Moreno Fulton (tauruskick0)

The leading-order dispersion and exchange-dispersion terms in symmetry-adapted perturbation theory (SAPT), Edisp(20) and Eexch-disp(20), suffer from slow convergence to the complete basis set limit. To alleviate this problem, explicitly correlated variants of these corrections, Edisp(20)-F12 and Eexch-disp(20)-F12, have been proposed recently. However, the original formalism (M., Kodrycka , J. Chem. Theory Comput. 2019, 15, 5965-5986), while highly successful in terms of improving convergence, was not competitive to conventional orbital-based SAPT in terms of computational efficiency due to the need to manipulate several kinds of two-electron integrals. In this work, we eliminate this need by decomposing all types of two-electron integrals using robust density fitting. We demonstrate that the error of the density fitting approximation is negligible when standard auxiliary bases such as aug-cc-pVXZ/MP2FIT are employed. The new implementation allowed us to study all complexes in the A24 database in basis sets up to aug-cc-pV5Z, and the Edisp(20)-F12 and Eexch-disp(20)-F12 values exhibit vastly improved basis set convergence over their conventional counterparts. The well-converged Edisp(20)-F12 and Eexch-disp(20)-F12 numbers can be substituted for conventional Edisp(20) and Eexch-disp(20) ones in a calculation of the total SAPT interaction energy at any level (SAPT0, SAPT2+3, ...). We show that the addition of F12 terms does not improve the accuracy of low-level SAPT treatments. However, when the theory errors are minimized in high-level SAPT approaches such as SAPT2+3(CCD)δMP2, the reduction of basis set incompleteness errors thanks to the F12 treatment substantially improves the accuracy of small-basis calculations.Nine new glucosyloxybenzyl 2-hydroxy-2-isobutylsuccinates, pleionosides M-U (1-9), and 12 known compounds (10-21) were isolated from the pseudobulbs of Pleione yunnanensis. Their structures and absolute configurations were established through a combination of HRESIMS and NMR data and supported by physical and chemical methods. learn more Compounds 5, 6, 10, and 15 showed significant in vitro hepatoprotective activity against d-galactosamine (d-GalN)-induced toxicity in HL-7702 cells with increasing cell viability by 27%, 22%, 19%, and 31% compared to the model group (cf. bicyclol, 14%) at 10 μM, respectively. Compounds 4, 9, and 11 exhibited moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells with increasing cell viability by 9%, 16%, and 12% compared to the model group (cf. bicyclol, 9%) at 10 μM, respectively.EZH2 mediates both PRC2-dependent gene silencing via catalyzing H3K27me3 and PRC2-independent transcriptional activation in various cancers. Given its oncogenic role in cancers, EZH2 has constituted a compelling target for anticancer therapy. However, current EZH2 inhibitors only target its methyltransferase activity to downregulate H3K27me3 levels and show limited efficacy because of inadequate suppression of the EZH2 oncogenic activity. Therefore, therapeutic strategies to completely block the oncogenic activity of EZH2 are urgently needed. Herein, we report a series of EZH2-targeted proteolysis targeting chimeras (PROTACs) that induce proteasomal degradation of PRC2 components, including EZH2, EED, SUZ12, and RbAp48. Preliminary assessment identified E7 as the most active PROTAC molecule, which decreased PRC2 subunits and H3K27me2/3 levels in various cancer cells. Furthermore, E7 strongly inhibited transcriptional silencing mediated by EZH2 dependent on PRC2 and transcriptional activation mediated by EZH2 independent of PRC2, showing significant antiproliferative activities against cancer cell lines dependent on the enzymatic and nonenzymatic activities of EZH2.We present a systematic investigation of the photophysical properties of diazocines in aqueous media. The Z-E photoconversion yields of CH2CH2- and CH2S-bridged diazocines decrease with increas