Volume 16 Issue 5, May 2024

X-ray diffraction analysis typically affords the static 3D structures of given compounds or materials, but to understand chemical processes, the visualization of fast structural changes is desirable. Time-resolved femtosecond crystallography has now been used to monitor the structural dynamics of a photoactive metal–organic framework.

Chlorine-containing waste streams pose potential risks to human health and the environment, so their remediation represents a significant challenge. Now, chlorinated wastes have been successfully repurposed as chlorinating reagents for use in the preparation of organic chemicals and pharmaceutical ingredients.

Understanding the ways by which metal-containing catalysts carry out a reaction is a chemical puzzle. Now, investigations of a multi-metallic molecular system uncover how the self-assembly of molecular catalysts facilitates cooperation between active species and improves the conversion of water to hydrogen gas.

Natural protein folding takes place in aqueous cell environments. Now, it has been found that proteins in a water-free environment undergo faster and more efficient folding.

A non-radical proximity labelling platform — BAP-seq — is presented that uses subcellular-localized BS2 esterase to convert unreactive enol-based probes into highly reactive acid chlorides in situ to label nearby RNAs. When paired with click-handle-mediated enrichment and sequencing, this chemistry enables high-resolution spatial mapping of RNAs across subcellular compartments.

Although generally perceived as an old-fashioned and unselective tool to build molecules, the photochemistry community is now re-discovering the power of UV light and is using key mechanistic information to develop new catalytic processes driven by visible light. This Perspective discusses the progress and impact of UV light in organic synthesis.

Time-resolved femtosecond crystallography (TR-SFX) is a powerful technique to monitor structural transitions in protein crystals at the atomic level, but its use in non-protein synthetic materials remains limited. Now TR-SFX has been used to visualize the structural dynamics of metal–organic frameworks, showing the potential of this tool to study the dynamic motion of crystalline porous materials.

While chlorinated compounds are ubiquitous in chemical synthesis, they have a negative impact on human health and the environment. Now, a sustainable tandem catalytic process has been developed that uses chlorine-containing waste as chlorination reagents. This approach represents a promising way for the viable management of chlorinated compounds.

Although the light-driven generation of hydrogen from water is a promising approach to renewable fuels, the H–H bond formation step represents a persistent mechanistic question. Now light-harvesting molecular catalysts have been shown to self-assemble into nanoscale aggregates that feature improved efficiency for photoelectrochemical H₂ evolution.

RNA localization is key to regulating cellular function but is challenging to measure in an unbiased manner. Now a combination of enol-masked acylating probes with a bioorthogonal esterase to locally unmask them provides a non-radical RNA proximity labelling platform—termed BAP-seq—that enables the generation of high-resolution spatial maps of RNA.

Atomistic simulations have a broad range of applications from drug design to materials discovery. Machine learning interatomic potentials (MLIPs) have become an efficient alternative to computationally expensive ab initio simulations. Now a general reactive MLIP (called ANI-1xnr) has been developed and validated against a broad range of condensed-phase reactive systems.

Valence tautomerism in lanthanide-based materials is rare. Now a one-dimensional samarium–pyrazine polymer has been shown to exhibit a temperature-induced hysteretic Sm(III)-to-Sm(II) reversible switch. The transition temperature is modulated in a 150 K window by alloying with Yb(II), presenting a strategy for developing new materials with chemically tunable magnetic switchability.

Skeletal editing enables diversification of compounds not possible by applying peripheral editing strategies. Now, a catalyst-free atom-pair swap strategy for pyridine editing has been developed via one-pot sequential dearomatization, cycloaddition and rearomative retrocyclization. Benzenes and naphthalenes with precisely installed functional groups are produced, and the mild conditions enable late-stage skeletal diversification of pyridine cores.

Single-atom alloys have emerged as highly active and selective catalysts that do not follow the traditional models of heterogeneous catalysis. Now it has been shown that the binding of adsorbates at their surface abides by a simple 10-electron count rule, which can identify promising catalysts for various applications.

Switching the magnetic state of a polycyclic conjugated hydrocarbon in a reversible and controlled manner is challenging. Now, by means of single-molecule scanning probe microscopy, an indenofluorene isomer on ultrathin NaCl films has been shown to adopt both open- and closed-shell states. Furthermore, bidirectional switching between the two states is achieved by changing the adsorption site of the molecule.

Lipidomics aims to uncover lipid functions in biological systems and disease. Quantifying lipids is challenging due to highly diverse chemical structures. Here a diazobutanone-assisted isobaric labelling method is developed that relies on diazobutanone and isobaric mass tags to target phosphate- and sulfate-containing lipids, enabling multiplexed lipidomic quantification in complex mixtures.

While saturated N-heterocycles are widespread motifs in drug discovery, the seven-membered ring azepane is highly underrepresented. Now nitroarenes have been validated as competent substrates for azepane synthesis through conversion into singlet nitrenes for ring enlargement via N insertion and hydrogenolysis. This enables a highly versatile access towards polysubstituted azepanes in just two steps.

Actinide–metal multiple bonds are relatively rare, with isolable examples under normal experimental conditions typically restricted to complexes containing a polar covalent σ bond supplemented by up to two dative π bonds. Now complexes featuring polar covalent double and triple bonds between thorium and antimony have been synthesized.

Achieving selectivity control in allylic arylations is a long-standing challenge in catalysis. Now a rhodium-catalysed system demonstrates chemo-, regio- and enantioselectivity, enabling Suzuki–Miyaura-type arylation with racemic, non-symmetrical, acyclic allylic systems; chelation is speculated to facilitate oxidative addition and enable both enantiomers of the starting material to converge onto a single product.

Chromophore supramolecular assemblies have long been studied for their exotic photophysical properties arising from their local geometry and long-range sensitive excitonic couplings. Now a high-resolution structure of a model nanotubular system has revealed a uniform brick-layer molecular arrangement and a non-biological supramolecular motif—interlocking sulfonates—enabling clear understanding of supramolecular structure–excitonic property relationships.

Although hydrogen gas could serve as a promising future fuel, its high-capacity storage is a challenge. Now, a nanoporous magnesium borohydride framework is shown to store hydrogen as densely packed penta-dihydrogen clusters having well-defined orientations and directional interactions with the framework.

The use of biocatalysis to support early-stage drug discovery campaigns remains largely untapped. Here, engineered biocatalysts enable the synthesis of sp³-rich polycyclic compounds through an intramolecular cyclopropanation of benzothiophenes, affording a class of complex scaffolds potentially useful for fragment-based drug discovery campaigns.

The design of highly oxidizing Earth-abundant transition metal complexes for photochemical applications is desirable, but progress in this area remains limited. Now a manganese(IV) diguanidylpyridine complex has been shown to photooxidize naphthalene, benzene and acetonitrile to their radical cations after excitation with near-infrared light. Experimental and theoretical studies indicate the presence of two distinct ligand-to-metal charge transfer excited states.

John Steele and Stephen Wallace discuss recent advances in the chemical and biotechnological synthesis of the prolific platform chemical adipic acid.