The Role of Redox-Inactive Metals in Modulating the Redox Potential of the Mn4CaO4 Model Complex.

Photosynthetic oxygen-evolving center (OEC), the "engine of life", is a unique Mn4CaO5 cluster catalyzing the water oxidation. The role of redox-inactive component Ca2+, which can only be functionally replaced by Sr2+ in a biological environment, has been under debate for a long time. Recently, its modulating effect on the redox potential of native OEC and artificial structural OEC model complex has received great attention, and linear relationship between the potential and the Lewis acidity of the redox-inactive metal has been proposed for the MMn3O4 model complex. In this work, the modulating effect has been studied in detail using the Mn4CaO4 model complex, which is the closest structural model to OEC to date and has a similar redox potential at the S1-S2 transition. We found the redox-inactive metal only has a weak modulating effect on the potential, which is comparable in strength to that of the ligand environments. Meanwhile, the net charge of the complex, which could be changed along with the redox-inactive metal, has a high impact on the potential and can be unified by protonation, deprotonation, or ligand modification. Although the modulating effect of the redox-inactive metal is not very strong, the linear relationship between the potential and the Lewis acidity is still valid for Mn4MO4 complexes. Our results of strong modulating effects for net charge and weak modulating effects for redox-inactive metal fit with the previous experimental observations on Mn4MO4 (M = Ca2+, Y3+, and Gd3+) model complexes, and suggest that Ca2+ can be structurally and electrochemically replaced with other metal cations, together with proper ligand modifications.

K-Ras-PI3K regulates H3K56ac through PCAF to elevate the occurrence and growth of liver cancer.

H3 modification is related to a wide range of tumors, including liver cancer. The Ras passageway is actuated in human diseases. Thus, we investigated the roles of Ras in liver cancer cells via acetylation of H3K56. Ras-carrying G12V and Y40C site mutation was transfected into liver cancer cell lines SNU-475 and SK-Hep-1. Acetylation of H3K56 and phosphatidylinositol 3-kinase (PI3K), P300/CBP-associated factor (PCAF) and Mouse double minute 2 homolog (MDM2) was tested via western blot. Cell activity, colonies, and migration were tested via Cell Counting Kit-8, soft-agar colony formation, and Transwell experiment, respectively. Sirtuin 6 (SIRT6) and PCAF were tested via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Chromatin immunoprecipitation was employed to test the relationship between Ras and downstream elements. Flow cytometry was employed to test cell cycle series. We found that RasG12V/Y40C transfection reduced the acetylation of H3K56 and activated phosphorylation of protein kinase B. H3K56Q (H3K56ac overexpression) suppressed cell activity, colonies, and migration. H3K56ac changed Ras downstream factors expression. RasG12V/Y40C bound to Ras-PI3K downstream elements' promoters. SIRT6 silencing raised H3K56ac and suppressed cell activity, migration and S phage cell percentage. SIRT6 silence transformed expression of downstream elements. PCAF and H3K56ac demonstrated the close current while MDM2 was conversed. In summary, the Ras-PI3K passageway promoted cell growth and metastasis via decreasing H3K56ac, in which MDM2-mediated PCAF was involved.

Regioselective N-1 and C-2 diacylation of 3-substituted indoles with arylglyoxal hydrates for the synthesis of indolyl diketones.

A highly regioselective N-1 and C-2 diacylation of 3-substituted indoles with arylglyoxal hydrates to afford N-1 and C-2 indolyl diketones in moderate to good yields is described. Notably, the control of regioselectivity is achieved by small changes in the Cu catalyst, additive and solvent. Importantly, the intermediates for N-1 and C-2 diacylation were detected and two plausible pathways were also proposed.