Research articles

African swine fever virus type II DNA topoisomerase (AsfvTop2) is known to change DNA topology by employing a complex catalytic cycle and is involved in the early stages of viral gene replication, however, the structural and regulatory functions of AsfvTop2 remain underexplored. Here, the authors use cryo-EM to demonstrate six conformers of apo-AsfvTop2 as well as the structures of AsfvTop2-DNA-inhibitor complexes, revealing experimental evidence of their substrate binding mechanism that also shed light to other enzymes.

The effects of co-solutes on protein solubility, stability and function have been well studied, however, some of the theories appear inconsistent and no clear theoretical framework has been established. Here, the authors investigate the NMR titrations of protein barnase with Hofmeister ions and osmolytes to distinguish binding effects from solvent perturbation and provide a coherent explanation for solute effects.

Dual-controlled molecular release is of importance in the construction of controlled delivery systems with high anti-interference capabilities, but has been underexplored in the context of guest release from supramolecular entities. Here, the authors report a coordination cage whereby changes in both the coordinative metal cation and the solvent system are needed to induce guest release.

The atomically precise on-surface synthesis of carbon-based nanostructures is of relevance for electronic and optoelectronic devices, but achieving control over such architectures remains challenging. Here, the authors demonstrate the selective stepwise on-surface synthesis of nitrogen-doped porous carbon nanoribbons with well-defined topologies and structures, and predict variable band gaps dependent on ribbon width.

Sorbicillactone A is a nitrogen-containing sorbicillinoid that displays various bioactivities, identified from a sponge-derived Penicillium chrysogenum strain. The first and so far obly total synthesis of sorbicillactone A led to the racemate in 12 linear steps and a 0.13% overall yield. Here, the authors develop a chemoenzymatic stereoselective total synthesis of sorbicillactone A in 4 steps and 11% yield by using the enzyme SorbC for the enantioselective oxidative dearomatization of sorbillin to sorbicillinol followed by addition of an azlactone unit.

Although depolymerization methods for various commodity plastics and several engineering plastics have been developed, such methods for robust super engineering plastics that have very high heat and chemical resistance are nearly unexplored. Here, the authors report the catalytic depolymerization-like chemical decomposition of oxyphenylene-based super engineering plastics such as polyetheretherketone, polysulfone, and polyetherimide using thiols via selective carbon–oxygen main chain cleavage to form monomer-type molecules, namely electron-deficient arenes with sulfur functional groups and bisphenols.

Recently, a medium-density amorphous ice (MDA) was synthesized via ball-milling of hexagonal ice, adding complexity to our understanding of the phase diagram of supercooled water and amorphous ice. Here, the authors use molecular dynamics simulations to show that, depending on the employed pressure, isobaric cooling can generate a continuum of amorphous ices with densities that expand in between those of low- and high-density amorphous ices, with some of these amorphous ices being remarkably similar to MDA.

Bivalent molecules comprising dual functional motifs often exhibit strong target binding, however arriving at the optimal structure is challenging. Here, the authors employ EGFR as a model system for understanding a subtle difference in the linker structure of bivalent inhibitors to enhance binding against drug-resistant EGFR mutants.

Ultraprecise spectral line lists of molecules such as water, omnipresent in various environments, can be used to calibrate high-resolution spectra, which is particularly relevant for exoplanet transit observations. Here, the authors use measured spectra and network theory to achieve ultraprecise characterization of H₂¹⁶O and H₂¹⁸O hubs, the most relevant quantum states within a spectroscopic network.

Electronic energy transfer (EET) between chromophores is a critical process for solar energy funneling, and recent studies using scanning tunneling microscopy have shown that chromophores deposited on solid substrates in such conditions display peculiar EET features. Here, hybrid ab initio and electromagnetic modeling provide a comprehensive theoretical analysis of tip-enhanced EET.

Nickel organic compounds play a crucial role in organic and bioinorganic chemistry, however, their potential role in prebiotic chemistry is not well understood. Here, the authors identify the formation of a nickel bis(dithiolene) from nickel sulfide under an acetylene-containing volcanic hydrothermal experimental environment and reveal its role in the transformation of acetylene to acetaldehyde.

Covalent probes are a powerful tool for investigating small molecule and protein interactions, however, the development of reactive warheads to form covalent probes remains underexplored. Here, the authors develop α-acyloxyenamide electrophiles to covalently bind to lysine residues, and selectively profile the conserved lysine residues of kinase in live cells.

Metal-organic frameworks have demonstrated great promise for application in CO₂ capture, but the enormous breadth of potential building blocks available makes searching the chemical space for the best-performing materials challenging via traditional methods. Here, the authors present a high-throughput computational framework based on a molecular generative diffusion model to accelerate the discovery of MOF structures with high CO₂ capacities and synthesizable linkers.

Collision-induced dissociation tandem mass spectrometry offers to resolve molecular structures through library searches, however, for de novo identifications, one must often rely on in silico-generated spectra as reference. Here, the authors evaluate in silico generated MSⁿ product ion structures by comparison with spectroscopically established structures and find that for 36 randomly selected MS/MS product ions, the vast majority of annotations in three major libraries are incorrect, primarily due to unaccounted for cyclization rearrangements.

Peptides or proteins containing aggregates are pivotal for the integrity of structure and function, however, monitoring the dynamics of such systems remains challenging. Here, the authors investigate the dynamic landscape of peptide-SDS micelles through a synergistic combination of solution-state NMR experiments and molecular dynamics simulations.

Mixed-metal cluster generating reaction solutions contain several species of similar composition and structure that often result in hard-to-separate product mixtures. Here, the authors analyze elemental compositions obtained via high-resolution mass spectrometry with a computational permutative approach and assign individual structures of nickel gallium intermetalloid clusters without the need to isolate pure clusters.

Deep eutectic solvents are promising, sustainable alternatives for diverse applications, including separation, gas capture, electrodeposition, or nanomaterial synthesis, but our fundamental understanding of the nature of these solvents remains limited. Here, the authors report a practical approach for estimating the solid–liquid equilibrium phase diagram of any binary mixture from structural information, using machine learning and quantum chemical techniques.

Molecular dynamics (MD) is a powerful tool for the simulation of proteins and other biomolecules, however, convergence and equilibrium in MD simulations remain underexplored. Here, the authors investigate long MD trajectories of several proteins and reveal that, although full convergence of all properties may not be reached, the most biologically interesting properties do, in fact, reach convergence during multi-microsecond simulation trajectories.

Controlling excited-state reactivity is a long-standing challenge in photochemistry, as desired pathways may be inaccessible or compete with unwanted channels, which is problematic for applications. Here, the authors show that 2,3,5-trifluorination on the phenolate ring of the green fluorescent protein chromophore leads to both pathway selectivity and doubles the photoisomerization quantum yield.

Enhancing the activity of the oxygen reduction reaction (ORR) is crucial for fuel cell development, but hydrophobic species used to boost ORR activity are often toxic. Here, the authors report that caffeine enhances the specific ORR activity of Pt(111) eleven-fold compared to that without caffeine in a 0.1 M HClO₄ aqueous solution, and find that the enhancement mechanism depends strongly on the surface structures of platinum.