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Recent advances in scanning probe microscopy combined with electron spin resonance have revealed that localized electron spins on or near surfaces can be utilized as building blocks for the bottom-up assembly of functional quantum-coherent nanostructures. In this perspective, we review the recent advances, lay out advantages of this platform and outline the challenges that lie ahead on the way to the application of on-surface atomic spins to quantum information science and quantum computing.

Chiroptical sensing of nitriles is achieved with excellent functional group tolerance by hydrozirconation and subsequent transmetalation of the corresponding iminate to a chromophoric palladium complex. A one-pot workflow that uses the Schwartz reagent and [(η 3 -1- tert -butylindenyl)(μ-Cl)Pd] 2 as sensor generates a palladium complex displaying red-shifted CD inductions and characteristic UV changes. These chiroptical responses are accurately correlated to the enantiomeric ratio and total concentration of the original nitrile.

Lithium iodide enables regioconvergent C-F bond functionalization of isomeric Morita-Baylis-Hillman fluorides with carbon, sulfur, and nitrogen nucleophiles. The defluorinative carbon-carbon and carbon-heteroatom bond formations give multifunctional compounds in excellent yields and with good to high diastereoselectivities at room temperature. The possibility of catalytic enantioselective allylation is also discussed.

The subnanometer distance between tip and sample in a scanning tunneling microscope (STM) enables the application of very large electric fields with a strength as high as ∼1 GV/m. This has allowed for efficient electrical driving of Rabi oscillations of a single spin on a surface at a moderate radiofrequency (RF) voltage on the order of tens of millivolts. Here, we demonstrate the creation of dressed states of a single electron spin localized in the STM tunnel junction by using resonant RF driving voltages. The read-out of these dressed states was achieved all electrically by a weakly coupled probe spin. Our work highlights the strength of the atomic-scale geometry inherent to the STM that facilitates the creation and control of dressed states, which are promising for the design of atomic scale quantum devices using individual spins on surfaces.

Fluorooxindoles undergo asymmetric Michael addition to para -quinone methides under phase-transfer conditions with 10 mol% of a readily available cinchona alkaloid ammonium catalyst. This reaction affords sterically encumbered, multifunctional fluorinated organic compounds displaying two adjacent chirality centers with high yields, ee 's and dr 's.

Investigating the quantum properties of individual spins adsorbed on surfaces by electron spin resonance combined with scanning tunneling microscopy (ESR-STM) has shown great potential for the development of quantum information technology on the atomic scale. A magnetic tip exhibiting high spin polarization is critical for performing an ESR-STM experiment. While the tip has been conventionally treated as providing a static magnetic field in ESR-STM, it was found that the tip can exhibit bistability, influencing ESR spectra. Ideally, the ESR splitting caused by the magnetic interaction between two spins on a surface should be independent of the tip. However, we found that the measured ESR splitting of a metal atom-molecule heterodimer can be tip-dependent. Detailed theoretical analysis reveals that this tip-dependent ESR splitting is caused by a different interaction energy between the tip and each spin of the heterodimer. Our work provides a comprehensive reference for characterizing tip features in ESR-STM experiments and highlights the importance of employing a proper physical model when describing the ESR tip, in particular, for heterospin systems.

Scanning-tunneling microscopy (STM) combined with electron spin resonance (ESR) has enabled single-spin spectroscopy with nanoelectronvolt energy resolution and angstrom-scale spatial resolution, which allows quantum sensing and magnetic resonance imaging at the atomic scale. Extending this spectroscopic tool to a study of multiple spins, however, is nontrivial due to the extreme locality of the STM tunnel junction. Here we demonstrate double electron-electron spin resonance spectroscopy in an STM for two coupled atomic spins by simultaneously and independently driving them using two continuous-wave radio frequency voltages. We show the ability to drive and detect the resonance of a spin that is remote from the tunnel junction while read-out is achieved via the spin in the tunnel junction. Open quantum system simulations for two coupled spins reproduce all double-resonance spectra and further reveal a relaxation time of the remote spin that is longer by an order of magnitude than that of the local spin in the tunnel junction. Our technique can be applied to quantum-coherent multi-spin sensing, simulation, and manipulation in engineered spin structures on surfaces.

