Research articles

The design of photoactivatable fluorophores—which are required for some super-resolution fluorescence microscopy methods—usually relies on light-sensitive protecting groups imparting lipophilicity and generating reactive by-products. Now, it has been shown that by exploiting a unique intramolecular photocyclization, bright and highly photostable fluorophores can be rapidly generated in situ from appropriately substituted 1-alkenyl-3,6-diaminoxanthone precursors.

Methods to access bicyclo[1.1.1]pentane building blocks are limited, with current routes requiring multiple steps. Now, a diverse array of bicyclo[1.1.1]pentane boronates can be accessed via a multi-component reaction in a single step. Alkyl, aryl and alkenyl substructures can be installed onto bicyclo[1.1.1]pentane boronates by the use of carboxylic acids and organohalides.

A genetically encoded phototrigger based on a xanthone amino acid can expand the scope of time-resolved serial femtosecond crystallography beyond naturally photoactive proteins. This approach has been used to uncover metastable reaction intermediates that occur prior to C–H bond activation in a human liver fatty-acid-binding protein mutant.

Metal-free amyloid-β (Aβ) and metal-bound Aβ (metal–Aβ) are found in the brain of patients with Alzheimer’s disease. Now, it has been shown that the conformation of a native neuropeptide, somatostatin, is changed in the presence of copper ions, Aβ and metal–Aβ. The conformational change results in a loss of function of somatostatin as a neurotransmitter and a gain of function as a modulator against metal–Aβ.

Designing long and highly conducting molecular wires has been a great challenge for decades. It has now been shown that a singly oxidized 2.6-nm-long oligophenylene-bridged bis(triarylamine) can show a single-molecule junction conductance over 0.1G₀.

The composition of toxic protein aggregates associated with neurodegenerative diseases is difficult to determine. Now, a method has been developed that can capture amyloid-containing aggregates in human biofluids using a structure-specific chemical dimer. This method—known as amyloid precipitation—enables unbiased determination of the molecular composition and structural features of the in vivo aggregates.

Proton wires in enzyme active sites enable stereoselective reactions under mild conditions by facilitating dual activation of a nucleophile and an electrophile through reciprocal proton transfer. Now it has been shown that such an activation mode can be mimicked inside a supramolecular capsule, enabling a general approach to β-glycosides.

Developing stimuli-responsive bioorthogonal tetrazine ligations remains highly challenging, but a versatile approach that uses photocaged dihydrotetrazines has now been developed. Photouncaging results in the spontaneous formation of reactive tetrazines that rapidly react with dienophiles such as trans-cyclooctenes. As a demonstration, the method was used for live-cell labelling with single-cell precision and light-triggered drug delivery.

Nucleotides are essential to the origins of life, and their synthesis is a key challenge for prebiotic chemistry. Contrary to prior expectation, non-canonical 3′-amino-TNA nucleosides are shown to be synthesized diastereoselectively and regiospecifically under prebiotically plausible conditions. The enhanced reactivity of 3′-amino-TNAs also promotes their selective non-enzymatic triphosphorylation in water.

The biochemical roles and mechanisms of multiphase membraneless organelles are not yet well understood. Now, multiphase peptide droplets have been shown to sort RNA based on whether it is single- or double-stranded, as well as impact RNA duplexation through in-droplet thermodynamic equilibria. This work provides insight into possible primitive mechanisms for multicompartment intracellular condensates and can aid in the design of functional artificial membraneless organelles.

Ions in salt solutions perturb the hydrogen bonding between the surrounding water molecules, altering the properties of water, but how ion polarity affects this is not fully understood. By monitoring the dissipation of terahertz energy in salt solutions, it has now been shown that intermolecular rotational-to-translational energy transfer is enhanced by highly charged cations and reduced by highly charged anions.

Despite mechanically axially chiral (MAC) catenanes being recognized in 1961, their stereoselective synthesis had not been disclosed until now. Closer inspection of the MAC stereogenic unit has also led to the identification of an analogous, but unremarked upon, form of rotaxane stereochemistry and the conceptualization of a general approach to prepare MAC molecules stereoselectively.

The strained topology of [n]paracyclophenylenes ([n]CPPs) typically prevents their π sysytem from being extended, but now the formation of a planar π-extended CPP has been achieved through a bottom-up on-surface synthesis approach. The planar π-extended [12]CPP produced by this method is a nanographene featuring an all-armchair edge, which leads to delocalized electronic states around the entire ring.

The direct copolymerization of carbon dioxide and commodity olefins has been a long-standing challenge in polymer science. Now, an indirect approach has been developed in which hydrogenated disubstituted valerolactones derived from telomerization of CO₂ and butadiene can undergo ring-opening polymerization, yielding chemically recyclable and degradable aliphatic polyesters with high CO₂ content.

A strategy for protecting redox-active ortho-quinones, which show promise as anticancer agents but suffer from redox-cycling behaviour and systemic toxicity, has been developed. The ortho-quinones are derivatized to redox-inactive para-aminobenzyl ketols. Upon amine deprotection, an acid-promoted, self-immolative C–C bond-cleaving 1,6-elimination releases the redox-active hydroquinone. The strategy also enables conjugation to a carrier for targeted delivery of ortho-quinone species.

Functionalizing an intact carbohydrate core with acetals allows for the dramatically simplified production of a plastic precursor directly during the initial fractionation of non-edible biomass. When polymerized, the rigid and polar carbohydrate core also leads to bioplastics with competitive material and end-of life properties.

Analogues of mRNA 5′ caps containing a photo-cleavable group have now been developed. These so-called FlashCaps can be used for routine in vitro transcription to make long mRNAs containing a cap. In cells, the capped mRNAs are translationally muted; however, upon irradiation by light, the photo-cleavable group is removed without leaving any remaining modification and mRNA is then translated into the corresponding protein.

Cytoskeletons are essential components of cells that perform a variety of tasks, and artificial cytoskeletons that perform these functions are required for the bottom-up assembly of synthetic cells. Now, a multi-functional cytoskeleton mimic has been engineered from DNA, consisting of confined DNA filaments that are capable of reversible self-assembly and transport of gold nanoparticles and vesicular cargo.