ACS Central Science最新文献

The implementationof green chemistry principles in catalysisisessential for sustainable production of specialty chemicals, whereselectivity and efficiency are paramount. Unspecific peroxygenases(UPOs) have emerged as promising biocatalysts for enantioselectiveC–H oxyfunctionalization reactions, using hydrogen peroxide(H₂O₂) as the sole oxidant. However, the instabilityof UPOs toward H₂O₂ and the nonsustainable productionof this reagent remain key challenges. Herein, we report the designof a hybrid chemo-enzymatic heterogeneous catalyst integrating anAu–Pd-based material with the PaDa-I UPO mutant, using an “enzyme-in-a-cage”immobilization strategy. This bifunctional system enables controlled in situ H₂O₂ generation directly fromH₂ and O₂, coupled with the enantioselectivehydroxylation of ethylbenzene in a single reactor. The catalyst exhibitshigh activity, excellent enantioselectivity (ee = 97.7%), and stabilitywithout enzyme leaching. This approach offers a robust and sustainableplatform for one-pot chemo-enzymatic cascade reactions in chemicalsynthesis.

N-Heterocyclic imines (NHIs) represent a promising classof sorbentsfor electrochemically mediated carbon capture (EMCC) due to theirability to bind CO₂ in the neutral state and operate reversiblyat redox potentials more positive than that of oxygen. In this study,the effect of electrolyte composition on the thermochemical and electrochemicalbehavior of NHI-based systems is examined. Using reaction calorimetryand Raman and NMR spectroscopy, we demonstrate that Lewis acid cationsstabilize the NHI–CO₂ adduct through charged interactions,and the solvent and anion donor number tune this stabilization bymodulating the effective cation Lewis acidity. As a result, electrolytesalts can substantially increase the magnitude of the NHI–CO₂ reaction enthalpy, leading to higher CO₂ loadingon NHI at low CO₂ partial pressure (10^–3 atm) and faster capture kinetics. The impacts of the electrolyteselection on NHI redox behavior as well as oxygen reduction were alsoinvestigated. The findings indicate that electrolyte design must balancethe strength of cation–NHI–CO₂ stabilization,NHI redox activity, and the redox potential separation from oxygenreduction. By providing a mechanistic framework for how individualelectrolyte components govern important process parameters, this workoffers insights for optimizing electrolyte environments to achievehigh-efficiency and reversible EMCC.

Engineering physiologically relevant cardiac substratesrequiresprecise control over both electrical and mechanical cues to guidecardiomyocyte functions and features. In this work, we report a biomolecular-basedapproach toward spatially controllable photostimulation of cardiacbehavior via digital light processing of conductive interfaces ona range of substrate stiffnesses. The symmetric peptide-quaterthiophene-peptideunits are designed to form conductive patterns atop biopolymeric hydrogels,allowing for microscale spatial control of photoconductive pathwaysthat can influence cardiomyocyte alignment and intercellular communicationin a light-activated manner. Substrate stiffness was modulated throughadjusting material composition across a physiologically relevant rangeto reflect healthy and fibrotic cardiac tissue conditions. The abilityto tailor the geometry of conductive pathways across a range of biomaterialinterfaces and stiffnesses enables systematic assessment of how electricalsignals from patterned optoelectronic peptides regulate cardiomyocytebehavior. Neonatal rat ventricular myocytes (NRVMs) cultured on π-conjugatedpeptide-based substrates exhibited enhanced alignment, synchronouscontractility, and altered calcium flux dynamics compared to nonconductivesubstrates. Furthermore, the optoelectronic cardiac biomaterial-basedscaffolds were shown to possess biological photostimulation capabilities,specifically enabling light-induced localized stimulation of excitablecells for high-resolution stimulation without the need for externalelectrodes or genetic modifications necessary for optogenetic approaches.Photostimulated NRVMs interfaced with optoelectronic peptide structureswere shown to be more confined to the printed conductive patterns,with more cell localization and structural remodeling with respectto the patterns than in non-photostimulated conditions. The peptide-basedplatform presented here provides a potential approach to control mechanicaland optoelectronic cues using microscale patterns in vitro, while opening avenues for advanced cardiac disease modeling, drugdevelopment, and the development of complex bioelectronic cardiacinterfaces.

Reactions of ionsin water are important in many areas of chemistryand biology, including the chemistry of seawater, atmospheric chemistry,and processes in proteins. Despite their importance, the microscopicmechanisms of these inherently complex and multistep reactions aremostly unknown so far. In this Outlook, we outline recent progresson atmospheric reactions of halogenated species with anions in water.These are found to proceed via halogen-bonded complexes, which arestabilized by the water environment. Such complexes were recentlycharacterized experimentally in the gas phase with structures similarto those computed in water. We highlight two such reactions: one thatleads to the formation of a dihalogen and is enhanced with acidity.The other reaction is of halogen exchange, which involves participationof water molecules that greatly catalyze the process. These findingssuggest searches for many other reactions that may involve halogen-bondedcomplexes as precursors. On the basis of the present studies, searchesfor such reaction mechanisms can be effectively pursued by ab initiomolecular dynamics (AIMD) simulations. The halogen-bonded complexescan be complementarily characterized by vibrational spectroscopy inmass spectrometry experiments.

