JACS Au最新文献

Phosphinopyridyl ligands are used to synthesize a class of Ni(II) bis(chelate) complexes, which have been comprehensively characterized in both solid and solution phases. The structures display a square-planar configuration within the primary coordination sphere, with axially positioned labile binding sites. Their electrochemical data reveal two redox couples during the reduction process, suggesting the possibility of accessing two-electron reduction states. Significantly, these complexes serve as robust catalysts for homogeneous photocatalytic H₂ evolution. In a system utilizing an organic photosensitizer and a sacrificial electron donor, an optimal turnover number of 27,100 is achieved in an alcohol-containing aqueous solution. A series of photophysical and electrochemical measurements were conducted to elucidate the reaction mechanism of photocatalytic hydrogen generation. Density function theory calculations propose a catalytic pathway involving two successive one-electron reduction steps, followed by two proton discharges. The sustained photocatalytic activity of these complexes stems from their distinct ligand system, which includes phosphine and pyridine donors that aid in stabilizing the low oxidation states of the Ni center.

In an era marked by a growing demand for sustainable and high-performance materials, the convergence of additive manufacturing (AM), also known as 3D printing, and the thermal treatment, or pyrolysis, of polymers to form high surface area hierarchically structured carbon materials stands poised to catalyze transformative advancements across a spectrum of electrification and energy storage applications. Designing 3D printed polymers using low-cost resins specifically for conversion to high performance carbon structures via post-printing thermal treatments overcomes the challenges of 3D printing pure carbon directly due to the inability of pure carbon to be polymerized, melted, or sintered under ambient conditions. In this perspective, we outline the current state of AM methods that have been used in combination with pyrolysis to generate 3D carbon structures and highlight promising systems to explore further. As part of this endeavor, we discuss the effects of 3D printed polymer chemistry composition, additives, and pyrolysis conditions on resulting 3D pyrolytic carbon properties. Furthermore, we demonstrate the viability of combining continuous liquid interface production (CLIP) vat photopolymerization with pyrolysis as a promising avenue for producing 3D pyrolytic carbon lattice structures with 15 μm feature resolution, paving way for 3D carbon-based sustainable energy applications.

Plastic-degrading enzymes facilitate the biocatalytic recycling of poly(ethylene terephthalate) (PET), a significant synthetic polymer, and substantial progress has been made in utilizing PET hydrolases for industrial applications. To fully exploit the potential of these enzymes, a deeper mechanistic understanding followed by targeted protein engineering is essential. Through advanced molecular dynamics simulations and free energy analysis methods, we elucidated the complete pathway from the initial binding of two PET hydrolases-the thermophilic leaf-branch compost cutinase (LCC) and polyester hydrolase 1 (PES-H1)-to an amorphous PET substrate, ultimately leading to a PET chain entering the active site in a hydrolyzable conformation. Our findings indicate that initial PET binding is nonspecific and driven by polar and hydrophobic interactions. We demonstrate that the subsequent entry of PET into the active site can occur via one of three key pathways, identifying barriers related to both PET-PET and PET-enzyme interactions, as well as specific residues highlighted through in silico and in vitro mutagenesis. These insights not only enhance our understanding of the mechanisms underlying PET degradation and facilitate the development of targeted enzyme enhancement strategies but also provide a novel framework applicable to enzyme studies across various disciplines.

As a means of tuning the electronic properties of tin-chalcogenide-based compounds, we present a strategy for the compositional and structural expansion of selenido stannate frameworks under mild conditions by introducing Cu⁺ ions into binary anionic Sn/Se aggregates in ionothermal reactions. The variable coordination modes of Cu⁺-contrasting with tetrahedral {SnSe₄} or trigonal bipyramidal {SnSe₅} units-and corresponding expansion toward ternary Cu/Sn/Se substructures helped to add another degree of freedom to the nanoarchitectures. As desired, the variation of the structural features was accompanied by concomitant changes of the physical properties. Upon treatment of alkali metal salts of the [SnSe₄]^4- anion at slightly elevated temperatures (120 or 150 °C) in ionic liquids, we isolated a series of compounds comprising ternary or quaternary cluster molecules or networks of cluster units, (C₂C₂Im)₉Li[Cu₁₀Sn₆Se₂₂] (1), (C₂C₂Im)₄[Cu₈Sn₆Se₁₈] (2), (C₂C₁Im)₃[Cu₅Sn₃Se₁₀] (3), and (C₂C₂Im)₅[Cu₈Sn₆Se₁₈F]·(C₂C₂Im)[BF₄] (4; C₂C₂Im = 1,3-diethyl-imidazolium, C₂C₁Im = 1-ethyl-3-methyl-imidazolium), which were investigated in terms of their optical gaps and photocurrent conversion properties. As illustrated by the synthesis and characterization of an additional salt that does not include Cu⁺, {(C₂C₂Im)₂[Sn₃Se₇]}₄·{(C₂C₂Im)[BF₄]}₂ (5), the significant role of Cu⁺ in this system was shown to be 3-fold: (a) structural expansion, (b) narrowing of the optical gap, and (c) photocurrent enhancement. By this three-in-one effect, the work offers an in-depth understanding of chalcogenido metalate chemistry with atomic precision.

