ACS Central Science最新文献

This study presents molecularly built ligand-based lysosome-targeting chimeras (MBL-LYTACs) as a versatile platform for membrane receptor degradation. MBL-LYTACs are engineered by conjugating targeting ligands (e.g., small molecules, oligopeptides, aptamers, nanobodies, and antibodies) with lysosome-localized molecules. Functional screening and mechanistic studies reveal that MBL-LYTACs significantly enhance internalization and lysosomal accumulation of membrane receptors, including folate receptor α, programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR), and protein tyrosine kinase 7 (PTK7), by leveraging morpholine, dimethylethanamine, or low-polymerized mPEGs as lysosome-localized moieties, leading to receptor degradation. This approach eliminates reliance on cell-surface lysosome-shuttling receptors, broadening its applicability. The efficacy of MBL-LYTACs in cancer therapy has been validated in two tumor xenograft models, with PD-L1 and EGFR as targets. Overall, this study establishes a robust and adaptable framework for targeted receptor degradation, expanding therapeutic opportunities in cancer management.

Molecularly engineered ligands induce membrane receptor degradation by increasing lysosomal retention, driven by pH-dependent hydrophilic changes in lysosome-localized molecules like morpholine.

Despite the ubiquity of the well-known phosphorus polyanion phosphite $\left({\mathrm{HPO}}_3^{2-}\right)$, it appears to be the case that no simple salt of the corresponding conjugate base $({\mathrm{PO}}_3^{3-}$, “ortho-phosphite”) has ever been reported. We report the synthesis and characterization of this elusive species as a major component of a mixture obtained upon mechanochemical reduction of condensed phosphates, as evidenced by solid-state ³¹P NMR and Raman spectroscopy as well as subsequent reactivity studies. To corroborate the ³¹P NMR spectroscopic assignment, we independently generated Na₃PO₃ and K₃PO₃ by deprotonation of Na₂HPO₃ with NaCH₂SiMe₃ and of K₂HPO₃ with KCH₂Ph, respectively, providing an orthogonal route to ${\mathrm{PO}}_3^{3-}$ salts whose spectroscopic signatures match those observed in the mixture obtained by mechanochemical reduction. We further found that ortho-phosphite can act as a precursor for various phosphorus chemicals, such as P(OSiMe₃)₃ (46%), which is already well established as a precursor to a plethora of useful organophosphorus compounds. Therefore, our results not only establish the first formal pathway from P(V) phosphate starting materials to P(OSiMe₃)₃ without the intermediacy of white phosphorus, but also open the door to a broad range of downstream transformations based on this sustainable pathway. Additionally, BaHPO₃·H₂O (66%), OP(OMe)₂Me (DMMP), and OP(OBn)₂Bn (DBBP) have been generated directly from ortho-phosphite, all traditionally synthesized from white phosphorus.

Little-known oxoanion ortho-phosphite $\left({\mathrm{PO}}_3^{3-}\right)$ has been generated in a solvent-free synthesis and its identity confirmed using a combination of theory, spectroscopy, reactivity studies and independent synthesis.

Contact electrification and mechanical breakup can charge neutral water droplets, providing a pathway for gas-phase ion formation.

The complete biochemical degradation of riboflavin converts a vital enzyme cofactor back into simple carbon and nitrogen sources.

Here we report the cloning and complete in vitro reconstitution of the enzymes of the riboflavin catabolic pathway. The pathway begins with the oxidative removal of ribose to form lumichrome, which is then solubilized by a P450-catalyzed oxidation of the C7 methyl group, followed by hydrolytic degradation of the C-ring pyrimidine. Loss of C4, in a thiamin-dependent heterocycle decarboxylation, is followed by a xanthine oxidase and Rieske dioxygenase-mediated degradation of the quinoxaline ring. Catechol dioxygenase then catalyzes the conversion of the resulting A-ring-derived catechol to form 4-methyl-6-carboxypyrone. This is cleaved through a hydrolysis/hydration/retroaldol sequence to form pyruvate and acetoacetate, both of which are substrates for the citric acid cycle. The elucidation of the riboflavin catabolic pathway fills an important gap in our understanding of riboflavin metabolism and sets the stage for evaluating the impact of riboflavin catabolism on human and animal nutrition as well as the function of lumichrome as a quorum sensor mimic in the rhizosphere.

The characterization of riboflavin breakdown, by a cascade of oxidative and hydrolytic enzymes, sets the stage for evaluating the impact of riboflavin catabolism on human and animal nutrition.

The efficiency of covalent organic framework (COF)-based photocatalysts depends on their electron transfer behavior, which can be rationalized in terms of conjugation effects and induction effects. While conjugation effects have been widely explored in COF-based photocatalysts, induction effects have largely been ignored despite being important to overall photocatalytic activity. Herein, a new isoreticular series of ordered COFs was rationally designed to determine the relative importance of conjugation and induction effects in promoting photocatalytic activity. Systematic component modulation revealed the importance of a balance of conjugation and induction effects in achieving optimum catalytic performance in COF-based photocatalysts. Our study shows that (i) induction effects lead to electrons accumulating in specific positions of COFs, while (ii) p−π and π–π conjugation enables accurate electron transfer to the electron-rich active sites, thereby facilitating photogenerated electron–hole separation and transport and boosting photocatalytic activity. One of our developed COFs (COF-3S) displayed excellent photocatalytic uranium extraction performance in contaminated groundwater and seawater. These results establish that both induction and conjugation effects affect the photocatalytic activity of COFs, which is expected to provide new insight into the rational design of high-performance COF-based photocatalysts.

A new strategy is reported to optimize the photocatalytic uranyl removal performance of COFs by tuning the relative extent of conjugation and induction effects.

The turnover number for decarboxylation catalyzed by UndB was taken to the next level. Still 3 orders of magnitude to go for industrial applications.

Precise, sustainable, and scalable bandgap tuning of metal halide perovskite (MHP) nanocrystals (NCs) is critical for their integration into advanced optoelectronic and photocatalytic systems. Photoinduced anion exchange reactions (PIAERs) enable uniform halide delivery with spatiotemporal control, yet their complex parameter space has limited mechanistic understanding and rational optimization. Here, we introduce a material-efficient fluidic self-driving laboratory (FSDL) that integrates a single-droplet microfluidic photoreactor, multimodal in situ spectroscopy, and a multiobjective Bayesian optimization framework to navigate the ∼10⁶-dimensional design space of PIAERs autonomously. Through machine learning-guided exploration of this coupled parameter landscape, the FSDL rapidly identifies synthesis conditions that simultaneously maximize photoluminescence quantum yield and minimize emission line width for any target emission wavelength across the UV–visible spectrum. Mechanistic trends derived from surrogate modeling revealed distinct kinetic regimes for Br^–→Cl^– and Br^–→I^– exchanges, governed respectively by reaction time and photon flux, enabling reaction-specific tuning strategies. Critically, synthesis protocols discovered at the droplet scale (∼10 μL) were directly translated to continuous-flow operation (∼50–250 mL·day^–1) without reoptimization, maintaining optical performance and establishing knowledge scalability across 4 orders of magnitude in throughput, with low energy demand. This study demonstrates a reproducible, mechanistically informed, and industrially relevant route for programmable light-directed bandgap tuning in MHP NCs.

A self-driving microfluidic platform uses UV light and AI-guided optimization to program halide exchange in perovskite quantum dots, scaling color tuning from droplets to continuous manufacturing.

Sumit Chanda’s search for antivirals is in limbo after NIH halted its pandemic-preparedness program.