ACS Publications最新文献

Human α-synuclein is an intrinsically disordered protein concentrated at presynaptic terminals and strongly linked to Parkinson's disease and other synucleinopathies. Its dynamic C-terminal region mediates interactions with small molecules and metal ions. Here, we used high-resolution nuclear magnetic resonance spectroscopy (NMR) and molecular dynamics (MD) simulations to characterize interactions between the C-terminal α-synuclein construct, the small molecule fasudil, and calcium ions. NMR data show that fasudil and Ca²⁺ bind preferentially to overlapping regions enriched in alternating tyrosine and acidic residues while preserving the protein's disordered nature. Side-chain-resolved spectra indicate distinct driving forces for fasudil and calcium binding. MD simulations reveal that Ca²⁺ modifies the local electrostatic environment, decreasing fasudil interaction frequency through electrostatic screening and steric effects. Despite this, fasudil retains dynamic, reversible contacts with key tyrosine residues. Overall, exposed α-synuclein conformations allow simultaneous, ligand-specific interactions, highlighting side-chain hotspots governing binding in Ca²⁺-rich conditions.

A major challenge in light-matter simulations is bridging the disparate time and length scales of electrodynamics and molecular dynamics. Current computational approaches often rely on heuristic approximations of either the electromagnetic (EM) or the material component, hindering the exploration of complex light-matter systems. Herein, MaxwellLink─a modular, open-source Python framework─is developed for the massively parallel, self-consistent propagation of classical EM fields interacting with a large heterogeneous molecular ensemble. The package utilizes a robust TCP/UNIX socket interface to couple EM solvers with a wide range of molecular drivers. In this initial release, MaxwellLink supports EM solvers spanning from single-mode cavities to full-feature three-dimensional finite-difference time-domain (FDTD) engines and molecules described by multilevel open quantum systems, force-field and first-principles molecular dynamics, and nonadiabatic real-time Ehrenfest dynamics. With the socket-based architecture, users can seamlessly switch between levels of theory of either the EM solver or molecules without modifying the counterpart. Moreover, the EM engine and molecular drivers scale independently across multiple high-performance computing (HPC) nodes, facilitating large-scale simulations previously inaccessible to existing numerical schemes. The versatility and accuracy of this code are further demonstrated through applications including superradiance, radiative energy transfer, vibrational strong coupling in Bragg resonators, and plasmonic heating of molecular gases. By providing a unified, extensible engine, MaxwellLink potentially offers a powerful platform for exploring emerging phenomena across the research fronts of spectroscopy, quantum optics, plasmonics, and polaritonics.

Isoprene, a major global precursor to secondary organic aerosol (SOA), affects air quality and radiative forcing. A key SOA formation pathway is the reactive uptake of isoprene epoxydiol (IEPOX), a process influenced by multiple environmental factors. Here, we simulate the spatial distribution and interannual trend of IEPOX-SOA over Eastern China from 2014 to 2019 using CMAQ and quantify the contributions of different factors. Our results indicate that ambient IEPOX-SOA concentrations are elevated in central and northeast China, averaging 135 ng·m^-3 and with a recent declining trend between -19.1 and -34.8 ng·m^-3·yr^-1. Long-term trends of IEPOX-SOA are primarily driven by changes in sulfate (-50.5 ng·m^-3·yr^-1), which serve as seed aerosols, while a decrease in organic carbon reduces the coating effects and partially offsets (+16.1 ng·m^-3·yr^-1) the decline. Aerosol acidity plays a key role in governing its spatial distribution by affecting reactive rates. In Eastern China, high ammonia levels effectively neutralize acidity, thereby suppressing abundant IEPOX-SOA formation, resulting in lower concentrations compared to other regions, such as the United States. Sensitivity tests indicate that substantial future NH₃ reductions in China could increase the IEPOX-SOA by up to 100%. This study clarifies the key chemical mechanisms governing IEPOX-SOA production and supports regional air pollution control strategies.

While traditional Pt-based catalysts suffer from inadequate selectivity and stability in electrocatalytic ethylene glycol oxidation reactions, we present a general and scalable synthesis strategy, fabricating a broad multimetallic Pt-based alloy nanowires (NWs) library from binary to quinary. Among these, the PtAgCuRhRu NWs exhibit exceptional performance, with a mass activity ∼8 times higher than that of Pt/C and a Faradaic efficiency for glycolic acid (GA) reaching 93.49%. In the membrane electrode assembly electrolyzer, the catalyst maintained its activity over 140 h with 99% GA selectivity. In situ experimental and theoretical calculations reveal oxygenophilic Rh and Ru promote *OH adsorption, facilitating the conversion of *COCH₂OH to GA and the oxidative removal of CO_ads, enhancing activity and stability. Additionally, the high energy barrier for C-C bond cleavage suppresses undesired decomposition due to the introduction of Ag and Cu, leading to superior GA selectivity.

