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Protein semi‐synthesis inside live cells from exogenous and endogenous parts offers unique possibilities for studying proteins in their native context. Split‐intein‐mediated protein trans‐splicing is predestined for such endeavors and has seen some successes, but a much larger variety of established split inteins and associated protocols is urgently needed. We characterized the association and splicing parameters of the Gp41‐1 split intein, which favorably revealed a nanomolar affinity between the intein fragments combined with the exceptionally fast splicing rate. Following bead‐loading of a chemically modified intein fragment precursor into live mammalian cells, we fluorescently labeled target proteins on their N‐ and C‐termini with short peptide tags, thus ensuring minimal perturbation of their structure and function. In combination with a nuclear‐entrapment strategy to minimize cytosolic fluorescence background, we applied our technique for super‐resolution imaging and single‐particle tracking of the outer mitochondrial protein Tom20 in HeLa cells., To chemically modify proteins inside cells with an exogenously prepared, labeled backbone fragment we have explored the fastest splicing split intein. Excess intein reagent is removed to the nucleus to increase the signal‐to‐noise ratio in the cytoplasm. We report synthetic fluorophore attachment for super‐resolution and single‐molecule tracking studies.

Liquid state self‐assembly is important for the understanding of the complex structures developed in abiogenesis and biogenesis as well as for numerous potential technological applications. Herein we report the first body‐centered cubic liquid crystalline phase with 8‐connected network topology and open octahedral network structure. It is formed by dynamic soft self‐assembly of X‐shaped polyphiles with oligo(para‐phenylene‐ethynylene) cores. The π‐conjugated rods with perfluorinated inner benzene rings form networks conjoined by eight‐way junctions, which are formed by nano‐segregated spheres involving hydrogen‐bonded polar end groups, while the branched aliphatic chains at opposite sides of the cores fill the continuum. This novel cubic phase is based on the I‐WP minimal surface separating the frameworks of polyaromatic cores from the most disordered chain segments. It can also be considered as a dense sphere packing. Such liquid organic frameworks, representing hybrids of sphere packings and networks could be of interest for organic photonics and other technologies., The first 8‐connected network based on the I‐WP minimal surface is formed by dynamic soft self‐assembly of X‐shaped polyphiles with oligo(para‐phenylene‐ethynylene) cores. This Im 3‾ m cubic liquid‐crystalline phase is one of a new kind of cubic phases combining a network structure of rod‐bundles interconnected by polar spheres.

The single‐domain GH11 glycosidase from Bacillus circulans (BCX) is involved in the degradation of hemicellulose, which is one of the most abundant renewable biomaterials in nature. We demonstrate that BCX in solution undergoes minimal structural changes during turnover. NMR spectroscopy results show that the rigid protein matrix provides a frame for fast substrate binding in multiple conformations, accompanied by slow conversion, which is attributed to an enzyme‐induced substrate distortion. A model is proposed in which the rigid enzyme takes advantage of substrate flexibility to induce a conformation that facilitates the acyl formation step of the hydrolysis reaction., The enzyme xylanase from Bacillus circulans (BCX) is involved in the breakdown of xylan, which is one of the most abundant materials in wood. NMR experiments demonstrate that in solution the enzyme is rigid and does not change its structure during turnover. Binding of the substrate occurs in many orientations, including a distorted form. A model is presented for the effect of substrate dynamics on enzyme function.

The ligands L1 and L2 form trinuclear self‐assembled complexes with Cu2+ (i.e. [(L1)2Cu3]6+ or [(L2)2Cu3]6+) both of which act as a host to a variety of anions. Inclusion of long aliphatic chains on these ligands allows the assemblies to extract anions from aqueous media into organic solvents. Phosphate can be removed from water efficiently and highly selectively, even in the presence of other anions., The ligands L1 and L2 form trinuclear self‐assemblies with Cu2+ (i.e. [L 2Cu3]6+) both of which act as hosts to a variety of anions. Inclusion of long aliphatic chains on these ligands allows the self‐assemblies to extract anions from aqueous media into organic solvents. Phosphate anions can be removed from water efficiently and highly selectively in the presence of other anions.

A sunlight‐powered process is reported that employs carbon dots (CDs) as light absorbers for the conversion of lignocellulose into sustainable H2 fuel and organics. This photocatalytic system operates in pure and untreated sea water at benign pH (2–8) and ambient temperature and pressure. The CDs can be produced in a scalable synthesis directly from biomass itself and their solubility allows for good interactions with the insoluble biomass substrates. They also display excellent photophysical properties with a high fraction of long‐lived charge carriers and the availability of a reductive and an oxidative quenching pathway. The presented CD‐based biomass photoconversion system opens new avenues for sustainable, practical, and renewable fuel production through biomass valorization., Biomass‐derived materials photoconvert biomass: A triple natural resource system is reported that uses solar energy to convert biomass from untreated water into sustainable H2 and organics. The process is photocatalyzed by scalable carbon dots produced from α‐cellulose that act as water‐soluble light absorbers to photoconvert lignocellulose with a Ni cocatalyst. The carbon dots function under ambient conditions and benign aqueous solution.

Narrow HOMO–LUMO gaps and high charge‐carrier mobilities make larger acenes potentially high‐efficient materials for organic electronic applications. The performance of such molecules was shown to significantly increase with increasing number of fused benzene rings. Bulk quantities, however, can only be obtained reliably for acenes up to heptacene. Theoretically, (oligo)acenes and (poly)acenes are predicted to have open‐shell singlet biradical and polyradical ground states, respectively, for which experimental evidence is still scarce. We have now been able to dramatically lower the HOMO–LUMO gap of acenes without the necessity of unfavorable elongation of their conjugated π system, by incorporating two boron atoms into the anthracene skeleton. Stabilizing the boron centers with cyclic (alkyl)(amino)carbenes gives neutral 9,10‐diboraanthracenes, which are shown to feature disjointed, open‐shell singlet biradical ground states., 9,10‐diboraanthracenes (DBAs) stabilized by cyclic (alkyl)(amino)carbenes (cAACs) are prepared. EPR spectroscopy and quantum chemistry established disjointed singlet biradical ground states for these molecules, which provides experimental evidence for the predicted open‐shell configurations of larger acenes. The incorporation of two boron atoms is a suitable way to lower the HOMO–LUMO band gaps of acene‐type species.

