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Combining a bulky bis(amide) and a reactive one-coordinate TMP (2,2,6,6-tetramethylpiperidide) ligand, a new mixed K/Zn heteroleptic base has been developed for regioselective zincation of fluoroarenes. This special ligand set allows for trapping and structural authentication of the first intermediates of direct Zn-H exchange of fluoroarenes obtained via deprotonative metallation, providing mechanistic insights of the processes involved.

Pseudomonas Aeruginosa (P. Aeruginosa) is a prevalent and opportunistic bacterium which frequently causes severe nosocomial infection. Current clinical detection methods are limited in terms of necessary time and equipment. Increasingly, P. Aeruginosa's electrochemically active virulence factor pyocyanin has facilitated its rapid detection, primarily through voltammetric methods such as cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square wave voltammetry (SWV). A comprehensive background on the synthesis and pathogenicity of P. Aeruginosa via pyocyanin (PyoC), is included herein. Innovative electrochemical sensor design and modification is reviewed, with a focus on screen-printed electrodes, paper-based devices, arrays, surface modification and biorecognition elements such as aptasensors.

Myoglobin (Mb) can react with hydrogen peroxide (H 2O 2) to form a highly active intermediate compound and catalyse oxidation reactions. To enhance this activity, known as pseudo-peroxidase activity, previous studies have focused on the modification of key amino acid residues of Mb or the heme cofactor. In this work, the Mb scaffold (apo-Mb) was systematically reconstituted with a set of cofactors based on six metal ions and two ligands. These Mb variants were fully characterised by UV-Vis spectroscopy, circular dichroism (CD) spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS) and native mass spectrometry (nMS). The steady-state kinetics of guaiacol oxidation and 2,4,6-trichlorophenol (TCP) dehalogenation catalysed by Mb variants were determined. Mb variants with iron chlorin e6 (Fe−Ce6) and manganese chlorin e6 (Mn−Ce6) cofactors were found to have improved catalytic efficiency for both guaiacol and TCP substrates in comparison with wild-type Mb, i. e. Fe-protoporphyrin IX-Mb. Furthermore, the selected cofactors were incorporated into the scaffold of a Mb mutant, swMb H64D. Enhanced peroxidase activity for both substrates were found via the reconstitution of Fe−Ce6 into the mutant scaffold.

Changes in the structural dynamics of double stranded (ds)DNA upon ligand binding have been linked to the mechanism of allostery without conformational change, but direct experimental evidence remains elusive. To address this, a combination of steady state infrared (IR) absorption spectroscopy and ultrafast temperature jump IR absorption measurements has been used to quantify the extent of fast (∼100 ns) fluctuations in (ds)DNA·Hoechst 33258 complexes at a range of temperatures. Exploiting the direct link between vibrational band intensities and base stacking shows that the absolute magnitude of the change in absorbance caused by fast structural fluctuations following the temperature jump is only weakly dependent on the starting temperature of the sample. The observed fast dynamics are some two orders of magnitude faster than strand separation and associated with all points along the 10-base pair duplex d(GCATATATCC). Binding the Hoechst 33258 ligand causes a small but consistent reduction in the extent of these fast fluctuations of base pairs located outside of the ligand binding region. These observations point to a ligand-induced reduction in the flexibility of the dsDNA near the binding site, consistent with an estimated allosteric propagation length of 15 Å, about 5 base pairs, which agrees well with both molecular simulation and coarse-grained statistical mechanics models of allostery leading to cooperative ligand binding.

As storage rocks rather than source rocks, shale reservoirs can potentially serve as energy storehouses for energy security and sequester CO 2in the long term to mitigate climate change. Despite extensive studies investigating the geochemical and geophysical properties of shale and gas adsorption and transport in the shale matrix, limited studies have been devoted to characterizing nanoscale gas storage mechanisms in shale at elevated high pressure. In this study, contrast-matching small-angle neutron scattering (SANS) has been conducted to quantify the gas storage mechanisms and capacity in three shale samples up to elevated high pressure using deuterated methane. The three-phase Porod invariant method is uniquely used to estimate the average scattering length density (SLD) in open pores over the measured pore range, in which open pores, closed pores, and rock matrix are the three phases. The estimated average SLD in open pores is smaller than the SLD of the bulk phase at the pressure between 10 MPa and the contrast-matched point (∼60-70 MPa, which is sample-dependent), while it is higher than that of the bulk at the pressure below 10 MPa and above the contrast-matched pressure, indicating a variation of average adsorbed phase density over the measured pressure range for the measured shale samples. The average adsorbed phase volume could first increase and then decrease with increasing pressure until the high-pressure region. Three essential factors, including the final injection pressure, total organic carbon (TOC), and accessible porosity, could be used to screen a potential targeted shale reservoir and maximize methane storage and long-term CO 2 sequestration.

Shell-isolated nanoparticles (SHINs) have attracted increasing interest for non-interfering plasmonic enhanced sensing in fields such as materials science, biosensing, and in various electrochemical systems. The metallic core of these nanoparticles is isolated from the surrounding environment preventing direct contact or chemical interaction with the metal surface, while still being close enough to enable localized surface plasmon enhancement of the Raman scattering signal from the analyte. This concept forms the basis of the shell isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique. To date, the vast majority of SHIN designs have focused on SiO2 shells around spherical nanoparticle cores and there has been very limited published research considering alternatives. In this article, we introduce a new polymer-based approach which provides excellent control over the layer thickness and can be applied to plasmonic metal nanoparticles of various shapes and sizes without compromising the overall nanoparticle morphology. The SHIN layers are shown to exhibit excellent passivation properties and robustness in the case of gold nanosphere (AuNP) and anisotropic gold nanostar (AuNS) core shapes. In addition, in situ SHINERS spectro-electrochemistry measurements performed on both SHIN and bare Au nanoparticles demonstrate the utility of the SHIN coatings. Correlated confocal Raman and SEM mapping was achieved to clearly establish single nanoparticle SERS sensitivity. Finally, confocal in situ SERS mapping enabled visualisation of the redox related molecular structure changes occurring on an electrode surface in the vicinity of individual SHIN-coated nanoparticles.

