Torressanford9257

Based on the Interacting Quantum Atoms approach, we present herein a conceptual and theoretical framework of short-range electrostatic interactions, whose accurate description is still a challenging problem in molecular modeling. For all the noncovalent complexes in the S66 database, the fragment-based and atomic decomposition of the electrostatic binding energies is performed using both the charge density of the dimers and the unrelaxed densities of the monomers. This energy decomposition together with dispersion corrections gives rise to a pairwise approximation to the total binding energy. It also provides energetic descriptors at varying distance that directly address the atomic and molecular electrostatic interactions as described by point-charge or multipole-based potentials. Additionally, we propose a consistent definition of the charge penetration energy within quantum chemical topology, which is mainly characterized in terms of the intramolecular electrostatic energy. Finally, we discuss some practical implications of our results for the design and validation of electrostatic potentials.Chagas disease, an infectious condition caused by Trypanosoma cruzi, lacks treatment with drugs with desired efficacy and safety profiles. To address this unmet medical need, a set of trypanocidal compounds were identified through a large multicenter phenotypic-screening initiative and assembled in the GSK Chagas Box. In the present work, we report the screening of the Chagas Box against T. cruzi malic enzymes (MEs) and the identification of three potent inhibitors of its cytosolic isoform (TcMEc). One of these compounds, TCMDC-143108 (1), came out as a nanomolar inhibitor of TcMEc, and 14 new derivatives were synthesized and tested for target inhibition and efficacy against the parasite. Moreover, we determined the crystallographic structures of TcMEc in complex with TCMDC-143108 (1) and six derivatives, revealing the allosteric inhibition site and the determinants of specificity. Our findings connect phenotypic hits from the Chagas Box to a relevant metabolic target in the parasite, providing data to foster new structure-activity guided hit optimization initiatives.The electrosynthesis of high-value-added multicarbon compounds coupled with hydrogen production is an efficient way to achieve carbon neutrality; however, the lack of effective bifunctional catalysts in electrosynthesis largely hinders its development. Herein, we report the first example on the highly efficient electrosynthesis of high-value-added 1,1-diethoxyethane (DEE) at the anode and high-purity hydrogen at the cathode using 1 nm PtIr nanowires (NWs) as the bifunctional catalysts. We demonstrate that the cell using 1 nm PtIr nanowires as the bifunctional catalysts can achieve a reported lowest voltage of 0.61 V to reach the current density of 10 mA cm-2, much lower than those of the Pt NWs (0.85 V) and commercial Pt/C (0.86 V), and also can have the highest Faraday efficiencies of 85% for DEE production and 94.0% for hydrogen evolution in all the reported electrosynthesis catalysts. The in situ infrared spectroscopy study reveals that PtIr NWs can facilitate the activation of O-H and C-H bonds in ethanol, which is important for the formation of acetaldehyde intermediate, and finally DEE. Miransertib concentration In addition, the cell using PtIr NWs as bifunctional catalysts exhibits excellent stability by showing almost no obvious decrease in the Faraday efficiency of the DEE production.Magnesium silicide (Mg2Si) is a promising eco-friendly thermoelectric material, which has been extensively studied in recent times. However, its phase behavior at high pressures and temperatures remains unclear. To this end, in this study, in situ X-ray diffraction analysis was conducted at high pressures ranging from 0 to 11.3 GPa and high temperatures ranging from 296 to 1524 K, followed by quenching. The antifluorite-phase Mg2Si decomposed to Mg9Si5 and Mg at pressures above 3 GPa and temperatures above 970 K. The antifluorite-phase Mg2Si underwent a structural phase transition to yield a high-pressure room-temperature (HPRT) phase at pressures above 10.5 GPa and at room temperature. This HPRT phase also decomposed to Mg9Si5 and Mg when heated at ∼11 GPa. When 5Mg2Si decomposed to Mg9Si5 and Mg, the volume reduced by ∼6%. Mg9Si5 synthesized at high pressures and high temperatures was quenchable under ambient conditions. Thermoelectric property measurements of Mg9Si5 at temperatures ranging from 10 to 390 K revealed that it was a p-type semiconductor having a dimensionless thermoelectric figure of merit (ZT) of 3.4 × 10-4 at 283 K.There is a challenge in supramolecular chemotherapy for constructing a system equipped with both sufficient protection and high-efficiency release of drugs. To this end, a new strategy of an activatable host-guest conjugate with self-inclusion property is proposed. Based on the binding affinity gain of intramolecular host-guest self-inclusion, an activatable host-guest conjugate was designed, bearing cucurbit[7]uril as the host, an alkyl ammonium moiety as the guest, and the redox-responsive disulfide linkage. Oxaliplatin, a clinical antitumor drug, could be firmly encapsulated by the activatable host-guest conjugate to form the supramolecular drug with high stability. Moreover, oxaliplatin loaded in the activatable host-guest conjugate could be almost completely released by self-inclusion triggered by glutathione in a tumor microenvironment, thus exhibiting comparable antitumor bioactivity with naked oxaliplatin through in vitro cell experiments. It is highly anticipated that this line of research may open new horizons for programmable and on-demand supramolecular chemotherapy with high antitumor efficiency.Multiplexing of analyses is essential to reduce sample and reagent consumption in applications with large target panels. In applications such as cancer diagnostics, the required degree of multiplexing often exceeds the number of available fluorescence channels in polymerase chain reaction (PCR) devices. The combination of photobleaching-sensitive and photobleaching-resistant fluorophores of the same color can boost the degree of multiplexing by a factor of 2 per channel. The only additional hardware required to create virtual fluorescence color channels is a low-cost light-emitting diode (LED) setup for selective photobleaching. Here, we present an assay concept for fluorescence color multiplexing in up to 10 channels (five standard channels plus five virtual channels) using the mediator probe PCR with universal reporter (UR) fluorogenic oligonucleotides. We evaluate the photobleaching characteristic of 21 URs, which cover the whole spectral range from blue to crimson. This comprehensive UR data set is employed to demonstrate the use of three virtual channels in addition to the three standard channels of a commercial dPCR device (blue, green, and red) targeting cancer-associated point mutations (KRAS G12D and G12V).