Volume 15 Issue 8, August 2023

Critical realism distinguishes the ‘real’ world from the ‘observable’ one, which scientists explore as actors rather than as passive, neutral observers. Through this lens, it is clear that a diverse community that interrogates the world from different angles is an asset to the practice of chemistry itself.

Different roles require different types of intelligences, and trainee chemists are often tested on their linguistic and logical–mathematical intelligences at the expense of other types. Bruce Gibb describes the types of intelligences that chemists use, and suggests ways to teach and test them.

The synthesis of natural products with important biological properties has always fascinated chemists, but the development of rapid, efficient and stereoselective transformations remains challenging. Now, a strategy has been developed to produce several strychnan alkaloids through formation of a common bridged morphan core structure.

Tandem cycloaddition reactions have significant applications in organic synthetic chemistry. Now, two enzymes are shown to catalyse tandem hetero-Diels–Alder reactions with a synergistic interplay between a calcium cofactor and N-glycan post-translational modifications during the biosynthesis of bistropolone-sesquiterpene secondary metabolites.

Lactams and pyridines are privileged scaffolds, but strategies for combining these groups into one molecule are lacking. Now, N–N pyridinium ylides have been shown to form triplet state diradicals under photoinduced energy transfer, and subsequent [3+2] cycloaddition with the tethered alkene enables the synthesis of diverse ortho-pyridyl lactams.

Low-coordinate lanthanide complexes with strong magnetic anisotropy could afford high-performance single-molecule magnets (SMMs) but are challenging to synthesize. Now, through ligand design, a near-linear pseudo-two-coordinate Yb(iii) complex that exhibits slow magnetic relaxation is reported. The complex has a large total splitting of the ground-state manifold, arising from the crystal field imposed by the ligands.

Challenges in the synthesis of heparan sulfate (HS) glycosaminoglycans have limited access to defined HS oligosaccharides bearing a diverse array of sulfation sequences. A concise, divergent synthetic approach now provides a library of 64 HS tetrasaccharides displaying a comprehensive set of sulfation sequences, offering insight into the elusive sulfation code of glycosaminoglycans.

Although several transition-metal carbene complexes have been isolated and used for catalytic carbene transfer reactions, few metal difluorocarbene complexes have been reported. Now, the synthesis, characterization and reactivity of isolable copper(I) difluorocarbene complexes has been reported, which has enabled the development of a copper-catalysed difluorocarbene transfer reaction to access fluorinated compounds from simple chemical feedstocks.

The morphan core is central to strychnan alkaloid synthesis and is typically formed during the middle or later stages of the process. Now it has been shown that an allene/ketone-equipped morphan core can be constructed early in the synthesis through ketone α-allenylation and then used to introduce other rings and functionalities, enabling access to nine targets including strychnine and geissolosimine.

Two glycosylated enzymes, EupfF and PycR1, have now been characterized and shown to independently catalyse the tandem intermolecular [4 + 2] cycloaddition in the biosynthesis of bistropolone-sesquiterpenes. Through analysis of enzyme–substrate co-crystal structures, together with computational and mutational studies, the origins of their catalytic activity and stereoselectivity were elucidated.

There is currently a lack of effective synthetic strategies for combining lactams and pyridines within a single molecular structure. Now, diastereoselective pyridyl lactamization has been developed using a photoinduced [3+2] cycloaddition of triplet diradical N–N pyridinium ylides with pendant alkenes. This method provides a useful synthon for preparing pyridyl γ- and δ-lactam scaffolds with syn-configuration.

A trivalent 4f cationic complex bearing two bis-silylamide ligands has been prepared that displays slow magnetic relaxation. The bulky ligands and weakly coordinating anion stabilize the pseudotrigonal geometry necessary to elicit strong ground-state magnetic anisotropy in this axially coordinated Yb(III) complex with well-localized charges.

Large collections of defined glycosaminoglycan (GAG) structures have been synthetically challenging to obtain but are required to understand this important class of biomolecules. Now, an efficient platform for synthesizing large libraries of heparan sulfate oligosaccharides has been developed, providing a detailed view into the sulfation code of GAGs.

Exciton–exciton annihilation is conventionally assumed to be limited by diffusion. Now, using time-resolved photoluminescence microscopy to determine exciton diffusion constants and annihilation rates in two substituted perylene diimide aggregates, along with a microscopic model, it has been shown that annihilation can be suppressed through quantum interference of the spatial phase of delocalized excitons.

Contrary to agonist binding being the sole driver for β₂-adrenergic receptor (β₂AR) activation, molecular metadynamics simulations now reveal a distinct activation mechanism. Coupling β₂AR with its cognate Gs protein induces considerable structural changes, activating both proteins. Gs opens its GDP binding pocket while β₂AR undergoes expansion.

The use of main-group elements in radical cross-coupling reactions has been little explored. Now, a low-valency bismuth complex has been shown to emulate the behaviour of first-row transition metals and undergo single-electron-transfer oxidative addition to redox-active electrophiles, leading to the development of a bismuth-catalysed C–N coupling reaction between amines and carboxylic acids.

Protein solutions can undergo liquid–liquid phase separation, by condensing into a dense phase that often resembles liquid droplets, which coexist with a dilute phase. Now it is shown that hydrophobic interactions, specifically at interfaces, can trigger a liquid–solid phase separation of a protein solution.

The ortho-substituted phenyl ring is a basic structural element in chemistry. Now, 2-oxabicyclo[2.1.1]hexanes have been developed as saturated bioisosteres of the ortho-substituted phenyl ring with improved physicochemical properties. Replacement of the phenyl ring with 2-oxabicyclo[2.1.1]hexanes in marketed agrochemicals fluxapyroxad and boscalid improved water solubility, reduced lipophilicity and retained bioactivity.

The biosynthesis of the methylated sesquiterpene sodorifen, which features a cryptic methylation pattern, has now been studied through extensive labelling experiments and computational chemistry. The methyl group formation is now understood to come from methylene carbons of the substrate farnesyl diphosphate and the absolute configuration of the biosynthetic intermediate presodorifen diphosphate has been revised.

Hybrid structures made up of quantum dots functionalized with molecules are highly tunable platforms for light-driven applications; however, the interaction between their components is often weak. Now it has been shown that by connecting molecules to silicon quantum dots via p-conjugated tethers, strongly coupled exciton states can be generated that prove advantageous for photon upconversion.

Microtubules carry patterns of post-translational modifications that are important for the regulation of key cellular processes. Now a semi-synthetic method facilitates the production of tubulins with defined post-translational modifications. Using these designer tubulins, polyglutamylation of α-tubulin is found to promote its detyrosination by enhancing the activity of the carboxypeptidase vasohibin/small vasohibin-binding protein.

The metal-dependent, bifunctional isoprenyl diphosphate synthase PcIDS1 from the leaf beetle Phaedon cochleariae integrates substrate, product and metal-ion concentrations to tune its dynamic reactivity. Now structural and functional analyses reveal that this enzyme uses both catalytic centres to form geranyl pyrophosphate, while one domain is inactivated during farnesyl pyrophosphate production.

Fiona C. Meldrum and Helmut Cölfen chalk up some of the myriad forms and uses of calcium carbonate to burnish a ‘dull’ reputation.