Articles in 2023

The synthesis of optically enriched atropisomers has so far been limited to molecules containing aryl groups. Now a variant of non-aryl atropisomerism has been identified in vinyl sulfoxonium ylides, and an organocatalytic method has been developed to produce these molecules. This type of axial chirality is characterized by restricted rotation of the central C(sp²)–C(sp²) bond.

Sequences of synthetic polymers are generally heterogeneous and dictate many of their physiochemical properties, but are challenging to determine. Now an imaging method, termed CREATS (coupled reaction approach toward super-resolution imaging), can count, localize and identify each monomer of single polymer chains during (co)polymerization.

Radium complexes are of interest for use as cancer therapeutic agents, but the structure and bonding are poorly understood. Here, the synthesis of a Ra²⁺ complex is reported, and the structure and bonding characteristics are elucidated using single-crystal X-ray diffraction.

The physicochemical driving forces of protein-free, RNA-driven phase transitions were previously unclear, but it is now shown that RNAs undergo entropically driven liquid–liquid phase separation upon heating in the presence of magnesium ions. In the condensed phase, RNAs can undergo an enthalpically favourable percolation transition that leads to arrested condensates.

Bottom-up assembly of protocells into networking superstructures represents a further key step towards rudimentary formation of life. Now it has been shown that a pool of biomolecules can self-organize into an interactive binary population of protocell coacervates with a self-sorting chain-like configuration, allowing for biomolecular extraction, translocation and macroscale separation.

The bicyclo[1.1.1]pentane (BCP) motif has drawn increasing attention recently in drug discovery. Now, a programmable bis-functionalization strategy has been developed to modularly access bridge-substituted BCP scaffolds, based on the inherent chemoselectivity of BCP bis-boronates (3° > 2°). This strategy should enable further structure–activity relationship studies of BCP-containing drug candidates and open the door to unexplored chemical space.

Although exciplex-forming systems are widely used for fabricating organic light-emitting diodes (OLEDs), their structural and thermodynamic characterization is limited. Now donor/acceptor inclusion complexes that demonstrate thermally activated delayed fluorescence have been generated. Their cocrystal structures have been resolved and the thermodynamics of exciplex formation determined, which has enabled the fabrication of efficient OLEDs.

Detecting genetic mutations, such as single nucleotide polymorphisms (SNPs), is essential for disease diagnostics but can be difficult using homomultivalent DNA hybridization-based approaches. Now, heteromultivalent hybridization is used to fine-tune binding specificity for the detection of one or two SNPs in a single target, enabling straightforward discrimination between adjacent and distant mutations and different viral strains.

Surface heterogeneity is generally acknowledged as the major cause of liquid–solid friction, affecting whether droplets slide off the surface or stick to it. Now, a model surface of self-assembled monolayers has been used to investigate how molecular-scale surface heterogeneity affects water contact angle hysteresis and contact line friction. The high-coverage hydrophobic surface is slippery, as—counter-intuitively—is the low-coverage hydrophilic surface.

Nucleoside diphosphates and triphosphates impact nearly every aspect of biochemistry. Now, a modular, reagent-based platform has been developed to enable the stereocontrolled and scalable synthesis of a library of such molecules. This operationally simple approach provides access to pure stereoisomers of nucleoside α-thiodiphosphates and α-thiotriphosphates.

Hypervalent iodine catalysis remains a powerful method to enable geminal difluoromethylenation of alkenes. However, the scope is mainly limited to styrene derivatives. Now, enynes have been validated as competent substrates where a formal 1,2-shift of the alkyne occurs, thereby enabling highly versatile homopropargylic difluorides to be generated.

Effective synthetic anion receptors are challenging to design. Now, star-shaped macrocycles, with a cavity defined by multiple convergent amide NH and phenyl CH groups, have been synthesized in one pot from their monomeric building blocks. These macrocycles strongly bind a variety of anions, selectively transport chloride across cell membranes and restore the function of cystic fibrosis cells.

Preparation of monocyclic 1,2-azaborines, a unique class of benzene isosteres, has been challenging. Now, an efficient and modular method has been developed to access diverse multi-substituted 1,2-azaborines from readily available cyclopropyl imines/ketones and dibromoboranes. The reaction goes through an unusual ring-opening BN-isostere benzannulation mechanism.

Tetrafluorenofulvalene (TFF) defies conventional rules of bond strength in organic chemistry. In particular, the central alkene bond of TFF becomes stronger in the quintet state and in the tetraanion. These changes arise from the unusual interplay between the twist, aromaticity and spin pairing in the π-electron system of TFF.

The reversible N–H activation and catalytic transformations of ammonia are a challenge. Now, a hidden frustrated Lewis pair is shown to activate non-aqueous ammonia thermoneutrally and split the N–H bond reversibly at ambient temperature. The N–H-activated ammonia was also utilized as an atom-economical nitrogen source for catalytic NH₃ transfer reactions.

Although amorphous calcium carbonate represents an important biomineralization precursor, its structure has been difficult to understand. Now, amorphous calcium carbonate’s structure is shown to arise from the different bridging modes available to the calcium ions. This effective multi-well potential that drives calcium arrangements creates a geometric incompatibility between preferred Ca–Ca distances and frustrates crystallization.

Understanding of the molecular mechanisms underlying the maturation of protein condensates into amyloid fibrils associated with neurodegenerative diseases has so far remained elusive. Now it has been shown that in condensates formed by the low-complexity domain of the amyotrophic lateral sclerosis-associated protein hnRNPA1, fibril formation is promoted at the interface, which provides a potential therapeutic target for counteracting aberrant protein aggregation.

While aromaticity is a useful concept for assessing the reactivity of organic compounds, the connection between aromaticity and on-surface chemistry remains largely unexplored. Now, scanning probe experiments on cyclization reactions of porphyrins on Au(111) show that the peripheral carbon atoms outside of the aromatic 18-π electron pathway exhibit a higher reactivity.

Covalent organic frameworks offer a highly tunable class of materials for a range of applications, although their dynamic structural transformations are challenging to analyse. Now single-crystal X-ray diffraction is shown to demonstrate single-crystal-to-single-crystal transformations of the imine linkages, showing a well-defined interpenetrating topology and affording structures that have high positive thermal expansion and anhydrous proton-conduction properties.

Shifts in temperature alter the structure and dynamics of macromolecules. Now, infra-red laser-induced temperature jump is combined with X-ray crystallography to observe protein structural dynamics in real time. Using this method, motions related to the catalytic cycle of lysozyme, a model enzyme, are visualized at atomic resolution and across broad timescales.