Kromanngormsen8376

Our findings illustrate conserved coupling principles within the complex I superfamily and provide functional insight into archaeal energy transduction mechanisms.The potential of ruthenium(II) compounds as an alternative to platinum-based clinical anticancer agents has been unveiled after extensive research for over 2 decades. As opposed to cisplatin, ruthenium(II) compounds have distinct mechanisms of action that do not rely solely on interactions with DNA. In a previous report from our group, we described the synthesis, characterization, and biological evaluation of a cationic, water-soluble, organometallic ruthenium(II) iminophosphorane (IM) complex of p-cymene, ([(η6-p-cymene)Ru(Ph3P═N-CO-2N-C5H4)-κ-N,OCl]Cl (1 or Ru-IM), that was found to be highly cytotoxic against a panel of cell lines resistant to cisplatin, including triple-negative breast cancer (TNBC) MDA-MB-231, through canonical or caspase-dependent apoptosis. Studies on a MDA-MB-231 xenograft mice model (after 28 days of treatment) afforded an excellent tumor reduction of 56%, with almost negligible systemic toxicity, and a favored ruthenium tumor accumulation compared to other organs. 1 is known to onential accumulation of the compound in the endoplasmic reticulum, mitochondria, and lysosomes. Inductively coupled plasma optical emission spectrometry (ICP-OES) analysis also confirms a greater ruthenium accumulation in the cytoplasmic fraction, including endoplasmic reticulum and lysosomes, and a smaller percentage of accumulation in mitochondria and the nucleus. ICP-OES analysis of the parent compound 1 indicates that it accumulates preferentially in the mitochondria and cytoplasm. Subsequent experiments in 1-treated MDA-MB-231 cells demonstrate significant reactive oxygen species generation.The gas-phase oxidation of organic compounds is an important chemical process in the Earth's atmosphere. It governs oxidant levels and controls the production of key secondary pollutants, and hence has major implications for air quality and climate. Organic oxidation is largely controlled by the chemistry of a few reactive intermediates, namely, alkyl (R) radicals, alkoxy (RO) radicals, peroxy (RO2) radicals, and carbonyl oxides (R1R2COO), which may undergo a number of unimolecular and bimolecular reactions. Our understanding of these intermediates, and the reaction pathways available to them, is based largely on studies of unfunctionalized intermediates, formed in the first steps of hydrocarbon oxidation. However, it has become increasingly clear that intermediates with functional groups, which are generally formed later in the oxidation process, can exhibit fundamentally different reactivity than unfunctionalized ones. In this Perspective, we explore the unique chemistry available to functionalized organic y. The continued use and development of such techniques and the close collaboration between experimentalists and theoreticians are necessary for a complete, detailed understanding of the chemistry of functionalized intermediates and their impact on major atmospheric chemical processes.High-energy X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) of amorphous solid water (ASW) were studied during vapor deposition and the heating process. From the diffraction patterns, the oxygen-oxygen pair distribution functions (PDFs) were calculated up to the eighth coordination shell and an r = 23 Å. The PDF of ASW obtained both during vapor deposition at 80 K as well as the subsequent heating are consistent with that of low-density amorphous ice. The formation and temperature-induced collapse of micropores were observed in the XRD data and in the FTIR measurements, more specifically, in the OH stretch and the dangling mode. Above 140 K, ASW crystallizes into a stacking disordered ice, Isd. It is observed that the fourth, fifth, and sixth peaks in the PDF, corresponding to structural arrangements between 8 and 12 Å, are the most sensitive to the onset of crystallization.The synthesis, chemical and biological characterization of seven Ru(II) polypyridyl complexes containing acetylacetonate (acac) ligands are reported. Electronic absorption spectra were determined and electrochemical potentials consistent with Ru(III/II) couples ranging from +0.60 to +0.73 V vs Ag/AgCl were measured. A series of complexes were screened against MDA-MB-231, DU-145, and MCF-10A cell lines to evaluate their cytotoxicities in cancer and normal cell lines. Although most complexes were either nontoxic or equipotent in cancer cells and normal cell lines, compound 1, [Ru(dpqy)(acac)(py)](PF6), where dqpy is 2,6-di(quinolin-2-yl)pyridine, showed up to 2.51.0 selectivity for cancer as compared to normal cells, along with nanomolar EC50 values in MDA-MB-231 cells. Lipophilicity, determined as the octanol/water partition coefficient, log Po/w, ranged from -0.33 (0.06) to 1.15 (0.10) for the complexes. Although cytotoxicity was not correlated with electrochemical potentials, a moderate linear correlation between lipophilicity and toxicities was observed. Cell death mechanism studies indicated that several of the Ru-acac compounds, including 1, induce apoptosis in MDA-MB-231 cells.Despite their significant potential, catalytic asymmetric reactions of olefins with formaldehyde are rare and metal-free approaches have not been previously disclosed. Here we describe an enantioselective intermolecular Prins reaction of styrenes and paraformaldehyde to form 1,3-dioxanes, using confined imino-imidodiphosphate (iIDP) Brønsted acid catalysts. Isotope labeling experiments and computations suggest a concerted, highly asynchronous addition of an acid-activated formaldehyde oligomer to the olefin. The enantioenriched 1,3-dioxanes can be transformed into the corresponding optically active 1,3-diols, which are valuable synthetic building blocks.In aquaculture, it is important to raise the nitrogen recovery efficiency (NRE) to improve sustainability. To