Malonoyl peroxide [6] is an effective reagent for the syn- or anti-oxyamination of alkenes. Reaction of [6] and an alkene in the presence of O-tert-butyl-N-tosylcarbamate (R3 = CO2tBu) leads to the anti-oxyaminated product in up to 99% yield. Use of O-methyl-N-tosyl carbamate (R3 = CO2Me) as the nitrogen nucleophile followed by treatment of the product with trifluoroacetic acid leads to the syn-oxyaminated product in up to 77% yield. Mechanisms consistent with the observed selectivities are proposed.

A charged oil droplet advancing into a charged capillary is considered, assuming the special case in which charges are opposite and equal. The droplet is surrounded by an aqueous phase that wets the capillary wall, such that a thin film adjacent to the wall is laid down as the droplet advances. Electro-osmotic conjoining pressures contrive to make the film even thinner than in an uncharged case. The pressure drop needed to drive the droplet along is examined. The pressure drop is dominated by capillarity but contains electro-osmotic and viscous corrections. The viscous correction is shown to be remarkably insensitive to the presence of electro-osmotic effects. The electro-osmotic pressure correction is negative, reflecting work done by the electro-osmotic conjoining pressure as film is laid down. The negative electro-osmotic correction to pressure drop can far exceed the positive viscous correction. As a result, in the presence of conjoining pressures, a droplet can be driven along a capillary channel with even less pressure drop than is seen for a static uncharged droplet.

When the SEGH international board released a short editorial paper back in 2019, we described an aim to increase the membership offering, whilst improving the diversity of input regionally, by scientific discipline and to ensure greater and more regular contact across the regions from 2020 onwards. Wider aspirations described in 2019 (Watts et al. 2019) are discussed within this short communication at the end of 2021 to evaluate progress made. In particular, how the SEGH community adapted to the unprecedented circumstances that have challenged each and every one of us throughout the COVID-19 pandemic since early 2020 and are likely to influence our activities for the foreseeable future.

Transmetalation is a key method for the construction of element-element bonds. Here, we disclose the reactivity of [NiII(Ar)(I)(diphosphine)] compounds with arylgold(I) transmetalating agents, which is directly relevant to cross-coupling catalysis. Both aryl-for-iodide and unexpected aryl-for-aryl transmetalation are witnessed. Despite the strong driving force expected for Au-I bond formation, aryl scrambling can occur during transmetalation and may complicate the outcomes of attempted catalytic cross-coupling reactions.

A molecular model of the orientationally ordered lamellar phase exhibited by asymmetric rod-coil-rod triblock copolymers has been developed using the density-functional approach and generalizing the molecular-statistical theory of rod-coil diblock copolymers. An approximate expression for the free energy of the lamellar phase has been obtained in terms of the direct correlation functions of the system, the Flory-Huggins parameter and the Maier-Saupe orientational interaction potential between rods. A detailed derivation of several rod-rod and rod-coil density-density correlation functions required to evaluate the free energy is presented. The orientational and translational order parameters of rod and coil segments depending on the temperature and triblock asymmetry have been calculated numerically by direct minimization of the free energy. Different structure and ordering of the lamellar phase at high and low values of the triblock asymmetry is revealed and analyzed in detail. Asymmetric rod-coil-rod triblock copolymers have been simulated using the method of dissipative particle dynamics in the broad range of the Flory-Huggins parameter and for several values of the triblock asymmetry. It has been found that the lamellar phase appears to be the most stable one at strong segregation. The density distribution of the coil segments and the segments of the two different rods have been determined for different values of the segregation strength. The simulations confirm the existence of a weakly ordered lamellar phase predicted by the density-functional theory, in which the short rods separate from the long ones and are characterized by weak positional ordering.

An operationally simple E → Z isomerization of activated dienes, based on the β-ionyl motif intrinsic to retinal, is reported using inexpensive (−)-riboflavin (vitamin B2) under irradiation at 402 nm. Selective energy transfer from photoexcited (−)-riboflavin to the starting E-isomer enables geometrical isomerization. Since the analogous process with the Z-isomer is inefficient, microscopic reversibility is circumvented, thereby enabling a directional isomerization to generate the contra-thermodynamic product (up to 99% yield, up to 99:1 Z/E). Prudent choice of photocatalyst enables chemoselective isomerization to be achieved in both inter- and intramolecular systems. The principles established from this study, together with a molecular editing approach, have facilitated the development of a regioselective isomerization of a truncated triene based on the retinal scaffold.

A series of new Mg(ii) amides featuring a bulky β-diketiminate backstop ligand, has been synthesised. These complexes are demonstrated to be excellent sources of nucleophilic amides that can participate in rapid C-F activation of several fluoroarenes at room temperature or using microwave assistance, leading to the installment of synthetically important C-N bonds via nucleophilic substitution.

