ACS Editors’ Choice

Poisoning by organophosphate (OP) nerve agents remains a pressing global threat due to their extensive use in chemical warfare agents and pesticides, potentially causing high morbidity and mortality worldwide. This urgent need for effective countermeasures has driven considerable interest in innovative detoxification approaches. Among these, nanoparticle technology stands out for its multifunctional potential and wide-ranging applications. This review highlights recent advancements in nanoparticle platforms developed for OP detoxification, focusing on five main types: inorganic nanoparticles, lipid-based nanoparticles, polymer-based nanoparticles, metal–organic framework nanoparticles, and cellular nanoparticles. For each platform, we discuss representative examples that illustrate how structural and functional properties enhance their effectiveness as nanocarriers, nanocatalysts, or nanoscavengers, ultimately enabling safe and efficient OP detoxification. This review aims to stimulate further technological innovation in OP-detoxifying nanoparticles and encourage broader development of detoxification strategies.

Per- and polyfluoroalkyl substances (PFAS) are used in a wide range of different industrial and consumer applications. However, due to their extreme environmental persistence and their impacts on human and ecosystem health, PFAS have been subject to many regulatory activities, including initiatives to incentivize industry to transition toward PFAS-free alternatives. Although efforts have been made to map all uses of PFAS, work is still needed to provide an overview of their potential alternatives. Based on the functional substitution approach, this study develops an online database that documents all known uses of PFAS, describes the functions provided by PFAS in these uses, lists potential alternatives that can deliver equivalent or similar functions to PFAS, and evaluates the suitability of the identified alternatives to replace PFAS. Overall, the database lists 325 different applications of PFAS across 18 use categories. In total, 530 PFAS-free alternatives are identified. Based on a screening of potential concerns of the identified alternatives, their performance compared to PFAS, and their availability on the market, it is concluded that potentially suitable alternatives to PFAS are available for 40 different applications. For 83 applications, no alternatives could be identified at the time of the study and should be the focus of further research activities.

The ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs) holds great potential for the efficient preparation of versatile and biocompatible poly(amino acid)s, such as polypeptides and polypeptoids. This perspective highlights the pivotal role of proton transfer in NCA ROP, emphasizing the use of proton transfer catalysts (PTCs) such as carboxylic acids and water to enhance polymerization kinetics and achieve (unprecedented) polymers with high molecular weights. Further studies on the exploration and rational design of PTCs offers promising opportunities to further innovate NCA ROP chemistry and broaden its applications in material science.

Thermal management in molecular systems presents challenges that require a deeper understanding of phonon transport, an essential aspect of heat conduction in single-molecule junctions. Our work introduces the use of heavy atoms as a strategy for suppressing phonon transport in organic molecules. Starting with a one-dimensional (1D) force-constant model and density functional theory calculations of model chemical systems, we illustrate how increasing the mass of a central atom affects phonon transmission and conductance. Following this, we turned our attention to the chemically accessible systems of metallapolyynes and extended metal atom chains (EMACs). Our findings suggest that several of the studied EMACs exhibit thermal conductance either near or below a recently proposed threshold of 10 pW/K─a crucial step toward reaching high thermoelectric figure of merits. Specifically, we predict that the molecule MoMoNi(npo)₄(NCS)₂ has a thermal conductance of just 8.3 pW/K at 300 K. Our results demonstrate that conceptually simple chemical modifications can markedly reduce the thermal conductance of single molecules; these results both deepen our understanding of the mechanisms driving single-molecule phonon thermal conductance and suggest a path toward using single molecules as thermoelectric materials.

