Dealweber2806

Diruthenium paddlewheel complexes supported by electron-rich anilinopyridinate (Xap) ligands were synthesized in the course of the first in-depth structural and spectroscopic interrogation of monocationic [Ru2(Xap)4Cl]+ species in the Ru26+ oxidation state. Despite paramagnetism of the compounds, 1H NMR spectroscopy proved highly informative for determining the isomerism of the Ru25+ and Ru26+ compounds. Etomoxir order While most compounds are found to have the polar (4,0) geometry, with all four Xap ligands in the same orientation, some synthetic procedures resulted in a mixture of (4,0) and (3,1) isomers, most notably in the case of the parent compound Ru2(ap)4Cl. The isomerism of this compound has been overlooked in previous reports. Electrochemical studies demonstrate that oxidation potentials can be tuned by the installation of electron donating groups to the ligands, increasing accessibility of the Ru26+ oxidation state. The resulting Ru26+ monocations were found to have the expected (π*)2 ground state, and an in-depth study of the electronic transitions by Vis/NIR absorption and MCD spectroscopies with the aid of TD-DFT allowed for the assignment of the electronic spectra. The empty δ* orbital is the major acceptor orbital for the most prominent electronic transitions. Both Ru25+ and Ru26+ compounds were studied by Ru K-edge X-ray absorption spectroscopy; however, the rising edge energy is insensitive to redox changes in the compounds due to the broad line shape observed for 4d transition metal K-edges. DFT calculations indicate the presence of ligand orbitals at the frontier level, suggesting that further oxidation beyond Ru26+ will be ligand-centered rather than metal-centered.The identification and characterization of binding sites is a critical component of structure-based drug design (SBDD). Probe-based/cosolvent molecular dynamics (MD) methods that allow for protein flexibility have been developed to predict ligand binding sites. However, cryptic pockets that appear only upon ligand binding and occluded binding sites with no access to the solvent pose significant challenges to these methods. Here, we report the development of accelerated ligand-mapping MD (aLMMD), which combines accelerated MD with LMMD, for the detection of these challenging binding sites. The method was validated on five proteins with what we term "recalcitrant" cryptic pockets, which are deeply buried pockets that require extensive movement of the protein backbone to expose, and three proteins with occluded binding sites. In all the cases, aLMMD was able to detect and sample the binding sites. Our results suggest that aLMMD could be used as a general approach for the detection of such elusive binding sites in protein targets, thus providing valuable information for SBDD.Nanoparticles exhibit unique properties due to their surface effects and small size, and their behavior at high pressures has attracted widespread attention in recent years. Herein, a series of in situ high-pressure X-ray diffraction measurements with a synchrotron radiation source and Raman scattering have been performed on HfO2 nanocrystals (NC-HfO2) with different grain sizes using a symmetric diamond anvil cell at ambient temperature. The experimental data reveal that the structural stability, phase transition behavior, and equation of state for HfO2 have an interesting size effect under high pressure. NC-HfO2 quenched to normal pressure is characterized by transmission electron microscopy to determine the changing behavior of grain size during phase transition. We found that the rotation of the nanocrystalline HfO2 grains causes a large strain, resulting in the retention of part of an orthorhombic I (OI) phase in the sample quenched to atmospheric pressure. Furthermore, the physical mechanism of the phase transition of NC-HfO2 under high pressure can be well explained by the first-principles calculations. The calculations demonstrate that NC-HfO2 has a strong surface effect, that is, the surface energy and surface stress can stabilize the structures. These studies may offer new insights into the understanding of the physical behavior of nanocrystal materials under high pressure and provide practical guidance for their realization in industrial applications.Triplet-triplet annihilation photon upconversion (TTA-UC) is a process in which triplet excitons combine to form emissive singlets and holds great promise in biological applications and for improving the spectral match in solar energy conversion. While high TTA-UC quantum yields have been reported for, for example, red-to-green TTA-UC systems, there are only a few examples of visible-to-ultraviolet (UV) transformations in which the quantum yield reaches 10%. In this study, we investigate the performance of six annihilators when paired with the sensitizer 2,3,5,6-tetra(9H-carbazol-9-yl)benzonitrile (4CzBN), a purely organic compound that exhibits thermally activated delayed fluorescence. We report a record-setting internal TTA-UC quantum yield (ΦUC,g) of 16.8% (out of a 50% maximum) for 1,4-bis((triisopropylsilyl)ethynyl)naphthalene, demonstrating the first example of a visible-to-UV TTA-UC system approaching the classical spin-statistical limit of 20%. Three other annihilators, of which 2,5-diphenylfuran has never been used for TTA-UC previously, also showed impressive performances with ΦUC,g above 12%. In addition, a new method to determine the rate constant of TTA is proposed, in which only time-resolved emission measurements are needed, circumventing the need for more challenging transient absorption measurements. The results reported herein represent an important step toward highly efficient visible-to-UV TTA-UC systems that hold great potential for driving high-energy photochemical reactions.TNP-2198, a stable conjugate of a rifamycin pharmacophore and a nitroimidazole pharmacophore, has been designed, synthesized, and evaluated as a novel dual-targeted antibacterial agent for the treatment of microaerophilic and