The processability and optoelectronic properties of organic semiconductors can be tuned and manipulated via chemical design. The substitution of the popular alkyl side chains by oligoethers has recently been successful for applications such as bioelectronic sensors and photocatalytic hydrogen evolution. Beyond the differences in polarity, the carbon–oxygen bond in oligoethers is likely to render the system softer and more prone to dynamical disorder that can be detrimental to charge transport for example. In this context, we use neutron spectroscopy as a master method of probe, in addition to characterisation techniques such as X-ray diffraction, differential scanning calorimetry and polarized optical microscopy to study the effect of the substitution of n-hexyl (Hex) chains by triethylene glycol (TEG) chains on the structural dynamics of two organic semiconducting materials: a phenylene–bithiophene–phenylene (PTTP) small molecule and a fluorene-co-dibenzothiophene (FS) polymer. Counterintuitively, inelastic neutron scattering (INS) reveals a general softening of the modes of PTTP and FS materials with Hex chains, pointing towards an increased dynamical disorder in the Hex-based systems. However, temperature-dependent X-ray and neutron diffraction as well as INS and differential scanning calorimetry evidence an extra reversible transition close to room temperature for PTTP with TEG chains. The observed extra structural transition, which is not accompanied by a change in birefringence, can also be observed by quasi-elastic neutron scattering (QENS). A fastening of the TEG chains dynamics is observed in the case of PTTP and not FS. We therefore assign this transition to the melt of the TEG chains. Overall the TEG chains are promoting dynamical order at room temperature, but if crystallising, may introduce an extra reversible structural transition above room temperature leading to thermal instabilities. Ultimately, a deeper understanding of chain polarity and structural dynamics can help guide new materials design and navigate the intricate balance between electronic charge transport and aqueous swelling that is being sought for a number of emerging organic electronic and bioelectronic applications.

The Grignard reagent, iPrMgCl and its lithium chloride-enhanced ‘turbo’ derivative iPrMgCl·LiCl have been employed to investigate the single iodo/magnesium exchange reactions of the trisubstituted arenes, 2,5-diiodo-N,N-diisopropylbenzamide 1 , 1,4-diiodo-2-methoxybenzene 2 , and 1,4-diiodo-2-(trifluoromethyl)benzene 3 . These three arenes themselves were initially prepared by a double ortho-, metaʹ-deprotonation of N,N-diisopropylbenzamide, anisole and (trifluoromethyl)benzene respectively, using a sodium magnesiate reagent, and subsequent electrophilic quenching with iodine/THF solution. Thus, by following a combined deprotonation and magnesium/halogen exchange strategy, the simple monosubstituted arenes can be converted to trisubstituted diiodoarenes, which can ultimately be transformed into the corresponding mono-magnesiated arenes, in THF at −40°C, within seconds in good yields. The other functional group (OMe, NiPr2 or CF3 respectively) present on the di-iodoarenes helps direct the exchange reaction to the ortho position whereas subsequent addition of different electrophiles permits the preparation of hetero-poly-functional-arenes, with three different substituents in their structure. Intriguingly, if water is used as the electrophile, a new and facile route to prepare meta-substituted arenes, which cannot be easily obtained by conventional processes, is forthcoming. In contrast to directed ortho-metalation (DoM) chemistry, this reaction sequence can be thought of as InDirect meta-Metalation (IDmM). The scope of the chemistry has been tested further by exposing the initial unreacted iodo-functionality at the meta-position to a second Mg/I-exchange reaction and subsequent functionalization.

This paper details a simple and efficient 3-component synthesis of 1-substituted 1,2,3-triazoles using a primary amine, 2,2-dimethoxyacetaldehyde and tosylhydrazide. The reaction proceeds in good to excellent yields using either aliphatic or aromatic amine substrates and is tolerant of a wide range of functional groups including electron-rich and deficient aryl groups, terminal alkynes, ketones and highly sterically encumbered amines.

International audience; Ionic liquids (ILs) are promising electrolytes for electrochemical applications due to their remarkable stability and high charge density. Molecular dynamics simulations are essential for a better understanding of the complex phenomena occurring at the electrode–IL interface. In this work, we have studied the interface between graphene and 1-ethyl-3-methyl-imidazolium tetrafluoroborate IL by density functional theory-based molecular dynamics (DFT-MD) simulations at variable surface charge densities. We have disassembled the electrical double layer potential drop into two main components: one involving atomic charges and the other dipoles. The former component arises due to the reorganization of ionic liquid and the latter due to the electronic polarization of the surface. It is related to concepts hotly debated in the literature, such as the Thomas–Fermi screening length, effective surface charge plane, and quantum capacitance.

Herein, the efficient serotonin (5-HT) sensing studies have been conducted using the (ZnO NRs)1−x(CNs)x nanocomposites (NCs) having appropriate structural and electrochemical properties. Initially, the different compositions of ZnO nanorods (NRs), with varying content of carbon nanostructures (CNs=MWCNTs and RGO), are prepared using simple in-situ wet chemical method and thereafter these NCs have been characterized for physico-chemical properties in correlation to the 5-HT sensing activity. XRD Rietveld refinement studies reveal the hexagonal Wurtzite ZnO NRs oriented in (101) direction with space group ‘P63mc’ and both orientation as well as phase of ZnO NRs are also retained in the NCs due to the small content of CNs. The interconnectivity between the ZnO NRs with CNs through different functional moieties is also studied using FTIR analysis; while phases of the constituents are confirmed through Raman analysis. FESEM images of the bare/NCs show hexagonal shaped rods with higher aspect ratio (4.87) to that of others. BET analysis and EIS measurements reveal the higher surface area (97.895 m2/g), lower charge transfer resistance (16.2 kΩ) for the ZCNT 0.1 NCs to that of other NCs or bare material. Thereafter, the prepared NCs are deposited on the screen printed carbon electrode (SPCE) using chitosan as cross-linked agent for 5-HT sensing studies; conducted through cyclic voltammetry (CV) and square wave voltammetry (SWV) measurements. Among the various composites, ZCNT0.1 NCs based electrodes exhibit higher sensing activity towards 5-HT in accordance to its higher surface area, lower particle size and lower charge transfer resistance. SWV measurements provide a wide linear response range (7.5–300 μM); lower limit of detection (0.66 μM), excellent limit of quantification (2.19 μM) and good reproducibility to ZCNT 0.1 NCs as compared to others for 5-HT sensing studies.