Hyperfine interactions have been widely used in material science, organic chemistry, and structural biology as a sensitive probe to local chemical environments. However, traditional ensemble measurements of hyperfine interactions average over a macroscopic number of spins with different geometrical locations and nuclear isotopes. Here, we use a scanning tunneling microscope (STM) combined with electron spin resonance (ESR) to measure hyperfine spectra of hydrogenated-Ti on MgO/Ag(100) at low-symmetry binding sites and thereby determine the isotropic and anisotropic hyperfine interactions at the single-atom level. Combining vector-field ESR spectroscopy with STM-based atom manipulation, we characterize the full hyperfine tensors of 47 Ti and 49 Ti and identify significant spatial anisotropy of the hyperfine interactions for both isotopes. Density functional theory calculations reveal that the large hyperfine anisotropy arises from highly anisotropic distributions of the ground-state electron spin density. Our work highlights the power of ESR-STM-enabled single-atom hyperfine spectroscopy in revealing electronic ground states and atomic-scale chemical environments.

Cross-coupling of alkyl fluorides and organocuprates is accomplished via aluminum halide mediated C-F bond activation and subsequent C sp2 -C sp3 and C sp3 -C sp3 bond formation. Relatively mild conditions allow for smooth activation of notoriously challenging primary and secondary alkyl fluorides while competing alkyl chain rearrangement, HF elimination, and homocoupling reactions are effectively controlled. The utility and functional group tolerance are demonstrated with 23 examples and a variety of coupling products obtained in up to 88% yield.

Here, we describe the prediction of the circular dichroism (CD) response of a three-component chiroptical sensor for enantiomeric excess ( ee ) determination of chiral amines using a multivariate fit to electronic and steric parameters. These computationally derived parameters can be computed for nearly any amine and correlate well with the CD response of the 12 amines comprising the training set. The resulting model was used to accurately predict the CD response of a test set of chiral amines. Theoretical calibration curves were then created and used to determine the ee of solutions of unknown ee . Using this method, the error in ee determination differed by less than 10% compared to experimentally generated calibration curves.

A palladium(phosphinoxazoline) catalyzed method for asymmetric allylic alkylation of α-aryl-α-fluoroacetonitriles is introduced. This reaction achieves C-C bond formation and incorporation of two adjacent chirality centers with moderate to good yields, high enantioselectivities, and up to 15:1 dr .

Tattooing has become increasingly popular throughout society. Despite the recognized issue of adverse reactions in tattoos, regulations remain challenging with limited data available and a missing positive list. The diverse chemical properties of mostly insoluble inorganic and organic pigments pose an outstanding analytical challenge, which typically requires extensive sample preparation. Here, we present a multimodal bioimaging approach combining micro X-ray fluorescence (μXRF) and laser desorption ionization-mass spectrometry (LDI-MS) to detect the elemental and molecular composition in the same sample. The pigment structures directly absorb the laser energy, eliminating the need for matrix application. A computational data processing workflow clusters spatially resolved LDI-MS scans to merge redundant information into consensus spectra, which are then matched against new open mass spectral libraries of tattoo pigments. When applied to 13 tattoo inks and 68 skin samples from skin biopsies in adverse tattoo reactions, characteristic signal patterns of isotopes, ion adducts, and in-source fragments in LDI-MS 1 scans yielded confident compound annotations across various pigment classes. Combined with μXRF, pigment annotations were achieved for all skin samples with 14 unique structures and 2 inorganic pigments, emphasizing the applicability to larger studies. The tattoo-specific spectral libraries and further information are available on the tattoo-analysis.github.io website.

Control of single electron spins constitutes one of the most promising platforms for spintronics, quantum sensing, and quantum information processing. Utilizing single molecular magnets as their hosts establishes an interesting framework since their molecular structure is highly flexible and chemistry-based large-scale synthesis directly provides a way toward scalability. Here, we demonstrate coherent spin manipulation of single molecules on a surface, which we control individually using a scanning tunneling microscope in combination with electron spin resonance. We previously found that iron phthalocyanine (FePc) molecules form a spin-1/2 system when placed on an insulating thin film of magnesium oxide (MgO). Performing Rabi oscillation and Hahn echo measurements, we show that the FePc spin can be coherently manipulated with a phase coherence time T 2 Echo of several hundreds of nanoseconds. Tunneling current-dependent measurements demonstrate that interaction with the tunneling electrons is the dominating source of decoherence. In addition, we perform Hahn echo measurements on small self-assembled arrays of FePc molecules. We show that, despite additional intermolecular magnetic coupling, spin resonance and T 2 Echo are much less perturbed by T 1 spin flip events of neighboring spins than by the tunneling current. This will potentially allow for individual addressable molecular spins in self-assemblies and with application for quantum information processing.

Suzuki cross-coupling of benzylic and unactivated aliphatic fluorides with aryl- and alkenylboronic acids has been achieved via mechanistically distinct Pd and Ni catalyzed pathways that outperform competing protodeboronation, β-hydride elimination, and homocoupling processes. The utility is demonstrated with more than 20 examples including heterocyclic structures, 1,1-disubstituted and trans -1,2-disubstituted alkenes, and by the incorporation of acetonitrile into functionalized (hetero)arenes.