Metal‐ligand cooperativity (MLC) had a remarkable impact on transition metal chemistry and catalysis. By use of the calix[4]pyrrolato aluminate, [1]−, which features a square‐planar AlIII, we transfer this concept into the p‐block and fully elucidate its mechanisms by experiment and theory. Complementary to transition metal‐based MLC (aromatization upon substrate binding), substrate binding in [1]− occurs by dearomatization of the ligand. The aluminate trapps carbonyls by the formation of C−C and Al−O bonds, but the products maintain full reversibility and outstanding dynamic exchange rates. Remarkably, the C−C bonds can be formed or cleaved by the addition or removal of lithium cations, permitting unprecedented control over the system's constitutional state. Moreover, the metal‐ligand cooperative substrate interaction allows to twist the kinetics of catalytic hydroboration reactions in a unique sense. Ultimately, this work describes the evolution of an anti‐van't Hoff/Le Bel species from their being as a structural curiosity to their application as a reagent and catalyst., The calix[4]pyrrolato aluminate enables a transfer of metal–ligand cooperativity from the d‐ into the p‐block. The compound traps carbonyls and delivers products that are showing highly dynamic–covalent behavior. Lithium ions provide full control over the formation and cleavage of C−C bonds. The adjustability in substrate activation enables a unique concept for rate control in catalysis.

The RHO gene encodes the G‐protein‐coupled receptor (GPCR) rhodopsin. Numerous mutations associated with impaired visual cycle have been reported; the G90D mutation leads to a constitutively active mutant form of rhodopsin that causes CSNB disease. We report on the structural investigation of the retinal configuration and conformation in the binding pocket in the dark and light‐activated state by solution and MAS‐NMR spectroscopy. We found two long‐lived dark states for the G90D mutant with the 11‐cis retinal bound as Schiff base in both populations. The second minor population in the dark state is attributed to a slight shift in conformation of the covalently bound 11‐cis retinal caused by the mutation‐induced distortion on the salt bridge formation in the binding pocket. Time‐resolved UV/Vis spectroscopy was used to monitor the functional dynamics of the G90D mutant rhodopsin for all relevant time scales of the photocycle. The G90D mutant retains its conformational heterogeneity during the photocycle., Rhodopsin is the major dim light receptor in vertebrate eyes. Numerous mutations associated with impaired visual cycles are known. The G90D mutation leads to a constitutively active mutant form of rhodopsin that causes congenital stationary night blindness (CSNB). We investigated the consequences of this mutation on the visual cycle, both in terms of structural aspects and dynamic changes.

We report a single‐molecule mechanistic investigation into 2‐cyanobenzothiazole (CBT) chemistry within a protein nanoreactor. When simple thiols reacted reversibly with CBT, the thioimidate monoadduct was approximately 80‐fold longer‐lived than the tetrahedral bisadduct, with important implications for the design of molecular walkers. Irreversible condensation between CBT derivatives and N‐terminal cysteine residues has been established as a biocompatible reaction for site‐selective biomolecular labeling and imaging. During the reaction between CBT and aminothiols, we resolved two transient intermediates, the thioimidate and the cyclic precursor of the thiazoline product, and determined the rate constants associated with the stepwise condensation, thereby providing critical information for a variety of applications, including the covalent inhibition of protein targets and dynamic combinatorial chemistry., Better off alone: A nanoreactor approach was used to investigate the chemistry of2‐cyanobenzothiazole (CBT), an important bioorthogonal reagent, at the single‐molecule level. Reactions with thiols and aminothiols revealed mechanistic and kinetic information with important implications for several essential applications of CBT reagents.

The bioorthogonal inverse‐electron‐demand Diels–Alder (IEDDA) cleavage reaction between tetrazine and trans‐cyclooctene (TCO) is a powerful way to control the release of bioactive agents and imaging probes. In this study, a pretargeted activation strategy using single‐walled carbon nanotubes (SWCNTs) that bear tetrazines (TZ@SWCNTs) and a TCO‐caged molecule was used to deliver active effector molecules. To optimize a turn‐on signal by using in vivo fluorescence imaging, we developed a new fluorogenic near‐infrared probe that can be activated by bioorthogonal chemistry and image tumours in mice by caging hemicyanine with TCO (tHCA). With our pretargeting strategy, we have shown selective doxorubicin prodrug activation and instantaneous fluorescence imaging in living cells. By combining a tHCA probe and a pretargeted bioorthogonal approach, real‐time, non‐invasive tumour visualization with a high target‐to‐background ratio was achieved in a xenograft mice tumour model. The combined advantages of enhanced stability, kinetics and biocompatibility, and the superior pharmacokinetics of tetrazine‐functionalised SWCNTs could allow application of targeted bioorthogonal decaging approaches with minimal off‐site activation of fluorophore/drug., Pretarget then activate: Functionalization of single‐walled carbon nanotubes (SWCNTs) with tetrazines led to a stable and biocompatible material that undergoes a rapid inverse‐electron‐demand Diels–Alder reaction with trans‐cyclooctene caged molecules. This approach enables bioorthogonal activation of responsive drugs or probes in solid tumours in a strictly controlled manner.

The geminal frustrated Lewis pair (F5C2)3SnCH2P(tBu)2 (1) reacted with N‐sulfinylaniline PhNSO to afford the first sulfur monoxide adduct of a main group metal, (F5C2)3SnCH2P(tBu)2⋅SO (2), which contains a SnCPSO ring. The second product is a phenylnitrene adduct of 1. The surprising stability of 2 was compared with the stabilities of the so far inaccessible O2 and S2 adducts of 1. Attempts to prepare these from 1 and the elemental chalcogens (O2, S8, Se∞, Te∞) led to four‐membered SnCPE ring systems. Quantum‐chemical investigations of 2 demonstrate the bond polarity of the SO unit to stabilize 2., The first adduct of SO to a main group metal system was found by reacting PhNSO with an intramolecular Sn/P frustrated Lewis pair; the exceptional stability of the adduct is attributed to the polarity of the incorporated SO unit.

Tirapazamine (TPZ) has been tested in clinical trials on radio‐chemotherapy due to its potential highly selective toxicity towards hypoxic tumor cells. It was suggested that either the hydroxyl radical or benzotriazinyl radical may form as bioactive radical after the initial reduction of TPZ in solution. In the present work, we studied low‐energy electron attachment to TPZ in the gas phase and investigated the decomposition of the formed TPZ− anion by mass spectrometry. We observed the formation of the (TPZ–OH)− anion accompanied by the dissociation of the hydroxyl radical as by far the most abundant reaction pathway upon attachment of a low‐energy electron. Quantum chemical calculations suggest that NH2 pyramidalization is the key reaction coordinate for the reaction dynamics upon electron attachment. We propose an OH roaming mechanism for other reaction channels observed, in competition with the OH dissociation., Low‐energy electrons make a choice: Upon the attachment of a low‐energy electron to the potential radiosensitizer compound tirapazamine in the gas phase, dissociation of the OH radical is by far the most abundant reaction obtained. Other dissociation channels as well as the metastable parent anion formed upon roaming of OH are computationally predicted.