Three-body interactions in water play a crucial role in accurately modeling its structural and thermodynamic properties. These interactions consist of a polarization term that decays as an inverse power of the intermolecular separations R_ab and a term that is usually assumed to describe exchange interactions and decay exponentially. Due to the complexity of fitting the latter term at large R_ab, it is often damped or truncated beyond a certain distance, also because the computational cost of including three-body effects in molecular simulations scales as N³ with the number of molecules, compared to the N² scaling of two-body interactions. Here, investigations of the impact of long-range three-body exchange interactions on the results of such simulations have been performed by systematically extending the average R_ab of trimers included. It is demonstrated that these long-range effects are important for accurately describing the density of liquid water, ρ(T), as a function of temperature, but are essentially negligible for several other properties of water. The effects of three-body damping onset on ρ(T) are larger than they would have been with an exponential decay; however, it is shown here that the decay is dominated by exponential components only at fairly small R_ab, while for large R_ab, the nonpolarization three-body effects decay as 1/R_abⁿ. These findings are rationalized by calculations with the symmetry-adapted perturbation theory. Another reason for the importance of three-body effects is their N³ scaling. Clearly, long-range three-body exchange interactions should be included in high-accuracy water models. It is shown that the reason these interactions have such large effects on ρ(T) is their extreme anisotropy affecting the structure of liquid water. Our work also sheds light on discrepancies between the theory and experiment for ρ(T).

Orthokeratology (OK) lenses for myopia correction are susceptible to biofouling by tear-derived biomolecules, escalating the risks of ocular infection and inflammation. Prevailing studies that rely on end point protein quantification fail to capture the real-time kinetics of fouling formation. Here, we fabricated a UV pressure-assisted polymer-grafted quartz crystal microbalance with dissipation monitoring (QCM-D) sensor exhibiting exceptional stability, nanoscale smoothness (RMS roughness ≈2 nm), and interfacial peel resistance. This platform enables in situ tracking of adsorption/desorption kinetics for four critical tear components: native/denatured lysozyme and oxidized/native lecithin. Key findings reveal a flow-dependent fouling behavior, wherein low flow rates increase biomolecule adsorption by 37-80% compared with higher flows. We further identify denatured lysozyme and native lecithin as resilient contaminants characterized by a stronger deposition affinity and pronounced resistance to elution. Quantitative screening of multipurpose solutions (MPSs) demonstrates that MPS #2 achieves 20-100% elution rate across biomolecules, outperforming commercial benchmarks. By leveraging dissipation-frequency (D-F) analysis, we clarify the fundamental mechanisms of biofouling formation at the molecular level. Collectively, this work establishes three critical advances: (1) a real-time biofouling diagnostic platform for OK lens interfaces, (2) molecular design principles for antifouling materials based on adhesion remodeling theory, and (3) an accelerated MPS formulation screening paradigm for ocular device safety.

Proton transfer reactions are ubiquitous in chemistry and biology. Here we explore the consequences of vibrational strong coupling (VSC) on excited state proton transfer in solution. The rates of proton transfer, as well as the internal dynamics and quantum yields, are significantly modified when the solvent and the photoacid are coupled cooperatively. These findings confirm that VSC can act on excited state reactivity and not just on ground state processes reported so far.

Digital immunoassays enable highly sensitive detection of biomolecules, offering absolute quantification rather than relying on bulk signal intensity. We adapt a digital immunoassay scheme for a nanopore sensor, a versatile platform for single-molecule counting. Current nanopore sensors have demonstrated great progress when counting nucleic acids but struggle with proteins due to variability in translocation behavior and limited recognition strategies. While recent advancements have highlighted the promise of nanopore platforms for protein studies, precise quantification remains a challenge. Here, building on previous work, we present a nanopore-based digital immunoassay that employs gold nanoparticle-mediated molecular amplification with a single-molecule readout. This approach translates protein recognition into quantifiable DNA, enabling a precise digital assay. This assay employs a DNA NanoLock probe combined with a paramagnetic bead-based immunocapture, where the target proteins trigger a structural transformation of the NanoLock, converting their presence into a binary DNA-based signal. By incorporating AuNPs carrying hundreds of DNA proxy reporters, we effectively amplify the detectable signal by 2 orders of magnitude, significantly improving sensitivity. We validate the performance of this system by detecting the glial fibrillary acidic protein, a biomarker for traumatic brain injury and neurodegenerative diseases, in plasma samples and demonstrate high femtomolar-level sensitivity (∼40 pg/mL). Using the NanoLock probe, we further mitigate previous challenges, with reduced assay times (hours) and extended dynamic range (3-log). The self-calibrating nature of this digital approach offers robust, reproducible measurements across different nanopores, eliminating interdevice variability.