Single lanthanide atoms and molecules are promising candidates for atomic data storage and quantum logic due to the long lifetime of their magnetic quantum states. Accessing and controlling these states through electrical transport requires precise knowledge of their electronic configuration at the level of individual atomic orbitals, especially of the outer shells involved in transport. However, no experimental techniques have so far shown the required sensitivity to probe single atoms with orbital selectivity. Here we resolve the magnetism of individual orbitals in Gd and Ho single atoms on MgO/Ag(100) by combining X-ray magnetic circular dichroism with multiplet calculations and density functional theory. In contrast to the usual assumption of bulk-like occupation of the different electronic shells, we establish a charge transfer mechanism leading to an unconventional singly ionized configuration. Our work identifies the role of the valence electrons in determining the quantum level structure and spin-dependent transport properties of lanthanide-based nanomagnets.

Single atom magnets offer the possibility of magnetic information storage in the most fundamental unit of matter. Identifying the parameters that control the stability of their magnetic states is crucial to design novel quantum magnets with tailored properties. Here, we use X-ray absorption spectroscopy to show that the electronic configuration of dysprosium atoms on MgO(100) thin films can be tuned by the proximity of the metal Ag(100) substrate onto which the MgO films are grown. Increasing the MgO thickness from 2.5 to 9 monolayers induces a change in the dysprosium electronic configuration from 4f 9 to 4f 10 . Hysteresis loops indicate long magnetic lifetimes for both configurations, however, with a different field-dependent magnetic stability. Combining these measurements with scanning tunneling microscopy, density functional theory, and multiplet calculations unveils the role of the adsorption site and charge transfer to the substrate in determining the stability of quantum states in dysprosium single atom magnets.

A novel approach to chiral recognition of small molecules using the classical ninhydrin agent is introduced. Well-defined dynamic covalent chemistry with amines and amino alcohols was developed and applied to quantitative ee sensing with good accuracy using a straightforward mixing protocol and subsequent circular dichroism measurements. This chiroptical assay is fast, broadly useful, practical and repurposes an inexpensive reagent known for more than 100 years in a new application.

Methods for the rapid determination of enantiomeric excess (ee) in asymmetric synthetic methodology development are increasingly in demand as high-throughput experimentation protocols in academia and industry are adopted. Optical approaches have been reported, many of which rely on the use of chemical derivatization or molecular assemblies, resulting in UV/vis, fluorescence, or circular dichroism (CD) signals that report the ee values. While UV/vis and fluorescence approaches benefit from readily available 96- and 384-well plate readers, until recently, no CD plate readers existed. Herein, we report the utility of using the EKKO CD plate reader to analyze a chlorocoumarin amine derivatization methodology for the ee determination of a diverse set of chiral amines with an error margin within ±7%. Linear calibration curves of ee versus CD responses for each amine were obtained, the minimum detectable and quantifiable ee values were calculated, the technique was applied to an asymmetric hydrogenation, and various interferents expected to be present in crude samples are explored. The technique described herein is found to be suitable for high-throughput experimentation that requires a parallel and rapid ee determination step.

Single spins are considered as a versatile candidate for miniaturizing information devices down to the nanoscale. To engineer the spin's properties, metal-organic frameworks provide a promising route which in turn requires thorough understanding of the metal-molecule interaction. Here, we investigate the magnetic robustness of a single iron (Fe) atom in artificially built Fe-tetracyanoethylene (TCNE) complexes by using low-temperature scanning tunneling microscopy (STM). We find that the magnetic anisotropy and spin relaxation dynamics of the Fe atom within the complexes remain unperturbed in comparison to well-isolated Fe atoms. Density functional theory (DFT) calculations support our experimental findings, suggesting that the 3d orbitals of the Fe atom remain largely undisturbed while the 4s and 4p orbitals are rearranged in the process of forming a complex. To precisely determine the location of the spin center within the complex, we utilize STM-based spin relaxometry, mapping out the spatial dependence of spin relaxation with subnanometer resolution. Our work suggests that the magnetic properties of atoms can remain unchanged while being embedded in a weakly bound molecular framework.

A generally useful palladium-catalyzed method for the asymmetric allylic amination with a large variety of isatins, sulfonamides, imides, amines, and N -heterocycles is introduced. A single protocol with a readily available catalyst accomplishes this reaction at room temperature with high yields and enantioselectivities often exceeding 90%, which is demonstrated with 31 examples.