Plastic food packaging containing silver nanoparticles (AgNPs) has received a lot of attention due to the antimicrobial properties of AgNPs, but these materials are not yet authorized for use in the United States. An important area of uncertainty is whether AgNPs can migrate to solid foods during prolonged direct contact. We manufactured laboratory-scale model food packages with AgNPs and low-density polyethylene (LDPE) and assessed the migration of Ag to four model foods under simulated long-term storage: cheese slices, wheat flour, spinach leaves, and ground rice. Ag migration was observed for all food types, regardless of the test conditions, with the amount of migration being dependent on both food particle size, food–polymer contact efficiency, and whether the Ag-contaminated food was washed prior to analysis. To explore migration mechanisms, we used laser-ablation ICP-MS and laser-scanning confocal microscopy to show that two types of model NPs (AgNPs and luminescent QDs) readily transfer out of polymers during long-term contact with abiotic surfaces, and transferred NPs were restricted largely to the surface of the material in contact with the NP-containing polymers. These experiments, as well as the migration experiments with foods, demonstrated that a liquid medium is not required to facilitate Ag migration out of AgNP-containing food contact polymers and that migrated Ag is likely located at the surface of contacted foods.

The selective insertion of membrane-impermeant amphiphiles such as detergents, (lipo)peptides, drugs, etc. into the cis leaflet of a membrane causes an imbalance between the intrinsic areas of the cis and trans leaflet, referred to as asymmetry stress or differential stress. The literature provides individual mechanisms of how membranes respond to such stress, which are relevant to membrane remodeling processes and leakage phenomena. By studying vesicle budding, membrane leakage, and isothermal titration calorimetry of liposomes interacting with digitonin, alkyl maltosides, miltefosine, and octyl glucoside, we developed a roadmap linking the stress-response mechanisms to each other. Initially, lateral compression or stretching of the leaflets accommodates a minor asymmetry stress. Then, either molecules flip to the trans leaflet or the membrane bends to form buds. Fast flip leads to the classic three-stage model. Budding proceeds up to its limit at 20–40% of the lipid. Beyond, insertion of further detergent is opposed by the pressure in the overpopulated leaflet. This “staying out” state can persist over hours or days and up to high detergent concentrations before detergent micelles induce “micellar solubilization”. Alternatively, the stress can be reduced by a transient failure of the membrane, allowing for “cracking in” of molecules, transferring them to the trans side.

Human-impacted rivers often contain a complex mixture of organic micropollutants, including pesticides, pharmaceuticals and industrial compounds, along with their transformation products. Combining chemical target analysis for exposure with in vitro bioassays for effect assessment offers a holistic view of water quality. This study targeted the River Elbe in Central Europe, known for its anthropogenic pollution exposure, to obtain an inventory of micropollutant contamination during base flow and to identify hotspots of contamination. We identified tributaries as sources of chemicals activating the aryl hydrocarbon receptor quantified with the AhR-CALUX assay, including historically contaminated tributaries and a newly identified Czech tributary. Increased neurotoxicity, detected by differentiated SH-SY5Y neurons’ cytotoxicity and shortened neurite length, was noted in some Czech tributaries. A hotspot for chemicals activating the oxidative stress response in the AREc32 assay was found in the middle Elbe in Germany. An increase in oxidative stress inducing chemicals was observed in the lower Elbe. While effect-based trigger values (EBT) for oxidative stress response, xenobiotic metabolism and neurotoxicity were not exceeded, estrogenicity levels surpassed the EBT in 14% of surface water samples, posing a potential threat to fish reproduction. Target analysis of 713 chemicals resulted in the quantification of 487 micropollutants, of which 133 were active in at least one bioassay. Despite this large number of bioactive quantified chemicals, the mixture effects predicted by the concentrations of the quantified bioactive chemicals and their relative effect potency explained only 0.002–1.2% of the effects observed in the surface water extracts, highlighting a significant unknown fraction in the chemical mixtures. This case study established a baseline for understanding pollution dynamics and spatial variations in the Elbe River, offering a comprehensive view of potential chemical effects in the water and guiding further water quality monitoring in European rivers.