DNA walkers are molecular machines that can move with high precision onthe nanoscale due to their structural and functional programmability. Despite recent advances in the field that allow exploring different energy sources, stimuli, and mechanisms of action for these nanomachines, the continuous operation and reusability of DNA walkers remains challenging because in most cases the steps, once taken by the walker, cannot be taken again. Herein we report the path regeneration of a burnt‐bridges DNA catenane walker using RNase A. This walker uses a T7RNA polymerase that produces long RNA transcripts to hybridize to the path and move forward while the RNA remains hybridized to the path and blocks it for an additional walking cycle. We show that RNA degradation triggered by RNase A restores the path and returns the walker to the initial position. RNase inhibition restarts the function of the walker., Making burnt bridges passable: A burnt‐bridges DNA walker that employs long RNA transcripts for moving along steps on a DNA‐nanotube path, can operate continuously when an enzymatic strategy is employed which consists of degrading the RNA that block the path through addition of RNase A and subsequently restarting the walking through the use of an RNA inhibitor.

Many interesting target guest molecules have low symmetry, yet most methods for synthesising hosts result in highly symmetrical capsules. Methods of generating lower symmetry pores are thus required to maximise the binding affinity in host–guest complexes. Herein, we use mixtures of tetraaldehyde building blocks with cyclohexanediamine to access low‐symmetry imine cages. Whether a low‐energy cage is isolated can be correctly predicted from the thermodynamic preference observed in computational models. The stability of the observed structures depends on the geometrical match of the aldehyde building blocks. One bent aldehyde stands out as unable to assemble into high‐symmetry cages‐and the same aldehyde generates low‐symmetry socially self‐sorted cages when combined with a linear aldehyde. We exploit this finding to synthesise a family of low‐symmetry cages containing heteroatoms, illustrating that pores of varying geometries and surface chemistries may be reliably accessed through computational prediction and self‐sorting., A sea of expanding shapes: A combined experimental–computational approach enabled the synthesis of low‐symmetry imine cages from mixtures of tetraaldehyde building blocks. This “social self‐sorting” approach was applied to obtain a family of new cages containing heteroatoms, showing that pores of varying geometries and surface chemistries may be reliably accessed.

The challenge of quantitatively forming self‐assembled heterodimers without other equilibrium by‐products is overcome through self‐sorting favored by the introduction of designed shape‐complementary moieties. Such a supramolecular strategy based on cucurbit[8]uril‐directed dimerization is further applied to generate hetero‐chromophore dimers quantitatively, leading to efficient energy transfer (>85 %) upon photoexcitation., Quantitative generation of hetero‐chromophore dimers is realized through cucurbit[8]uril‐directed self‐sorting, favored by the introduction of designed, shape‐complementary moieties. This process results in discrete heterodimeric stacking through supramolecular confinement, enabling efficient interchromophoric energy transfer upon photoexcitation.

The immune scavenger protein DC‐SIGN interacts with glycosylated proteins and has a putative role in facilitating viral infection. How these recognition events take place with different viruses is not clear and the effects of glycosylation on the folding and stability of DC‐SIGN have not been reported. Herein, we report the development and application of a mass‐spectrometry‐based approach to both uncover and characterise the effects of O‐glycans on the stability of DC‐SIGN. We first quantify the Core 1 and 2 O‐glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing. Using ion mobility mass spectrometry, we show how specific O‐glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas‐phase stability of the DC‐SIGN isoforms. We find that rather than the mass or length of glycoprotein modifications, the stability of DC‐SIGN is better correlated with the number of glycosylation sites., Uncovering stability of DC‐SIGN glycoforms with native mass spectrometry: A combined strategy of exoglycosidase sequencing, native mass spectrometry, ion mobility, and gas‐phase unfolding uncovered the occupancy and structural detail of O‐glycans present on the carbohydrate binding domain of DC‐SIGN. Collision‐induced unfolding by ion mobility revealed differences in stability among glycoforms, independent of glycoprotein mass.

The ability to precisely measure and monitor temperature at high resolution at the nanoscale is an important task for better understanding the thermodynamic properties of functional entities at the nanoscale in complex systems, or at the level of a single cell. However, the development of high‐resolution and robust thermal nanosensors is challenging. The design, assembly, and characterization of a group of thermal‐responsive deoxyribonucleic acid (DNA) joints, consisting of two interlocked double‐stranded DNA (dsDNA) rings, is described. The DNA nanojoints reversibly switch between the static and mobile state at different temperatures without a special annealing process. The temperature response range of the DNA nanojoint can be easily tuned by changing the length or the sequence of the hybridized region in its structure, and because of its interlocked structure the temperature response range of the DNA nanojoint is largely unaffected by its own concentration; this contrasts with systems that consist of separated components., A precise thermal sensing DNA nanojoint comprised of two interlocked DNA rings switches reversibly between a static and mobile state at different temperatures. The temperature response range is tuned by changing the length or sequence of the hybridizing region between two rings, which, unlike non‐interlocked systems, is independent from its concentration.

Interactions between carbonyl groups are prevalent in protein structures. Earlier investigations identified dominant electrostatic dipolar interactions, while others implicated lone pair n→π* orbital delocalisation. Here these observations are reconciled. A combined experimental and computational approach confirmed the dominance of electrostatic interactions in a new series of synthetic molecular balances, while also highlighting the distance‐dependent observation of inductive polarisation manifested by n→π* orbital delocalisation. Computational fiSAPT energy decomposition and natural bonding orbital analyses correlated with experimental data to reveal the contexts in which short‐range inductive polarisation augment electrostatic dipolar interactions. Thus, we provide a framework for reconciling the context dependency of the dominance of electrostatic interactions and the occurrence of n→π* orbital delocalisation in C=O⋅⋅⋅C=O interactions., Carbonyls reconciled: Electrostatics and orbital interactions have both been implicated in governing carbonyl interactions. A combined experimental and computational approach reconciles these conflicting explanations of the physiochemical origin of the interaction, demonstrating that orbital delocalisation augments electrostatic control, but for very close carbonyl contacts.