Scanning probe microscopy and spectroscopy, and more recently, single-atom electron spin resonance, have allowed the direct observation of electron dynamics at the atomic limit. The interpretation of data is strongly dependent on model Hamiltonians. However, fitting effective spin Hamiltonians to experimental data lacks the ability to explore a vast number of potential systems of interest. By using plane-wave density functional theory as starting point, we build a multiplet Hamiltonian making use of maximally localized Wannier functions. The Hamiltonian contains spin-orbit and electron-electron interactions needed to obtain the relevant spin dynamics. The resulting reduced Hamiltonian is solved by exact diagonalization. We compare three prototypical cases of 3d transition metals Mn (total spin S = 5/2), Fe ( S = 2), and Co ( S = 3/2) on MgO with experimental data and find that our calculations can accurately predict the spin orientation and anisotropy of the magnetic adatom. Our method does not rely on experimental input and allows us to explore and predict the fundamental magnetic properties of adatoms on surfaces.

Quantitative chirality sensing of terpenes and terpenoids exhibiting a single double bond as the only functional group, such as α-pinene, β-pinene and camphene, or two alkene moieties like limonene, valencene, and β-caryophyllene is among the most difficult molecular recognition tasks. In this work, a fast chiroptical sensing method that accomplishes determination of the enantiomeric excess and overall amount of a large variety of terpenes and terpenoids using readily available phosphine derived late transition metal complexes is presented. The terpene coordination is complete within 10 min and coincides with spontaneous induction of strong CD signals at long wavelengths and distinct UV changes which together allow accurate ee and concentration quantification.

The comprehensive determination of the absolute configuration, enantiomeric ratio, and total amount of standard amino acids by optical methods adaptable to high-throughput screening with modern plate readers has remained a major challenge to date. We now present a small-molecular probe that smoothly reacts with amino acids and biothiols in aqueous solution and thereby generates distinct chiroptical responses to accomplish this task. The achiral sensor is readily available, inexpensive, and suitable for chiroptical analysis of each of the 19 standard amino acids, biothiols, aliphatic, and aromatic amines and amino alcohols. The sensing method is operationally simple, and data collection and processing are straightforward. The utility and practicality of the assay are demonstrated with the accurate analysis of 10 aspartic acid samples covering a wide concentration range and largely varying enantiomeric compositions. Accurate er sensing of 85 scalemic samples of Pro, Met, Cys, Ala, methylpyrrolidine, 1-(2-naphthyl)amine, and mixtures thereof is also presented.

The determination of the enantiopurity and the concentration of chiral compounds by chiroptical sensing with molecular probes is increasingly attractive for high-throughput screening applications including streamlined asymmetric reaction development. In this study, we use stereodynamic aluminum biphenolate complexes for quantitative ee and concentration analysis of amino alcohols and α-hydroxy acids. An important feature of the tropos biphenolate ligand used is the presence of a phenylacetylene antenna for optimal chirality recognition and CD/UV responses at high wavelengths. The complexation-driven chirality amplification yields strong CD signals, which allows quantitative chiroptical sensing with good accuracy. We show that aluminate biphenolate sensors can exhibit linear and nonlinear correlations between the induced CD signals and the enantiomeric composition or concentration of the chiral substrate.

Diastereodivergent and enantioselective conversion of isatin ketimines to α-fluoro-β-aminonitriles with vicinal tetrasubstituted stereocenters is achieved by a chiral copper complex/guanidine base catalyzed Mannich reaction with proper choice of the bisphosphine ligand. The reaction is broad in scope, scalable, and provides efficient access to a series of 3-aminoindolinones exhibiting a quaternary carbon-fluorine stereocenter with high yields and stereoselectivities. Selective transformations of the Mannich reaction products into multifunctional 3-aminooxindoles without erosion of enantiomeric and diastereomeric purity highlight the synthetic utility., Competing Interests: The authors declare no competing financial interest.

A multiparameter gas sensor based on distributed feedback interband cascade lasers emitting at 4.35 μm and ultrafast electro-spun luminescence oxygen sensors has been developed for the quantification and continuous monitoring of 13 CO 2 / 12 CO 2 isotopic ratio changes and oxygen in exhaled mouse breath samples. Mid-infrared absorption spectra for quantitatively monitoring the enrichment of 13 CO 2 levels were recorded in a miniaturized dual-channel substrate-integrated hollow waveguide using balanced ratiometric detection, whereas luminescence quenching was used for synchronously detecting exhaled oxygen levels. Allan variance analysis verified a CO 2 measurement precision of 1.6‰ during a 480 s integration time. Routine online monitoring of exhaled mouse breath was performed in 14 mechanically ventilated and instrumented mice and demonstrated the feasibility of online isotope-selective exhaled breath analysis within microliters of probed gas samples using the reported combined sensor platform.

