Ready for the open waters? Recent developments have fundamentally changed our knowledge of vinyl cation reactivity. The myth that they are too reactive for a predictable reaction design has been debunked, and the applicability of their most distinguished feature, namely their carbene-like reactivity, has taken a major leap forwards. Vinyl cations have thus matured into distinct reactive intermediates with a bright future ahead.

Ingestible medical devices could significantly improve human health. Recent examples of ingestible biomedical devices include edible cameras, biosensors, and drug delivery systems. This Minireview summarizes recent advances in materials, structures, fabrication techniques, and systems integration, which are relevant to the design of next-generation ingestible biomedical devices. (Picture adapted from Bonacchini et al., Adv. Mat. 2018.)

Microarrays come of age: As indicated by case studies from clinical diagnostics, proteome research, fundamental cell biology, and materials science, DNA-modified surfaces have evolved from nucleic acid sensors into a versatile platform for life sciences and materials research.

Round about NaOCP: The chemistry of the 2-phosphaethynolate anion, a heavier phosphorus-containing analogue of the cyanate anion, is comprehensively reviewed. This simple anion allows a wide breadth of chemical transformations leading to heterocycles, π-conjugated molecules, and metal phosphides.

Zn–CO₂ battery: The first reversible aqueous Zn–CO₂ battery is prepared using 3D porous Pd interconnected nanosheets as the cathode which bifunctionally electrocatalyzes CO₂ reduction and HCOOH oxidation with high activity and selectivity at low overpotentials.

Two elastic and fluorescent organic single crystals were successfully created based on an original molecular design. The crystals showed bending mechanofluorochromism and high performance as a flexible waveguide.

Mechanism-based crosslinking is a vital tool to trap states within multimodular enzymatic systems. A caged system is described that applies silylcyanohydrin chemistry to mask a reactive ketone warhead. Given the diversity of different silyl groups, this system can be tuned to deliver high yields of protein–protein crosslinking as defined in the context of large polyketide and fatty acid synthases.

Frozen but not for long: A few picoseconds after its excitation, a quadrupolar dye forms a tight and asymmetric hydrogen-bond complex with the solvent. Transient 2D-IR spectroscopy reveals that this results in a dramatic slowing down of the solvent dynamics on one side of the dye. The surrounding solvent exhibits a glass-like behavior.

Polarized polymers: Dipolar 2,3-difluorobenzene units are introduced into the backbone of PPE. The difluorinated benzene rings behave as molecular rotors at high temperature, while at room temperature, stacking of such rings clamps the ring orientation to generate a remanent polarization. The molecular dipoles are oriented by moderate external electrical fields, and this PPE is then a ferroelectric conjugated polymer.

Alpha-particle radiation efficiently damages biologically relevant systems by initiating various intermolecular proton and energy transfer processes.

Hydrogels comprised entirely of enzymes self-assemble under physiological conditions by covalent SpyTag/SpyCatcher interaction to porous hydrogels. Mounted in microfluidic reactors, the gels exhibit excellent stability, stereoselectivity, and cofactor retention without the need for additional carriers or membranes.

Two original dithiolenes, mimicking molybdopterin (MPT) present in the active site of formate dehydrogenases (FDHs), have been synthesized and characterized. MoO(dithiolene)₂ complexes have been also prepared and are reported as the first functional and stable catalysts inspired by the Mo center of FDHs: they indeed catalyze the photoreduction of CO₂ into formic acid as the major product.

Self-assembled monolayers of the π-expanded macrocyclic isomers Z,Z-8mer and E,E-8mer at solid–liquid interfaces undergo reversible in situ photoisomerization upon irradiation with UV/visible light. Given the host–guest capabilities of these macrocycles, these results reveal their potential for photoresponsive cargo delivery systems.

Misleading signals: The first application of hydrophobic tagging to an existing inhibitor of protein-protein interactions is presented. Poloxin-2HT targets the Plk1 polo-box domain, and induces Plk1 degradation, characteristic mitotic phenotypes, and apoptosis in human tumor cells.

Light up and release: A new DNA aptamer-grafted photoresponsive hyperbranched polymer (HBP) was synthesized. The polymer can self-assemble into nanoparticles, which show biocompatibility, target specificity, and light-controllable release behavior for drug delivery applications.

