Research articles

Marmycin A is an anthraquinone natural product with antiproliferative properties. Now the chemical synthesis of marmycin A—through a Diels–Alder cycloaddition, an Ullmann aromatic amination and a Friedel–Crafts cyclization—has enabled a study of its biological activity. Fluorescence microscopy reveals that marmycin A accumulates in lysosomes and promotes cell death independently of genome targeting.

A method for high-throughput analysis of whole-cell biocatalysts for industrial biotechnology has been developed. The process relies on a combination of specifically tailored bacterial sensor cells that are incubated with biocatalyst variants within nanolitre-sized compartments. The product is secreted by the whole-cell biocatalysts and taken up by the sensor cells, which initiates a sequence of reactions that finish with the synthesis of green fluorescent protein.

Based initially on the outcome of certain reactions but later backed up by spectroscopic evidence, chemists have proposed — for more than a century — the existence of arynes as extremely reactive intermediates in chemical transformations. Now, with the help of atomic force microscopy, it is finally possible to generate and directly visualize this elusive intermediate.

Rigid star-shaped azobenzene tetramers form a porous molecular crystal when the azobenzene moieties are in the trans configuration, and a non-porous amorphous material on their isomerization to the cis configuration. These two forms are reversibly interconverted in the solid state by light irradiation, thus enabling the photoswitching of optical and gas-capture properties.

Often reactions can be described by classical mechanics; however, this is prohibited in cases in which quantum phenomena emerge. Now angular distributions measured for the H + D₂ reaction have been seen to display characteristic oscillation patterns in backward scattering — theory shows that they are caused by quantum interferences between classical mechanisms similar to those found in the double-slit experiment.

The reactivity of a monooxygenase (P450 PikC) has been modified through protein and substrate engineering, and applied to the oxidation of unactivated methylene C–H bonds. The protein engineering was guided by using molecular dynamics and quantum mechanical calculations to develop a predictive model for substrate scope, site selectivity and stereoselectivity of the C–H hydroxylation.

Regulation of bioorthogonal catalysis in living systems is challenging because of the complex intracellular environment. Now, the activity of protein-sized bioorthogonal nanozymes has been regulated by binding a supramolecular cucurbit[7]uril ‘gate-keeper’ onto the monolayer surface. This arrangement enables the controlled activation of profluorophores and prodrugs inside living cells for imaging and therapeutic applications.

Biorenewable carbohydrate feedstocks can be efficiently converted into a diverse set of oxygen-functionalized chiral synthons using a combination of a tertiary silane and the catalyst B(C₆F₅)₃. The deoxygenation mechanism involves cyclic intermediates, which provide a means of controlling chemo- and diastereoselectivity.

The total chemical synthesis of large proteins requires the development of methodology that rapidly couples unprotected peptide fragments. Here a highly strained four-membered-ring amino acid is described that enables such couplings by the formation of serine residues.

The facile, spontaneous dimerization of a simple alkenylbutenolide monomer is relevant to the biosynthesis of racemic paracaseolide A. As supported by computation, a fully (C₂-)symmetric, bis-pericyclic Diels–Alder cycloaddition transition state structure is invoked to account for the atypical exo-selectivity and room-temperature reactivity.

A chemical synthesis of (–)-jiadifenolide, a small molecule neurotrophin, has been achieved in eight steps. The route relies on a stereoselective coupling of two simple butenolides to build the entire skeleton in a single step and produce one gram of the target for broad distribution to the biomedical community.

Surface-enhanced resonant Raman optical activity (SERROA) reveals the through-space transfer of chirality from biomolecules to achiral benzotriazole dye-conjugated nanotags. The chiroptical responses generated by the stereoisomers of ribose and tryptophan establish this as the basis for a stereoselective nanosensor platform.

The nature of actinide–ligand bonding is attracting attention, in particular in the context of nuclear waste separations. Structurally authenticated one-, two- and threefold uranium–arsenic bonding interactions are now reported. Computational analysis suggests the presence of polarized σ², σ²π², and σ²π⁴ in the arsenide, terminal arsinidene, and arsenido complexes, respectively.

Roaming — a new and unusual reaction mechanism in gas-phase chemical transformations — is now shown to occur in solution. Following ultraviolet excitation of geminal tribromides, what initially seems to be the simple fission of a bond is in fact isomerization occurring through the roaming of molecular fragments.

The analysis of circulating cell-free nucleic acids (cfNA) in the blood of cancer patients permits the analysis of tumour mutations without requiring invasive sampling of tissue. Now, the development of an electrochemical assay that uses a collection of clamp molecules to sequester interfering cfNAs enables the accurate detection of mutated sequences in serum collected from people with lung cancer or melanoma.

The use of kinetic simulations to guide the design of competitive hybridization probe systems is shown to enable high selectivity for single-nucleotide variants. Using this approach across 44 cancer mutation/wild-type sequence pairs showed between a 200- and 3,000-fold higher binding affinity than the corresponding wild-type sequence. In combination with PCR amplification this method enabled the detection of a 1% concentration of variant alleles in human genomic DNA.

Better understanding of the chemistry of rechargeable metal–oxygen batteries is needed to fulfil their potential. It is now shown that proton phase-transfer catalysts drive Na–O₂ batteries, transporting superoxide between the electrode surface and the electrolyte as HO₂. The chemistry uncovered gives rise to the system's high reversible capacity.

The rapid and selective regulation of a target protein within living cells containing closely related family members is a longstanding challenge. Now the introduction of genetically directed bioorthogonal ligand tethering (BOLT) and the demonstration of selective inhibition (iBOLT) and optical switching (photo-BOLT) of protein function in live mammalian cells addresses this challenge.

Two semi-synthetic processes for the production of the antimalarial natural product artemisinin have been developed by applying the principles of green chemistry. Solvent manipulation allows catalyst recycling and reduction of waste, ultimately leading to a purification-free process with lower environmental and economic costs; a potential contribution to the world-wide fight against malaria.

Equilibrium adsorption of non-racemic mixtures of enantiomers onto an achiral surface is shown to lead to enantioenrichment by formation of homochiral clusters. Such auto-amplification must influence enantioselective processes such as heterogeneous catalysis, adsorption-based separations, and perhaps the processes that lead to the homochirality of life on Earth.