achieve this, recovery of microbial protein (RMP), instead of nitrification/denitrification in conventional wastewater treatment, is a promising approach whose microbiological mechanisms must be characterized. Here, periodic RMP was conducted in an in situ biofloc-based aquaculture system (IBAS) and a separating assimilation reactor-based recirculating aquaculture system (SRAS). Kinetic analysis indicated that a microbial biomass level of 3 g L-1 was optimal for inorganic N removal, and excess biomass was harvested to improve the NRE. Unlike the IBAS, the SRAS eliminated the fluctuation in water quality caused by the RMP. Periodic RMP significantly increased the NRE to 44-57% by promoting the filamentous bacterium Herpetosiphon and suppressing anaerobic denitrifiers. Aerobic chemoheterotrophy was the main microbial metabolic process for energy. After RMP, nitrate reductase-encoded functional genes (napA and narG) significantly decreased, while nitrite reductase-encoded functional genes, especially nirK, significantly increased. Co-occurrence networks analysis indicated that the cooperation and competition among organic matter degraders, filamentous bacteria, nitrifiers, and denitrifiers determined the microbial protein yield. These results provide fundamental insights into the influence of the RMP on microbial communities and functions, which is important for realizing sustainable aquaculture.Phthalates are widely used in consumer products and are well-known for adverse endocrine outcomes. Di-(2-ethylhexyl) phthalate (DEHP), one of the most extensively used phthalates, has been rapidly substituted with alternative plasticizers in many consumer products. The aim of this study was to assess urinary phthalate and alternative plasticizer exposure and associated risks in children of three Asian countries with different geographical, climate, and cultural characteristics. Children were recruited from elementary schools of Saudi Arabia (n = 109), Thailand (n = 104), and Indonesia (n = 89) in 2017-2018, and their urine samples were collected. Metabolites of major phthalates and alternative plasticizers were measured in the urine samples by HPLC-MS/MS. Urinary metabolite levels differed substantially between the three countries. Metabolite levels of diisononyl phthalate (DiNP), diisodecyl phthalate (DiDP), di(2-ethylhexyl) terephthalate (DEHTP), and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) were the highest in Saudi children Median urinary concentrations of oxo-MiNP, OH-MiDP, 5cx-MEPTP, and OH-MINCH were 8.3, 8.4, 128.0, and 2.9 ng/mL, respectively. Urinary DEHP metabolite concentrations were the highest in the Indonesian children. The hazard index (HI) derived for the plasticizers with antiandrogenicity based reference doses (RfDAA) was >1 in 86%, 80%, and 49% of the Saudi, Indonesian, and Thai children, respectively. DEHP was identified as a common major risk driver for the children of all three countries, followed by DnBP and DiBP depending on the country. Among alternative plasticizers, urinary DEHTP metabolites were detected at levels comparable to those of DEHP metabolites or higher among the Saudi children, and about 4% of the Saudi children exceeded the health based human biomonitoring (HBM)-I value. Priority plasticizers that were identified among the children of three countries warrant refined exposure assessment for source identification and relevant exposure reduction measures.The spin-crossover reaction of thiophosgene has drawn broad attention from both experimenters and theoreticians as a prime example of radiationless intramolecular decay via intersystem crossing. Despite multiple attempts over 20 years, theoretical predictions have typically been orders of magnitude in error relative to the experimentally measured triplet lifetime. We address the T1 → S0 transition by the first application of semiclassical golden-rule instanton theory in conjunction with on-the-fly electronic-structure calculations based on multireference perturbation theory. Our first-principles approach provides excellent agreement with the experimental rates. This was only possible because instanton theory goes beyond previous methods by locating the optimal tunneling pathway in full dimensionality and thus captures "corner cutting" effects. Since the reaction is situated in the Marcus inverted regime, the tunneling mechanism can be interpreted in terms of two classical trajectories, one traveling forward and one backward in imaginary time, which are connected by particle-antiparticle creation and annihilation events. The calculated mechanism indicates that the spin crossover is sped up by many orders of magnitude due to multidimensional quantum tunneling of the carbon atom even at room temperature.Covalent labeling of proteins in combination with mass spectrometry has been established as a complementary technique to classical structural methods, such as X-ray, NMR, or cryogenic electron microscopy (Cryo-EM), used for protein structure determination. CIL56 mw Although the current covalent labeling techniques enable the protein solvent accessible areas with sufficient spatial resolution to be monitored, there is still high demand for alternative, less complicated, and inexpensive approaches. Here, we introduce a new covalent labeling method based on fast fluoroalkylation of proteins (FFAP). FFAP uses fluoroalkyl radicals formed by reductive decomposition of Togni reagents with ascorbic acid to label proteins on a time scale of seconds. The feasibility of FFAP to effectively label proteins was demonstrated by monitoring the differential amino acids modification of native horse heart apomyoglobin/holomyoglobin and the human haptoglobin-hemoglobin complex. The obtained data confirmed the Togni reagent-mediated FFAP is an advantageous alternative method for covalent labeling in applications such as protein footprinting and epitope mapping of proteins (and their complexes) in general.