Dimensionality plays an important role in the charge transport properties of organic semiconductors. Although three‐dimensional semiconductors, such as Si, are common in inorganic materials, imparting electrical conductivity to covalent three‐dimensional organic polymers is challenging. Now, the synthesis of a three‐dimensional π‐conjugated porous organic polymer (3D p‐POP) using catalyst‐free Diels–Alder cycloaddition polymerization followed by acid‐promoted aromatization is presented. With a surface area of 801 m2 g−1, full conjugation throughout the carbon backbone, and an electrical conductivity of 6(2)×10−4 S cm−1 upon treatment with I2 vapor, the 3D p‐POP is the first member of a new class of permanently porous 3D organic semiconductors., 3D p‐POP! A 3D π‐conjugated porous organic polymer incorporating in situ formed pentacene linkers was synthesized through a catalyst‐free Diels–Alder cycloaddition polymerization and an acid‐promoted aromatization reaction. The resulting polymer shows high electrical conductivity and is the first member of a class of permanently porous 3D organic semiconductors.

Asymmetric pallada‐electrocatalyzed C−H olefinations were achieved through the synergistic cooperation with transient directing groups. The electrochemical, atroposelective C−H activations were realized with high position‐, diastereo‐, and enantio‐control under mild reaction conditions to obtain highly enantiomerically‐enriched biaryls and fluorinated N−C axially chiral scaffolds. Our strategy provided expedient access to, among others, novel chiral BINOLs, dicarboxylic acids and helicenes of value to asymmetric catalysis. Mechanistic studies by experiments and computation provided key insights into the catalyst's mode of action., EE: E nantioselective E lectrocatalysis was realized in terms of asymmetric C−H activation through transient directing group (TDG)‐enabled pallada‐electrocatalysis. Experiments and calculations rationalize the key transition states, while asymmetric electrocatalysis provided step‐economical access to axially chiral bi(hetero)aryl diols, diacids and helicenes.

Diamondoid cations are reactive intermediates in their functionalization reactions in polar solution. Hydration is predicted to strongly activate their C−H bonds in initial proton abstraction reactions. To study the effects of microhydration on the properties of diamondoid cations, we characterize herein the prototypical monohydrated adamantane cation (C10H16 +–H2O, Ad+–W) in its ground electronic state by infrared photodissociation spectroscopy in the CH and OH stretch ranges and dispersion‐corrected density functional theory (DFT) calculations. The water (W) ligand binds to the acidic CH group of Jahn–Teller distorted Ad+ via a strong CH⋅⋅⋅O ionic H‐bond supported by charge–dipole forces. Although W further enhances the acidity of this CH group along with a proton shift toward the solvent, the proton remains with Ad+ in the monohydrate. We infer essentially free internal W rotation from rotational fine structure of the ν3 band of W, resulting from weak angular anisotropy of the Ad+–W potential., C−H bond activation and free internal rotation: The infrared spectrum of the monohydrated adamantane cation reveals the hydration‐induced activation of its acidic C−H bond. Despite the strong CH⋅⋅⋅O ionic hydrogen bond in this prototypical reaction intermediate, the water ligand undergoes essentially free internal rotation because of weak angular anisotropy of the intermolecular bond.

The catalytic reduction of carbon dioxide (CO2) is considered a major pillar of future sustainable energy systems and chemical industries based on renewable energy and raw materials. Typically, catalysts and catalytic systems are transforming CO2 preferentially or even exclusively to one of the possible reduction levels and are then optimized for this specific product. Here, we report a cobalt‐based catalytic system that enables the adaptive and highly selective transformation of carbon dioxide individually to either the formic acid, the formaldehyde, or the methanol level, demonstrating the possibility of molecular control over the desired product platform., Let it be adaptive: A cobalt‐based molecular system capable of selectively reducing carbon dioxide either to the formic acid, formaldehyde, or methanol level has been developed. This approach shows that molecular control over product formation is possible with suitable catalysts that allow the reaction conditions to be adapted appropriately.

The highly conserved HIV‐1 transactivation response element (TAR) binds to the trans‐activator protein Tat and facilitates viral replication in its latent state. The inhibition of Tat–TAR interactions by selectively targeting TAR RNA has been used as a strategy to develop potent antiviral agents. Therefore, HIV‐1 TAR RNA represents a paradigmatic system for therapeutic intervention. Herein, we have employed biotin‐tagged TAR RNA to assemble its own ligands from a pool of reactive azide and alkyne building blocks. To identify the binding sites and selectivity of the ligands, the in situ cycloaddition has been further performed using control nucleotide (TAR DNA and TAR RNA without bulge) templates. The hit triazole‐linked thiazole peptidomimetic products have been isolated from the biotin‐tagged target templates using streptavidin beads. The major triazole lead generated by the TAR RNA presumably binds in the bulge region, shows specificity for TAR RNA over TAR DNA, and inhibits Tat–TAR interactions., Taking the lead: The highly dynamic secondary TAR RNA structure of HIV‐1 is used to template cycloaddition reactions leading to the generation of triazole‐containing thiazole peptidomimetics as selective leads. The triazole ligand with flexible methylene units selectively binds to TAR RNA over TAR RNA without a bulge and TAR DNA. The ligand presumably binds in the bulge region of the TAR RNA and inhibits its interaction with the Tat peptide.

Cyanines comprising either a benzo[e]‐ or benzo[c,d]indolium core facilitate initiation of radical photopolymerization combined with high power NIR‐LED prototypes emitting at 805 nm, 860 nm, or 870 nm, while different oxime esters function as radical coinitiators. Radical photopolymerization followed an initiation mechanism based on the participation of excited states, requiring additional thermal energy to overcome an existing intrinsic activation barrier. Heat released by nonradiative deactivation of the sensitizer favored the system, even under conditions where a thermally activated photoinduced electron transfer controls the reaction protocol. The heat generated internally by the NIR sensitizer promotes generation of the initiating reactive radicals. Sensitizers with a barbiturate group at the meso‐position preferred to bleach directly, while sensitizers carrying a cyclopentene moiety unexpectedly initiated the photosensitized mechanism., Tackling the impossible: Photoinduced electron transfer between an NIR sensitizer and oxime esters results in unexpected initiation of radical photopolymerization using cyanines as sensitizers. This strategy facilitates unexpected chemistry with environmentally friendly devices.

