Back to the future: Selected current developments in analytical chemistry are discussed in this Viewpoint and traced back to original work published up to 150 years ago. Discussed topics include selective mass determination, molecular spectroscopy, chemical sensors, separation methods, and bioinspired receptors such as antibodies.

Walking the tightrope above the ground state: The absolute stereochemical outcome of a photochemical reaction can be controlled by activating the starting material with Lewis acids or Brønsted acids or through the formation of iminium ions.

Trapping transient protein–protein interactions: Site-specific incorporation of unnatural amino acids bearing chemical groups that allow covalent crosslinking with molecules in their vicinity provides a powerful tool for mapping weak and transient protein–protein interactions and for defining the structure and topology of protein complexes both in vitro and in vivo.

Two isomeric monoterpenes, α-pinene and β-pinene, which can easily be isolated in large scale from different plants (also from non-edible parts of them), can be conveniently transformed into a variety of sustainable polymers and advanced materials. Recent studies on this are summarized in this Minireview with a focus on synthetic strategies and properties of the obtained polymers.

The relationship of molecular intermetalloid clusters and intermetallic compounds reminds us of a complex ecosystem: in our metaphor, woodpecker scientists release in a top-down approach preformed clusters and metal atoms from solid-state trees. Bustling ant chemists collect the falling pieces and transform them into new intermetalloid clusters, which may constitute a fertile soil for new modifications of intermetallic compounds. Cover art: K. Mayer.

Experimentally challenging and intellectually intriguing, the field of aluminium homo- and heterodiatomic multiply bonded complexes and their reactivity has made signficant progress in recent years. This Review outlines some of the cutting edge synthetic approaches and careful ligand design that have paved the way for this success.

Take up the challenge: The development of orally active peptides is a complex challenge as several requirements are necessary to achieve essential criteria: high selectivity, high affinity, low toxicity, enzymatic stability, and oral bioavailability. The biological background, various chemical modifications, and some successful examples are presented in this Review.

Fit for the future: The discovery of novel antibacterials is a highly interdisciplinary field which relies on input from various research areas. This Review encompasses several aspects of antibiotic development—from very early strategies to mature drugs in clinical trials. An overview is given of methods suitable for mining novel antibacterials and for the elucidation of their bacterial targets.

Light on biaryls: A novel metal-free approach to biaryls is reported that involves the tethering and photochemical fusion of phenyl groups through sulfonamides. Using a flow reactor biaryl pharmacophores of numerous therapeutics, antibiotics, antitumor and neuroprotective agents, non-steroidal antiinflammatory drugs, sartans, and cannabinol, were prepared in excellent yields.

Let there be light: A simple, two-step photodriven reverse-water-gas-shift (rWGS) cycle at ambient temperature and pressure is reported. The CO₂ to CO hydrogenation is mediated by a molecular nickel hydride. The reaction relies on photochemical abnormal CO₂ insertion into the Ni−H bond and cooperative, heterolytic H₂-activation by the metal and the functional pincer ligand.

Nitrogen-modified titanium structures: Cobalt catalysts were prepared by impregnation of titania with an aqueous solution of cobalt acetate and melamine. The resulting material has a distinctive nitrogen-modified titanium structure and shows good activity and selectivity for pyridine hydrogenation in water.

Ring, ring: The first enantioselectively catalyzed synthesis of the spirotropanyl oxindole scaffold, which is characteristic of bioactive alkaloids like alstonisine and chitosenine, was developed. The method involves a bimetallic relay catalysis strategy, with a highly enantioselective 1,3-dipolar cycloaddition as the key step.

Ultra-highfield NMR magnet development requires robust radio frequency pulses to cover the increasing frequency spectral bandwidth. Cooperative excitation pulses are presented with pulse durations on the order of tens of microseconds, which provide ultrabroadband excitation for present and future magnetic field strengths well beyond 28 T (1.2 GHz ¹H). The performance is demonstrated for proteins and nucleic acids.

Taking the lead: Amyloid self-assembly is linked to Alzheimer's disease (AD) and type 2 diabetes (T2D). In a minimalistic approach, macrocyclic peptides (MCIPs) were designed as potent amyloid inhibitors of Aβ40(42) and IAPP and a selective MCIP (see structure) for Aβ40(42) with high proteolytic stability in human plasma and blood–brain-barrier-crossing ability in a cell model was discovered. MCIPs are promising leads for amyloid targeting in AD or in both AD and T2D.

Multifunctional Cluster Compounds: Threefold phosphine-functionalized clusters are easily accessible via one-step synthesis from the Zintl phase K₄Ge₉. The novel species reveal various reactive sites that can be approached by Lewis acids, comprising the lone pairs at P, single Ge atoms or Ge₃ triangular clusters faces (red arrows).