This Perspective highlights the advances of optical methods for asymmetric reaction discovery. Optical analysis allows for the determination of absolute configuration, enantiomeric excess and reaction yield that is amenable to high-throughput experimentation. Thus, the synthetic organic community is encouraged to incorporate the methods discussed to expedite the development of high-yielding, enantioselective transformations.

We have achieved high-efficiency polycrystalline perovskite light-emitting diodes (PeLEDs) based on formamidinium (FA) and cesium (Cs) mixed cations without quantum dot synthesis. Uniform single-phase FA 1- x Cs x PbBr 3 polycrystalline films were fabricated by one-step formation with various FA:Cs molar proportions; then the influences of chemical composition on film morphology, crystal structure, photoluminescence (PL), and electroluminescence (EL) were systematically investigated. Incorporation of Cs + cations in FAPbBr 3 significantly reduced the average grain size (to 199 nm for FA:Cs = 90:10) and trap density; these changes consequently increased PL quantum efficiency (PLQE) and PL lifetime of FA 1- x Cs x PbBr 3 films and current efficiency (CE) of PeLEDs. Further increase in Cs molar proportion from 10 mol % decreased crystallinity and purity, increased trap density, and correspondingly decreased PLQE, PL lifetime, and CE. Incorporation of Cs also increased photostability of FA 1- x Cs x PbBr 3 films, possibly due to suppressed formation of light-induced metastable states. FA 1- x Cs x PbBr 3 PeLEDs show the maximum CE = 14.5 cd A -1 at FA:Cs = 90:10 with very narrow EL spectral width (21-24 nm); this is the highest CE among FA-Cs-based PeLEDs reported to date. This work provides an understanding of the influences of Cs incorporation on the chemical, structural, and luminescent properties of FAPbBr 3 polycrystalline films and a breakthrough to increase the efficiency of FA 1- x Cs x PbBr 3 PeLEDs.

Ozone is an effective disinfectant against all types of waterborne pathogens. However, accurate and quantitative kinetic data regarding virus inactivation by ozone are scarce, because of the experimental challenges associated with the high reactivity of ozone toward viruses. Here, we established an experimental batch system that allows tailoring and quantifying of very low ozone exposures and simultaneously measuring virus inactivation. Second-order ozone inactivation rate constants (k O 3 -virus ) of five enteric viruses [laboratory and two environmental strains of coxsackievirus B5 (CVF, CVEnv1, and CVEnv2), human adenovirus (HAdV), and echovirus 11 (EV)] and four bacteriophages (MS2, Qβ, T4, and Φ174) were measured in buffered solutions. The k O 3 -virus values of all tested viruses ranged from 4.5 × 10 5 to 3.3 × 10 6 M -1 s -1 . For MS2, k O 3 -MS2 depended only weakly on temperature (2-22 °C; E a = 22.2 kJ mol -1 ) and pH (6.5-8.5), with an increase in k O 3 -MS2 with increasing pH. The susceptibility of the selected viruses toward ozone decreases in the following order: Qβ > CVEnv2 > EV ≈ MS2 > Φ174 ≈ T4 > HAdV > CVF ≈ CVEnv1. On the basis of the measured k O 3 -Virus and typical ozone exposures applied in water and wastewater treatment, we conclude that ozone is a highly effective disinfectant for virus control.

A highly diastereoselective organocatalytic method that produces 3-fluoro-3'-hydroxy-3,3'-bisoxindoles and the corresponding 3-fluoro-3'-amino derivatives having two adjacent chirality centers from fluorooxindoles and isatins in high yields is described. The reaction occurs in protic solvents at room temperature, it can be upscaled without compromising yield and stereoselectivity, and chromatographic product purification is not required.

Asymmetric thiourea and squaramide catalysis provides access to synthetically versatile α-oxetanyl and α-azetidinyl alkyl halides exhibiting a tetrasubstituted chiral carbon center with high yields and enantioselectivities. The products are readily transformed with negligible erosion of enantiopurity and excellent diastereoselectivity to a diverse group of multifunctional compounds including fluorooxindoles with two contiguous chirality centers, fluorinated heterocyclic spiranes, and polyspiro compounds.

