Volume 14 Issue 7, July 2022

Antibody-mediated delivery of therapeutics has been primarily limited to agents containing amine, alcohol or thiol functional groups. Now, an approach has been developed to create stable and bio-reversible prodrugs that mask ortho-quinones. Drug release requires both protease activation followed by acid-assisted elimination.

Photoredox catalysts offer a promising approach to performing reactions with high energetic requirements, however, the influence of solvent and counter ions is not fully understood. Now, a microwave-based technique is shown to give direct insight into their effects on charge reorganization during catalysis.

Over the past 25 years, the photo-induced spin-crossover behaviour of Fe(II) complexes has puzzled scientists. Now, a symmetry-breaking twisting mode has been observed during the relaxation of such a complex. Controlling its configuration using enantiopure counterions has also been shown to slow down the relaxation.

This year marks the 50th anniversary of Baird’s rules of aromaticity — a set of perturbational molecular orbital theory analyses that has garnered considerable attention in the past ten years in light of its many real-world applications in photochemistry.

Amino-containing four-carbon threose nucleic acids (TNAs) have long been considered to be prebiotically irrelevant due to their difficult formation. Now, a prebiotically plausible route to 3′-amino-TNA nucleoside triphosphate has been developed, raising the possibility of 3′-amino-TNA as a non-canonical nucleic acid during the origin of life.

Chemically fuelled synthetic molecular machines are capable of driving and sustaining non-equilibrium motion, analogous to the biomachinery that underpins life. This Review discusses the chemical and physical features of biological and synthetic chemical fuels and highlights potential challenges and opportunities for the development of synthetic chemically fuelled machinery.

Despite much research, the high-spin-state relaxation mechanism of Fe(II) spin-crossover complexes is unresolved. Using ultrafast circular dichroism spectroscopy it has now been revealed that the spin relaxation is driven by a torsional twisting mode, which breaks the chiral symmetry of a prototypical Fe(II) compound. Stereocontrolling the configuration of the complex can thus be used to slow down the spin relaxation.

Ion pairing is ubiquitous in low-dielectric-constant solvents, but whether it influences the reactivity of common cationic photoredox catalysts has been unclear. However, it has now been shown that ion pairing is responsible for a 4-fold modulation in reactivity in a prototypical Ir(III) complex and is explained by excited-state ion-pair reorganization.

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.

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 molecular driving forces underlying the liquid–liquid phase separation (LLPS) of RNA are not well understood. Now simulations show that low-complexity RNA sequences undergo LLPS at high RNA concentrations, driven by the formation of Watson–Crick base pairs between distinct RNA polymers. LLPS occurs by merger of small droplets into larger ones and RNA chains in the large droplets exhibit reptation dynamics.

Molecular π-stacked chromophores are promising photonic materials, but much of our understanding is limited to covalent dimers. Now it has been shown that, in a slip-stacked perylenediimide trimer, coherent vibronic coupling to high-frequency modes facilitates ultrafast state mixing between the Frenkel exciton and charge-transfer states, which then collapses by solvent fluctuations and low-frequency vibronic coupling, resulting in ultrafast symmetry-breaking charge separation.

The planar hexazine dianion ring (N₆^2–), which had previously been predicted to exist, has now been synthesized from potassium azide (KN₃) under laser heating in a diamond anvil cell above 45 GPa; it remains metastable down to 20 GPa. By contrast, at 30 GPa an unusual N₂-containing compound with the formula K₃(N₂)₄ was produced.

Catalytic transformations of methane frequently involve the formation of a metal–methane complex, but these compounds are challenging to observe. Now, a relatively long-lived osmium–methane complex has been characterized using NMR spectroscopy and forms from the direct binding of methane to a photolytically generated, coordinatively unsaturated cationic osmium–carbonyl complex dissolved in an inert hydrofluorocarbon solvent at –90 °C.

Oscillations are widespread throughout the natural world and a number of fascinating inorganic oscillating reactions are known—but the formation and control of oscillating, self-replicating synthetic systems has remained challenging. Now, it has been shown that chemically fuelled oscillations within a network of organic replicators can drive supramolecular assembly and disassembly.

HCN and its isomer HNC are both observed in the interstellar medium and inelastic collisions with helium and other species strongly influence their derived abundances. Now it has been shown experimentally and theoretically that HNC is much more strongly excited than HCN in collisions with helium at the low temperatures of interstellar space.

Flexible metal–organic frameworks (MOFs) in which guest uptake and release occur above certain threshold pressures are attractive adsorbents. Now, the gated sorption behaviour of such a zinc-based mixed-ligand MOF has been tuned to match the narrow temperature and pressure range required for safe, efficient acetylene storage by adjusting the ratio of two different functional groups on its benzenedicarboxylate ligands.

Phytochromes regulate plant growth by sensing far-red light through the photoisomerization of their protein-bound chromophores. In the phytochrome Agp2, it has now been demonstrated that ultrafast proton-transfer occurs from the chromophore to a protein–water network before photoisomerization, inducing protein changes on the ultrafast timescale. These protein changes develop further on longer timescales, resulting in an activated protein conformation.

SynGAP and PSD-95 are two abundant proteins that form a complex and undergo liquid–liquid phase separation (LLPS) in the postsynaptic density of neurons. Now, O-GlcNAcylation of SynGAP has been found to suppress LLPS of the SynGAP/PSD-95 complex, and O-GlcNAc-dependent LLPS was also shown to be dynamically regulated by the enzymes O-GlcNAc transferase and O-GlcNAcase.

Choline 2-hexenoate is an ionic compound that is a liquid at room temperature, and is just one of a class of compounds that have huge potential in biomedical research and clinical applications, explains Eden E. L. Tanner.