Research articles

Creating hierarchical synthetic materials that can modulate microbial communities remains a great challenge due to the complex interactions between microbiota and their colonized environments. Now, a soil-inspired chemical system that responds to chemical, optical and mechanical stimuli has been developed. The soil-inspired chemical system can enhance microbial cultures and biofuel production, enrich gut bacterial diversity and alleviate ulcerative colitis symptoms.

The rapid assembly of complex scaffolds in a single step from simple precursors would be an ideal reaction in terms of efficiency and sustainability. Now, the single-step construction of alkaloid-like frameworks from three dynamically assembled precursors has been reported. Using a dual-catalytic system, the transformation involves a hydride shuttle process initiated by a hydride donation event.

Meso–meso linked porphyrin arrays have been described as rod-like photonic wires. Now it has been shown that they can be bent into rings using template-directed synthesis. These rings of porphyrins mimic the light-harvesting arrays of chlorophyll molecules responsible for photosynthesis.

Sterically demanding 2′-modified nucleotides used in antisense therapeutics have thus far been challenging to synthesise enzymatically. Now, it has been shown that mutation of two gatekeeper residues in an archaeal DNA polymerase unlocks efficient synthesis of the modified nucleic acid oligomers 2′-O-methyl-RNA and 2′-O-(2-methoxyethyl)-RNA and enables the evolution of 2′-O-methyl-RNA enzymes.

Protein–carbohydrate interactions remain challenging to study due to their low binding affinity and non-covalent nature. Now, a genetically encoded bioreactive unnatural amino acid containing sulfonyl fluoride has been shown to crosslink a protein with its bound glycan, offering a solution to probe and exploit protein–carbohydrate interactions.

Technologies for profiling biological environments with high spatiotemporal resolution are in demand to enable the discovery of new targets for addressing unmet clinical needs. Now, a deep red light-mediated photocatalytic strategy for the targeted activation of aryl azides has been developed. This platform enables mapping of protein microenvironments in physiologically relevant systems.

Automated systems, nowadays more commonly used in laboratory settings, are typically fixed to a narrow set of reactions and used within a complex laboratory environment. Now, a portable platform has been developed for the on-demand and on-site multistep synthesis of organic molecules, oligonucleotides and oligopeptides mapped into reactionware systems.

Protein–RNA interactions regulate RNA fate and function, and are generally non-covalent and reversible. Genetically introducing a latent bioreactive amino acid into a protein is now shown to enable the protein to covalently crosslink a bound RNA molecule in vivo. This method offers innovative avenues for developing protein–RNA research and applications.

Tigilanol tiglate is a therapeutic lead for the treatment of a broad range of cancers. Now, it has been shown that tigilanol tiglate can be synthesized in a time and step economical fashion from phorbol—its naturally abundant biosynthetic precursor. This synthesis provides rapid access to analogues with unprecedented protein kinase C binding activity.

Intersystem crossing in reaction entrance channels usually arises from ‘heavy-atom’ effects. Now molecular-beam experiments show that even without heavy atoms, the O(³P) + pyridine reaction leads to spin-forbidden pyrrole + CO products. Theoretical calculations reveal efficient intersystem crossing before the entrance barrier for O-atom addition to the N-atom lone pair, which dominates reactivity at low to moderate temperatures.

General synthetic methods to access pleuromutilin antibiotics are limited due to their complex carbocyclic skeleton. Now, a synthetic platform has been developed to access structurally diverse pleuromutilins with variations at the quaternary C12 position and hydrindanone cores. Seventeen structurally distinct derivatives were prepared and evaluated against a panel of Gram-positive and -negative bacteria.

Alkyl and aryl polycyanurate networks have now been prepared through polymerization of diols and substituted triazines via a dynamic S_NAr reaction. When treated with excess mono alcohol or phenol, the polycyanurate networks can be depolymerized into the starting monomers, which can be separated and reused, thus achieving closed-loop recycling.

On-surface synthesis enables highly reactive structures to be produced under vacuum, but they need to be passivated to be incorporated into practical devices. Here, the facile protection of air-sensitive chiral graphene nanoribbons has been shown, by either hydrogenation or synthesis of an oxidized form. The chemically stable forms can subsequently be deprotected.

Proteins rich in phenylalanine-glycine (FG) repeats can phase separate through FG–FG interactions. The molecular interactions of an important FG-repeat protein, nucleoporin 98, have now been studied in liquid-like transient and amyloid-like cohesive states. These interactions underlie the behaviour of FG-repeat proteins and their function in physiological and pathological cell activities.

A method has been developed to identify RNA transcript isoforms at the single-molecule level using solid-state nanopore microscopy. In this method, target RNA is refolded into RNA identifiers with designed sets of complementary DNA strands. Each reshaped molecule carries a unique sequence of structural (pseudo)colours that enables identification and quantification using solid-state nanopore microscopy.

The principal mid-visible light-harvesting system in cyanobacteria is the phycobilisome. Now, using broadband multidimensional spectroscopy, delocalized vibronic excitations and sub-picosecond excitation transfer pathways have been observed in the rods of intact phycobilisomes. An observed kinetic bottleneck in the phycobilisome’s core arises from the intramolecular charge-transfer character of the bilin chromophores, enabling photoregulatory processes to operate on the >10-ps timescale.

The total synthesis and complete stereochemical assignment of the cyclic peptide natural product SR-A3—which has potential as a cancer therapeutic—has now been reported. Single-molecule biophysical and cellular experiments reveal a crucial, stereospecific role for a side-chain hydroxyl in SR-A3, which confers enhanced target residence time and efficacy in a mouse tumour model.

Noyori-type hydrogenation catalysts consist of an N–H moiety coordinated to a metal centre. Now, a metal-hydride amidate complex (HMn–NLi) has been isolated and found to have superior reactivity and catalytic performance compared with the corresponding HMn–NH complex, highlighting the superiority of M/NM′ bifunctional catalysis over the classic M/NH bifunctional catalysis for hydrogenation reactions.

The reduction of nitrite (NO₂⁻) to nitric oxide (NO), relevant to the biogeochemical nitrogen cycle as well as radioactive waste, typically occurs at redox-active metal centres. Now, a Lewis acid-capped nitrite has been reduced to the nitrite dianion (NO₂²⁻), a nitrogen-centred radical that connects three redox levels in the global nitrogen cycle through NO₂⁻, NO and N₂O.

In silico chemical prediction of a polyketide synthase gene cluster in the bacterium Gynuella sunshinyii has led to the discovery of a class of natural products called janustatins. The absolute configuration of the stereocentres in these compounds was determined by a combination of techniques including DFT calculations and 2D NMR experiments—and finally confirmed by total synthesis. Janustatins were found to cause delayed, synchronized cell death at subnanomolar concentrations.