We report the preparation of lithium‐salt‐free KDA (potassium diisopropylamide; 0.6 m in hexane) complexed with TMEDA (N,N,N′,N′‐tetramethylethylenediamine) and its use for the flow‐metalation of (hetero)arenes between −78 °C and 25 °C with reaction times between 0.2 s and 24 s and a combined flow rate of 10 mL min−1 using a commercial flow setup. The resulting potassium organometallics react instantaneously with various electrophiles, such as ketones, aldehydes, alkyl and allylic halides, disulfides, Weinreb amides, and Me3SiCl, affording functionalized (hetero)arenes in high yields. This flow procedure is successfully extended to the lateral metalation of methyl‐substituted arenes and heteroaromatics, resulting in the formation of various benzylic potassium organometallics. A metalation scale‐up was possible without further optimization., Potassium in flow: Functionalized(hetero)arenes were metalated using a commercial continuous‐flow setup, leading to the corresponding potassium organometallics. Trapping with various electrophiles gave polyfunctionalized (hetero)aromatics in good yields. Further, the flow procedure was extended to the lateral metalation of methyl‐substituted (hetero)arenes.

This report discloses the photochemical homolytic cleavage of iodine azide after its formation following release from polymer‐bound bisazido iodate(I) anions. A series of radical reactions are reported including the 1,2‐functionlization of alkenes and the unprecedented chemoselective oxidation of secondary alcohols in the presence of primary alcohols., Give me azide radicals! Stable and storable polymer‐bound bisazido‐iodate(I) anions are a source of azide radicals upon photochemical activation. These promote azidooxygenations of alkenes and C−H abstraction of alcohols. The latter reactivity initiates the chemoselective oxidation of secondary alcohols and C−H abstraction of aldehydes.

Quinoidal azaacenes with almost pure diradical character (y=0.95 to y=0.99) were synthesized. All compounds exhibit paramagnetic behavior investigated by EPR and NMR spectroscopy, and SQUID measurements, revealing thermally populated triplet states with an extremely low‐energy gap ΔE ST′ of 0.58 to 1.0 kcal mol−1. The species are persistent in solution (half‐life≈14–21 h) and in the solid state they are stable for weeks., Best of two worlds: Lateral fusion of azaacenes onto a quinoidal system furnishes stable diradicals with a radical character (y) of up to 0.99. All compounds exhibit paramagnetic behavior as determined by EPR and NMR spectroscopy and SQUID measurements, revealing thermally populated triplet states with an extremely low‐energy gap ΔE ST of 0.58 to 1.0 kcal mol−1. The species are persistent in solution (half‐life≈14–21 h), and they are stable for weeks in the solid state.

The perfluorinated dihydrophenazine derivative (perfluoro‐5,10‐bis(perfluorophenyl)‐5,10‐dihydrophenazine) (“phenazineF”) can be easily transformed to a stable and weighable radical cation salt by deelectronation (i.e. oxidation) with Ag[Al(ORF)4]/ Br2 mixtures (RF=C(CF3)3). As an innocent deelectronator it has a strong and fully reversible half‐wave potential versus Fc+/Fc in the coordinating solvent MeCN (E°′=1.21 V), but also in almost non‐coordinating oDFB (=1,2‐F2C6H4; E°′=1.29 V). It allows for the deelectronation of [FeIIICp*2]+ to [FeIV(CO)Cp*2]2+ and [FeIV(CN‐tBu)Cp*2]2+ in common laboratory solvents and is compatible with good σ‐donor ligands, such as L=trispyrazolylmethane, to generate novel [M(L)x]n+ complex salts from the respective elemental metals., Innocence is bliss: A novel perfluorinated phenazine ammoniumyl radical cation is shown to be a very strong deelectronator (oxidant). It has broad solvent compatibility, can be used together with good sigma donor ligands, and allows access to tetravalent dicationic iron complexes in common laboratory solvents.

Queuosine (Q) is a hypermodified RNA nucleoside that is found in tRNAHis, tRNAAsn, tRNATyr, and tRNAAsp. It is located at the wobble position of the tRNA anticodon loop, where it can interact with U as well as C bases located at the respective position of the corresponding mRNA codons. In tRNATyr and tRNAAsp of higher eukaryotes, including humans, the Q base is for yet unknown reasons further modified by the addition of a galactose and a mannose sugar, respectively. The reason for this additional modification, and how the sugar modification is orchestrated with Q formation and insertion, is unknown. Here, we report a total synthesis of the hypermodified nucleoside galactosyl‐queuosine (galQ). The availability of the compound enabled us to study the absolute levels of the Q‐family nucleosides in six different organs of newborn and adult mice, and also in human cytosolic tRNA. Our synthesis now paves the way to a more detailed analysis of the biological function of the Q‐nucleoside family., The first total synthesis of the hypermodified RNA nucleoside galactosyl‐queuosine (galQ) was achieved. Moreover, the distribution of this nucleoside as well as mannosyl‐queuosine and queuosine was determined in tissues of newborn and adult mice, and in human cytosolic tRNAs.

The preparation of a molecule with two alkyl‐tethered silylium‐ion sites from the corresponding bis(hydrosilanes) by two‐fold hydride abstraction is reported. The length of the conformationally flexible alkyl bridge is crucial as otherwise the hydride abstraction stops at the stage of a cyclic bissilylated hydronium ion. With an ethylene tether, the open form of the hydronium‐ion intermediate is energetically accessible and engages in another hydride abstraction. The resulting bis(silylium) ion has been NMR spectroscopically and structurally characterized. Related systems based on rigid naphthalen‐n,m‐diyl platforms can only be converted into the dications when the positively charged silylium‐ion units are remote from each other (1,8 versus 1,5 and 2,6)., Supercharged: A single silylium ion is hard to handle but what about two of these superelectrophiles in one molecule in close proximity? Depending on the distance between these Lewis acidic sites, such a previously elusive bidentate Lewis acid can be accessible, characterized, and stored at room temperature.

Herein we report the development of a turn‐on lanthanide luminescent probe for time‐gated detection of nitroreductases (NTRs) in live bacteria. The probe is activated through NTR‐induced formation of the sensitizing carbostyril antenna and resulting energy transfer to the lanthanide center. This novel NTR‐responsive trigger is virtually non‐fluorescent in its inactivated form and features a large signal increase upon activation. We show that the probe is capable of selectively sensing NTR in lysates as well as in live bacteria of the ESKAPE family which are clinically highly relevant multiresistant pathogens responsible for the majority of hospital infections. The results suggest that our probe could be used to develop diagnostic tools for bacterial infections., Illuminating pathogens: A terbium‐based luminescent turn‐on probe was developed capable of tracing nitroreductase in live bacteria using fluorescence lifetime imaging. The probe thus could be used as a new tool for the imaging of bacterial infections.

