. EphA7 protein was positively expressed in normal basal cells, benign skin diseases, and compound nevus cells, but lost in areas of BCC tissues. We detected hypermethylation in BCC tissue samples with reduced expression of EphA7. There is a significant relationship between the expression level of EphA7 receptor protein and the methylation status of CpG islands in the EphA7 promoter region ( P < 0.001 ). To our knowledge, this is the first study to report the EphA7 expression profile and hypermethylation of EphA7 in BCC. The role of the EphA7 gene and the status of hypermethylation in tumorigenesis and treatment of BCC warrant further investigation.