Tuberculosis (TB) continues to be a major cause of death worldwide despite having an effective combinatorial therapeutic regimen and vaccine. Being one of the most successful human pathogens, Mycobacterium tuberculosis retains the ability to adapt to diverse intracellular and extracellular environments encountered by it during infection, persistence, and transmission. Designing and developing new therapeutic strategies to counter the emergence of multidrug-resistant and extensively drug-resistant TB remains a major task. DNA topoisomerases make up a unique class of ubiquitous enzymes that ensure steady-state level supercoiling and solve topological problems occurring during DNA transactions in cells. They continue to be attractive targets for the discovery of novel classes of antibacterials and to develop better molecules from existing drugs by virtue of their reaction mechanism. The limited repertoire of topoisomerases in M. tuberculosis, key differences in their properties compared to topoisomerases from other bacteria, their essentiality for the pathogen’s survival, and validation as candidates for drug discovery provide an opportunity to exploit them in drug discovery efforts. The present review provides insights into their organization, structure, function, and regulation to further efforts in targeting them for new inhibitor discovery. First, the structure and biochemical properties of DNA gyrase and Topoisomerase I (TopoI) of mycobacteria are described compared to the well-studied counterparts from other bacteria. Next, we provide an overview of known inhibitors of DNA gyrase and emerging novel bacterial topoisomerase inhibitors (NBTIs). We also provide an update on TopoI-specific compounds, highlighting mycobacteria-specific inhibitors.

This study quantifies the contribution of the H₂O₂-dependent pathway to hydroxyl radical (^•OH) production from the photolysis of dissolved organic matter (DOM). ^•OH formation rates were cross-validated using benzoate and terephthalate as probe compounds for diverse DOM sources (reference isolates and whole waters). Catalase addition revealed that the H₂O₂-dependent pathway accounts for 10–20% of the total ^•OH production in DOM isolate materials, but no significant correlation was observed between ambient iron (Fe) concentrations and H₂O₂-dependent ^•OH formation. This lack of correlation was likely due to lower total Fe levels in isolated materials, thus limiting the concentration of photochemically produced Fe(II) available for reaction with H₂O₂. Notably, the H₂O₂-dependent pathway contributed 11 ± 3% to ^•OH formation from Pony Lake fulvic acid, which had the lowest Fe content, implicating additional H₂O₂-driven formation mechanisms independent of Fe. Experiments with the DOM model compounds acetophenone and p-benzoquinone indicated no ^•OH production from triplet DOM reactions with H₂O₂. However, ^•OH formation rate increased 6-fold when H₂O₂ was reduced by ketyl radicals formed from the reaction between excited triplet acetophenone and 2,4,6-trimethylphenol. This study advances the knowledge of ^•OH production mechanisms from DOM photolysis, providing insight into the role of H₂O₂ in aquatic photochemical processes.

Ion atmospheres play a critical role in modulating the interactions between charged components in solutions. However, a detailed description of the nature of ion atmospheres remains elusive. Here, we use Kirkwood–Buff theory, an exact theory of solution mixtures, together with a series of local and bulk electroneutrality constraints to provide relationships between all the net ion–ion distributions in bulk electrolyte mixtures. The validity of the underlying relationships is then confirmed using classical explicit solvent molecular simulations of a range of electrolyte mixtures. Further analysis indicates the ion distributions can be separated into two contributions, one resulting in charge neutralization, for which each ion contributes in proportion to its ionic strength, and the other accounting for all the solution thermodynamics. The relationships hold for atomic and molecular ions of any size and valency regardless of ionic strength, temperature, or pressure, in any solvent system.