Aminocyclopropenium ions have raised much attention as organocatalysts and redox active polymers. However, the self‐assembly of amphiphilic aminocyclopropenium ions remains challenging. The first deltic ionic liquid crystals based on aminocyclopropenium ions have been developed. Differential scanning calorimetry, polarizing optical microscopy and X‐ray diffraction provided insight into the unique self‐assembly and nanosegregation of these liquid crystals. While the combination of small headgroups with linear p‐alkoxyphenyl units led to bilayer‐type smectic mesophases, wedge‐shaped units resulted in columnar mesophases. Upon increasing the size and polyphilicity of the aminocyclopropenium headgroup, a lamellar phase was formed., Cyclopropenium‐based liquid crystals form lamellar or columnar mesophases, depending on the substitution of the head group and the number of peripheral chains. The effective volume of headgroup versus hydrophobic part determines the mesophase type. These compounds bridge the gap between low molecular weight organocatalysts and polymeric electrolytes based on cyclopropenium.

Presented here is that isolated, long‐lived electronic states of ReC+ serve as the root cause for distinctly different reactivities of this diatomic ion in the thermal activation of dihydrogen. Detailed high‐level quantum chemical calculations support the experimental findings obtained in the highly diluted gas phase using FT‐ICR mass spectrometry. The origin for the existence of these long‐lived excited electronic states and the resulting implications for the varying mechanisms of dihydrogen splitting are addressed., As a rare example, the coexistence of the ground and long‐lived, low‐lying electronic states for the bare ReC+ ion is identified. These different electronic states cause distinctly different reactivities towards the thermal activation of dihydrogen.

The formation of excitons in OLEDs is spin dependent and can be controlled by electron‐paramagnetic resonance, affecting device resistance and electroluminescence yield. We explore electrically detected magnetic resonance in the regime of very low magnetic fields (, Perdeuteration of a common OLED emitter allows the detection of paramagnetic resonances at field strengths comparable to Earth's. The competition between narrow resonance spectra and a quasistatic zero‐field feature resulting from reduced hyperfine coupling points at a low‐field limit for detecting paramagnetic resonances in radical‐pair‐based systems.

In vitro selected ribozymes are promising tools for site‐specific labeling of RNA. Previously known nucleic acid catalysts attached fluorescently labeled adenosine or guanosine derivatives through 2′,5′‐branched phosphodiester bonds to the RNA of interest. Herein, we report new ribozymes that use orthogonal substrates, derived from the antiviral drug tenofovir, and attach bioorthogonal functional groups, as well as affinity handles and fluorescent reporter units through a hydrolytically more stable phosphonate ester linkage. The tenofovir transferase ribozymes were identified by in vitro selection and are orthogonal to nucleotide transferase ribozymes. As genetically encodable functional RNAs, these ribozymes may be developed for potential cellular applications. The orthogonal ribozymes addressed desired target sites in large RNAs in vitro, as shown by fluorescent labeling of E. coli 16S and 23S rRNAs in total cellular RNA., A strategy for illuminating RNA with fluorescent derivatives of the antiviral acyclic nucleoside phosphonate Tenofovir is presented. Tenofovir transferase ribozymes were identified by in vitro selection and are shown to be orthogonal to nucleotidyl transferase ribozymes, thus enabling site‐specific dual labeling of RNA.

Electrodes based on organic matter operating in aqueous electrolytes enable new approaches and technologies for assembling and utilizing batteries that are difficult to achieve with traditional electrode materials. Here, we report how thiophene‐based trimeric structures with naphthoquinone or hydroquinone redox‐active pendent groups can be processed in solution, deposited, dried and subsequently polymerized in solid state to form conductive (redox) polymer layers without any additives. Such post‐deposition polymerization offers efficient use of material, high mass loading (up to 10 mg cm−2) and good flexibility in the choice of substrate and coating method. By employing these materials as anode and cathode in an acidic aqueous electrolyte a rocking‐chair proton battery is built. The battery shows good cycling stability (85 % after 500 cycles), withstands rapid charging, with full capacity (60 mAh g−1) reached within 100 seconds, allows for direct integration with photovoltaics, and retains its favorable characteristics even at −24 °C., Combining naphthoquinone or hydroquinone redox‐active pendent groups, an all‐organic battery was designed to operate in aqueous electrolyte. This battery does not only show good capacity retention over 500 cycles but can also be charged ultra‐rapidly using a potential step, enabling easy integration with an organic solar cell.

Patterned functionalization can, on the one hand, open the band gap of graphene and, on the other hand, program demanding designs on graphene. The functionalization technique is essential for graphene‐based nanoarchitectures. A new and highly efficient method was applied to obtain patterned functionalization on graphene by mild fluorination with spatially arranged AgF arrays on the structured substrate. Scanning Raman spectroscopy (SRS) and scanning electron microscopy coupled with energy‐dispersive X‐ray spectroscopy (SEM‐EDS) were used to characterize the functionalized materials. For the first time, chemical patterning on the bottom side of graphene was realized. The chemical nature of the patterned functionalization was determined to be the ditopic scenario with fluorine atoms occupying the bottom side and moieties, such as oxygen‐containing groups or hydrogen atoms, binding on the top side, which provides information about the mechanism of the fluorination process. Our strategy can be conceptually extended to pattern other functionalities by using other reactants. Bottom‐side patterned functionalization enables utilization of the top side of a material, thereby opening up the possibilities for applications in graphene‐based devices., Bottoms up! Patterned bottom‐side functionalization of graphene was realized using a 2D substrate patterning method. A very high degree of functionalization and patterned fluorination are demonstrated. Ditopic functionalization is observed with fluorine atoms on the bottom side and moieties, such as oxygen‐containing groups or hydrogen atoms, on the top side.

The use of di(2‐pyridyl)ketone in subcomponent self‐assembly is introduced. When combined with a flexible triamine and zinc bis(trifluoromethanesulfonyl)imide, this ketone formed a new Zn4L4 tetrahedron 1 bearing twelve uncoordinated pyridyl units around its metal‐ion vertices. The acid stability of 1 was found to be greater than that of the analogous tetrahedron 2 built from 2‐formylpyridine. Intriguingly, the peripheral presence of additional pyridine rings in 1 resulted in distinct guest binding behavior from that of 2, affecting guest scope as well as binding affinities. The different stabilities and guest affinities of capsules 1 and 2 enabled the design of systems whereby different cargoes could be moved between cages using acid and base as chemical stimuli., A strategy for improving the acid resistance of a tetrahedral cage has been developed by incorporating additional free pyridyl units on its vertices. The guest binding properties of the cage are also altered compared to the analogous tetrahedron without these peripheral groups, allowing the functions of complete cargo delivery and exchange between the two capsules by using acid and base as chemical stimuli.

