Research articles

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.

Amines and carboxylic acids are abundant chemical feedstocks, however, the current reaction space of those two building blocks is focused on amide coupling. Here, the authors extensively explore the amine–acid reaction space via systematic reaction enumeration using graph editing and demonstrate its utility in retrosynthetic analysis as well as late-stage diversification.

Protein tyrosine kinase Src is known to phosphorylate Ras protein on tyrosine32 and 64, and uncouple Ras from the signaling cascade, however, the mechanisms through which phosphorylation modulates these interactions remain poorly understood. Here, the authors quantify the major mono-phosphorylation level on tyrosine64 by ³¹P NMR and mutagenesis, and reveal the key conformational changes of phosphorylated Ras using BeF₃⁻ complexes by X-ray crystallography and ¹⁹F NMR, providing new mechanistic and conformational insights into Ras dynamics regulation.

Single-molecule fluorescent probes can be used for nanoreporting, localization, and now multiplexing, but understanding their stochastic fluctuations in emission intensity is crucial for accurate signal interpretation. Here, the authors elucidate the blinking dynamics of rhodamine, BODIPY, and antraquinone dyes, demonstrate that multiplexing performance improves with photophysical differences, and suggest guidelines for the selection and design of organic fluorophores for single-molecule multiplexing.

Protease inhibitors represent attractive antiviral agents against coronaviruses, however, current inhibitors show restricted efficiency which limits their use. Here, the authors develop covalent reversible peptidyl inhibitors with nitroalkene warheads, showing inhibition against main protease and human Cathepsin L, preventing viral infection in a cellular assay.

Isotope ratios of mollusk shell carbonates are commonly used to reconstruct past environmental conditions, but the shell organic matrix is often overlooked. Here, the authors find the hydrogen and oxygen isotope compositions of the organic matrix of modern Mytilus galloprovincialis shells from sites along a coast-to-upper-estuary environmental gradient reflect environmental variables.

Gangliosides are composed of oligosaccharide chains attached to ceramides and are employed as targeted drugs and diagnostic biomarkers, however, their industrially-relevant synthesis remains challenging. Here, the authors develop a modular chemoenzymatic cascade assembly strategy for the customized and large-scale synthesis of ganglioside analogues with various glycan and ceramide epitopes.

Protein binding plays an important role in the function and design of protein complexes, however, the relationships among protein sequences, structures, and interactions shaped by evolution remain underexplored. Here, the authors use computational simulations to study the binding specificity of a two-component system under protein sequence evolution and reveal that the binding specificity is modulated by both direct intermolecular interactions and long-range epistasis across the binding complex.

Capsid proteins (CPs) of various icosahedral and rod-shaped viruses exhibit structural diversity and tunability as well as application in smart hybrid nanoparticles, however, the potential of CPs of filamentous plant viruses remains underexplored. Here, the authors exploit the structure-based design of CP from potato virus Y to tune the shape, size, RNA encapsidation ability, symmetry, stability, and surface functionalization of nanoparticles.

Descriptor design in catalyst informatics necessitates adequate prior knowledge for delving into unknown territories, particularly when confronted with limited data, thus presenting a logical contradiction. Here, the authors report a technique for automatic feature engineering that works on small catalyst datasets without reliance on pre-existing knowledge about the target catalysis.

High resolution force measurements of molecules on surfaces using non-contact atomic force microscopy are typically performed at cryogenic temperatures. Here, the authors outline a reliable protocol for acquiring three-dimensional force map data at room temperature, demonstrating such capabilities on isolated cobalt phthalocyanine molecules and islands of C60 molecules.

Inositol requiring enzyme 1 (IRE1) is a conserved protein kinase involved in the endoplasmic reticulum secretory pathway, however, IRE1 from S. cerevisiae and human show opposite responses to flavonoid quercetins. Here, the authors apply in silico and in vitro approaches to reveal the different binding modes of quercetins on IRE1, providing molecular insight into their opposite effects on S. cerevisiae and humans.

Pyrroles are an important scaffold in medicinal chemistry with various bioactivities; however, the selective chemical halogenation of pyrroles remains challenging. Here, the authors develop an enzymatic site-selective chlorination of pyrrolic heterocycles by a flavin-dependent halogenase PrnC and apply it to the chemoenzymatic synthesis of a chlorinated analogue of the fungicide Fludioxonil.

Peptide-based coacervates display interesting properties for biomedical applications, however, the link between peptide structure and coacervate material properties remains unclear. Here, the authors report a direct correlation between the primary and secondary structures of the peptides and the viscoelastic properties of the coacervates.

Sulfatinib is a multi-target angio-immuno kinase inhibitor for treating neuroendocrine tumors, selectively targeting FGFR1 and CSF-1R. Here, the authors elucidate the molecular mechanisms behind its binding and kinase selectivity, highlighting interactions with a hydrophobic pocket for FGFR selectivity, and rotatory flexibility to potentially overcome CSF-1R^T663I gatekeeper mutation.

Colloidal nanocrystals find applications from electronics to catalysis and biological sensors, but their complex surface structures are challenging to explore. Here, the authors use graphene liquid cell transmission electron microscopy to show that solubilized platinum crystals of less than 3 nm in size have individual, ordered cores surrounded by mobile surface atoms.

Dual asymmetric catalysis is powerful for the synthesis of multi-stereocenter molecules, however, the integration of dual catalysts remains challenging due to the intrinsic deactivation of dual-species and extrinsic conflict of reaction conditions. Here, the authors develop a compartmental and thermoresponsive poly(N-isopropylacrylamide)-hydrogel-supported bifunctional catalyst to overcome these challenges.

Natural products are a rich source of lead compounds in drug discovery. Here, the authors report the discovery and synthesis of five nitrogenous polycyclic polyprenylated acylphloroglucinols named hyperelanitriles A–D and hyperelamine A from the plant Hypericum elatoides with anti-inflammatory activity against lipopolysaccharides-activated nitric oxide production.

Conversion of methane to methanol via methanol derivatives such as methyl bisulfate (MBS) allows to achieve high selectivity and yield, but separating MBS from oxidizing agents such as sulfuric acid is an energy-intense step. Here, the authors eliminate the need for separation of MBS from sulfuric acid by replacing the former with methyl trifluoroacetate, which is subsequently hydrolyzed into high-purity methanol.