Academia–industrypartnerships are an important driver ofinnovation in drug discovery, and their success depends on intentionalproblem selection, effective resource sharing, and robust communicationduring project execution. This outlook highlights select Merck Sharp& Dohme Discovery Chemistry (MSD DC) collaborations reported overthe past five years to illustrate principles that underpin productiveacademia–industry partnerships. Through representative casestudies in synthesis collaborations, we illustrate two complementarycollaboration strategies: targeted development of synthetic methodsthat address key medicinal chemistry bottlenecks, and capability-buildingefforts that enable technology transfer to accelerate drug discovery.We also highlight a few nonsynthetic collaborations by MSD DC in computationalchemistry, structure elucidation, and chemical biology subfields,underscoring the cross-functional impact of these efforts on drugdiscovery. Beyond scientific advances, these collaborations also providemeaningful training and professional development opportunities forthe next generation of chemists.

Direct air capture(DAC) is a promising strategy for mitigatingatmospheric CO₂ accumulation, yet sorbent evaluation remainsdominated by equilibrium uptake under static conditions that failto capture kinetic, humid, and process-level constraints relevantto real operation. Here we establish a dynamic evaluation frameworkthat replaces equilibrium-centric metrics with a unified platformintegrating high-precision gravimetric measurements, ppm-level CO₂ nondispersion infrared detection, and capacitive humiditysensing, enabling direct quantification of adsorption kinetics, H₂O/CO₂ coadsorption, breakthrough behavior, andregeneration energy under low CO₂ concentration and dry/humidconditions. Using TAEA@MIL-101(Cr) as a benchmark system, we introducea sonication-assisted impregnation strategy that enables coordinatedamine anchoring with preserved porosity and strong CO₂ chemisorption.The optimized material exhibits a high equilibrium CO₂ of3.12 mmol g^–1 (13.8 wt %) at 298 K, a dynamic breakthroughcapacity of 12.4 wt % under dry conditions, and a retained capacityof 9.7 wt % at 50% relative humidity. Complete regeneration is achievedat 50 °C, enabling low-energy temperature-swing operation. Thiswork establishes a generalizable dynamic benchmarking framework forDAC sorbents and positions TAEA@MIL-101(Cr) as a reference platformbridging molecular design, kinetic performance, and process-levelenergy requirements to complement conventional equilibrium evaluation.

Clostridium difficile (C. difficile), a Gram-positive bacterium responsible for life-threatening diarrhea,causes approximately 12 800 deaths annually in the United States,yet no licensed vaccine is currently available. PS-III, a cell-surfaceglycan composed of 6,6′-phosphodiester-linked di-N-acetylglucosamine (di-GlcNAc) repeats, has been identified as apromising vaccine antigen because of its potent immunogenicity. However,the lack of efficient synthetic method limited the availability ofstructurally defined PS-III antigens, hampering systematic immunologicalanalysis. Herein, we report a solid-phase synthesis strategy employingMerrifield resin that enables efficient assembly of PS-III oligosaccharidesup to a tridecasaccharide─the largest well-defined structuresynthesized up to date. Three CRM197-conjugated vaccines bearing preciselydefined glycotopes ranging from pentasaccharide to tridecasaccharidewere constructed and evaluated in both in vitro and in vivo immunizationstudies. Glycan microarray profiling of sera from immunized mice revealedglycotope length-dependent IgG/IgM responses, with the nonasaccharide(1d-CRM197) and tridecasaccharide conjugate (1f-CRM197) eliciting the strongest binding. In a murine challenge model, mostglycoconjugate vaccines conferred superior protection against C. difficile compared with inactivated whole cell bacteriavaccine. Notably, 1f-CRM197 induced a nearly completebacterial killing in the opsonophagocytic assay. Collectively, wehave established an efficient solid-phase synthesis for well-defined C. difficile PS-III glycans. The resulting CRM197-conjugatevaccines with short-to-long glycans showed potent activity in opsonophagocyticand murine models, paving the way for preclinical development of C. difficile glycoconjugate vaccines.

Cyclic polymers, lacking chain ends, exhibit unique behaviorwhenblended with linear analogues. In such cyclic/linear mixtures, cyclicpolymers permit chain threading, wherein linear chains penetrate thering-like structure, increasing entropy and enhancing interfacialdiffusion relative to linear/linear or cyclic/cyclic blends. Althoughtheory has long predicted this topological entropy-driven miscibility,experimental evidence has been scarce due to challenges in synthesisand characterization. Here, we provide the first direct experimentalvalidation using neutronreflectivity on cyclic and linear poly(lactic acid) (PLA) analoguesassembled as bilayers of higher-molecular-weight, isotopically labeledlinear PLA in thin films. The results show that topological entropymarkedly reduces the effective interaction parameter, χ_eff, promoting interfacial miscibility. This demonstrates thatmolecular topology alone can alter macroscopic thermodynamics, offeringa fundamental route to control phase behavior in soft condensed matter.