The enantioselective intermolecular C2‐allylation of 3‐substituted indoles is reported for the first time. This directing group‐free approach relies on a chiral Ir‐(P, olefin) complex and Mg(ClO4)2 Lewis acid catalyst system to promote allylic substitution, providing the C2‐allylated products in typically high yields (40–99 %) and enantioselectivities (83–99 % ee) with excellent regiocontrol. Experimental studies and DFT calculations suggest that the reaction proceeds via direct C2‐allylation, rather than C3‐allylation followed by in situ migration. Steric congestion at the indole‐C3 position and improved π–π stacking interactions have been identified as major contributors to the C2‐selectivity., An enantioselective C2‐allylation of 3‐substituted indoles is reported, providing C2‐allylated products with excellent regiocontrol. Experimental studies and DFT calculations suggest that the reaction proceeds via direct C2‐allylation with steric congestion at the indole‐C3 position and π–π stacking interactions identified as major contributors to the selectivity observed.

Current antisense oligonucleotide (ASO) therapies for the treatment of central nervous system (CNS) disorders are performed through invasive administration, thereby placing a major burden on patients. To alleviate this burden, we herein report systemic ASO delivery to the brain by crossing the blood–brain barrier using glycemic control as an external trigger. Glucose‐coated polymeric nanocarriers, which can be bound by glucose transporter‐1 expressed on the brain capillary endothelial cells, are designed for stable encapsulation of ASOs, with a particle size of about 45 nm and an adequate glucose‐ligand density. The optimized nanocarrier efficiently accumulates in the brain tissue 1 h after intravenous administration and exhibits significant knockdown of a target long non‐coding RNA in various brain regions, including the cerebral cortex and hippocampus. These results demonstrate that the glucose‐modified polymeric nanocarriers enable noninvasive ASO administration to the brain for the treatment of CNS disorders., The sweet spot: Antisense‐oligonucleotide‐loaded glucosylated‐polyion‐complex micelles can be used for RNA knockdown in various brain regions using blood‐glucose level as an external trigger. Glucose transporter‐1 expressed on the brain capillary endothelial cells binds the glucose‐coated nanocarrier and transports it, along with its cargo, across the blood–brain barrier. This could be used for the treatment of disorders of the central nervous system.

Carbon dots (CDs) have been used for the first time as a sensitizer to initiate and activate free radical and controlled radical polymerization, respectively, based on an ATRP protocol with blue LEDs. Consideration of diverse heteroatom‐doped CDs indicated that N‐doped CDs could serve as an effective photocatalyst and photosensitizer in combination with LEDs emitting either at 405 nm or 470 nm. Free radical polymerization was initiated by combining the CDs with an iodonium or sulfonium salt in tri(propylene glycol) diacrylate. Polymerization of methyl methacrylate (MMA) by photo‐induced ATRP was achieved with CDs and ethyl α‐bromophenylacetate using CuII as catalyst in the ppm range. The polymers obtained showed temporal control, narrower dispersity ≲1.5, and chain‐end fidelity. The first‐order kinetics and ON/OFF experiments additionally gave evidence of the constant concentration of polymer radicals. No remarkable cytotoxic activity was observed for the CDs, underlining their biocompatibility., On the dot: Carbon dots isolated from seaweed work well as a photocatalyst and sensitizer in living and free radical polymerization, while their low cytotoxic activity makes them interesting for medical applications.

Amphiphilic surface groups play an important role in many biological processes. The synthesis of amphiphilic polyphenylene dendrimer branches (dendrons), providing alternating hydrophilic and lipophilic surface groups and one reactive ethynyl group at the core is reported. The amphiphilic surface groups serve as biorecognition units that bind to the surface of adenovirus 5 (Ad5), which is a common vector in gene therapy. The Ad5/dendron complexes showed high gene transduction efficiencies in coxsackie‐adenovirus receptor (CAR)‐negative cells. Moreover, the dendrons offer incorporation of new functions at the dendron core by in situ post‐modifications, even when bound to the Ad5 surface. Surfaces coated with these dendrons were analyzed for their blood‐protein binding capacity, which is essential to predict their performance in the blood stream. A new platform for introducing bioactive groups to the Ad5 surface without chemically modifying the virus particles is provided., Amphiphilic polyphenylene dendrons were prepared and bound to gene vector adenovirus 5 (Ad5) through polar and nonpolar surface groups that control its cellular uptake. The new dendron layer at the Ad5 surface provides reactive groups that are accessible for post‐modifications at the virus surface.

Herein, we report a regioselective alkenyl electrophile synthesis from unactivated olefins that is based on a direct and regioselective C−H thianthrenation reaction. The selectivity is proposed to arise from an unusual inverse‐electron‐demand hetero‐Diels–Alder reaction. The alkenyl sulfonium salts can serve as electrophiles in palladium‐ and ruthenium‐catalyzed cross‐coupling reactions to make alkenyl C−C, C−Cl, C−Br, and C−SCF3 bonds with stereoretention., The regioselective synthesis of sulfonium‐based alkenyl electrophiles was achieved directly through C−H functionalization of simple olefins. The alkenyl sulfonium salts participate in palladium‐catalyzed cross‐coupling and ruthenium‐catalyzed (pseudo)halogenation reactions.

The sensitivity of conventional thin‐film OFET‐based sensors is limited by the diffusion of analytes through bulk films and remains the central challenge in sensing technology. Now, for the first time, an ultrasensitive (sub‐ppb level) sensor is reported that exploits n‐type monolayer molecular crystals (MMCs) with porous two‐dimensional structures. Thanks to monolayer crystal structure of NDI3HU‐DTYM2 (NDI) and controlled formation of porous structure, a world‐record detection limit of NH3 (0.1 ppb) was achieved. Moreover, the MMC‐OFETs also enabled direct detection of solid analytes of biological amine derivatives, such as dopamine at an extremely low concentration of 500 ppb. The remarkably improved sensing performances of MMC‐OFETs opens up the possibility of engineering OFETs for ultrasensitive (bio)chemical sensing., MMCs make sense: Two‐dimensional porous and nonporous monolayer molecular crystals (MMCs) of NDI3HU‐DTYM2 (NDI) were controllably synthesized by drop‐casting on different substrates. Both MMC sensors based on organic field‐effect transistors show high‐sensitivity performance to NH3 vapor. The porous MMC showed relative sensitivity of 72 % upon exposure to 0.1 ppb NH3, while the fluorescent intensity decreased by 40.9 % when exposed to 10 ppb NH3.

