Volume 16 Issue 4, April 2024

Biological and synthetic catalysts often utilize iron in high oxidation states (+IV and greater) to perform challenging molecular transformations. A coordination complex featuring an Fe(VII) ion has now been synthesized through sequential oxidations of nonheme iron–nitrido precursors.

Chiral amines possessing a stereogenic carbon atom bearing three carbon substituents and one nitrogen substituent are challenging structural motifs to prepare enantioselectively. Now, such motifs have been accessed in high enantiopurities by asymmetric Cu-catalysed propargylic amination using sterically confined ligands.

Expansion of the genetic code can enable precise manipulation of proteins through selective functionalization of specific residues. Now, control of tryptophan interactions in proteins can be established by encoding of a vinyl-caged tryptophan analogue that can be selectively decaged to rescue protein activity.

A protein-templated selection approach has been developed for the discovery of full ligands from dual-pharmacophore DNA-encoded libraries by incorporating fragment linking into the selection process. The performance of this method was demonstrated with selections against protein–protein interaction and protein–DNA interaction targets, through which potent and selective inhibitors were identified.

A method for carbon isotope exchange involving a metal-catalysed metathesis reaction of in situ formed acyl chlorides is demonstrated. The platform provides access to ¹³C- or ¹⁴C-enriched carboxylic acids, including natural products and pharmaceuticals, without the need for radioactive gases, using a single carboxylic acid carbon donor.

Lack of standardization, transparency and interaction creates information gaps in scientific publications. Through strategies such as voluntary information management, standardization of reaction set-ups, and smart screening approaches, this Perspective gives guidelines on how to improve data management in publications reporting chemical reactions, focusing on reproducibility, standardization and evaluation of synthetic transformations.

Light-induced ultrafast switching between the molecular isomers norbornadiene and quadricyclane can reversibly store and release a substantial amount of chemical energy. Two competing pathways have now been identified by which electronically excited quadricyclane molecules relax to the electronic ground state, facilitating interconversion between the two isomers on different timescales.

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.

Complexes of iron in high oxidation states play a pivotal role as active intermediates in numerous catalytic processes. Now, using a multimethod approach on a single molecular system, it has been shown that a stable high-valent Fe(VI) nitride can be converted to a reactive, superoxidized, heptavalent Fe(VII) nitride.

Enantioenriched α-disubstituted α-ethynylamines are valuable synthons to chiral α-tertiary amines and azacycles, but their facile access remains challenging. Now, sterically confined pyridinebisoxazoline ligands have been developed to facilitate highly enantioselective Cu(I)-catalysed propargylic amination of both aliphatic and aryl ketone-derived propargylic carbonates to give α-tertiary ethynylamines. Related tandem sequences are reported to synthesize quaternary azacycles.

Developing a generalizable method for blocking and rescuing tryptophan (Trp) interactions would enable the gain-of-function manipulation of various Trp-containing proteins but has so far been challenging. Now a genetically encoded N¹-vinyl-caged Trp capable of rapid and bioorthogonal decaging enables site-specific activation of Trp on a protein of interest within living cells.

Dual-pharmacophore DNA-encoded chemical libraries enable the identification of two synergistic binders for a biological target, but subsequent linking of this pair is required to obtain a full ligand, which can be challenging. Here we report a protein-templated selection of DNA-encoded dynamic library that can identify full ligands from fragment libraries without the need for subsequent fragment linking.

The preparation of ¹⁴C-labelled compounds is a crucial step in pharmaceutical development but typically requires using toxic, radioactive gases. Now a broadly applicable functional group metathesis reaction has been developed that forms ¹⁴C-labelled carboxylic acids in one pot, without added gases, via dynamic exchange with an easily handled carboxylic acid ¹⁴C source.

Enzyme-initiated polymerization-induced self-assembly has been used to generate various biomimetic structures. Now, myoglobin’s activity is used for biocatalytic polymerization-induced self-assembly to generate vesicular artificial cells. As various cargoes can be encapsulated during polymerization, these artificial cells are capable of protein expression and can act as microreactors for distinct enzymatic reactions.