Excited CuO: Franck–Condon analysis of vibrationally resolved photodissociation uncovered the complex structure of acetonitrile-supported CuO⁺ species with several triplet excited states. Benchmarked multireference theoretical calculations explain how the character of the Cu−O bond shifts from copper(I)-oxygen towards copper(II)-oxyl in ligated systems.

Gas–liquid reactions form the basis of our lives, yet they suffer from poor reaction efficiency and are difficult to monitor in situ, especially at ambient conditions. An inert gas–liquid reaction between aniline and CO₂ is driven at 1 atm and 298 K. Real-time reaction monitoring was performed by selectively concentrating these immiscible reactants at the interface between metal–organic framework and solid nanoparticles.

Thermoelectrics: A fast and simple solution-based method is presented to synthesize flower-like SnSe₂ nanostructures and crystallographically textured SnSe₂ nanomaterials, which display highly anisotropic charge and heat transport properties. Unprecedented thermoelectric performance of SnSe₂ is achieved through modulation doping by combining SnSe₂ nanoplates with metal nanoparticles.

Two peaks are better than one: Native chemical ligation was used to segmentally label α-synuclein with ¹³C. This labeling results in two spectroscopically distinct amide-I bands that independently report on region-specific conformational changes of the protein backbone. The N-terminal region was seen to adopt a β-sheet structure first in the formation of amyloid.

The chemoselective ligation of cysteine residues on a solid phase using a variety of aliphatic electrophiles is achieved by a new stapling method. This approach can be applied to the preparation of single-turn, double-turn, and double-stapled peptides. Its application has led to the identification of a potent inhibitor of the catalytic activity of the polycomb-repressive group of proteins (PRC2).

A coiled-coil-based conformational switch was designed that enables the detection of proteins in real time.

Special agents on the job: Supramolecular curcumin nanoagents were fabricated by amino acid coordination driven self-assembly (see picture). The biological stability of curcumin was significantly improved through both coordination and molecular stacking in the nanoagents, the size of which could be readily manipulated. These favorable therapeutic features substantially enhanced the antitumor activity of curcumin without discernible side effects.

3D magnetic toroics: Molecular materials that have a toroidal moment associated to a non-magnetic ground state are known as single-molecule toroics (SMTs) and are usually planar molecules. Such a toroidal moment is observed in a Dy₄ cubane, transposing this property to a tridimensional structure (3D-SMT).

Water do: A catalyst with Pt₁¹⁺ exclusively coordinated to H₂O molecules can be prepared on a gram scale within a metal–organic framework (MOF). It transfers two H₂O molecules to CO and gives, very efficiently, CO₂ and H₂ (water–gas shift reaction) at 50–150 °C.

Via acyl azoliums: A quadruple domino sequence proceeding via α,β-unsaturated acyl azolium intermediates is catalyzed by an N-heterocyclic carbene. This strategy provides a convenient direct route to functionalized tricyclic chromenone derivatives and cyclopentanes. DFT studies and control experiments provide insight into the reaction mechanism.

Golden solution: The rapid dissolution of gold is facilitated by a reactive combination of pyridine-4-thiol and H₂O₂ in DMF solution. The ligand assists the dissolution as it stabilizes gold(I) centers and serves as the source of a sulfate counteranion.

Molecular-dynamics-aided spectroscopy: A method for guiding spectroscopic experiment selection that permits efficient refinement of protein conformational ensembles has been developed. This method employs molecular dynamics simulation and information theory and is tested via DEER spectroscopy.

Aqueous phosphorescence: An unprecedented organic-inorganic hybrid co-assembly approach is proposed to obtain aqueous state as well as amorphous red-emitting room temperature phosphorescence. Heavy-atom effect in the NDI derivative along with its J-aggregation enhance the intersystem crossing efficiency whereas rigid and oxygen tolerant laponite templates stabilize the triplets.

Heat of the moment: A label-free method for real-time monitoring of carbapenemase activity in live bacteria is based on measurement of heat changes induced by hydrolysis of the substrate imipenem. This in-cell calorimetry approach offers major advantages in rapid screening of carbapenemase-producing Enterobacteriaceae in clinical bacterial isolates, with superior sensitivity and excellent specificity compared to conventional methods.

