Volume 16 Issue 3, March 2024

Replicating the ability of enzymes and transport proteins to effectively bind anions is a considerable challenge for supramolecular chemists. A neutral organic cage has now been developed that selectively binds sulfate anions in water.

Electrocatalytic transformations often involve the concerted transfer of electrons and protons at electrode interfaces; however, these processes are not well understood. Now, experiments on an electrode that features well-defined molecular sites deepen fundamental understanding of such transfers to pave the way for future catalysts.

Molecules containing a chiral S(VI) moiety have found extensive applications in drug design and organic synthesis, despite a lack of diverse asymmetric methods for their creation. Now, a ligand-mediated process has enabled the production of enantioenriched S(VI)–F motifs, providing a foundation for further stereospecific elaborations.

Single-particle cryo-electron microscopy and all-atom molecular dynamics simulations provide atomic details of ATP hydrolysis in the multimeric enzyme p97.

Trans–cis photoisomerization is a fundamental photochemical reaction that is thought to proceed through an intermediate with a perpendicular conformation. However, unambiguous identification of this state has proved challenging. The combination of state-of-the-art ultrafast spectroscopy and quantum chemical calculations now provides evidence for its structural observation in stilbene photoisomerization.

Dinitrogen (N₂) fixation to ammonia (NH₃) is typically challenging under mild conditions. Now, lithium hydride (LiH) is shown to mediate photodriven N₂ fixation under ambient conditions. Under ultraviolet illumination, LiH is photolysed to release H₂, leaving electrons residing in surface hydrogen vacancies, which facilitate N₂ activation and photocatalytic NH₃ synthesis.

Covalent protein conjugation facilitates the study of biological processes and the synthesis of therapeutic biomacromolecules. A method that uses vinyl thianthrenium reagents for the site-selective formation of highly reactive episulfonium species on proteins is demonstrated. These in situ-formed intermediates react with diverse nucleophiles, providing access to protein conjugates in one step without purification.

Nanopore label-free sequencing of DNA and RNA at the single-molecule level offers rapid readout, high accuracy, low cost and portability. This Review surveys technologies underpinning commercial and academic nanopore sequencing, and examines how underlying biochemical advances can fuel future developments in nanopore-based protein sequencing.

Very few charge-neutral synthetic anion receptors can function in water, and those known typically select weakly hydrated anions such as iodide. Now a neutral molecular cage capable of donating 12 hydrogen bonds has been synthesized and found to bind highly hydrated sulfate in water with a strong selectivity over weakly hydrated anions.

Although interfacial proton-coupled electron transfers are critical reaction steps in chemical and biological processes, studies investigating these reactions are complicated by surface heterogeneity. Now, interfacial proton-coupled electron transfer kinetics are studied and modelled at isolated, well-defined active sites to provide a foundation for understanding complex reactions involved in energy conversion and catalysis.

Chirality is an intrinsic property in unsymmetric three-dimensional molecular assembly, contributing to the utility of the corresponding process and the resulting scaffolds. Now, on the sulfur(VI) hub, a three-step sequential ligand-exchange method has been established with precise stereocontrol, enabling the enantioselective synthesis of optically active S(VI) functional molecules.

The human ATP-hydrolysing enzyme p97 populates a metastable reaction intermediate, the ADP·P_i state, which is poised between hydrolysis and product release. Now, molecular motions at the active site in the temporal window immediately before and after ATP hydrolysis have been elucidated by merging cryo-EM, NMR spectroscopy and molecular dynamics simulations.

Photon-driven dinitrogen reduction to ammonia is a promising but challenging reaction. Now it has been shown that lithium hydride undergoes photolysis upon ultraviolet illumination to yield long-lived photon-generated electrons residing in hydrogen vacancies, favouring the activation of the N≡N bond and achieving photocatalytic ammonia synthesis.

Cysteine bioconjugation is an important method to modify biomolecules, but synthetic efforts to diversify reactive warheads and the low reactivity of introducible linchpins often impede application in biological laboratories. Now, a thianthrenium-based reagent permits site-selective installation of episulfonium on biomacromolecules, enabling one-step addition of bioorthogonal nucleophiles and further applications in quantitative proteomics and cross-linking.

Current electrochemical-based protein labelling methods suffer from limited site-selectivity and off-target reactivity owing to required radical/electrophilic reagents. Now an electrochemical strategy enables chemoselective labelling of proteins at a site-specifically incorporated 5-hydroxytryptophan residue using aromatic amines as coupling partners. This approach works on various proteins, including a full-length antibody, and is compatible with established click reactions.

Robust protocols for the synthesis of chiral α-tertiary amino acids remain scarce due to the challenge of constructing congested tetrasubstituted stereocentres. Now a cobalt-catalysed enantioselective aza-Barbier reaction of ketimines with various unactivated alkyl halides has been developed, forming diverse chiral α-tertiary amino esters with high enantioselectivity and excellent functional group tolerance.

The umpolung functionalization of imines bears vast synthetic potential, but polarity inversion is less efficient compared with the carbonyl counterparts. Now, an alternative strategy exploiting chiral phosphoric acid catalytic aromatization has been developed, affording structures possessing a central chirality or a stereogenic C–N axis with high efficiency and enantiocontrol.

Activation of H₂ by a metal–olefin complex is characterized experimentally and computationally using a nickel pincer complex, showing that the reaction proceeds via a direct ligand-to-ligand hydrogen transfer mechanism. An application of this cooperative H₂-activation mechanism is demonstrated in the nickel-catalysed semihydrogenation of diphenylacetylene.

Orthogonal click reactions enable the rapid assembly of molecules of all sizes. Now, it has been shown that a nitrile, an allene, a diborane and a hydrazine or aniline can be catalytically merged in a click process that is orthogonal to SuFEx and CuAAC, delivering fluorescent linkages.

Borenium ions have traditionally served as main group (pre-)catalysts, and their use in materials-related applications have been limited by their instability. Now, a series of fully π-conjugated azaboraacenium ions derived from carbodicarbene have been developed that exhibit high air and moisture stability with full colour-tunable luminescence. Furthermore, these azaboraacene cations mimic the electronic structures of higher-order carbonaceous acenes while featuring enhanced resistance to photo-oxidation.

Light-induced azobenzene cis/trans isomerization has been extensively investigated, but the mechanical strength of its cis/trans structure is not well understood. Now it has been shown that cis azobenzene is mechanically less stable than the trans isomer due to its regiochemical structure, as revealed by single-molecule force spectroscopy.

In contrast to photothermal therapy requiring high powers over extended times and photodynamic therapy being abrogated by inhibitors of reactive oxygen species, actuation of vibronic modes in single molecules—molecular jackhammers—can now induce efficient cancer cell death. Here, the mechanical disassembly of cell membranes is characterized as the underlying mechanism by which this vibronic-driven action promotes necrotic cell death.

Methods for transition-metal-catalysed enantioselective C(sp³)–S bond construction are underdeveloped. Now, by taking advantage of the biomimetic radical homolytic substitution manifold, the copper-catalysed enantioconvergent C(sp³)–S cross-coupling of racemic secondary and tertiary alkyl halides with highly transformable sulfur nucleophiles has been realized. This reaction provides access to an array of α-chiral alkyl organosulfur compounds.

Ciro Romano, Jack I. Mansell, and David J. Procter have explored the versatility and selectivity of samarium diiodide, and its use as a radical relay catalyst.