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Liquid droplets form in cells to concentrate specific biomolecules (while excluding others) in order to perform specific functions. The molecular mechanisms that determine whether different macromolecules undergo co-partitioning or exclusion has so far remained elusive. Now, two studies uncover key principles underlying this selectivity.
The synthesis of cationic all-metal aromatic systems without covalent functionalization remains an underexplored area in chemistry. Now a tetracationic [Bi4]4+ featuring all-metal σ-aromaticity has been stabilized through a supramolecular approach relying on dianionic calix[4]pyrrolato indiumbromide shells. This planar rhomboid represents the global minimum for 16 valence electron systems.
Multi-payload antibody–drug conjugates (ADCs) are an emerging class of targeted therapeutics. Comprising a monoclonal antibody with multiple unique payloads attached, these constructs have the potential to produce synergistic anticancer effects with reduced therapeutic resistance. In this Review, methods for generating multi-payload ADCs are discussed, highlighting some key preclinical results.
The chemistry of beryllium, one of the periodic table’s lightest elements, remains poorly understood. Now, a nucleophilic beryllium complex with a highly polarized Be–Be bond has been prepared—this compound could be seen as a mixed-oxidation state Be(0)/Be(II) complex. The Be–Be bond is cleaved upon reaction with an organic substrate.
Engineering new ligands that specifically target multiple G protein-coupled receptors with desired activity profiles requires time-consuming and expensive cycles of design-make-test-analyse work. Now it has been shown that limited experimental data can be used to train sophisticated machine learning models to accurately predict the activity of previously uncharacterized peptide ligand variants.
Understanding how membrane-bound styrene oxide isomerase (SOI) catalyses the Meinwald rearrangement—a Lewis-acid-catalysed isomerization of an epoxide to a carbonyl compound—can be useful as SOI represents a green alternative to chemical synthesis. Here, the catalytic mechanism of SOI was determined using cryo-EM, EPR spectroscopy, mutagenesis, functional assays and docking experiments.
Calcium difluoride is a source of fluorochemicals, but the reactivity of Ca–F moieties is not well understood. Now a library of molecular Ca–F complexes featuring unique structural motifs has been synthesized, including via fluorochemical defluorination. Studies of mono- and dinuclear systems provided structure–activity relationships for E–F bond formation.
Dimetallocenes are a narrow class of compounds represented by the homobimetallic examples dizincocene and diberyllocene. Now a heterobimetallic dimetallocene featuring lithium and aluminium centres has been synthesized. The Al–Li bond is shown to cleave upon reaction with N-heterocyclic carbenes and heteroallenes.
Chiral sulfur pharmacophores are crucial in drug discovery, but the controlled synthesis of sulfinamides with stereogenic-at-sulfur(IV) centres is a long-standing challenge. Now a method for the catalytic asymmetric synthesis of sulfinamides and sulfinate esters has been developed that features the acyl transfer sulfinylation of diverse nucleophiles, including aromatic amines and alcohols, using chiral 4-arylpyridine N-oxides as catalysts.
Fusicoccane diterpenoids are complex natural products with intricate tricyclic skeletons and intriguing biological activities. Now a chemoenzymatic strategy has been developed for modularly synthesizing a number of compounds from the family. This approach combines de novo skeletal construction and hybrid C–H oxidations, allowing the synthesis of ten different natural products.
The number of known high-oxidation-state transuranic compounds remains limited, and these typically feature high coordination numbers and/or multiply-bonded donor atoms. Now, a tetrahedral, pentavalent neptunium complex supported by four monoanionic ligands has been isolated and characterized. This complex is stable in the solid state and undergoes a proton-coupled electron transfer reaction in solution.
Evolution separates complex modern enzymes from their hypothetical simpler early ancestors, which raises the question of how unevolved sequences can develop new functions. Here a library of non-natural protein sequences was subjected to ultrahigh-throughput screens in microfluidic droplets, leading to the isolation of a phosphodiesterase enzyme capable of hydrolysing the biological second messenger, cyclic AMP.
Two-dimensional covalent organic frameworks (2D COFs) enable the construction of bespoke functional materials, but designing dynamic 2D COFs is challenging. Now it has been shown that perylene-diimide-based COFs can open and close their pores upon uptake or removal of guests, while fully retaining their crystalline long-range order. Moreover, the variable COF geometry enables stimuli-responsive optoelectronic properties.
A robust organometallic platform is developed for stoichiometric cross-couplings of common aryl and alkyl electrophiles under a single set of conditions. Inexpensive and persistent organonickel complexes are prepared by electrolysis and implemented in the diversification of drug-like molecules with high reliability from a diverse set of alkyl precursors.
X-ray diffraction analysis typically affords the static 3D structures of given compounds or materials, but to understand chemical processes, the visualization of fast structural changes is desirable. Time-resolved femtosecond crystallography has now been used to monitor the structural dynamics of a photoactive metal–organic framework.
The precision synthesis of cyclic polymers with ultrahigh molar mass (UHMM) and circularity is challenging. Now, a method that involves superbase-mediated living linear-chain growth followed by macromolecular cyclization triggered by protic quenching enables the on-demand production of UHMM cyclic polymers with a narrow dispersity and closed-loop chemical recyclability.
Excited by the prospect of future missions to the Jupiter system, Bruce Gibb explores the chemistry of Jupiter’s moons and wonders whether there could be life on Europa.
Overcrowded alkene-derived molecular motors convert light and heat into chirality-directed unidirectional rotary motion, but the efficiency of their photochemical isomerization remains limited. Now formylation of the motor core has been shown to boost all aspects of motor photochemistry by improving photochemical efficiency, diminishing competing processes and redshifting absorption.
The construction of analogues of natural gap junctions would provide a bottom–up strategy for building intercellular communication pathways for synthetic cells. Now artificial intercellular gap junctions have been prepared from unimolecular tubular channels by mimicking the hydrophobic–hydrophilic–hydrophobic triblock structure of natural junction channels.
