Holderbergmann0470

We report a new reversible lysine conjugation that features a novel diazaborine product and much slowed dissociation kinetics in comparison to the previously known iminoboronate chemistry. Incorporating the diazaborine-forming warhead RMR1 to a peptide ligand gives potent and long-acting reversible covalent inhibitors of the staphylococcal sortase. CTP-656 nmr The efficacy of sortase inhibition is demonstrated via biochemical and cell-based assays. A comparative study of RMR1 and an iminoboronate-forming warhead highlights the significance and potential of modulating bond dissociation kinetics in achieving long-acting reversible covalent inhibitors.Organic photovoltaics (OPV) is an emerging solar cell technology that offers vast advantages such as low-cost manufacturing, transparency, and solution processability. However, because the performance of OPV devices is still disappointing compared to their inorganic counterparts, better understanding of how controlling the molecular-level morphology can impact performance is needed. To this end, one has to overcome significant challenges that stem from the complexity and heterogeneity of the underlying electronic structure and molecular morphology. In this Letter, we address this challenge in the context of the DBP/C70 OPV system by employing a modular workflow that combines recent advances in electronic structure, molecular dynamics, and rate theory. We show how the wide range of interfacial pairs can be classified into four types of interfacial donor-acceptor geometries and find that the least populated interfacial geometry gives rise to the fastest charge transfer (CT) rates.An earth-abundant and inexpensive Mn(I)-catalyzed alkylation of 2-pyridone with maleimide has been reported for the first time, in contrast to previously reported Diels-Alder products. Notably, an unexpected rearrangement has been discovered in the presence of acetic acid, which also provides a unique class of compounds bearing three different N-heterocycles with an all-carbon quaternary center. Furthermore, single crystal X-ray and HRMS revealed a five-membered manganacycle intermediate. This methodology tolerates a wide variety of functional groups delivering the alkylated products in moderate to excellent yields.A general phase-transfer-catalyzed asymmetric (n+1) (n = 4 or 5) annulation reaction, featuring the direct coupling of simple oxindoles with alkyl dihalides that are allylic/benzylic and non-allylic/benzylic, has been developed to provide previously inaccessible cyclopentane- and cyclohexane-fused spirooxindole scaffolds with high yields and enantioselectivities (88-95% ee). Along with a broad scope and mild conditions, the new protocol also enables a two-step and gram-scale synthesis of the core of the drug ubrogepant.Considerable efforts have been devoted to developing oxygen evolution reaction (OER) catalysts based on transition metal oxides. Polyoxometalates (POMs) can be regarded as model compounds of transition metal oxides, and cobalt-containing POMs (Co-POMs) have received significant interest as candidates. Nanocomposites based on Co-POMs have been reported to show high OER activities due to synergistic effects among the components; however, the role of each component is unclear due to its complex structure. Herein, we utilize porous ionic crystals (PICs) based on Co-POMs, which enable a composition-structure-function relationship to be established to understand the origin of the synergistic catalysis. Specifically, a Keggin-type POM [α-CoW12O40]6- and a Cr complex [Cr3O(OOCCH2CN)6(H2O)3]+ are implemented as PIC building blocks for the OER under nonbasic conditions. The potentially OER-active but highly soluble [α-CoW12O40]6- was successfully anchored in the crystalline PIC matrix via Coulomb interactions and hydrogen bonding induced by polar cyano groups of the Cr complex. The PIC exhibits efficient and sustained OER catalytic activity, while each building block is inactive. The Tafel slope of the linear sweep voltammetry curve and the relatively large kinetic isotope effect value suggest that elementary steps closely related to the OER rate involve single-electron and proton transfer reactions. Electrochemical and spectroscopic studies clearly show that the synergistic catalysis originates from the charge transfer from the Cr complex to [α-CoW12O40]6-; the increased electron density of [α-CoW12O40]6- may increase its basicity and accelerate proton abstraction as well as enhance electron transfer to stabilize the reaction intermediates adsorbed on [α-CoW12O40]6-.Understanding the mechanism that connects heat transport with crystal structures and order/disorder phenomena is crucial to develop materials with ultralow thermal conductivity (κ), for thermoelectric and thermal barrier applications, and requires the study of highly pure materials. We synthesized the n-type sulfide CuPbBi5S9 with an ultralow κ value of 0.6-0.4 W m-1 K-1 in the temperature range 300-700 K. In contrast to prior studies, we show that this synthetic sulfide does not exhibit the ordered gladite mineral structure but instead forms a copper-deficient disordered aikinite structure with partial Pb replacement by Bi, according to the chemical formula Cu1/3□2/3Pb1/3Bi5/3S3. By combining experiments and lattice dynamics calculations, we elucidated that the ultralow κ value of this compound is due to very low energy optical modes associated with Pb and Bi ions and, to a smaller extent, Cu. This vibrational complexity at low energy hints at substantial anharmonic effects that contribute to enhance phonon scattering. Importantly, we show that this aikinite-type sulfide, despite being a poor semiconductor, is a potential matrix for designing novel, efficient n-type thermoelectric compounds with ultralow κ values. A drastic improvement in the carrier concentration and thermoelectric figure of merit have