Pure green light-emitting diodes (LEDs) are essential for realizing an ultrawide color gamut in next-generation displays, as is defined by the recommendation (Rec.) 2020 standard. However, because the human eye is more sensitive to the green spectral region, it is not yet possible to achieve an ultrapure green electroluminescence (EL) with a sufficiently narrow bandwidth that covers >95% of the Rec. 2020 standard in the CIE 1931 color space. Here, we demonstrate efficient, ultrapure green EL based on the colloidal two-dimensional (2D) formamidinium lead bromide (FAPbBr 3 ) hybrid perovskites. Through the dielectric quantum well (DQW) engineering, the quantum-confined 2D FAPbBr 3 perovskites exhibit a high exciton binding energy of 162 meV, resulting in a high photoluminescence quantum yield (PLQY) of ∼92% in the spin-coated films. Our optimized LED devices show a maximum current efficiency (η CE ) of 13.02 cd A -1 and the CIE 1931 color coordinates of (0.168, 0.773). The color gamut covers 97% and 99% of the Rec. 2020 standard in the CIE 1931 and the CIE 1976 color space, respectively, representing the "greenest" LEDs ever reported. Moreover, the device shows only a ∼10% roll-off in η CE (11.3 cd A -1 ) at 1000 cd m -2 . We further demonstrate large-area (3 cm 2 ) and ultraflexible (bending radius of 2 mm) LEDs based on 2D perovskites.

Colloidal metal-halide perovskite quantum dots (QDs) with a dimension less than the exciton Bohr diameter D B (quantum size regime) emerged as promising light emitters due to their spectrally narrow light, facile color tuning, and high photoluminescence quantum efficiency (PLQE). However, their size-sensitive emission wavelength and color purity and low electroluminescence efficiency are still challenging aspects. Here, we demonstrate highly efficient light-emitting diodes (LEDs) based on the colloidal perovskite nanocrystals (NCs) in a dimension > D B (regime beyond quantum size) by using a multifunctional buffer hole injection layer (Buf-HIL). The perovskite NCs with a dimension greater than D B show a size-irrespective high color purity and PLQE by managing the recombination of excitons occurring at surface traps and inside the NCs. The Buf-HIL composed of poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS) and perfluorinated ionomer induces uniform perovskite particle films with complete film coverage and prevents exciton quenching at the PEDOT:PSS/perovskite particle film interface. With these strategies, we achieved a very high PLQE (∼60.5%) in compact perovskite particle films without any complex post-treatments and multilayers and a high current efficiency of 15.5 cd/A in the LEDs of colloidal perovskite NCs, even in a simplified structure, which is the highest efficiency to date in green LEDs that use colloidal organic-inorganic metal-halide perovskite nanoparticles including perovskite QDs and NCs. These results can help to guide development of various light-emitting optoelectronic applications based on perovskite NCs.

We extracted the electronic disorder energy of the organic-inorganic lead-halide hybrid perovskite CH 3 NH 3 PbBr 3 from temperature-dependent absorption data. We showed that the disorder at room temperature is ∼30 meV and is due to strong electron-phonon coupling with the longitudinal-optical mode of energy 16 meV. This mode can be attributed to longitudinal-optical phonons of the inorganic PbBr 6 frame; this conclusion highlights the polaronic nature of electronic excitations in CH 3 NH 3 PbBr 3 . We showed that structural disorder is of the same impact as thermal disorder. A temperature-dependence of the exciton binding energy was observed close to the orthorhombic-to-tetragonal phase-transition temperature.

Pyridoxal-5'-phosphate (PLP) is introduced to a biomimetic indicator displacement assay for simultaneous determination of the absolute configuration, enantiomeric composition and concentration of unprotected amino acids, amino alcohols and amines. The chiroptical assay is based on fast imine metathesis with a PLP aryl imine probe to capture the target compound for circular dichroism and fluorescence sensing analysis. The substrate binding yields characteristic Cotton effects that provide information about the target compound ee and the synchronous release of the indicator results in a nonenantioselective off-on fluorescence response that is independent of the enantiomeric sample composition and readily correlated to the total analyte concentration.

An organocatalytic method that achieves insertion of isatins into aryl difluoronitromethyl ketones under mild conditions is described. The reaction occurs in the presence of 20 mol % of DBU and with 100% atom economy. A series of isatin derived difluoronitromethyl substituted tertiary alcohol benzoates and naphthoates were prepared in 81-99% yield. The general synthetic usefulness of these 3-hydroxyoxindole derivatives is demonstrated with the selective reduction to fluorooximes.

Self-assembly of a stereodynamic phosphine ligand, Pd(II), and a chiral amine, amino alcohol, or amino acid generates characteristic UV and CD signals that can be used for quantitative stereochemical analysis of the bound substrate. A robust mix-and-measure chiroptical sensing protocol has been developed and used to determine the absolute configuration, ee, and yield of an amine produced by Ir-catalyzed asymmetric hydrogenation of an iminium salt. The analysis requires only 1 mg of the crude reaction mixture and minimizes cost, labor, time, and waste.