Radiofrequency field inhomogeneity: Heteronuclear dipolar recoupling experiments with substantially larger responsive volume and increased sensitivity compared to the traditional Hartmann–Hahn sequences have been designed using optimal control strategies. Compensation is essential for temporal modulations induced by sample rotation in a spatially inhomogeneous radiofrequency field of a solenoidal coil.

Let the sunshine in: A comparison of all published bacterial genomes was conducted to identify novel prolific natural product sources among ecologically and phylogenetically unusual bacteria. This suggested the plant-root-associated halophilic bacterium Gynuella sunshinyii as a top candidate. Its richness was confirmed in an extensive study of its chemical repertoire, revealing diverse metabolites with new scaffolds and promising activities.

Gold bullet: The binding modes and free-energy landscape of two Au^I/N-heterocyclic carbene complexes interacting with G-quadruplexes (G4), namely a human telomeric (hTelo) and a promoter sequence (C-KIT1), are studied here for the first time by metadynamics. The theoretical results are validated by FRET DNA melting assays and provide an accurate estimate of the absolute gold complex/DNA binding free energy.

Nickel-catalyzed stereoconvergent cross-couplings of racemic alkyl electrophiles have been expanded to include carbon–heteroatom bond construction for the first time. Specifically, a chiral nickel/pybox catalyst has been shown to borylate benzylic chlorides to produce enantioenriched benzylic boronic esters, a useful family of compounds in organic synthesis.

High score: 2D HYSCORE EPR spectroscopy augmented with DFT calculations makes it possible to detect and characterize Ti^III alkyl species in silica-supported ethylene polymerization catalysts.

Re-loaded: Highly conductive rhenium and rhenium nitride thin films are deposited at moderate temperatures. The films grow in a highly controllable manner from ammonia and rhenium pentachloride at temperatures up to 500 °C by atomic layer deposition. As thin as 3 nm rhenium film is already continuous and has a low resistivity of 90 μΩ cm.

Core fucosylation on-the-fly: A highly α-selective method was developed for the introduction of α1,6-linked core fucose into N-glycans as the final step. A modular approach based on N-TFAc protection for the antennae provides all the natural combinations of bisecting GlcNAc and core fucose found in mammalian complex-type N-glycans via a single pathway.

Metallotropism in tautomers arises from stereoelectronic fine-tuning of (Fe or Co){N(SiMe₃)₂}₂ bonding to C_NHC or remote N in NHCs/imidazolium salts with amine/aminide substituents, respectively. Thermally induced unexpected formation of a Co^I−Co^II dinuclear complex and NHC ring opening leading to metallaketenimines were observed.

Distinct active sites on MoS₂ and WS₂ consisting of accessible Mo or W cations and SH groups at the slab edge have been identified. Addition of Ni on both sulfides generates a Ni-(SH)_x site that is significantly more active than the sites associated with Mo or W and has a distinct regioselectivity for H-addition. For all sites the ratio between the metal cation and the SH groups is constant.

Acids to acids: A practical method for the preparation of highly valuable enantiomerically pure α-amino acids has been developed. The described transformation rapidly converts feedstock alkyl carboxylic acids to α-amino acids, and is enabled by innate radical cross-coupling with a chiral imine radical acceptor. The scope of this transformation is broad and has been field-tested in three different industrial medicinal chemistry laboratories.

Mind the gap: Silica-supported cationic Mo-imido alkylidene complexes have been developed; these display unusual and contrasting catalytic metathesis activity for internal and terminal olefins, with a strong preference for the latter. The tailored ligand environment also allowed the first supported metallacyclobutane intermediate to be observed.

Meta-LOL: 3-Borylborole was prepared by a sequential 1,1-carboboration route. It reacted with an alkyne by [4+2]-cycloaddition followed by rearrangement to form a tetraaryldiborane(4) product.

In pursuit of precision: The double donor–acceptor-type Si=Si bond of a (Z)-imino(silyl)disilene was exploited to selectively activate NH₃, leading to the corresponding trans-1,2-adduct under kinetic and the monomeric aminosilane under thermodynamic reaction control. Furthermore, its reactivity toward Lewis acid B(C₆F₅)₃ and the oxygen-atom transfer agents N₂O, O₂, and CO₂ was elucidated.

Direct play: A carboxylate-directed ortho-allylation of benzoic acids is achieved in the presence of [Ru(p-cymene)Cl₂]₂. The reaction is based on widely available, structurally diverse (hetero)aromatic carboxylate substrates and proceeds under remarkably mild reaction conditions. It is widely applicable to (hetero)aromatic benzoic acids and the products can be transformed in situ by acyloxylation, double-bond isomerization, or protodecarboxylation.