Quinone methide dimers are prepared via mild anodic oxidation mediated by a cheap and readily available amine base with excellent yield and regiocontrol. This strategy provides rapid access to intermediates for the synthesis of phenylpropenoid oligomers in a catalytic fashion, providing a new tool for the total synthesis of these complex molecules.

Handpicked: A homochiral zeolitic imidazolate framework-8 (ZIF-8) membrane was synthesized by incorporating a natural amino acid, l-histidine (l-His), into a ZIF framework. The amino acid functions as a chiral (enantiopure) ligand. The l-His-ZIF-8 membrane demonstrates good homochirality and an ability to separate racemic 1-phenylethanol with up to 76 % ee.

Triazole you might: In the oxygen reduction reaction (ORR) triazole-based C₃N₅ (MCN-11) and its graphene hybrids show significantly improved diffusion-limiting current density compared to g-C₃N₄. The enhanced activity is attributed to features of MCN-11 such as strong adsorption between O₂ and active carbons in the triazole moiety.

Neutral serine octamer: Nebulization coupled with gentle on-line protonation and MS analysis is used to isolate and characterize the neutral serine octamer (Ser₈). Ser₈ was transmitted from the nebulizer into the ionization region while any residual protonated octamer was deflected. Nebulized near-racemic serine solutions exhibited homochiral preference for the octamer, which is proposed to be the origin of the homochiral preference observed in Ser₈H⁺.

A templating/covalent capture strategy enables photochemical formation of eight cyclobutanes in one noncovalent assembly. KI and 16 units of 5′-cinnamate guanosine form a G-quadruplex where C=C bonds in neighboring G₄-quartets are separated by 3.3 Å, enabling [2+2] photocycloaddition in solution. This reaction is high-yielding (>90 %), regio- and diastereoselective.

A Pd-catalyzed atroposelective C−H allylation with allylic surrogates is reported. tert-Leucine was identified as an efficient catalytic transient chiral auxiliary. A range of enantioenriched biaryls were prepared in synthetically useful yields with enantioselectivities up to >99 % ee through β-O elimination. The reaction could be scaled up and the products could be further converted into enantiomerically pure axially chiral carboxylic acids.

All aboard: A conceptually new docking–migration strategy for the difunctionalization of alkenes under visible-light photoredox catalysis is disclosed. Both activated and unactivated alkenes are suitable substrates. A vast array of functional groups are compatible with the mild reaction conditions.

One approach, four targets: The asymmetric total synthesis of brasilicardin A, a hybrid natural product with highly potent immunosuppressive activity, has been developed. The synthesis features a Michael addition based strategy for the stereoselective formation of the highly strained anti-syn-anti-fused perhydrophenanthrene skeleton, and brasilicardins B–D are also synthesized based on the unified approach.

Cooperative active sites in nitrogen-cycle enzymes inspired the design of a multi-doped, efficient electrocatalyst for hydrazine oxidation. The catalytic oxidation occurs on Fe₂MoC nanoparticles and on edge-positioned nitrogen dopants, all well-dispersed on a hierarchically porous, graphitic carbon matrix.

Relay races: An entirely earth-abundant chromophore-relay water oxidation catalyst triad system, which is robust and efficient at neutral pH, is presented. It involves a porphyrin derivative coordinating to a bridging Fe(CN)₅ group, which is then reacted with Co ions to prepare a covalently linked chromophore–Prussian blue analogue assembly.

A lock on affinity: The simultaneous display of protein ligands and of 2-hydroxybenzaldehyde derivatives on either two complementary LNA strands or a small-organic molecule leads to an enhanced binding affinity by reversible covalent interaction with proximal lysine residues.

It does get in: A non-peptidic cell-penetrating motif is able to efficiently and specifically deliver small-molecule and peptidyl cargoes into the mitochondrial matrix of mammalian cells by crossing both plasma and mitochondrial membranes.

The chirality transfer process and the pathway complexity of a series of chiral pincer-type Pt^II complexes are described. A chiral doping approach can be used to induce the chirality of an achiral Pt^II complex at the supramolecular level. [Pt]=Pt^II complex; counteranion X⁻.