anaerobic bacterial infections. TNP-2198 exhibits greater activity than a 11 molar mixture of the parent drugs and exhibits activity against strains resistant to both rifamycins and nitroimidazoles. A crystal structure of TNP-2198 bound to a Mycobacterium tuberculosis RNA polymerase transcription initiation complex reveals that the rifamycin portion of TNP-2198 binds to the rifamycin binding site on RNAP and the nitroimidazole portion of TNP-2198 interacts directly with the DNA template-strand in the RNAP active-center cleft, forming a hydrogen bond with a base of the DNA template strand. TNP-2198 is currently in Phase 2 clinical development for the treatment of Helicobacter pylori infection, Clostridioides difficile infection, and bacterial vaginosis.Pathogens such as Plasmodium and Trypanosoma spp. are unable to synthesize purine nucleobases. They rely on the salvage of these purines and their nucleosides from the host cell to synthesize the purine nucleotides required for DNA/RNA production. The key enzymes in this pathway are purine phosphoribosyltransferases (PRTs). Here, we synthesized 16 novel acyclic nucleoside phosphonates, 12 with a chiral center at C-2', and eight bearing a second chiral center at C-6'. Of these, bisphosphonate (S,S)-48 is the most potent inhibitor of the Plasmodium falciparum and P. vivax 6-oxopurine PRTs and the most potent inhibitor of two Trypanosoma brucei (Tbr) 6-oxopurine PRTs yet discovered, with Ki values as low as 2 nM. Crystal structures of (S,S)-48 in complex with human and Tbr 6-oxopurine PRTs show that the inhibitor binds to the enzymes in different conformations, providing an explanation for its potency and selectivity (i.e., 35-fold in favor of the parasite enzymes).For the biomedical application of engineered bacteria, strictly regulating the function of engineered bacteria has always been the goal pursued. However, the existing regulation methods do not meet the needs of the in vivo application of engineered bacteria. Therefore, the exploration of the precise regulation of engineered bacteria is necessary. Herein, heat-sensitive engineered bacteria that can respond to thermal stimuli within 30 min were constructed, and the precise control of functions was verified in the intestines of various model organisms (including C. elegans, bees, and mice). Subsequently, heat-sensitive engineered bacteria were shown to colonize the mouse tumor microenvironment. Finally, thermal stimulation was proven to control engineered bacteria to produce the therapeutic protein tumor necrosis factor α (TNF-α) in the tumor. After three heat stimulation treatments, the growth of the tumor was significantly inhibited, suggesting that heat can be used as a strategy to precisely control engineered bacteria in vivo.It is estimated that 90% of deaths from food poisoning in China can be attributed to Amanita poisoning, whose main toxin is α-amanitin. Studies showed that apoptosis plays a critical role in liver injuries induced by α-amanitin. Although the relationship between autophagy and apoptosis in different liver models has been addressed many times, whether autophagy plays a pro or con effect on α-amanitin-induced apoptosis has not been clarified. Therefore, this study was conducted to explore the effect of autophagy in α-amanitin-induced apoptosis in Hepa1-6 liver cells. A 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay was applied to determine cell viability, a 2',7'-dichlorofluorescin diacetate probe was used to monitor reactive oxygen species (ROS) levels, a flow cytometer and dansylcadaverine (MDC) staining were used to observe α-amanitin-induced apoptosis and autophagy, respectively, and apoptosis and autophagy proteins were assessed by western blotting. The results showed that α-amanils. This research provides a theoretical basis for the study of the toxicological mechanism of α-amanitin-induced liver injuries.As one of the most attractive inorganics to improve the thermoelectric (TE) performance of the conducting polymers, tellurium (Te) has received intense concern due to its superior Seebeck coefficient (S). However, far less attention has been paid to polypyrrole (PPy)/Te TE composites to date. In this work, we present an innovative full-electrochemical method to architect PPy/Te TE composite films by sequentially depositing Te with large S and PPy with high electrical conductivity (σ). Consequently, the PPy/Te composite films achieved excellent TE performance, with the largest power factor (PF) reaching up to 234.3 ± 4.1 μW m-1 K-2. To the best of our knowledge, this value approaches the reported highest PF record (240.3 ± 5.0 μW m-1 K-2) for PPy-based composites. This suggests that the modified full-electrochemical method is a feasible and effective strategy for achieving high-performance TE composite films, which would probably provide a general guideline for the design and preparation of excellent TE materials in the future.The complex synthesis of photoelectric materials and the difficulty of fixing the identification elements on the photoelectrode are long-standing problems in the field of photoelectrochemical (PEC) biosensing. In this work, a simple PEC aptasensor construction strategy based on a sulfur-doped g-C3N4 (SCN)/n-GaN heterostructure photoelectrode was proposed. The SCN/n-GaN heterostructure can be formed through self-assembly in solution since SCN can be uniformly dispersed in solution. In addition, as a dual-function mediate, an aptamer can be fixed on an SCN substrate automatically because of the good adsorption performance of SCN. Therefore, tedious steps of PEC electrode preparation and the fixing of recognition elements were both avoided. Compared with the traditional ones, the construction difficulty and time cost of the prepared PEC aptasensors are greatly reduced. The simplified experimental process improves the stability and reproducibility of the aptasensor. Finally, tetracycline (TET) was used as a model target to verify the sensing performance of the proposed PEC strategy.