Altermagnets, characterized by spontaneous spin-splitting without net magnetization, are challenging to realize due to their unique spin group symmetries. Two-dimensional (2D) magnetic metal–organic frameworks (MOFs), with tunable topologies and spins, offer promising platforms for achieving altermagnetism. In this study, we propose a general strategy to create 2D altermagnetic monolayers by bridging Cr with organic ligands exhibiting nonbonding molecular orbitals (NBMOs) based on the Hückel molecular orbital theory and first-principles calculations. Three 2D MOFs, namely, Cr(diz)₂, Cr(c-pyr)₂, and Cr(f-pid)₂ (diz = 1,3-diazete, c-pyr = pyrrolo[3,4-c]pyrrole, f-pid = pyrrolo[3,4-f]isoindole), are constructed using this strategy and exhibit the altermagntic ground state. These MOFs possess the spin point group ²4̅¹m²2 and exhibit critical temperatures reaching up to 183 K. Analyses of orbital symmetry and energy levels rationalize the presence of altermagnetism. Our findings highlight the critical role of NBMOs in realizing 2D-MOF-based altermagnets with enhanced critical temperatures.

Alkyl nickel intermediates relevant to catalytic processes often feature agostic stabilization, but relatively little is known about the situation in oligonickel systems. The dinickel(I) complex K[LNi^I₂], which is based on a compartmental pyrazolato-bridged ligand L^3– with two β-diketiminato chelate arms, or its masked version, the dihydride complex [KL(Ni^II–H)₂] that readily releases H₂, oxidatively add methyl tosylate to give diamagnetic [LNi^II₂(CH₃)] (1) with d(Ni···Ni) ≈ 3.7 Å. Structural characterization shows that the methyl group in 1 is bound to one Ni^II and exhibits an intramolecular agostic interaction with the more distant Ni^II. This is supported spectroscopically (viz., a ν(C–H) stretch at 2658 cm^–1 and lowered ¹J_C–H of 114 Hz) and by DFT calculations, including topological analysis of the computed electron density for 1. NMR spectroscopy reveals very fast hopping of the CH₃ group between the two Ni^II ions, which according to DFT has a minute barrier of 4 kcal mol^–1 and proceeds via a planar CH₃ moiety in the transition state (Walden-like inversion). The alkylidene group in K[LNi₂(μ-CHSi(Me₃)₃)], obtained from the reaction of [KL(Ni–H)₂] with N₂CHSiMe₃, is symmetrically bridging. This work provides new insight into the stabilization and dynamics of alkyl ligands at dinickel sites with a constrained metal···metal distance.

We disclose a stereodivergent strategy to prepare vicinal difluorinated tetralins from γ-substituted tetralones via a combination of catalyst-controlled transfer hydrogenation and substrate-controlled fluorinations. This process is easily scalable and amenable to highly functionalized substrates, as demonstrated here in the late-stage synthesis of casdatifan, a clinical-stage inhibitor of hypoxia-inducible factor-2α. Analysis of the physicochemical properties of casdatifan, which features a cis-vicinal difluoride, revealed a higher level of facial polarization compared to its trans-vicinal difluoride isomers.

Graphitic carbon nitride (g-C₃N₄) has gained attention as a metal-free photocatalyst to generate solar chemicals via efficient solar-driven CO₂ reduction reactions. Even though the pristine g-C₃N₄ and its analogous ones have excellent chemical properties, a disordered structure observed in various types of g-C₃N₄ hinders the efficient charge separation process as well as the transport of photoexcited charge carriers linked to the photocatalytic performance. To overcome this limitation, we employed the introduction of a heterojunction architecture into sulfur-doped g-C₃N₄ with CdS. By using the self-assembled method, we fabricated the CdS/S-g-C₃N₄ heterojunction photocatalyst and designed a hybrid artificial photosynthetic module including a CdS/S-g-C₃N₄ photocatalyst and biological enzyme for the generation of HCOOH from CO₂. From the photocatalytic test, it was confirmed that the presence of the interfacial heterojunction in CdS/S-g-C₃N₄ showed the enhanced production of formic acid that is much higher than that in the pristine S-g-C₃N₄. The systematic spectroscopic measurements provide mechanistic insights for the photoinduced electronic dynamics linked to the macroscopic photocatalytic performance in the CdS/S-g-C₃N₄ heterojunction photocatalyst. Our study suggests that the artificial photosynthesis based on the heterojunction architecture-embedded photocatalyst will offer a promising and sustainable strategy for fixing CO₂ and generating solar chemicals.

