Hoppercain2853

To reveal the delicate function of mitochondria, spatiotemporally precise detection tools remain highly desirable. However, current probes with positively charged warheads for targeting mitochondria diffuse out of the mitochondria as the potential of the mitochondrial membrane changes, which directly influences the accuracy of the detection. Herein, we assembled carbonylpyridinium and chromene to afford the probe CM-Mit. Following the ultrafast response to thiol and the dissociation of carbonylpyridinium, the formation of o-quinone methide from CM-Mit was proposed to label proteins, thus avoiding diffusion out of the mitochondria. Therefore, the accurate spatiotemporal detection of thiol in mitochondria was realized. With this excellent probe, ferroptosis inducers were proved to stimulate thiol starvation in mitochondria for the first time in cancer cells. Moreover, CM-Mit was used to screen a compound library developed in-house and the stemona alkaloid analog SA-11 was shown to induce ferroptosis in various cancer cell lines, including a drug-resistant one.The synthesis of a novel family of homoleptic COT-based heterotrimetallic self-assemblies bearing the formula [LnKCa(COT)3(THF)3] (Ln(iii) = Gd, Tb, Dy, Ho, Er, Tm, and Yb) is reported followed by their X-ray crystallographic and magnetic characterization. All crystals conform to the monoclinic P21/c space group with a slight compression of the unit cell from 3396.4(2) Å3 to 3373.2(4) Å3 along the series. All complexes exhibit a triple-decker structure having the Ln(iii) and K(i) ions sandwiched by three COT2- ligands with an end-bound Ca2+(THF)3 moiety to form a non-linear (153.5°) arrangement of three different metals. The COT2- ligands act in a η8-mode with respect to all metal centers. A detailed structural comparison of this unique set of heterotrimetallic complexes has revealed consistent trends along the series. From Gd to Yb, the Ln to ring-centroid distance decreases from 1.961(3) Å to 1.827(2) Å. In contrast, the separation of K(i) and Ca(ii) ions from the COT-centroid (2.443(3) and 1.914(3) Å, respectively) is not affected by the change of Ln(iii) ions. Selleck RU58841 The magnetic property investigation of the [LnKCa(COT)3(THF)3] series (Ln(iii) = Gd, Tb, Dy, Ho, Er, and Tm) reveals that the Dy, Er, and Tm complexes display slow relaxation of their magnetization, in other words, single-molecule magnet (SMM) properties. This behaviour is dominated by thermally activated (Orbach-like) and quantum tunneling processes for [DyKCa(COT)3(THF)3] in contrast to [ErKCa(COT)3(THF)3], in which the thermally activated and Raman processes appear to be relevant. Details of the electronic structures and magnetic properties of these complexes are further clarified with the help of DFT and ab initio theoretical calculations.Lead halide perovskite nanocrystals as promising ultrapure emitters are outstanding candidates for next-generation light-emitting diodes (LEDs) and display applications, but the thermal quenching behavior of light emission has severely hampered their real-world applications. Here, we report an anion passivation strategy to suppress the emission thermal quenching behavior of CsPbBr3 perovskite nanocrystals. By treating with specific anions (such as SO4 2-, OH-, and F- ions), the corresponding wide-bandgap passivation layers, PbSO4, Pb(OH)2, and PbF2, were obtained. They not only repair the surface defects of CsPbBr3 nanocrystals but also stabilize the phase structure of the inner CsPbBr3 core by constructing a core-shell like structure. The photoluminescence thermal resistance experiments show that the treated sample could preserve 79% of its original emission intensity up to 373 K, far superior to that (17%) of pristine CsPbBr3. Based on the thermally stable CsPbBr3 nanocrystals, we achieved temperature-stable white LED devices with a stable electroluminescence spectrum, color gamut and color coordinates in thermal stress tests (up to 373 K).Electrochemical conversion of CO2 into value-added chemicals continues to draw interest in renewable energy applications. Although many metal catalysts are active in the CO2 reduction reaction (CO2RR), their reactivity and selectivity are nonetheless hindered by the competing hydrogen evolution reaction (HER). The competition of the HER and CO2RR stems from the energy scaling relationship between their reaction intermediates. Herein, we predict that bimetallic monolayer electrocatalysts (BMEs) - a monolayer of transition metals on top of extended metal substrates - could produce dual-functional active sites that circumvent the scaling relationship between the adsorption energies of HER and CO2RR intermediates. The antibonding interaction between the adsorbed H and the metal substrate is revealed to be responsible for circumventing the scaling relationship. Based on extensive density functional theory (DFT) calculations, we identify 11 BMEs which are highly active and selective toward the formation of formic acid with a much suppressed HER. The H-substrate antibonding interaction also leads to superior CO2RR performance on monolayer-coated penta-twinned nanowires.To improve the efficacy of antibody drug conjugates (ADCs), there has been significant focus on increasing the drug-to-antibody ratio (DAR) in order to deliver more payload. However, due to the hydrophobicity of many cytotoxics, highly-loaded conjugates often have lower physicochemical stability and poorer pharmacokinetic outcomes, requiring the development of new hydrophilic linkers. Herein, we report a platform for the preparation of functional, sequence-defined polymers for conjugation to antibodies. We demonstrate the successful synthesis of novel diazido macrocyclic sulfate monomers of varied size ranging from 4 to 7 ethylene glycol repeat units. These monomers were then successively ring-opened to produce sequence-defined polymers that contained either 4 or 6 azides for post-synthesis functionalization. Given the hydrophilic ethylene glycol backbone and chemically defined nature of the polymers, we envisioned this as a useful strategy