Not to be IgG-nored: An integrative strategy combining ion mobility mass spectrometry (IM-MS) with molecular modelling can be used to study the conformational dynamics of human IgG antibodies. Predictive models of all four human IgG subclasses were assembled and their dynamics sampled in the transition from extended to collapsed state during IM-MS. The structural representation is in good agreement with the observed collision cross sections.

Golden oldie: A combination of gold(I) and chiral phosphoric acid (CPA) catalyzes a Mannich-type reaction cooperatively. Asymmetric trapping of a gold enolate intermediate involved in alkyne oxidations occurs via an α-oxo gold carbene route. Alkyne transformation involves 1) chemical N−O bond cleavage, 2) fragment modification, and 3) reassembly.

PFS-b-PI (poly(ferrocenyldimethylsilane)-block-polyisoprene) diblock copolymers self-assemble into biomorphic structures with shapes that depend on the assembly conditions. Long fiber-like micelles of uniform width are formed with a crystalline PFS core in decane. Injection of a THF polymer solution into THF/decane leads to micrometer-scale barbed and branched structures with shapes that depend upon the final THF content.

POC Zika detection: A valve-enabled lysis, paper-based RNA enrichment, and RNA amplification device (VLEAD) is designed for sample-to-answer Zika virus detection. RNA is enriched with VLEAD in 25 min. A colorimetric signal is generated with SYBR Green dye and a blue LED flashlight after 25 min of reverse transcription loop-mediated amplification (RT-LAMP).

An inside job: An intermolecular C(sp³)−H amination reaction is reported that is promoted by internal oxidants and is realized under mild conditions. Trifluoroacetylated hydrazones that are generated upon C=N bond formation are further transformed into various useful compounds decorated with a trifluoromethyl group.

Photocarboxylation: Visible-light-promoted metal-free difunctionalization of alkenes using CO₂ and readily available Si−H and C(sp³)−H reagents has been realized by the merging of photoredox and hydrogen-atom-transfer catalysis. A variety of valuable compounds, such as β-silacarboxylic acids and acids bearing a γ-heteroatom (e.g., N, O, S) can be directly accessed from simple alkenes in a redox-neutral fashion.

A cooperative catalytic method for the asymmetric oxa-Pictet–Spengler reaction has been developed. This method, demonstrated in the synthesis of substituted tetrahydropyranoindoles, has enabled a six-step asymmetric synthesis of (−)-coixspirolactam C.

An immortal FLP system composed of organophosporus superbase and organoaluminum promoted the living polymerization of methyl methacrylate, achieving polymers with medium to ultrahigh molecular weight (M_n up to 1927 kg mol⁻¹) and narrow molecular weight distribution.

Spice up your life! Covalent attachment of a fluorescent BODIPY dye has been exploited to enhance the aggregation propensity of capsaicin—the major active component of chili peppers—in aqueous media. Due to the improved delivery of active capsaicin-based molecules to the tumour tissue upon aggregation, the effective doses for prostate cancer treatment could be successfully reduced by two orders of magnitude.

As easy as one, two, three: Consecutive three-component coupling-(3+3)-anellation reactions of acid chlorides, alkynes, and cyclic amidines rapidly furnish water-soluble blue-emissive tricyclic 2-aminopyridinium salts in a diversity-oriented fashion.

Chemical processes within biological cells often occur inside organelles. This high degree of intracellular organization has inspired the development of gel-based artificial organelles that enable sequence-specific and programmable localization of cell-free transcription and translation reactions inside an artificial cellular system.

A highly chemoselective chloromethylenation of functionalized esters using (di)chloroacetic acid and LiHMDS was carried out in a continuous-flow setup under unprecedented mild and scalable conditions. The resulting (crude) products were reacted either in cyclcocondensations or a novel catalyst-free substitution reaction to give valuable 1,4-diketones.

Mechanically compliant organic crystals from a simple anthracene derivative were tested as optical waveguides for both active and passive light transduction. The mode of operation depends on the wavelength of the incident light.

Strengths and weaknesses: Dimeric chalcogen-bonding capsules display a distinct behavior depending on the association strength, as shown by X-ray structures and confirmed by NMR spectroscopy solution studies. While capsules based on weak S⋅⋅⋅N interactions rely on solvation and the associated hemisphere preorganization, capsular assemblies formed by strong Te⋅⋅⋅N interactions are beyond external influences.