Templating pores in polymers: Reduction of non-porous cationic insulating coordination polymers (see picture, left) yields porous neutral conductive polymers (right). The porosity varies with the size of the anion that departs the parent polymer.

Metathesis inside a host: A supramolecular host was used to develop a general method for Brønsted acid-catalyzed carbonyl–olefin metathesis. This system provides comparable yields to the current Lewis acid benchmark catalyst. A mechanistic study indicated stepwise oxetane formation for some of the employed substrates.

Chromophore activation at its best: Lewis acid catalysis enables an enantioselective photocycloaddition of olefins to the C9/C10 double bond of phenanthrene-9-carboxaldehydes in which up to four stereogenic centers are created. The chromophore is significantly modified by Lewis acid coordination.

The classical iron carbonyl complex [Cp*₂Fe(CO)](AsF₆)₂, containing formally tetravalent iron, has been prepared by treating [Cp*₂Fe]²⁺ with carbon monoxide in anhydrous HF. The complex was characterized by various spectroscopic techniques, including ⁵⁷Fe Mössbauer spectroscopy and DFT computational analysis.

A species-selective small molecule activator (D9) of human ClpP was identified. Crystallography and docking studies revealed binding into a tailored aromatic pocket characteristic for ClpPs of higher organisms.

Come together: The dissipative self-assembly of silicon nanocrystals (SiNCs) is coupled to a fuel-driven chemical reaction network, thereby enabling kinetic control over the self-assembled structures. For example, the amount of fuel determines the lifetime of the assemblies. Using this mechanism, the uptake of SiNCs by cells could be delayed.

ZrO₂-promoted methane dry reforming on Pd_xC: C-saturated Pd⁰ nanoparticles with extended phase boundary to ZrO₂ evolve from a Pd⁰Zr⁰ precatalyst under CH₄ dry reforming conditions. This highly active catalyst state fosters bifunctional action: CO₂ is efficiently activated at oxidic phase boundary sites and Pd_xC provides fast supply of C-atoms toward the latter.

High-affinity molecular recognition of metal-complexed petrobactin, a specific siderophore of Bacillus anthracis, was achieved with an engineered human lipocalin protein that normally scavenges enterobactin and bacillibactin to control the systemic spreading of bacteria by restricting iron supply. The picture shows the crystal structure of the petrocalin/petrobactin⋅Ga^III complex.

Breaking the cage: Fungi use siderophores to scavenge Fe³⁺ from the environment. Intracellular iron release occurs through hydrolysis of the siderophore backbone by esterases. Structural and biochemical analyses of two homologous EstB esterases, as well as EstA and SidJ, reveal how a common fold adapts to diverse substrates. A structure of an active enzyme in complex with its siderophore substrate reveals a tetrahedral intermediate at the catalytic serine.

Superatomic: The reaction of [AlCp*]₄ and [CuMes]₅ yields the Mackay 55-metal atom two-shell icosahedral cluster [Cu₄₃Al₁₂](Cp*)₁₂. The intermetalloid cluster has a unique 67-electron open-shell superatomic [Cu₄₃Al₁₂]¹²⁺ core, embedded inside an all-hydrocarbon shell of twelve Cp*⁻ ligands. Its electronic structure comprises a set of entangled HOMO und low-lying LUMOs, prefiguring the formation of a conduction band.

Electric ligands: Upon the addition of a closed-shell ligand CO₂, the inertness of [TaO₂]⁺ towards CH₄ (or H₂) is removed (see scheme, Ta purple). This remarkable ligand effect can be modeled by an electric field.

Fluorine bridges: The fluoronium ions [Br₂F₅]⁺ and [Br₃F₈]⁺ are the first polyheterohalogen cations with bridging F atoms. They have been isolated in form of their [SbF₆]⁻ salts.

A metadynamics-driven drug design strategy was employed to transform a helical nonapeptide into a cyclic pentapeptide as a potent and selective ligand of the RGD-recognizing αvβ6 integrin. This compound was further developed into a PET tracer for specific αvβ6-mapping in vivo, prompting its use for cancer diagnosis and therapy.

Sorbicillinoids made easy: The first stereoselective total syntheses of the structurally diverse sorbicillinoids oxosorbicillinol, sorrentanone, rezishanones B and C, sorbicatechol A, bisvertinolone, and (+)-epoxysorbicillinol are based on a unified chemo-enzymatic approach that involves a regio- and enantioselective oxidative dearomatization of sorbicillin-type precursors harnessing the catalytic activity of the monooxygenase SorbC.