Effective inventory management can be overshadowed by conflicting priorities in organizational procedures, particularly in research-focused institutions such as national laboratories that handle expensive, delicate, and hazardous materials. This study investigated the potential of radiofrequency identification (RFID) technology, currently used for hazardous chemical inventory, in applications with higher metal interference and absorption, specifically pressure release device (PRD) compliance and nuclear container management, at Lawrence Livermore National Laboratory (LLNL). This study was done to document best practices to enhance inventory identification speeds for inventory reconciliation and inventory recall and to explore optimal configurations for RFID implementation compared to traditional manual methods of equipment management. Tests were conducted to determine the ideal RFID tag orientation (read at angles of 0°, 90°, and 270°), various container layouts (linear, separated, curved, operational), and ID methods such as manual, barcode, and RFID performing three trials per method per orientation. Results indicated that 0° was the optimal read angle for minimizing metallic interference, and the operational and curved arrangements significantly outperformed the linear and separated configurations in read speed. 3D printed mounts were developed and tested, increasing the read range of the RFID reader by up to 235% in cases of high metallic interference. The RFID technology demonstrated an average speed increase of 65% over a simplified manual identification, which supports the conclusion that RFID is a more efficient method for large hazardous inventory management and equipment reconciliation. Additionally, capturing meta-data, such as location and date, can be used to query for inventory recall and automated updating of record information.

Cysteine thioesters are involved in a myriad of central biological transformations due to their unique reactivity. Despite their well-studied properties, we discovered an unexpected transamidation reaction of cysteine thioesters that leads to peptide backbone cleavage. S-Acylcysteine-containing peptides were found to spontaneously fragment by cleavage of the amide bond in the i-1 position to the acylated cysteine residue at pH 8–10. We present compelling evidence of a mechanism involving a central reversible thioester-to-imide acyl transfer step. The discovered transamidation reaction was found to be highly sequence dependent and to occur in peptides containing post-translational modifications (PTMs) such as cysteine S-acetylation and S-palmitoylation as well as in peptide–peptide branched thioesters, mimicking class I intein splicing. Thus, the inherent reactivity of peptide backbones containing S-acylcysteine residues should represent a starting point for investigation of endogenous protein behavior and may serve as a foundation for the discovery of mild new peptide and protein transformations.

Redox-active micelles undergo reversible association and dissociation in response to their redox potential and are promising materials for various applications, such as drug delivery and bioimaging. Evaluation of the micellization entropy is critical in controlling the thermodynamics of micelle formation. However, conventional methods such as isothermal titration calorimetry and surface tensiometry require a long measurement time to observe changes in the heat flow or the surface tension caused by the micellization. Here we report a thermoelectrochemical method to quantify the entropy change produced by redox-active micelles. A set of poly(ethyl glycidyl ether-b-ethylene oxide)phenothiazine (PT-EGE-EO) with varied chain length were synthesized, and their micellization entropy was calculated from the temperature-dependent changes of the equilibrium potential. This thermoelectrochemical method enables a quick evaluation of the micellization entropy with only a single sample preparation and temperature sweep. The obtained results showed a reasonable agreement with the conventional surface tensiometry and isothermal titration calorimetry, indicating that the thermoelectrochemical method is a promising alternative for quantification of the micellization entropy.

