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Cellular membranes contain numerous lipids, and efforts to understand the biological functions of individual lipids demand approaches for controlled modulation of membrane composition in situ. Now, click chemistry-based directed evolution of a microbial phospholipase within mammalian cells affords an editor for optogenetic, targeted modification of phospholipids in cell membranes.
In vitro screening of a ribosomally synthesized macrocyclic peptide library containing cyclic γ2,4-amino acids (cγAA) afforded the discovery of potent inhibitors of the SARS-CoV-2 main protease (Mpro). A co-crystal structure revealed the contribution of this cγAA to Mpro binding and the proteolytic stability of these macrocycles.
Electronic spin influences chemistry profoundly, but its role in surface chemistry is poorly established. Now the spin-dependent reaction probabilities of oxygen atoms with a graphite surface have been studied. Molecular dynamics simulations help elucidate the mechanism for spin-flipping, which is observed to occur with low probability in surface scattering experiments.
The diverse site-selective functionalization, including multi-functionalization, of C=C double bonds and C(sp3)–H bonds remains a largely unmet challenge. Now, a palladium-catalysed aerobic oxidative method has been developed for the multi-site programmable functionalization of terminal olefins via a strategy that controls the reaction sequence between alkene isomerization and oxidative functionalization.
In situ chirality identification for single-molecule systems is not a straightforward task. Now, real-time chirality identification during a Michael addition reaction has been realized by continuous measurements of spin-polarized currents through a single-molecule junction, providing a promising method for studying symmetry-breaking reactions.
Catenanes are topologically non-trivial and, perhaps for this reason, molecules composed of two oriented rings have always simply been referred to as ‘topologically chiral’. Now it has been shown that the same stereogenic unit can arise in systems whose stereochemistry is Euclidean, suggesting a need to rethink this fundamental form of mechanical chirality.
The metallophilic interaction between cyclometalated palladium complexes can facilitate supramolecular nanostructure formation in living mice, providing a phototoxic prodrug with a long circulation time and high tumour-targeting efficiency. Upon green light irradiation, this palladium-based drug destroys solid tumours, leaving non-irradiated organs intact.
Catalytic enantioselective approaches to access chiral organophosphorus compounds are rare. A two-stage catalytic strategy for the synthesis of diverse enantioenriched P(V) compounds has now been developed: a bifunctional iminophosphorane superbase enables enantioselective nucleophilic desymmetrization, followed by downstream enantiospecific diversification of the resulting intermediate by substitution with medicinally relevant O-, N- and S-based nucleophiles.
The inability to access well-defined polysaccharides in sufficient quantities has hampered our understanding of their structure–function relationships. Now it has been shown that native precision polysaccharides can be readily prepared via living polymerization of 1,6-anhydrosugars. The obtained polymers display excellent chemical recyclability, suggesting their potential utility as a class of sustainable materials.
Precise analysis of DNA–protein interactions can help to better understand various biological processes. Now, the ‘light-induced lysine (K) enabled crosslinking’ strategy (shortened to ‘LIKE-XL’) has been developed for spatiotemporal and global profiling of DNA–protein interactions, affording the discovery of low-affinity interactions between transcription factors and DNA using sequence-specific DNA baits.
Functionalization of unsymmetrical internal alkenes usually takes place with low regioselectivity, giving a mixture of isomers. Now, a highly regio- and enantioselective remote 1,n-dioxygenation of internal alkenes using a palladium catalyst has been developed for the synthesis of chiral 1,n-diols. Regioselectivity tuning was demonstrated by altering the rate-determining step, enabled by the phenyl-substituted Pyox ligand.
Continuous-rotation 3D electron diffraction is a powerful technique to determine structures from nanocrystals. A data treatment method that takes into account dynamical diffraction effects has now been shown to lead to more accurate structure models, better sensitivity to weak signals and a reliable determination of absolute configuration—even for materials containing only light atoms.
The synthesis of two-dimensional nanostructures with controlled dimensions from polymeric precursors remains challenging. Now, two-dimensional nanoparticles with chemically different spatially defined cores have been fabricated through seeded growth and are shown to undergo a programmable degradation process.
Techniques to specifically modulate protein activity are needed to interrogate spatial effects in cellular processes. A genetically encoded method for site-specific protein–protein conjugation based on a photoclick chemical reaction has now been developed. This method permits rapid and irreversible reassembly of bioactive proteins from non-functional split fragment pairs with full spatiotemporal control in solution, biomaterials and living mammalian cells.
Methods for the direct construction of 1,3-disubstituted planar chiral ferrocenes are elusive. Now, a modular platform enables the construction of planar chirality in 1,3-disubstituted ferrocenes/ruthenocenes via enantioselective relay remote C–H arylation. The strategy involves an initial enantiodetermining ortho-C‒H activation enabled by a Pd(II)/chiral amino-acid ligand, followed by relay to the remote meta-position by a bridgehead-substituted norbornene mediator.
Large biomolecules cannot be loaded into conventional Janus nanoparticles with small mesopores, preventing the establishment of efficient logic-gate systems in single Janus nanoparticles. Now, an emulsion-oriented assembly approach has been shown to fabricate Janus double-spherical nanoparticles with dual-tunable mesopores, enabling the design of various single-particle-level logic systems.
β-Amino acids are broadly found in biomimetic drugs and therapeutics, but the general synthesis of chiral β-amino amides remains limited. An organocatalytic four-component reaction has now been developed for their asymmetric synthesis with notable efficiency, chemoselectivity and stereoselectivity. This protocol shows broad product scope and provides a shortcut to other important structures.
Covalent organic frameworks (COFs) have remained difficult to grow as single crystals. Now, amphiphilic amino-acid derivatives that assemble in micelles in aqueous solutions have been shown to promote the growth of a variety of imine-bridged COFs into single crystals, in a step-by-step fashion, within their hydrophobic compartment.
Indole-5,6-quinone (IQ) is a long-sought intermediate and structural subunit of eumelanin pigments whose instability has precluded isolation and characterization. It has now been shown that a sterically shielded derivative of IQ exhibits hallmark eumelanin properties, including near-infrared absorption, ultrafast nonradiative decay and a persistent semiquinone radical formed by comproportionation.
Polyhydroxyalkanoates are potential substitutes for non-degradable polyolefin plastics. Now, it has been shown that structurally related methylated polyhydroxybutyrates, synthesized from carbon monoxide and 2-butenes, can provide a full suite of polyolefin-like polymers. These materials can be recycled or upcycled, and their properties can be easily tuned by varying the cis/trans ratio of the starting materials.