Influence of the Net Charge on the Reactivity of a Manganese(IV) Species: Leading to the Correlation of Its Physicochemical Properties with Reactivity

Clarifying how versatile physicochemical parameters of an active metal intermediate affect its reactivity would help to understand its roles in chemical and enzymatic oxidations. The influence of the net charge on electron transfer and hydrogen abstraction reactions of a manganese­(IV) species having hydroxide ligand has been investigated here. It was found that increasing one unit of the positive net charge from 2+ to 3+ would accelerate its electron-transfer rate by 10–20 fold in oxygenation of tris­(4-methoxyphenyl)­phosphine. In contrast, the hydrogen abstraction rate is insensitive to its net charge change, and the insensitivity has been attributed to the compensation effect between the redox potential and p<i>K</i>_a, which determine the hydrogen abstraction capability of a metal ion. Similar net-charge-promoted electron transfer but not hydrogen abstraction has also been observed in intramolecular electron transfer and hydrogen abstraction reactions when using thioxanthene as substrate. Together with the previous understanding of the reactivity of the identical manganese­(IV) species having Mn^IV–OH or Mn^IV=O functional groups, the relationships of the oxidative reactivity of an active metal intermediate with its physicochemical parameters such as the net charge, the redox potential and the metal–oxygen bond order (M–O versus MO) have been discussed with this manganese­(IV) model

DataSheet_1_Metabolic reprogramming involves in transition of activated/resting CD4+ memory T cells and prognosis of gastric cancer.docx

BackgroundLittle is known on how metabolic reprogramming potentially prompts transition of activated and resting CD4+ memory T cells infiltration in tumor microenvironment of gastric cancer (GC). The study aimed to evaluate their interactions and develop a risk model for predicting prognosis in GC.MethodsExpression profiles were obtained from TCGA and GEO databases. An immunotherapeutic IMvigor210 cohort was also enrolled. CIBERSORT algorithm was used to evaluate the infiltration of immune cells. The ssGSEA method was performed to assess levels of 114 metabolism pathways. Prognosis and correlation analysis were conducted to identify metabolism pathways and genes correlated with activated CD4+ memory T cells ratio (AR) and prognosis. An AR-related metabolism gene (ARMG) risk model was constructed and validated in different cohorts. Flow cytometry was applied to validate the effect of all-trans retinoic acid (ATRA) on CD4+ memory T cells.ResultsSince significantly inverse prognostic value and negative correlation of resting and activated CD4+ memory T cells, high AR level was associated with favorable overall survival (OS) in GC. Meanwhile, 15 metabolism pathways including retinoic acid metabolism pathway were significantly correlated with AR and prognosis. The ARMG risk model could classify GC patients with different outcomes, treatment responses, genomic and immune landscape. The prognostic value of the model was also confirmed in the additional validation, immunotherapy and pan-cancer cohorts. Functional analyses revealed that the ARMG model was positively correlated with pro-tumorigenic pathways. In vitro experiments showed that ATRA could inhibit levels of activated CD4+ memory T cells and AR.ConclusionOur study showed that metabolic reprogramming including retinoic acid metabolism could contribute to transition of activated and resting CD4+ memory T cells, and affect prognosis of GC patients. The ARMG risk model could serve as a new tool for GC patients by accurately predicting prognosis and response to treatment.</p

Pd(II)-Catalyzed <i>meta</i>-C–H Olefination, Arylation, and Acetoxylation of Indolines Using a U‑Shaped Template

<i>meta</i>-C–H olefination, arylation, and acetoxylation of indolines have been developed using nitrile-containing templates. The combination of a monoprotected amino acid ligand and the nitrile template attached at the indolinyl nitrogen via a sulfonamide linkage is crucial for the <i>meta</i>-selective C–H functionalization of electron-rich indolines that are otherwise highly reactive toward electrophilic palladation at the <i>para</i>-positions. A wide range of synthetically important and advanced indoline analogues are selectively functionalized at the <i>meta</i>-positions