Cells communicate with their environment via surface receptors, but nanoscopic receptor organization with respect to complex cell surface morphology remains unclear. This is mainly due to a lack of accessible, robust and high-resolution methods. Here, we present an approach for mapping the topography of receptors at the cell surface with nanometer precision. The method involves coating glass coverslips with glycine, which preserves the fine membrane morphology while allowing immobilized cells to be positioned close to the optical surface. We developed an advanced and simplified algorithm for the analysis of single-molecule localization data acquired in a biplane detection scheme. These advancements enable direct and quantitative mapping of protein distribution on ruffled plasma membranes with near isotropic 3D nanometer resolution. As demonstrated successfully for CD4 and CD45 receptors, the described workflow is a straightforward quantitative technique to study molecules and their interactions at the complex surface nanomorphology of differentiated metazoan cells.

Extracellular vesicles (EVs) have numerous potential applications in the field of healthcare and diagnostics, and research into their biological functions is rapidly increasing. Mainly because of their small size and heterogeneity, there are significant challenges associated with their analysis and despite overt evidence of the potential of EVs in clinical diagnostic practice, guidelines for analytical procedures have not yet been properly established. Here, we present an overview of the main methods for studying the properties of EVs based on the principles of fluorescence. Setting aside the isolation, purification and physicochemical characterization strategies which answer questions about the size, surface charge and stability of EVs (reviewed elsewhere), we focus on available optical tools that enable the direct analysis of phenotype and mechanisms of interaction with tissues. In brief, the topics on which we elaborate range from the most popular approaches such as nanoparticle tracking analysis and flow cytometry, to less commonly used techniques such as fluorescence depolarization and microarrays as well as emerging areas such as fast fluorescence lifetime imaging microscopy (FLIM). We highlight that understanding the strengths and limitations of each method is essential for choosing the most appropriate combination of analytical tools. Finally, future directions of this rapidly developing area of medical diagnostics are discussed.

The liquid-liquid transition in supercooled liquid water, predicted to occur around 220 K, is controversial due to the difficulty of studying it caused by competition from ice crystallization (the so-called "no man's land"). In aqueous solutions, it has been predicted to give rise to phase separation on a nanometer scale between a solute-rich high-density phase and a water-rich low-density phase. Here we report direct experimental evidence for the formation of a nanosegregated phase in eutectic aqueous solutions of LiCl and LiSCN where the presence of crystalline water can be experimentally excluded. Femtosecond infrared and Raman spectroscopies are used to determine the temperature-dependent structuring of water, the solvation of the SCN- anion, and the size of the phase segregated domains.

The Community Bureau of Reference (BCR) four-step sequential extraction has been adapted for fractionation of potentially toxic elements (PTE) in simulant airborne particulate matter (APM) samples presented on 47 mm filter dynamics measurement system (FDMS) filters as used in routine air quality monitoring. Simulants were prepared from an urban soil reference material and from BCR CRM 701, which is certified for analytes extractable by the BCR procedure. Analysis was performed by inductively coupled plasma mass spectrometry using an Agilent 7700x instrument. Fractionation patterns similar to the full-scale protocol were obtained when test portions as small as 0.0625 g were extracted in 2–3 mL of reagents. However, changing the extraction vessel used was found to affect the outcome. This highlights the operational nature of sequential extraction procedures and the need carefully to evaluate the effects of procedural modifications. When the method developed was applied to blank FDMS filters, large amounts of Zn were detected, especially in step 3, the oxidisable fraction, and step 4, the residual fraction. Despite this, following blank-correction, fractionation patterns similar to certified values were obtained for BCR CRM 701, with overall recoveries (∑(steps 1–4)) of 84.2-113%. Given the increased awareness of public health risks associated with poor air quality, a sequential extraction procedure specifically designed for use with APM samples collected during routine air quality represents a valuable tool for use in source apportionment and to improve understanding of human exposure to PTE through inhalation.

Successful applications of a topological insulator (TI) in spintronics require its bandgap to be wider then in a typical TI and the energy position of the Dirac point in the dispersion relations to be away from the valence and conduction bands. In this study we grew Bi1.1Sb0.9Te2S crystals and examined their elemental composition, structural, optical and electronic properties as well as the electronic band structure. The high structural quality of the grown crystals was established by X-ray diffraction and Raman spectroscopy. Angular resolved photoelectron spectroscopy demonstrated a near parabolic character of the valence and conduction bands and a direct bandgap of 0.36 eV. The dispersion relations also revealed a Dirac cone, confirming the topological insulator nature of this material, with the position of the Dirac point being 100 meV above the valence band maximum. Far infrared reflectivity spectra revealed a plasma edge and two phonon dips. Fitting these spectra with theoretical functions based on the Drude-Lorentz model allows determination of the high frequency dielectric constant (41.3), plasma frequency (936 cm−1) and the frequencies of two infrared phonons (177.7 cm−1 and 77.4 cm−1). © 2021 Elsevier B.V. The reported study was funded by RFBR, project number 19-29-12061 . The part of optical research was carried out within the state assignment of Ministry of Science and Higher Education of the Russian Federation (theme "Spin" No AAAA-A18-118020290104-2 and No AAAA-A19-119081990020-8 and theme "Electron" No AAAAA18-118020190098-5 ). The study was also supported by the Russian Science Foundation (Project No. 17-12-01047 ) in the part of the crystal growth and state assignment of ISP SB RAS ( 0306–2019-0007 ) and IGM SB RAS. The Raman measurements were partially supported by the grant of the Russian Foundation for Basic Research (Project No. 19-52-18008 ). This work is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) through project-ID 258499086 – SFB 1170 (A01), the Würzburg-Dresden Cluster of Excellence on Complexity and Topology in Quantum Matter–ct.qmat Project-ID 390858490 – EXC 2147 .

