Research articles

Luminescent iridium(III) complexes have several appealing properties such as wide color-tunability and high photo- and chemical stabilities, whereas the properties of related diiridium(II) systems are largely unexplored. Here, the authors synthesize and characterize a series of tetracationic dinuclear iridium(II) complexes, which feature unsupported Ir(II)–Ir(II) single bonds and exhibit photoluminescence in various media.

Prediction of material properties is crucial for early stages of material research, but current experimental data-based strategies possess limited accuracy. Here, the authors develop a machine learning-based semi-automated material exploration scheme to predict the solubility of tetraphenylporphyrin derivatives with an accuracy above 0.8.

Preassembled materials are ubiquitous in our everyday life due to their readiness and functionality; an end-user simply follows instructions to assemble them and harness function. Here, metastable rotaxanes are utilized to approach preassembled materials: a multicomponent, preprogrammed system can be conveniently (via heating) transformed into colorful polymer networks at the end-user’s will.

The antiviral drug nirmatrelvir is the active ingredient in Paxlovid, a SARS-CoV-2 M^pro inhibitor developed by Pfizer, however, its synthetic procedure faces limitations for meeting urgent demand. Here, the authors optimize the key synthetic steps and develop a sustainable route to nirmatrelvir in 7 steps and 3 pots with an overall 70% yield.

Carbocyclic nucleosides show a broad spectrum of antiviral activity with enhanced flexibility, lipophilicity and metabolic stability, however, synthetic access to carbocyclic C-nucleosides (CC-Ns) remains very challenging. Here, the authors use an asymmetric Suzuki-Miyaura coupling reaction as the key C-C bond forming step to produce a variety of enantiomerically enriched CC-Ns, including antiviral showdomycin.

Incommensurate double-wall carbon nanotubes give rise to unique stereochemistry originating from twisted stacks of hexagon arrays, but atomic-level studies of molecular analogues are hindered by the challenges in designing and synthesizing pairs of chiral cylindrical molecules. Here, a molecular version of incommensurate double-wall carbon nanotubes is designed by development of a roadmap of synthetically accessible chiral indices.

Atomically and structurally precise silver nanoclusters hold great potential for catalytic and optoelectronic applications. Here, the authors synthesize and characterize a series of atomically defined dithio- and diselenophosphate-protected eight-electron superatomic palladium-doped silver nanoclusters, including an unprecedented pair of selenolate-protected isomers.

Gallium-modified HZSM-5 zeolites demonstrate increased selectivity towards aromatics during methanol conversion, but the mechanism and the nature of the active sites that lead to this enhanced selectivity are poorly understood. Here, in situ synchrotron radiation photoionization mass spectrometry experiments reveal that increased formaldehyde generation over Ga₂O₃ species plays a key role in promoting the production of aromatic compounds.

The reductive functionalization of CO₂ to value-added chemicals using powdered silicon as a reducing agent is a promising sustainable route, but the behavior of employed fluoride catalysts remains largely unknown. Here, the authors use tetrabutylammonium fluoride to catalyze the conversion of a variety of amines to amides with CO₂ and H₂O reduced by metallic silicon recovered from solar panel production waste and show that the catalyst effectively oxidizes Si atoms on both the surface and interior of the powdered silicon particles.

Data-driven methodology plays an important role in the rapid identification of appropriate chemical conditions, however, optimization of multiple variables in the flow reaction remains challenging. Here, the authors report a Bayesian optimization-assisted multi-parameter screening to predict the suitable conditions to achieve the efficient synthesis of biaryl compounds in a flow system.

Protoamphiphiles – prebiotically plausible components of protocell membranes – could originate from a diverse set of amphiphiles, but studies so far have mostly been limited to fatty acid-based model systems. Here, the authors elucidate the abiotic synthesis of N-acyl amino acids under wet-dry cycles from amino acids and monoglycerides, characterize their vesicle formation and ability to act as a substrate for lipopeptide synthesis, thereby demonstrating N-acyl amino acids as a promising model protoamphiphile.

Intermolecular (4 + 2) cycloaddition with alkynes is a powerful approach to construct isocoumarin moieties, however, regioselectivity remains challenging for the transition metal-catalyzed approach. Here, the authors report copper-catalyzed regioselective (4 + 2) annulations between diaryliodonium salts and alkynes to synthesize isocoumarin-type natural products.

Crystal structure elucidation of terpene synthases plays an important role to understand the sequence-structure-function relationships of this enzyme class. Here, the authors determine the crystal structure of bacterial terpene synthase Tpn2, probe the catalytic mechanism by structure-guided mutation, and change the product preference from a clerodane skeleton to a syn-labdane skeleton.

Proton transfer between DNA bases can lead to mutagenic tautomers, but as their lifetimes are thought to be much shorter than DNA separation times their role during the DNA replication cycle is often overlooked. Here, the authors model the separation of the DNA base pair guanine-cytosine using density functional theory and find increased stability of the tautomer when the DNA strands unzip as they enter a helicase enzyme, effectively trapping the tautomer population.

Organophosphates are essential to facilitate information storage and energy transfer in living organisms, but their prebiotic origins remain unknown. Here, the authors report a liquid sulfur dioxide-mediated phosphorylation of nucleosides from phosphorous acid in a single reaction step at room temperature.

Site-selective thionation is a powerful strategy to access heavyatom-free small-molecule photosensitizers for photodynamic therapy. Here, a series of sulfur-substituted benzothioxanthene chromophores is synthesized and the sequential insertion of sulfur atoms is shown to result in strong and concomitant optimization of both light absorption and therapeutic activity.

Photoinduced isomerization reactions can be used to efficiently dissipate absorbed energy in photosystems such as molecular motors, but the ultrafast processes are challenging to characterize. Here, the authors track the formation of the E and Z isomers of ethyl sinapate in real time via transient vibrational absorption spectroscopy and find that photoinduced internal conversion occurs at multiple points along the potential energy surface.

Hexahydromethanocarbazole is a bridged polycyclic scaffold present in drugs and photoactive organic materials, however the efficient synthesis of this scaffold remains challenging. Here, the authors develop a multicomponent reaction cascade via phenylnorbornyl palladium species to generate hexahydromethanocarbazole-based libraries with CYP11B1 inhibition activity.

The SET-domain containing protein 2 (SETD2) is a protein lysine methyltransferase that has been shown to methylate the super-substrate peptide ssK36 100 times faster than the corresponding natural H3K36 peptide. Here, a combination of molecular dynamics simulations and biochemical experiments are applied to identify the mechanisms responsible for the increased activity of SETD2 towards ssK36.

NMR spectroscopy could be a robust and reliable method for binding detection in drug discovery, but DNA/RNA targets remain challenging to analyze. Here, the authors explore the perturbation of the ligand reactivity caused by complex formation as a binding indicator to identify best binders within mixtures of significant complexity, providing a conceptually different reactivity-based alternative within NMR screening methods.