The progress in nanomedicine (NM) using nanoparticles (NPs) is mainly based on drug carriers for the delivery of classical chemotherapeutics. As low NM delivery rates limit therapeutic efficacy, an entirely different approach was investigated. A homologous series of engineered CuO NPs was designed for dual purposes (carrier and drug) with a direct chemical composition–biological functionality relationship. Model‐based dissolution kinetics of CuO NPs in the cellular interior at post‐exposure conditions were controlled through Fe‐doping for intra/extra cellular Cu2+ and biological outcome. Through controlled ion release and reactions taking place in the cellular interior, tumors could be treated selectively, in vitro and in vivo. Locally administered NPs enabled tumor cells apoptosis and stimulated systemic anti‐cancer immune responses. We clearly show therapeutic effects without tumor cells relapse post‐treatment with 6 % Fe‐doped CuO NPs combined with myeloid‐derived suppressor cell silencing., A pharmacokinetic model: Dissolution kinetics from iron‐doped copper oxide nanoparticles were modelled to establish structure–release relationships. With those finely tuned kinetics, a cancer treatment orthogonal to conventional chemotherapy was achieved both in vitro and in vivo. Immunization of all animals occurred, rendering them protected against tumor relapse, even upon re‐engraftment of tumor cells.

Solid electrolyte materials are crucial for the development of high‐energy‐density all‐solid‐state batteries (ASSB) using a nonflammable electrolyte. In order to retain a low lithium‐ion transfer resistance, fast lithium ion conducting solid electrolytes are required. We report on the novel superionic conductor Li9AlP4 which is easily synthesised from the elements via ball‐milling and subsequent annealing at moderate temperatures and which is characterized by single‐crystal and powder X‐ray diffraction. This representative of the novel compound class of lithium phosphidoaluminates has, as an undoped material, a remarkable fast ionic conductivity of 3 mS cm−1 and a low activation energy of 29 kJ mol−1 as determined by impedance spectroscopy. Temperature‐dependent 7Li NMR spectroscopy supports the fast lithium motion. In addition, Li9AlP4 combines a very high lithium content with a very low theoretical density of 1.703 g cm−3. The distribution of the Li atoms over the diverse crystallographic positions between the [AlP4]9− tetrahedra is analyzed by means of DFT calculations., Lightweight and with fast lithium ion conduction: Solid electrolytes with a fast ion conduction are crucial for all‐solid‐state batteries. The new material Li9AlP4 combines a high lithium content and a high ionic mobility of 3 mS cm−1 at 25 °C with a very low theoretical density of 1.703 g cm−3.

Constraining a molecule in its bioactive conformation via macrocyclization represents an attractive strategy to rationally design functional chemical probes. While this approach has been applied to enzyme inhibitors or receptor antagonists, to date it remains unprecedented for bifunctional molecules that bring proteins together, such as PROTAC degraders. Herein, we report the design and synthesis of a macrocyclic PROTAC by adding a cyclizing linker to the BET degrader MZ1. A co‐crystal structure of macroPROTAC‐1 bound in a ternary complex with VHL and the second bromodomain of Brd4 validated the rational design. Biophysical studies revealed enhanced discrimination between the second and the first bromodomains of BET proteins. Despite a 12‐fold loss of binary binding affinity for Brd4, macroPROTAC‐1 exhibited cellular activity comparable to MZ1. Our findings support macrocyclization as an advantageous strategy to enhance PROTAC degradation potency and selectivity between homologous targets., Closing the circle: A macrocyclic PROTAC has been designed and synthesized by adding a cyclizing linker to MZ1, a PROTAC targeting the bromodomain of the BET protein, Brd4. A co‐crystal structure of macroPROTAC‐1 bound in a ternary complex with E3 ligase VHL and the second bromodomain of Brd4 validated the rational design. This macrocyclization strategy enhanced the target specificity and cellular activity of the PROTAC.

Photoactive metal complexes employing Earth‐abundant metal ions are a key to sustainable photophysical and photochemical applications. We exploit the effects of an inversion center and ligand non‐innocence to tune the luminescence and photochemistry of the excited state of the [CrN6] chromophore [Cr(tpe)2]3+ with close to octahedral symmetry (tpe=1,1,1‐tris(pyrid‐2‐yl)ethane). [Cr(tpe)2]3+ exhibits the longest luminescence lifetime (τ=4500 μs) reported up to date for a molecular polypyridyl chromium(III) complex together with a very high luminescence quantum yield of Φ=8.2 % at room temperature in fluid solution. Furthermore, the tpe ligands in [Cr(tpe)2]3+ are redox non‐innocent, leading to reversible reductive chemistry. The excited state redox potential and lifetime of [Cr(tpe)2]3+ surpass those of the classical photosensitizer [Ru(bpy)3]2+ (bpy=2,2′‐bipyridine) enabling energy transfer (to oxygen) and photoredox processes (with azulene and tri(n‐butyl)amine)., Super‐long luminescence lifetime (4500 μs) at room temperature, high quantum yield (8.2 %) and reversible redox chemistry in the complex [Cr(tpe)2]3+ containing an Earth‐abundant first row transition metal ion is enabled by ligand bite angle, inversion symmetry and ligand non‐innocence (tpe=1,1,1‐tris (pyrid‐2‐yl)ethane). [Cr(tpe)2]3+ is competent in light‐induced energy and electron transfer processes similar to classical noble metal ion complexes.

Upon injury, psychotropic psilocybin‐producing mushrooms instantly develop an intense blue color, the chemical basis and mode of formation of which has remained elusive. We report two enzymes from Psilocybe cubensis that carry out a two‐step cascade to prepare psilocybin for oxidative oligomerization that leads to blue products. The phosphatase PsiP removes the 4‐O‐phosphate group to yield psilocin, while PsiL oxidizes its 4‐hydroxy group. The PsiL reaction was monitored by in situ 13C NMR spectroscopy, which indicated that oxidative coupling of psilocyl residues occurs primarily via C‐5. MS and IR spectroscopy indicated the formation of a heterogeneous mixture of preferentially psilocyl 3‐ to 13‐mers and suggest multiple oligomerization routes, depending on oxidative power and substrate concentration. The results also imply that phosphate ester of psilocybin serves a reversible protective function., Magic mushroom blues: Hallucinogenic Psilocybe mushrooms turn blue when injured. We report that the phosphatase PsiP and the laccase PsiL degrade psilocybin and initiate blueing. MALDI‐MS and in situ NMR spectroscopy show that the blue color is due to a mixture of quinoid psilocyl oligomers, primarily coupled via carbon 5.