In this work, we describe the development of a computational screening approach for tripeptide-dipeptide co-assembly. Studies are carried out both in water and in oil–water mixtures, to evaluate possible candidates that give rise to hydrogels or more stable emulsions, respectively, through nanofibre formation. The results give rise to design rules for the identification of promising systems for numerous types of soft materials. The possibility of achieving innovative functional materials through the co-assembly of tripeptides and dipeptides is studied. In particular, coarse-grained simulations allowed for the extraction of some promising dipeptides that, together with H-aspartyl-phenylalanyl-phenylalanine-OH (DFF), are able to act as hydrogelators or emulsifiers with superior characteristics relative to DFF on its own.

Reduction of nitrobenzene by excess organic electron donor, 12, affords diphenylhydrazine in a reaction where azobenzene oxide and azobenzene are likely intermediates. No cleavage of the N-N σ-bond is seen under photoactivation conditions, whereas traces are seen under thermal activation. Hydrazone derivatives were prepared to explore the cleavage of N-N σ-bonds; the results show that a low-lying LUMO assists the transition state for accepting an electron, and the stabilisation that the potential fragments from N-N bond cleavage afford to the fragments is important in determining whether cleavage is observed.

The focus of this review is to provide an overview of the field of organocatalysed photoredox chemistry relevant to synthetic medicinal chemistry. Photoredox transformations have been shown to enable key transformations that are important to the pharmaceutical industry. This type of chemistry has also demonstrated a high degree of sustainability, especially when organic dyes can be employed in place of often toxic and environmentally damaging transition metals. The sections are arranged according to the general class of the presented reactions and the value of these methods to medicinal chemistry is considered. An overview of the general characteristics of the photocatalysts as well as some electrochemical data is presented. In addition, the general reaction mechanisms for organocatalysed photoredox transformations are discussed and some individual mechanistic considerations are highlighted in the text when appropriate.

Ligand metathesis of Pd(II) complexes is mechanistically essential for cross-coupling. We present a study of halide→OH anion metathesis of (Ar)Pd(II) complexes using vinylBPin as a bifunctional chemical probe with Pd(II)-dependent cross-coupling pathways. We identify the variables that profoundly impact this event and allow control to be leveraged. This then allows control of cross-coupling pathways via promotion or inhibition of organoboron transmetalation, leading to either Suzuki-Miyaura or Mizoroki-Heck products. We show how this transmetalation switch can be used to synthetic gain in a cascade cross-coupling/Diels-Alder reaction, delivering borylated or non-borylated carbocycles, including steroid-like scaffolds.

Spatially offset Raman spectroscopy (SORS) provides chemical analysis at depth even when obscuring barriers such as plastic or tissue are present. As the collection probe is moved further away from the point of laser excitation, scattered photons from deeper layers begin to dominate the acquired spectra, thus giving rise to through barrier detection. Here, we demonstrate the potential of conventional Raman (CR) and SORS for through barrier detection using handheld spectrometers. We report the collection of Raman signals from an ethanol solution through plastic at thicknesses of up to 21 mm using SORS in combination with multivariate analysis. SORS is compared to CR, where we also demonstrate impressive through barrier detection of ethanol at depths up to 9 mm. We also highlight the advantage of applying multivariate analysis for through barrier detection using CR or SORS, particularly when peaks with similar spectral features are present in both the barrier and analyte spectra. In addition, to the best of our knowledge, this is the first report of the assessment of the maximum level of through barrier detection using handheld CR and SORS instruments with a backscattering geometry.

Designing molecular disorder Melanins are a group of natural pigments that are the primary factor affecting skin color. Lampel et al. examined a family of melanin-inspired materials based on tripeptides containing tyrosine as precursors for polymeric pigments. They found that the supramolecular organization of the tripeptide assembly is the most important factor for the enzymatic oxidation, with the position of the tyrosine residue playing a dominant role. Thus, simply juggling the order of the peptides allowed tuning of the optical and electrical properties of the resulting polymers. Science , this issue p. 1064

Nanozymes are metal nanoparticles with catalytic properties that can be used to oxidise peroxidase substrates giving a colorimetric response which can be detected using UV-vis, and recently, Raman spectroscopy. Due to their ease of synthesis and increased stability, nanozymes are being increasing investigated to replace conventional enzymes for the detection of biomolecules. Here we exploit the catalytic activity of iron oxide (Fe2O3) nanoparticles combined with the substrate 2,2-Azinobis(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) in a decolourisation assay for the detection of antioxidants. Fe2O3 nanoparticles were used to catalyse the oxidation of ABTS to its green radical cation which, upon the addition of an antioxidant, resulted in a decolourisation due to the reduction of the radical cation caused by the hydrogen donating antioxidant. The assay was applied for the detection of multiple antioxidants (glutathione, chlorogenic acid and ascorbic acid), and was followed by monitoring the resonance Raman scattering from the ABTS solution using a portable Raman system with 785 nm laser excitation. This novel assay has the potential to be optimised to detect antioxidant activity in body fluid with low limits of detection with point of use monitoring.

Jüngste Entwicklungen in der experimentellen und theoretischen Chemie haben zur Identifizierung einer schnell wachsenden Klasse von nukleophilen aromatischen Substitutionsreaktionen geführt, die einem konzertierten Mechanismus (cSNAr) folgen, und nicht dem klassischen, zweistufigen SNAr-Mechanismus. Während klassische SNAr-Reaktionen auf die substantielle Aktivierung des aromatischen Ringes durch elektronenziehende Substituenten angewiesen sind, ist eine solche Aktivierung für den konzertierten Reaktionsverlauf nicht zwingend nötig.

The fluorescent dye 8-hydroxypyrene-1,3,6-trisulfonate (pyranine) combines high photostability with ratiometric pH detection in the physiological range, making it a prime candidate for optical sensors in biomedical applications, such as pH-based chronic wound monitoring. However, pyranine's high water solubility and the difficulty of covalent attachment pose severe limitations in terms of leaching from sensor matrices. Herein, pyranine-modified nanophase-separated amphiphilic polymer conetworks (APCNs) are reported as fluorescent ratiometric pH sensors. The thin, freestanding APCN membranes composed of one hydrophilic and one hydrophobic polymer provide an optically transparent, flexible, and stable ideal matrix that enables contact between dye and aqueous environment. An active ester-based conjugation approach results in a highly homogeneous and stable pyranine modification of the APCN's hydrophilic phase. This concept effectively solves the leaching challenge for pyranine without compromising its functionality, which is demonstrated by ratiometric pH detection in the range of pH 5-9.