Precision synthesis of polyorganosiloxanes and temporal control over the polymerization process during ring-opening polymerization (ROP) of cyclosiloxanes remain challenging due to the occurrence of side reactions, e.g., intramolecular transfer (backbiting) and intermolecular chain transfer, and irreversible catalyst transformation. In this study, a merocyanine-based photoacid catalyst is developed for cationic ROP of different cyclosiloxanes. A series of well-defined cyclotrisiloxane polymers with predetermined molar masses and low dispersities (Đ < 1.30) are successfully synthesized under various conditions (i.e., different catalyst loadings, initiator concentrations, solvents, and monomer types). Mechanistic insights by experiments and theoretical calculations suggest that the cationic active species, siloxonium ions, are combined with the catalyst anions to form tight ion pairs, thereby attenuating the reactivity of active species and subsequently minimizing side reactions. An efficient photocatalytic cycle is established among the catalyst, monomer, and polymer chain due to the rapid and reversible isomeric phototransformation of the catalyst, which endows the polymerization process with excellent temporal control. Successful in situ chain extension further confirms the controlled characteristics of photomediated CROP. This as-developed polymerization strategy effectively addresses long-standing challenges in the field of polyorganosiloxane synthesis.

The rapid performance decay with potentials is a significant obstacle to achieving an efficient electrocatalytic N₂ reduction reaction (eNRR), which is typically attributed to competition from hydrogen evolution. However, the potential-dependent competitive behavior and reaction mechanism are still under debate. Herein, we theoretically defined N₂ adsorption, H mediation, and H₂ evolution as three crucial regions along the potentials by revisiting the potential-dependent competitive adsorption between N₂ and H on FeN₄ and RuN₄ catalysts. We revealed that the surface H-mediated mechanism makes eNRR feasible at low potentials but introduces sluggish reaction kinetics, showing a double-edged sword nature. In view of this, we proposed a new possibility to achieve high-performance NH₃ synthesis by circumventing the H-mediated mechanism, where the ideal catalyst should have a wide potential interval with N₂-dominated adsorption to trigger direct eNRR. Using this mechanistic insight as a new criterion, we proposed a theoretical protocol for eNRR catalyst screening, but almost none of the theoretically reported electrocatalysts passed the assessment. This work not only illustrates the intrinsic mechanism behind the low-performance dilemma of eNRR but also points out a possible direction toward designing promising catalysts with high selectivity and high current density.

TAR DNA/RNA-binding protein 43 kDa (TDP-43) proteinopathy is a hallmark of neurodegenerative disorders, such as amyotrophic lateral sclerosis, in which cytoplasmic aggregates containing TDP-43 and its C-terminal fragments, such as TDP-25, are observed in degenerative neuronal cells. However, few reports have focused on small molecules that can reduce their aggregation and cytotoxicity. Here, we show that short RNA repeats of GGGGCC and AAAAUU are aggregation suppressors of TDP-43 and TDP-25. TDP-25 interacts with these RNAs, as well as TDP-43, despite the lack of major RNA-recognition motifs using fluorescence cross-correlation spectroscopy. Expression of these RNAs significantly decreases the number of cells harboring cytoplasmic aggregates of TDP-43 and TDP-25 and ameliorates cell death by TDP-25 and mislocalized TDP-43 without altering the cellular transcriptome of molecular chaperones. Consequently, short RNA repeats of GGGGCC and AAAAUU can maintain proteostasis by preventing the aggregation of TDP-43 and TDP-25.

