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Disulfide bonds formed between two cysteine residues are important in the folding and stability of proteins. Now, unnatural amino acids with side-chains that contain two thiol groups are described. Incorporation of these dithiol amino acids into a serine protease inhibitor and a nicotinic acetyl choline receptor antagonist is shown to increase their inhibitory activity.
The relationship between electron-transfer properties and the structure of molecular electronics is still not fully understood. Now, a rigid and flat molecular wire has been shown to significantly enhance the rate of electron transfer compared with conventional flexible molecular wires. This enhancement is attributable to both conjugation-induced electronic coupling and inelastic electron tunnelling-enabled electron–vibration coupling.
A discovery approach termed activity-directed synthesis is described; it exploits arrays of reactions whose outcome is critically dependent on the conditions used, and prioritizes reactions that yield bioactive product mixtures. The discovery of both bioactive small molecules and associated synthetic routes thus occurs in parallel.
The oxygen reduction reaction limits fuel cell performance and currently requires costly electrocatalysts with high platinum content to achieve adequate power densities. Now a silver–cobalt surface alloy electrocatalyst has been developed for the oxygen reduction reaction that is stable in alkaline electrolytes and is more economical than traditional platinum-based materials.
Anion transporters that disrupt cellular ion homeostasis could represent a new approach for generating therapeutic lead compounds. Now, two pyridine diamide-strapped calix[4]pyrroles have been shown to induce coupled chloride anion and sodium cation transport in liposomal models and cells. These compounds promote cell death by increasing intracellular chloride and sodium ion concentrations.
Macromolecular functionalization and linking are often facilitated by using ‘click’ chemistries. Now, triazolinediones have been used in ultrafast click reactions under additive-free, ambient conditions for polymer conjugation. Clicking to indoles gives an adduct that is dynamic at elevated temperatures, which produces properties such as polymer-network healing, reshaping and recycling.
Hydrogenases are efficient and promising catalysts for fuel cells; however, they suffer from oxygen sensitivity and deactivation at high potentials. Integration of hydrogenases into redox-active hydrogels provides a redox buffer and a self-activated oxygen-scavenging mechanism. This tandem protection makes the hydrogenase a possible alternative to noble metal catalysts.
Water-soluble metallohelices containing an antiparallel head-to-head-to-tail arrangement of strands are reported. This amphipathic functional topology is akin to that of host-defence peptides. The metallohelices show high and selective toxicity to a cancer cell line, causing dramatic changes in the cell cycle without DNA damage. In contrast, there is no significant toxicity to MRSA and Escherichia coli.
Accessing synthetic two-dimensional polymers that are analogous to graphene is synthetically and analytically challenging. Now, single crystals of a simple-to-make monomer have been grown and then photopolymerized to form layered single crystals of covalently bonded two-dimensional polymer. Much like natural graphite, these crystals can be exfoliated to form thin sheets and single layers of the polymer.
Coupling of carbamates with boronic esters followed by protodeboronation creates a new carbon–carbon bond, leaving behind no trace of the functional groups used to create it. Now, methodology for the protodeboronation of alkyl pinacol boronic esters has been developed and an iterative lithiation–borylation–protodeboronation strategy used in a 14-step stereocontrolled synthesis of hydroxyphthioceranic acid.
Two-dimensional synthetic polymers can be produced through solid-state topochemical polymerization, but achieving this through a single-crystal-to-single-crystal transformation has not yet been demonstrated. Now, a fluorinated Y-shaped monomer has been preorganized in a lamellar crystal, which goes through two successive single-crystal-to-single-crystal phototransformations to give a 2D polymer; single-crystal X-ray diffraction has been used to elucidate its structure.
Multi-electron redox chemistry is important in transition-metal-mediated processes, but is rarely observed with uranium due to its propensity to undergo single-electron reactions. Now, uranium can use its electrons, coupled with those stored in redox-active ligands, to perform multi electron reduction of organoazides and form uranium tris(imido) derivatives.
Several solutions to the ‘missing xenon’ problem have been proposed that involve the selective sorption of Xe in minerals found in the Earth. It is now shown that a zeolite, Ag-natrolite, absorbs and retains 28 wt% Xe at 1.7 GPa and 250 °C, conditions found in subsurface Earth, through expulsion of metallic Ag(0).
Directed evolution has emerged as a powerful tool for the identification of improved enzyme catalysts. Now, gel-shell beads are introduced as compartments that cage an enzyme with its encoding DNA, constituting a new genotype–phenotype linkage. Screening of 107 gel-shell beads by flow cytometry leads to an improved phosphotriesterase bioremediation catalyst.
Conjugation of DNA to proteins often involves a choice between either expressing recombinant proteins with a specific handle, or labelling wild-type proteins with low site-selectivity. Now preorganization of a DNA–ligand complex to a metal-binding site enables site-selective conjugation of a DNA strand to lysine residues of wild-type proteins and antibodies.
A self-blinking fluorophore suitable for super-resolution imaging has been developed. The blinking arises from a reversible intramolecular spirocyclization in a rhodamine-based fluorophore that switches between a fluorescent open form and a non-fluorescent closed form. The advantages over existing methodologies are demonstrated using single-molecule localization microscopy imaging inside cells.
Amiloride is a widely used diuretic that blocks epithelial sodium channels (ENaCs); however, the functional role of the different ENaC isoforms is still poorly understood and no pharmacological tools exist to differentiate between them. Now, photoswitchable amilorides that enable the optical control of ENaCs, and can distinguish between different ENaC isoforms have been developed.
Shaping potential energy surfaces by tailored strong laser pulses has now been shown to be a powerful method for controlling product yields in an ultrafast polyatomic photodissociation reaction. Control over the velocity of the product fragments is also achieved through the generation of light-induced conical intersections and modulating the potentials around them.
The widespread use of fuel cells requires improved catalysts to reduce oxygen efficiently at the cathode. It is shown that model, well-characterized size-selected PtxY nanoparticles can be synthesized by the gas aggregation technique, and that they are highly active for this reaction.