Fourier transform-infrared spectroscopy (FT-IR) represents an attractive molecular diagnostic modality for translation to the clinic, where comprehensive chemical profiling of biological samples may revolutionize a myriad of pathways in clinical settings. Principally, FT-IR provides a rapid, cost-effective platform to obtain a molecular fingerprint of clinical samples based on vibrational transitions of chemical bonds upon interaction with infrared light. To date, considerable research activities have demonstrated competitive to superior performance of FT-IR strategies in comparison to conventional techniques, with particular promise for earlier, accessible disease diagnostics, thereby improving patient outcomes. However, amidst the changing healthcare landscape in times of aging populations and increased prevalence of cancer and chronic disease, routine adoption of FT-IR within clinical laboratories has remained elusive. Hence, this perspective shall outline the significant clinical potential of FT-IR diagnostics and subsequently address current barriers to translation from the perspective of all stakeholders, in the context of biofluid, histopathology, cytology, microbiology, and biomarker discovery frameworks. Thereafter, future perspectives of FT-IR for healthcare will be discussed, with consideration of recent technological advances that may facilitate future clinical translation.

The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article., Funding is acknowledged from the European Research Council (ERC Advanced Grant No. 787510-4DBIOSERS to L.M.L.-M., ERC Advanced Grant No. 789104-eNANO to F.J.G.A., ERC Starting Grant No. 259432-MULTIBIOPHOT to J.K., ERC Consolidator Grant No. 772108-DarkSERS); the Department of Education of the Basque Government (Grant No. IT1164-19 to J.A.); the Spanish MINECO (CTQ2017-88648-R to R.A.-P., MAT2016-77809-R to I.P.-S. and J.P.-J.); the EPSRC (EP/P034063/1 to S.B., EP/L027151/1 to J.B., EP/L014165/1 to D.G. and K.F.); IDUN-Danish National Research Foundation (DNRF122) and Villum Fonden (Grant No. 9301) to A.B.; the National Research Foundation of Korea (Grant No. 2019R1A2C3004375 to J.B.); the German Science Foundation, DFG (SFB 1278 Polytarget (Project B4) to V.D., Grant No. SCHL 594/13-1 to S.S., Germany’s Excellence Strategy (EXC 2089/1-390776260) to S.M.); the Federal Ministry of Education and Research, Germany (BMBF) (Grant InfectoGnostics 13GW0096F to D.C.-M. and J.P.); DARPA-16-35-INTERCEPT-FP-018 to L.F.; the UK BBSRC (Grant No. BB/L014823/1 to R.G.); the Department of Science and Technology (DST Nanomission Project SR/NM/NS-23/2016 to K.G.T.); the U.S. National Science Foundation (Grant No. CHE-1707859 to A.J.H., Center for Sustainable Nanotechnology CHE-1503408 (Centers for Chemical Innovation Program) to C.L.H., Center for Chemical Innovation Chemistry at the Space-Time Limit (CaSTL) CHE-1414466 to G.C.S. and R.P.V.D., Grant No. CHE-1807269 to K.A.W.); the Knut and Alice Wallenberg Foundation to M.K.; the Office of Naval Research (Grant No. N00014-18-1-2876 to N.A.K.); Royal Society of New Zealand Te Apa̅rangi to E.L.R. and B.A.; Singapore Ministry of Education, Tier 1 (RG11/18) to X.Y.L.; the Photoexcitonix Project in Hokkaido Univ., Japan, to K.M.; BioNano Health-Guard Research Center funded by the Ministry of Science and ICT (MSIT) of Korea as Global Frontier Project (Grant No. H-GUARD_2013M3A6B2078947) to J.-M.N.; NSFC of P. R. China (Grant No. 21705015 to Y.O., Grant No. 21633005 to B.R.); National Key R&D Program (2017YFA0206902) to C.X. This work was coordinated under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency—Grant No. MDM-2017-0720.

Main group bimetallic complexes, while being increasingly used in stoichiometric deprotonation and metal–halogen exchange reactions, have not yet made a significant impact in catalytic applications. This paper explores the ability of alkali metal magnesiates to catalyse the intermolecular hydroamination of alkynes and alkenes using sytrene and diphenylacetylene as principle setting model substrates. By systematically studying the role of the alkali–metal and the formulation of the heterobimetallic precatalyst, this study establishes higher order potassium magnesiate [(PMDETA)2K2Mg(CH2SiMe3)4] (7) as a highly effective system capable of catalysing hydroamination of styrene and diphenylacetylene with several amines while operating at room temperature. This high reactivity contrasts with the complete lack of catalytic ability of neutral Mg(CH2SiMe3)2, even when harsher reaction conditions are employed (24 h, 80 °C). A pronounced alkali metal effect is also uncovered proving that the alkali metal (Li, Na, or K) is not a mere spectating counterion. Through stoichiometric reactions, and structural and spectroscopic (DOSY NMR) investigations we shed some light on the potential reaction pathway as well as the constitution of key intermediates. This work suggests that the enhanced catalytic activity of 7 can be rationalised in terms of the superior nucleophilic power of the formally dianionic magnesiate {Mg(NR2)4}2− generated in situ during the hydroamination process, along with the ability of potassium to engage in π-interactions with the unsaturated organic substrate, enhancing its susceptibility towards a nucleophilic attack by the amide anion.