Keratinocyte-specific deletion of ADAM17 in mice impairs terminal differentiation of keratinocytes leading to severe epidermal barrier defects. Mice deficient for ADAM17 in keratinocytes phenocopy mice with a keratinocyte-specific deletion of epidermal growth factor receptor (EGFR), which highlights the role of ADAM17 as a "ligand sheddase" of EGFR ligands. In this study, we aim for the first proteomic/degradomic approach to characterize the disruption of the ADAM17-EGFR signaling axis and its consequences for epidermal barrier formation. Proteomic profiling of the epidermal proteome of mice deficient for either ADAM17 or EGFR in keratinocytes at postnatal days 3 and 10 revealed highly similar protein alterations for ADAM17 and EGFR deficiency. These include massive proteome alterations of structural and regulatory components important for barrier formation such as transglutaminases, involucrin, filaggrin, and filaggrin-2. Cleavage site analysis using terminal amine isotopic labeling of substrates revealed increased proteolytic processing of S100 fused-type proteins including filaggrin-2. Alterations in proteolytic processing are supported by altered abundance of numerous proteases upon keratinocyte-specific Adam17 or Egfr deletion, among them kallikreins, cathepsins, and their inhibitors. This study highlights the essential role of proteolytic processing for maintenance of a functional epidermal barrier. Furthermore, it suggests that most defects in formation of the postnatal epidermal barrier upon keratinocyte-specific ADAM17 deletion are mediated via EGFR.

Immobilization of bioactive molecules (BAMs) on a nanometer scale is of great interest for functionalization of implant and scaffold surfaces in current biomaterials research. A system for immobilization of one or more compounds is described, which is based on nanomechanical fixation of single-stranded nucleic acids into an anodic titanium oxide layer and their subsequent hybridization with BAMs conjugated to the respective complementary strands. This paper focuses on further development and in depth understanding of the immobilization system, as some of the major findings established for common sensor applications for immobilization of single-stranded DNA onto gold surfaces cannot be transferred to the TiO2 surface. The first approach concerning the influence of the internal spacer sequence revealed the best performance for a polyadenine based sequence out of four homologous spacer sequences (A30, T30, C30, and G30). This overall best performance of the A30 spacer is attributed to an increased contour length by nucleotide staggering, which resulted in the best protection of the hybridization sequence from unfavorable interactions with the surface or damaging attacks by reactive oxygen species. The second approach comprises the implementation of a lateral spacer, also based on a homologous sequence of A30. Simultaneous as well as sequential adsorption of anchor strands and spacer strands were performed, and it could be shown that a preadsorption with high density of the spacer was most effective to increase hybridization efficiency.

Molecular hosts capable of chiroptical sensing of complexed guest molecules offer an attractive alternative to conventional methods for the analysis of the absolute configuration and enantiopurity. Sensors based on the Pfeiffer effect rely on complexation-driven asymmetric transformation of the first kind and can produce a chiroptical signal against an otherwise null background. To be most effective, the wavelength of the induced chiroptical sensor readout should be free and clear of interfering signals coming from the sample under investigation. In this study, we report the introduction of stereodynamic zinc complexes of antenna biphenols, a new class of sensors bearing antenna-like appendages that can extend the wavelength of the chiroptical signal while also improving enantioselective guest recognition.

The conformational preference of 2,2'-bisanilides was investigated by variable-temperature NMR spectroscopy, NMR titration and diffusion experiments, IR spectroscopy, computational analysis, and X-ray crystallography. The formation of a conformation having the two amide moieties linked by an intramolecular hydrogen bond was detected at low temperatures. The interconversion kinetics of the two conformational species of bisanilide 2 were determined by NMR line shape analysis. The formation of a supramolecule linked by intermolecular hydrogen bonds was ruled out by means of DMSO titration, DOSY experiments, and steric considerations.

Celiac disease is characterized by intestinal inflammation triggered by gliadin, a component of dietary gluten. Oral administration of proteases that can rapidly degrade gliadin in the gastric compartment has been proposed as a treatment for celiac disease; however, no protease has been shown to specifically reduce the immunogenic gliadin content, in gastric conditions, to below the threshold shown to be toxic for celiac patients. Here, we used the Rosetta Molecular Modeling Suite to redesign the active site of the acid-active gliadin endopeptidase KumaMax. The resulting protease, Kuma030, specifically recognizes tripeptide sequences that are found throughout the immunogenic regions of gliadin, as well as in homologous proteins in barley and rye. Indeed, treatment of gliadin with Kuma030 eliminates the ability of gliadin to stimulate a T cell response. Kuma030 is capable of degrading >99% of the immunogenic gliadin fraction in laboratory-simulated gastric digestions within physiologically relevant time frames, to a level below the toxic threshold for celiac patients, suggesting great potential for this enzyme as an oral therapeutic for celiac disease.