Understanding how the electrolyte pH affects electrocatalytic activity is a topic of crucial importance in a large variety of systems. However, unraveling the origin of the pH effects is complicated often by the fact that both the reaction driving forces and reactant concentrations in the electric double layer (EDL) change simultaneously with the pH value. Herein, we employ the hydrogen evolution reaction (HER) at Au(111)-aqueous solution interfaces as a model system to disentangle different pH-dependent factors. In 0.1 M NaOH, the HER current density at Au(111) in the potential range of −0.4 V < E_RHE < 0 V is up to 60 times smaller than that in 0.1 M HClO₄. A reaction model with proper consideration of the local reaction conditions within the EDL is developed. After correcting for the EDL effects, the rate constant for HER is only weakly pH-dependent. Our analysis unambiguously reveals that the observed pH effects are mainly due to the pH-dependent reorganization free energy, which depends on the electrostatic potential and the local reaction conditions within the EDL. Possible origins of the pH and temperature dependence of the activation energy and the electron transfer coefficients are discussed. This work suggests that factors influencing the intrinsic pH-dependent kinetics are easier to understand after proper corrections of EDL effects.

Metal–organic frameworks (MOFs) are a rapidly growing class of crystalline porous materials known for their high surface area and tunable porosity, making them ideal for various applications, including gas separation. While the utility of MOFs primarily stems from their intrinsic micropores, fabricating MOF-based membranes further enhances their applicability, particularly in CO₂ separation from flue gas (CO₂/N₂) and natural gas (CO₂/CH₄). In this work, we developed an in situ synthesis method to fabricate MIL-160 membranes on ceramic tubular substrates for gas separation. MIL-160, with its three-dimensional interconnected channels and a pore-limiting diameter of 4.3 Å, is well-suited for separating small gas molecules. Through multiple synthesis trials, we produced MIL-160 membranes with distinct crystal morphologies─ball, flake, and cuboid─and characterized them using X-ray diffraction, scanning electron microscopy, nitrogen physisorption, gas adsorption, thermogravimetric analysis, and confocal microscopy. The crystal morphology was found to significantly influence membrane quality, particularly in reducing grain boundaries and pinholes. Confocal microscopy revealed substantial defects in the ball- and flake-shaped membranes, while the cuboid-shaped membrane showed minimal dye infiltration, indicating fewer defects and a more uniform structure. Single-gas permeation tests confirmed the superior performance of the cuboid-shaped MIL-160 membrane, achieving ideal CO₂/N₂ and CO₂/CH₄ selectivities of 56.8 and 130, respectively, with a CO₂ permeance of 75.5 GPU. In mixed-gas tests, the membrane reached a CO₂/N₂ selectivity of 259 at X_CO2 = 0.5, and a CO₂/CH₄ selectivity of 224 at X_CO2 = 0.2. Additionally, molecular simulations of binary gas adsorption supported these findings, demonstrating competitive CO₂ adsorption in the presence of N₂ and CH₄. This study highlights the potential of in situ synthesis of MIL-160 membranes on tubular substrates as a scalable and effective solution for CO₂ removal from flue gas and natural gas.

Chiral organic molecules with a complementing π-structure are highly desired to obtain materials with good semiconducting properties and pronounced chirality effects in the visible region. Herein, we introduce a novel design strategy to achieve an axially chiral and rigid perylene bisimide (PBI) dye by attaching the chirality-inducing 2,2′-biphenoxy moiety at one side of the bay area and the rigidity-inducing di-tert-butylsilanediol bridge on the other side. This yielded a new bay-functionalized PBI derivative carrying the combination of a highly rigid and, simultaneously, an axially chiral perylene core. As a result, the derivative exhibits well-resolved absorption and emission spectra in the visible region, with a fluorescence quantum yield close to unity. Furthermore, the M- and P-enantiomers were found to be stable with a racemization barrier of 102 kJ mol^–1 and, hence, could be successfully separated by chiral chromatography and studied by circular dichroism (CD) spectroscopy. This rigidified chiral-PBI could also be crystallized and analyzed by X-ray diffraction, showing the highest torsion angle of the perylene core with a value of up to 30.3° in the family of PBIs carrying the same di-tert-butylsilanediol bridge.