Lysozyme is one of the most commonly used proteins for encapsulating gold nanoclusters, yielding Ly-AuNC complexes. While possible applications of Ly-AuNCs in environmental, biological and trace metal sensing in solution have been demonstrated, there is currently a poor understanding of the physical characteristics of the Ly-AuNC complex. In this study we have employed fully atomistic molecular dynamics simulations to gain an understanding of the formation of Au clusters within the protein. It was found that in order to form AuNCs in the simulations, an approach of targeted insertion of Au atoms at a critical surface residue was needed. Tyrosine is known to be crucial for the reduction of Au salts experimentally, and our simulations showed that Tyr20 is the key residue for the formation of an AuNC beneath the protein surface in the α-helical domain. It is hoped these observations will aid future improvements and modification of Ly-AuNCs via alterations of the alpha-helix domain or Tyr20.

Treatment of a sulfide with a catalytic amount of a 1,3 diketone in the presence of silica sulfuric acid as a co-catalyst and hydrogen peroxide (50% aq) as the stoichiometric oxidant leads to the corresponding sulfoxide product. The reaction is effective for diaryl, aryl-alkyl and dialkyl sulfides and is tolerant of oxidisable and acid sensitive functional groups. Investigations have shown that the tris-peroxide 2, formed on reaction of pentane-2,4-dione with hydrogen peroxide under acidic reaction conditions, can oxidise two equivalents of sulfide using the exocyclic peroxide groups whereas the endocyclic peroxide remains intact. Calculations provide a mechanism consistent with experimental observations and suggest the reaction proceeds via an initial acid catalysed ring opening of a protonated tris-peroxide prior to oxygen transfer to a sulfur nucleophile.

It is generally accepted that the transition into the twist–bend nematic phase (NTB) is driven by an elastic instability related to the reduction of the bend elastic constant. Here we use a molecular–statistical theory to show that sufficiently strong polar interactions between bent–shaped molecules may lead to experimentally observed reduction of the bend elastic constant in the nematic phase even if electrostatic dipole-dipole interactions are not taken into account. We propose a simple model of bent–core particles and derive explicit analytical expressions which enable one to understand how polar molecular shape affects the elastic constants, and, in particular, the important role of the bend angle. Numerical graphs showing temperature variations of all elastic constants are also presented including the variation of the bend and splay elastic constants before and after the renormalization determined by local polar order of molecular steric dipoles and the corresponding polar correction to the one–particle distribution function.

This study establishes a new trans‐metal‐trapping (TMT) procedure based on a mixture of LiTMP (the base) and tris(trimethylsilylmethyl)gallium [Ga(CH2SiMe3)3, GaR3] (the trap) that, operating in a tandem manner, is effective for the regioselective deprotonation of sensitive diazines in hydrocarbon solution, as illustrated through reactions of pyrazine, pyridazine, and pyrimidine, as well as through the N‐S heterocycle benzothiazole. The metallo‐activated complexes of all of these compounds were isolated and structurally defined.

Aromatic peptide amphiphiles are known to self-assemble into nanostructures but the molecular level structure and the mechanism of formation of these nanostructures is not yet understood in detail. Molecular dynamic simulations using the CHARMM force field have been applied to a wide variety of peptide-based systems to obtain molecular level details of processes that are inaccessible with experimental techniques. However, this force field does not include parameters for the aromatic moieties which dictate the self-assembly of these systems. The standard CHARMM force field parameterization protocol uses hydrophilic interactions for the non-bonding parameters evaluation. However, to effectively reproduce the self-assembling behaviour of these molecules, the balance between the hydrophilic and hydrophobic nature of the molecule is essential. In this work, a modified parameterization protocol for the CHARMM force field for these aromatic moieties is presented. This protocol is applied for the specific case of the Fmoc moiety. The resulting set of parameters satisfies the conformational and interactions analysis and is able to reproduce experimental results such as the Fmoc-S-OMe water/octanol partition free energy and the self-assembly of Fmoc-S-OH and Fmoc-Y-OH into spherical micelles and fibres, respectively, while also providing detailed information on the mechanism of these processes. The effectiveness of the parameters for the Fmoc moiety validates the protocol as a robust approach to paramterise this class of compounds.

Acetylation of histone lysine residues is one of the most well-studied post-translational modifications of chromatin, selectively recognized by bromodomain ‘reader’ modules. Inhibitors of the Bromodomain and Extra Terminal domain (BET) family of bromodomains have shown profound anti-cancer and anti-inflammatory properties, generating much interest in targeting other bromodomain-containing proteins for disease treatment. Herein, we report the discovery of I-BRD9, the first selective cellular chemical probe for Bromodomain-containing protein 9 (BRD9). I-BRD9 was identified through structure-based design, leading to greater than 700-fold selectivity over the BET family and 200-fold over the highly homologous Bromodomain-containing protein 7 (BRD7). I-BRD9 was used to identify genes regulated by BRD9 in Kasumi-1 cells involved in oncology and immune response pathways and to the best of our knowledge, represents the first selective tool compound available to elucidate the cellular phenotype of BRD9 bromodomain inhibition.

Hydrogen atom transfer-mediated intramolecular C-C coupling reactions between alkenes and nitriles, using PhSiH3 and catalytic Fe(acac)3 , are described. This introduces a new strategic bond disconnection for ring-closing reactions, forming ketones via imine intermediates. Of note is the scope of the reaction, including formation of sterically hindered ketones, spirocycles and fused cyclic systems.

In this work, we present a new method for predicting complex physicalchemical properties of organic molecules. The approach utilizes 3D convolutional neural network (ActivNet4) that uses solvent spatial distributions around solutes as input. These spatial distributions are obtained by a molecular theory called threedimensional reference interaction site model (3D-RISM). We have shown that the method allows one to achieve a good accuracy of prediction of bioconcentration factor (BCF) which is difficult to predict by direct application of methods of molecular theory or simulations. Our research demonstrates that combination of molecular theories with modern machine learning approaches can be effectively used for predicting properties that are otherwise inaccessible to purely theory-based models.