Targeted protein degradation (TPD) is emerging as a promising therapeutic approach for cancer and other diseases, with an increasing number of programs demonstrating its efficacy in human clinical trials. One notable method for TPD is Proteolysis Targeting Chimeras (PROTACs) that selectively degrade a protein of interest (POI) through E3-ligase induced ubiquitination followed by proteasomal degradation. PROTACs utilize a warhead-linker-ligand architecture to bring the POI (bound to the warhead) and the E3 ligase (bound to the ligand) into proximity. The resulting non-native protein-protein interactions (PPIs) formed between the POI and E3 ligase lead to the formation of a stable ternary complex, enhancing cooperativity for TPD. A significant challenge in PROTAC design is the screening of the linkers to induce favorable non-native PPIs between POI and E3 ligase. Here, we present a physics-based computational protocol to predict noncanonical and metastable PPI interfaces between an E3 ligase and a given POI, aiding in the design of linkers to stabilize the ternary complex and enhance degradation. Specifically, we build the non-Markovian dynamic model using the Integrative Generalized Master equation (IGME) method from ∼1.5 ms all-atom molecular dynamics simulations of linker-less encounter complex, to systematically explore the inherent PPIs between the oncogene homologue protein and the von Hippel-Lindau E3 ligase. Our protocol revealed six metastable states each containing a different PPI interface. We selected three of these metastable states containing promising PPIs for linker design. Our selection criterion included thermodynamic and kinetic stabilities of PPIs and the accessibility between the solvent-exposed sites on the warheads and E3 ligand. One selected PPIs closely matches a recent cocrystal PPI interface structure induced by an experimentally designed PROTAC with potent degradation efficacy. We anticipate that our protocol has significant potential for widespread application in predicting metastable POI-ligase interfaces that can enable rational design of PROTACs.

Membrane proteins are integral to numerous cellular processes, yet their conformational dynamics in native environments remains difficult to study. This study introduces a nanodelivery method using nanodiscs to transport spin-labeled membrane proteins into the membranes of living cells, enabling direct in-cell double electron-electron resonance (DEER) spectroscopy measurements. We investigated the membrane protein BsYetJ, incorporating spin labels at key positions to monitor conformational changes. Our findings demonstrate successful delivery and high-quality DEER data for BsYetJ in both Gram-negative E. coli and Gram-positive B. subtilis membranes. The delivered BsYetJ retains its ability to transport calcium ions. DEER analysis reveals distinct conformational states of BsYetJ in different membrane environments, highlighting the influence of lipid composition on the protein structure. This nanodelivery method overcomes traditional limitations, enabling the study of membrane proteins in more physiologically relevant conditions.

Fucosyl transferases (FUTs) are enzymes that transfer fucose (Fuc) from GDP-Fuc to acceptor substrates, resulting in fucosylated glycoconjugates that are involved in myriad physiological and disease processes. Previously, it has been shown that per-O-acetylated 2-F-Fuc can be taken up by cells and converted into GDP-2-F-Fuc, which is a competitive inhibitor of FUTs. Furthermore, it can act as a feedback inhibitor of de novo biosynthesis of GDP-Fuc resulting in reduced glycoconjugate fucosylation. However, GDP-2-F-Fuc and several other reported analogues are slow substrates, which can result in unintended incorporation of unnatural fucosides. Here, we describe the design, synthesis, and biological evaluation of GDP-2,2-di-F-Fuc and the corresponding prodrugs as an inhibitor of FUTs. This compound lacks the slow transfer activity observed for the monofluorinated counterpart. Furthermore, it was found that GDP-2-F-Fuc and GDP-2,2-di-F-Fuc have similar K_i values for the various human fucosyl transferases, while the corresponding phosphate prodrugs exhibit substantial differences in inhibition of cell surface fucosylation. Quantitative sugar nucleotide analysis by Liquid chromatography-mass spectrometry (LC-MS) indicates that the 2,2-di-F-Fuc prodrug has substantially greater feedback inhibitory activity. It was also found that by controlling the concentration of the inhibitor, varying degrees of inhibition of the biosynthesis of different types of fucosylated N-glycan structures can be achieved. These findings open new avenues for the modulation of fucosylation of cell surface glycoconjugates.