in the preparation of highly-loaded ADCs. To demonstrate this, we prepared a model polymer-fluorophore scaffold composed of 4 coumarin molecules and conjugated it to Herceptin. We fully characterized the conjugate via mass spectrometry, which yielded a polymer-to-antibody ratio of 6.6, translating to a total of 26 fluorophores conjugated to the antibody at the inter-chain disulfides. We believe this technology to not only be a meaningful contribution to the field of sequence-defined polymers and conjugates, but also as a general and tunable platform for drug delivery.Chiral α-amino ketones are common structural motifs in natural products and pharmaceuticals, as well as important synthons in organic synthesis. Thus, establishing efficient methods for preparing compounds with these privileged scaffolds is an important endeavor in synthetic chemistry. Herein we disclose a new catalytic asymmetric approach for the synthesis of chiral α-amino ketones through a chiral palladium-catalyzed arylation reaction of in situ generated challenging α-keto imines from previously unreported C-acyl N-sulfonyl-N,O-aminals, with arylboronic acids. The current reaction offers a straightforward approach to the asymmetric synthesis of acyclic α-amino ketones in a practical and highly stereocontrolled manner. Meanwhile, the multiple roles of the chiral Pd(ii) complex catalyst in the reaction were also reported.Photoaffinity labeling (PAL) is a powerful tool for the identification of non-covalent small molecule-protein interactions that are critical to drug discovery and medicinal chemistry, but this approach is limited to only a small subset of robust photocrosslinkers. The identification of new photoreactive motifs capable of covalent target capture is therefore highly desirable. Herein, we report the design, synthesis, and evaluation of a new class of PAL warheads based on the UV-triggered 1,2-photo-Brook rearrangement of acyl silanes, which hitherto have not been explored for PAL workflows. Irradiation of a series of probes in cell lysate revealed an iPr-substituted acyl silane with superior photolabeling and minimal thermal background labeling compared to other substituted acyl silanes. Further, small molecule (+)-JQ1- and rapamycin-derived iPr acyl silanes were shown to selectively label recombinant BRD4-BD1 and FKBP12, respectively, with minimal background. Together, these data highlight the untapped potential of acyl silanes as a novel, tunable scaffold for photoaffinity labeling.A palladium-catalyzed enantioselective ring-opening/carbonylation of cyclic diarylsulfonium salts is reported. In comparison to thioethers, the sulfonium salts displayed high reactivity and enabled the reaction to be performed under mild conditions (room temperature). The steric repulsion of the two non-hydrogen substituents adjacent to the axis led cyclic diarylsulfonium salts to be distorted, which enabled the ring-opening reaction to proceed with significant preference for breaking the exocyclic C-S bond.We present condensed-phase first-principles molecular dynamics simulations to elucidate the presence of different electron trapping sites in liquid methanol and their roles in the formation, electronic transitions, and relaxation of solvated electrons (emet -) in methanol. Excess electrons injected into liquid methanol are most likely trapped by methyl groups, but rapidly diffuse to more stable trapping sites with dangling OH bonds. After localization at the sites with one free OH bond (1OH trapping sites), reorientation of other methanol molecules increases the OH coordination number and the trap depth, and ultimately four OH bonds become coordinated with the excess electrons under thermal conditions. The simulation identified four distinct trapping states with different OH coordination numbers. The simulation results also revealed that electronic transitions of emet - are primarily due to charge transfer between electron trapping sites (cavities) formed by OH and methyl groups, and that these transitions differ from hydrogenic electronic transitions involving aqueous solvated electrons (eaq -). Such charge transfer also explains the alkyl-chain-length dependence of the photoabsorption peak wavelength and the excited-state lifetime of solvated electrons in primary alcohols.Herein we introduce a simple, efficient and transition-metal free method for the preparation of valuable and sterically hindered 3,3-disubstituted oxindoles via polar-radical crossover of ketene derived amide enolates. Various easily accessible N-alkyl and N-arylanilines are added to disubstituted ketenes and the resulting amide enolates undergo upon single electron transfer oxidation a homolytic aromatic substitution (HAS) to provide 3,3-disubstituted oxindoles in good to excellent yields. A variety of substituted anilines and a 3-amino pyridine engage in this oxidative formal [3 + 2] cycloaddition and cyclic ketenes provide spirooxindoles. Both substrates and reagents are readily available and tolerance to functional groups is broad.Proton-coupled electron transfer (PCET), an essential process in nature with a well-known example of photosynthesis, has recently been employed in metal complexes to improve the energy conversion efficiency; however, a profound understanding of the mechanism of PCET in metal complexes is still lacking. In this study, we synthesized cyclometalated Ir complexes strategically designed to exploit the excited-state intramolecular proton transfer (ESIPT) of the ancillary ligand and studied their photoinduced PCET in both aprotic and protic solvent environments using femtosecond transient absorption spectroscopy and density functional theory (DFT) and time-dependent DFT calculations. The data reveal solvent-modulated PCET, where charge transfer follows proton transfer in an aprotic solvent and the temporal order of charge transfer and proton transfer is reversed in a protic solvent. In the former case, ESIPT from the enol form to the keto form, which precedes the charge transfer from Ir to the ESIPT ligand, improves the efficiency of metal-to-ligand charge transfer.