Articles in 2022

Cyclic polymers are topologically interesting and envisioned as a lubricant material, but methods for the scalable synthesis of pure cyclic polymers are currently elusive. Now, a scalable process has been developed by leveraging heterogeneity of the catalysts with the help of compartmentalized custom glassware, namely, a cyclic polymer dispenser.

Oligonucleotide catalysts such as ribozymes and DNAzymes can cleave RNA efficiently and specifically but are typically dependent on high concentrations of divalent cations, limiting their biological applications. A modular XNAzyme catalyst composed of 2′-deoxy-2′-fluoro-β-d-arabino nucleic acid (FANA) has now been developed that can cleave long (>5 kb), highly structured mRNAs under physiological conditions and enables allele-specific catalytic RNA knockdown inside cells.

The study of rare isotopes is hampered by their scarcity, cost and sometimes toxicity. Now polyoxometalate ligands have been shown to facilitate the capture of f-block elements and their characterization. Single-crystal X-ray diffraction structures have been obtained for several molecular complexes, including three of the rare curium-248, from minute amounts (micrograms) of material.

Given the importance of amine compounds, methods for their synthesis continue to be in high demand. Now, a palladium-catalysed strategy has been developed for the selective oxidative amination of unactivated olefins with Lewis basic amines, via C(sp³)–H activation, forming architecturally versatile and functionally diverse allylamines in a single step.

In some cases, hydrogen adsorption close to its boiling temperature shows unusually high monolayer capacities, but the microscopic nature of this adsorbate phase is not well understood. Now, H₂ adsorbed on a well-ordered mesoporous silica surface has been shown to form a 2D monolayer with very short H₂···H₂ intermolecular distances and a density more than twice that of bulk-solid H_2.

The biosynthesis of fuscimiditide, a ribosomally synthesized post-translationally modified peptide, has now been reported. Heterologous expression and analysis of fuscimiditide showed it contained two side-chain–side-chain ester linkages and an aspartimide in its backbone. The aspartimide moiety is unexpectedly stable, suggesting this structure is the intended natural product.

Butafulvene is a constitutional isomer of benzene, comprising a cyclobutene skeleton bearing two exocyclic conjugated methylene units. Strategies for the synthesis of butafulvene compounds are currently limited due to its intrinsic high strain energy and anti-aromaticity. Now, palladium-catalysed couplings have been developed for the rapid assembly of symmetric and non-symmetric anti-aromatic butafulvene derivatives.

The β₁-adrenergic receptor (β₁AR) contains empty cavities in its preactive conformation, which disappear in the active one. Now, using X-ray crystallography of xenon-derivatized β₁AR crystals, a cavity has been shown to be in contact with the cholesterol-binding pocket. Monitoring the binding of a cholesterol analogue in solution has explained the function of cholesterol as a negative allosteric modulator of β₁AR.

The influence that liquid environments have on the ultrafast excited-state dynamics of molecules is poorly understood. Using time-resolved photoelectron spectroscopy, the dynamics of the photoisomerization of stilbene in the gas and liquid phases have now been shown to be qualitatively similar—including the observation of vibrational coherences—but the timescales are significantly longer in the liquid phase.

Synthetic chemical networks with far-from-equilibrium dynamics akin to genetic regulatory networks in living cells could precisely regulate the kinetics of chemical synthesis or self-assembly. Now standardized excitable chemical regulatory elements, termed genelets, that enable predictive bottom-up construction of in vitro networks with designed temporal and multistable behaviour have been developed.

Most proteins must fold co-translationally on the ribosome to adopt biologically active conformations, yet structural, mechanistic descriptions are lacking. Using ¹⁹F NMR spectroscopy to study a nascent multi-domain protein has now enabled the identification of two co-translational folding intermediates that are significantly more stable than intermediates formed off the ribosome, suggesting that the ribosome may thermodynamically regulate folding.

Although neutral and anionic low-valent aluminium complexes are widespread, their cationic counterparts have remained rare. Now, a salt of [Al(AlCp*)₃]⁺ featuring a formal low-valent Al⁺ cation has been isolated that dimerizes in concentrated solutions and the solid state, and also forms Al₄ clusters on coordinating with Lewis bases.

The majority of methods to prepare β-amino acid derivatives require metal-mediated multistep manipulations of pre-functionalized substrates. Now, a metal-free, energy-transfer enabled, highly regioselective aminocarboxylation reaction has been developed, for the single-step installation of both amine and ester functionalities into alkenes or (hetero)arenes. An oxime oxalate ester is used as a bifunctional reagent, supplying C-centred ester and N-centred iminyl radicals.

Intermolecular Coulombic decay (ICD) is a process whereby a photoexcited molecule relaxes while ionizing a neighbouring molecule. ICD is efficient when intermolecular interactions are active and consequently it is usually observed in weakly bound systems. Now, an efficient ICD is shown to occur even between unbound pyridine molecules excited at ambient-light intensities.

Burkholderia pseudomallei is a species of bacteria that poses a global health threat and, more generally, bacteria of the Burkholderia pseudomallei group cause severe diseases that are recalcitrant to treatment with antibiotics. Now, it has been shown how these infamous pathogens repurpose the widespread enzyme BurG to produce a reactive cyclopropanol head group found in the virulence-promoting malleicyprol toxins. Interrupting the synthesis of the cyclopropanol warhead is a potential route for developing antivirulence treatments.

The apparent disconnect between prebiotic aldehyde-based Strecker synthesis of amino acids and the α-ketoacid-based metabolism of extant biochemistry necessitates an evolutionary switch between these disparate chemistries. Now it has been shown that Bucherer–Bergs reactions of α-ketoacids produce α-amino acids and dihydroorotate, paralleling the biochemical synthesis of orotate and suggesting a more congruent evolutionary pathway from cyanide-based chemistries.

Supramolecular interactions play an essential role in organic electronic materials and biological systems. Now, it has been demonstrated that the σ–σ stacking interactions between neighbouring non-conjugated molecules can offer an efficient pathway for charge transport through supramolecular junctions, which provides a new guideline for the design and fabrication of organic materials and devices.

Intermolecular cyclization reactions using nitrogen-containing building blocks are scarce. Now, bifunctional sulfilimines have been shown to enable the modular construction of a diverse range of N-heterocycles by reacting with alkenes in a single photocatalysed step. Both sulfilimines and alkenes are easily accessible, providing access to a wide range of N-heterocycles with different ring types, ring sizes and substituents on the skeleton.

The introduction of fluorine into a drug molecule can alter the biological responses to it, including modulating bioavailability, pharmacokinetics and selectivity. Now, a hybrid polyketide/fatty acid synthase multienzyme has been designed to incorporate fluorinated precursors during polyketide biosynthesis in an approach that provides new chemoenzymatic access to fluorinated natural compounds.

Laser cooling of molecules with more than six atoms is challenging, mainly due to vibrational loss to dark states. Now, taking a step towards the development of a ‘quantum functional group’, it has been shown that such vibrational loss in molecules like phenol can be greatly restricted by functionalizing with a Ca(I)–O unit, which may serve as a generic qubit moiety.