been obtained upon Cl for S and Bi for Pb substitution. The Cu1-x□xPb1-xBi1+xS3 series provides a new, interesting structural prototype for engineering n-type thermoelectric sulfides by controlling disorder and optimizing doping.In this paper, the application of differentiating catalysis in the [4 + 2]-cycloaddition between 2-alkyl-3-formylheteroarenes and α,β-unsaturated aldehydes is described. Within the developed approach, the same aminocatalyst is employed for the independent activation of both starting materials, differentiating their properties via LUMO-lowering and HOMO-rising principles. By the combination of dearomative dienamine activation with iminium ion chemistry high enantio- and diastereoselectivity of the doubly asymmetric process was accomplished. Selected transformations of products were also demonstrated.The dimerization of transactive response DNA-binding protein of 43 kDa (TDP-43) is crucial for the RNA metabolism, and the higher-order aggregation of TDP-43 would induce several neurodegenerative diseases. The dimerization and aggregation of TDP-43 are regulated by the phosphorylation on its N-terminal domain (NTD). Understanding the regulation mechanism of TDP-43 NTD dimerization is crucial for the preventing of harmful aggregation and the associated diseases. In this study, the dimerization processes of wild-type (WT), phosphorylated S48 (pS48), and phosphomimic S48E mutation (S48E) of TDP-43 NTD are characterized by the enhanced sampling technology. Our results show that the phosphorylation not only shift the conformation population of bound and unbound state of TDP-43 NTD, but also would regulate the dimerization processes, including increase the binding free-energy barrier. The phosphomimic mutation would also shift the conformational space of TDP-43 NTD dimer to the unbound structures; however, the thermodynamic and kinetic properties of the dimerization processes between the phosphorylated and phosphomimic mutant systems are distinct, which reminds us to carefully study the phosphorylation regulation by using the phosphomimic mutations.A photochemical approach for the preparation of α-keto-N-acyl sulfoximines from NH sulfoximines and gem-difluoroalkenes has been developed. In the presence of NBS, the reactions proceed in air without the need of a photocatalyst or additional oxidant. Results of mechanistic studies suggest that the two oxygens in the products stem from water and dioxygen.A highly modular 1,4-difunctionalization of 1,3-dienes with bromodifluoroacetamides and sulfinates/amines through a photoinduced palladium-catalyzed radical relay process is described herein. This developed protocol offers a facile and general route to access a variety of value-added CF2-incorporated alkenes in moderate to good yields. The versatility and flexibility of this approach have been well illustrated by readily accessible starting materials, synthetic convenience, and wide functional group compatibility.Mechano-bactericidal surfaces deliver lethal effects to contacting bacteria. Until now, cell death has been attributed to the mechanical stress imparted to the bacterial cell envelope by the surface nanostructures; however, the process of bacterial death encountering nanostructured surfaces has not been fully illuminated. Here, we perform an in-depth investigation of the mechano-bactericidal action of black silicon (bSi) surfaces toward Gram-negative bacteria Pseudomonas aeruginosa. We discover that the mechanical injury is not sufficient to kill the bacteria immediately due to the survival of the inner plasma membrane. Instead, such sublethal mechanical injury leads to apoptosis-like death (ALD) in affected bacteria. In addition, when the mechanical stress is removed, the self-accumulated reactive oxygen species (ROS) incur poststress ALD in damaged cells in a nonstressed environment, revealing that the mechano-bactericidal actions have sustained physiological effects on the bacterium. This work creates a new facet and can introduce many new regulation tools to this field.Complex van der Waals heterostructures from layered molecular stacks are promising optoelectronic materials offering the means to efficient, modular charge separation and collection layers. The effect of stacking in the electrodynamics of such hybrid organic-inorganic two-dimensional materials remains largely unexplored, whereby molecular scale engineering could lead to advanced optical phenomena. For instance, tunable Fano engineering could make possible on-demand transparent conducting layers or photoactive elements, and passive cooling. We employ an adapted Gersten-Nitzan model and real time time-dependent density functional tight-binding to study the optoelectronics of self-assembled monolayers on graphene nanoribbons. We find Fano resonances that cause electromagnetic induced opacity and transparency and reveal an additional incoherent process leading to interlayer exciton formation with a characteristic charge transfer rate. These results showcase hybrid van der Waals heterostructures as paradigmatic 2D optoelectronic stacks, featuring tunable Fano optics and unconventional charge transfer channels.Dynamic covalent bonds are useful tools in a wide range of applications. Although various reversible chemical reactions have been studied for this purpose, the requirement for harsh conditions, such as high temperature and low or high pH, to activate generally stable covalent bonds limits their potential applications involving biomolecules or household utilization. Here, we report the design, synthesis, characterization, and dynamic covalent bonding properties of 1,2-disubstituted 1,2-dihydro-1,2,4,5-tetrazine-3,6-dione (TETRAD). Hetero-Diels-Alder reactions of TETRAD with furan derivatives and their retro-reactions proceeded rapidly at room temperature under neutral conditions, enabling a chemically induced sol-gel transition system.