Cells secrete extracellular vesicles (EVs) into their microenvironment that act as mediators of intercellular communication under physiological conditions and in this context also actively participate in spreading various diseases. Large efforts are currently made to produce reliable EV samples and to develop, improve, and standardize techniques allowing their biophysical characterization. Here, we used ultrafiltration and size-exclusion chromatography for the isolation and a model-free fluorescence fluctuation analysis for the investigation of the physical and biological properties of EVs secreted by mammalian cells. Our purification strategy produced enriched samples of morphologically intact EVs free of extravesicular proteins and allowed labeling of marker molecules on the vesicle surface for single-vesicle analysis with single-molecule sensitivity. This novel approach provides information on the distribution profile of both EV size and relative expression level of a specific exosomal marker, deciphering the overall heterogeneity of EV preparations.

The attachment of a salicylaldehyde ring and a cofacial aryl or heteroaryl N-oxide chromophore onto a naphthalene scaffold affords stereodynamic probes designed to rapidly bind amines, amino alcohols, or amino acids and to translate this binding event via substrate-to-receptor chirality amplification into a dual (chir)optical response. 1-(3'-Formyl-4'-hydroxyphenyl)-8-(9'-anthryl)naphthalene (1) was prepared via two consecutive Suzuki cross-coupling reactions, and the three-dimensional structure and racemization kinetics were studied by crystallography and dynamic HPLC. This probe proved successful for chirality sensing of several compounds, but in situ IR monitoring of the condensation reaction between the salicylaldehyde moiety in 1 and phenylglycinol showed that the imine formation takes 2 h. Optimization of the substrate binding rate and the circular dichroism (CD) and fluorescence readouts led to the replacement of anthracene with smaller fluorophores capable of intramolecular hydrogen bonding. 1-(3'-Formyl-4'-methoxyphenyl)-8-(4'-isoquinolyl)naphthalene N-oxide (2) and its pyridyl analogue 3 combine fast substrate binding with distinctive chiral amplification. This asymmetric transformation of the first kind prompts CD and fluorescence responses that can be used for in situ determination of the absolute configuration, ee, and total concentration of many compounds. The general utility of the three chemosensors was successfully tested on 18 substrates.

The addition of ynamides to acyl chlorides and N-heterocycles activated in situ with ethyl chloroformate has been accomplished at room temperature using copper iodide as catalyst. This economical and practical carbon-carbon bond formation provides convenient access to a variety of 3-aminoynones from aliphatic and aromatic acyl chlorides in up to 99% yield. The addition to pyridines and quinolines occurs under almost identical conditions and proceeds with good to high regioselectivity, producing the corresponding 1,2-dihydro-N-heterocycles in up to 95% yield.

The relative stabilities of three conformational isomers of 2,2'-binaphthalene-1,1'-diol diisobutyrate and the energy barriers to rotation about the pivotal aryl-aryl bond and the two aryl-oxygen bonds were investigated by variable-temperature NMR spectroscopy in conjunction with DFT computations. The experimental and calculated data were found to be in very good agreement and provide new insights into the dynamic stereochemistry of BINOL-derived tropos ligands.

A stereodynamic probe for determination of the absolute configuration and enantiomeric composition of chiral amines, diamines, amino alcohols, amino acids, and α-hydroxy carboxylic acids is described. The chirality sensing is based on spontaneous asymmetric transformation of the first kind with stereolabile binaphtholate boron and zinc complexes. The substrate binding and chiral amplification processes yield a distinctive chiroptical sensor output at high wavelength that can be used for rapid and accurate ee detection of minute sample amounts.

A stereodynamic chemosensor having a parallel arrangement of a substrate-binding salicylaldehyde unit and an adjacent pyridyl N-oxide fluorophore undergoes rapid condensation with chiral amino alcohols and subsequent asymmetric transformation of the first kind toward a single rotamer. Crystallographic analysis shows that the concomitant central-to-axial chirality imprinting is controlled by minimization of steric repulsion and by intramolecular hydrogen bonding between the bound amino alcohol and the proximate N-oxide group. The substrate binding event results in strong CD effects and characteristic fluorescence changes which can be used for instantaneous in situ determination of the absolute configuration, enantiomeric composition and total concentration of a variety of chiral amino alcohols. This chemosensing approach avoids time-consuming workup and purification steps, and it is applicable to minute sample amounts which reduces the use of solvents and limits waste production.

The LHMDS-promoted in situ generation of difluoroenolates from readily available 1-aryl and 1-alkyl 2,2,4,4,4-pentafluorobutan-1,3-dione hydrates has been used to produce a series of pentafluorinated β-hydroxy ketones in up to 95% yield. The reaction proceeds under mild conditions, tolerates a wide range of functional groups, and is complete within 10 min. Reduction toward the corresponding 1,3-diol with DIBAL gives quantitative amounts and favors the formation of the syn-isomer.