The heterogeneous catalytic dehydrogenation of hydrocarbons usually suffers from a negative pressure dependence on H₂. Now it has been shown that for propane dehydrogenation on gallium oxide-based catalysts, a positive activity dependence on H₂ partial pressure arises from a metastable hydride-mediated catalysis in which gallium hydrides promote C–H activation.

Metal-mediated self-assembly of organic building blocks is a powerful strategy to generate complex supramolecular objects. The non-statistical combination of multiple different components, however, has been a major challenge. Now integrative self-sorting of low-symmetry multicomponent cages has been achieved by combining shape complementarity and selective backbone interactions under thermodynamic control.

The lack of effective methods for mirror-image (d-) protein sequencing hampers the development of mirror-image biology systems and related applications. Now, total chemical synthesis of mirror-image trypsin enables the sequencing of long d-peptides and d-proteins, which may facilitate applications of d-peptides and d-proteins as potential therapeutic and informational tools.

Single-step addition of an aryl ring and a protected amine across an alkene is a succinct route to valuable phenethylamine products, but existing methods suffer from limited scope. Now a family of compounds containing a sulfinamide functional group have been developed to react via electrophilic radicals to yield phenethylamines through an aryl migration with precise stereochemical control.

Single-electron-mediated difunctionalizations of internal olefins allow the simultaneous formation of two contiguous Csp³-stereocentres. Here, we describe enantioenriched arylsulfinylamides as all-in-one reagents for the efficient asymmetric, intermolecular aminoarylation of alkenes. Mechanistic studies revealed an interesting dichotomy in the initiation of the reaction depending on the olefin redox potential.

Selectivity of photochemical reactions is notoriously difficult to model. Now it has been shown that by employing an analogy to ground-state reactions with post-transition-state bifurcations, selectivity for a complex photochemical denitrogenation reaction can be captured and rationalized, and its dynamical origins understood.

Photoinduced electron transfer forms the basis for photosynthesis and DNA repair. Ultrafast structural changes recorded for a DNA-repairing photolyase now reveal specific and directed protein motions accompanying the electron transfer.

High-throughput experimentation (HTE) has great utility for chemical synthesis. However, robust interpretation of high-throughput data remains a challenge. Now, a flexible analyser has been developed on the basis of a machine learning-statistical analysis framework, which can reveal hidden chemical insights from historical HTE data of varying scopes, sizes and biases.

The organization of electrolytes at the air/water interface affects the structure of interfacial water and therefore numerous natural processes. It has now been demonstrated that the surface of an electrolyte solution is stratified and consists of an ion-depleted outer surface and an ion-enriched subsurface layer, jointly determining the water interfacial structure.

The synthesis, structure and reactivity of room-temperature-stable [Cp(C₆F₅)₅]⁺[Sb₃F₁₆]⁻ is presented. Coordination of the cyclopentadienyl cation by [Sb₃F₁₆]⁻ or C₆F₆ stabilizes the antiaromatic singlet state in the solid state. Calculated hydride and fluoride ion affinities of the [Cp(C₆F₅)₅]⁺ cation are higher than those of the tritylium cation [C(C₆F₅)₃]⁺.

The activation of dioxygen at metal centres, and subsequent functionalization of unactivated C‒H bonds, requires the generation of high-energy radical intermediates that often result in undesirable side reactions. Now an elusive oxygen-derived reactive iron(II)–radical intermediate is spectroscopically characterized as part of a strategy to stabilize phenoxyl radical cofactors during substrate oxidation reactions.

Serotonin is known by many names — in science as 5-hydroxytryptamine (5-HT) or enteramine, and in popular culture as the ‘feel good’ chemical or the ‘happy hormone’. Cameron Movassaghi and Anne Andrews discuss the knowns and unknowns of this well-studied yet elusive neurotransmitter.