International audience; In-solution small-angle X-ray and neutron scattering (SAXS/SANS) have become popular methods to characterize the structure of membrane proteins, solubilized by either detergents or nanodiscs. SANS studies of protein-detergent complexes usually require deuterium-labeled proteins or detergents, which in turn often lead to problems in their expression or purification. Here, we report an approach whose novelty is the combined analysis of SAXS and SANS data from an unlabeled membrane protein complex in solution in two complementary ways. First, an explicit atomic analysis, including both protein and detergent molecules, using the program WAXSiS, which has been adapted to predict SANS data. Second, the use of MONSA which allows one to discriminate between detergent head- and tail-groups in an ab initio approach. Our approach is readily applicable to any detergent-solubilized protein and provides more detailed structural information on protein-detergent complexes from unlabeled samples than SAXS or SANS alone.

Ten isostructural single-crystal diffraction studies of mixed cation Ca/Sr salt forms of the salicylate anion are presented, namelycatena-poly[[diaquacalcium(II)/strontium(II)]-bis(μ2-2-hydroxybenzoato)], [Ca1–xSrx(C7H5O3)2(H2O)2]n, wherex= 0, 0.041, 0.083, 0.165, 0.306, 0.529, 0.632, 0.789, 0.835 and 1. The structure of an isostructural Sr/Ba species, namelycatena-poly[[diaquastrontium(II)/barium(II)]-bis(μ2-2-hydroxybenzoato)], [Sr0.729Ba0.271(C7H5O3)2(H2O)2], is also described. The Ca/Sr structures form a series where, with increasing Sr content, the unit cell expands in both the crystallographicaandcdirections (by 1.80 and 3.18%, respectively), but contracts slightly in thebdirection (−0.31%). The largest percentage structural expansion lies parallel to the direction of propagation of the one-dimensional coordination polymer that is the primary structural feature. This structural expansion is thus associated with increasedM—O distances. Aqueous solubility measurements show that solubility generally increases with increasing Sr content. Thus, tuning the composition of these mixed counter-ion salt forms leads to systematic structural changes and allows solubility to be tuned to values between those for the pure Ca and Sr species.

An NMR spectroscopic study has been conducted into the reactivity of alkali metal benzyls [M(CH2Ph)], (M = Li, Na, K) with lanthanide tris(amide) complexes [Ln(N″)3] (Ln = Y, Ce, Nd; N″ = N(SiMe3)2) and [Ce(TMP)3] (TMP = 2,2,6,6-tetramethylpiperidide). It was found that for [Ln(N″)3], benzyl adducts [M][Ln(N″)3(CH2Ph)] were initially formed, and the molecular structure for M = Li(TMEDA)2 and Ln = Nd was determined revealing a distorted tetrahedral [Nd(N″)3(CH2Ph)] anion. In all cases, these adduct complexes were unstable, intramolecularly deprotonating a methyl arm of a N″ ligand via benzyl basicity and eliminating toluene to prepare cyclometallated complexes of the form [M][Ln(N″)2{κ2-CH2Si(Me)2N(SiMe3)}]. In parallel studies, reactions of [Li(Ph)] with [Ln(N″)3] (Ln = Ce, Nd) afforded [Li(N″)], whilst for (Ln = Y) adduct formation was observed. [Ce(TMP)3] did not generate any characterisable bimetallic adducts. The reaction of [Li(Ph)] with [Li(TMP)] afforded the hexanuclear [{Li(TMP)}2{Li(μ-Ph)}]2, which features lithium in three different coordination environments.

Raman spectroscopy can be used to identify molecules such as DNA by the characteristic scattering of light from a laser. It is sensitive at very low concentrations and can accurately quantify the amount of a given molecule in a sample. The presence of a large, nonuniform background presents a major challenge to analysis of these spectra. To overcome this challenge, we introduce a sequential Monte Carlo (SMC) algorithm to separate each observed spectrum into a series of peaks plus a smoothly-varying baseline, corrupted by additive white noise. The peaks are modelled as Lorentzian, Gaussian, or pseudo-Voigt functions, while the baseline is estimated using a penalised cubic spline. This latent continuous representation accounts for differences in resolution between measurements. The posterior distribution can be incrementally updated as more data becomes available, resulting in a scalable algorithm that is robust to local maxima. By incorporating this representation in a Bayesian hierarchical regression model, we can quantify the relationship between molecular concentration and peak intensity, thereby providing an improved estimate of the limit of detection, which is of major importance to analytical chemistry.

Successful pathogen detection is crucial for public health as the threat of infectious disease is dramatically increasing globally due to bacteria developing resistance to many anti-microbial drugs. The increase in bacterial infections has led to urgent demands for simpler, faster and more reliable detection methods to be developed, so that the most appropriate therapy can be provided. Surface enhanced Raman scattering (SERS) is an analytical technique which has gained a great deal of interest for biosensing due to its sensitivity, selectivity and multiplexing capabilities. A new bionanosensor has been developed for the isolation and detection of multiple bacterial pathogens via magnetic separation and SERS. This novel assay format involves using lectin functionalised magnetic nanoparticles for capture and isolation of bacteria from the sample matrix followed by specifically detecting bacterial pathogens using SERS active nanoparticles functionalised with antibodies which are strain specific. Therefore, the sample is captured using a ‘magnetic plug’ and interrogated with a laser allowing simple and fast optical detection. Three bacterial pathogens – Escherichia coli, Salmonella typhimurium and methicillin-resistant Staphylococcus aureus – were successfully isolated and detected, with the lowest concentration for each of the strains detected at just 101 colony forming units per mL (CFU/mL). In addition to single pathogen detection, a mixture of all three bacterial strains were isolated and identified within the same sample matrix using SERS with the triplex detection also being confirmed using principal component analysis. Herein, we demonstrate that this multiplexed bionanosensor is capable of providing rapid and sensitive discrimination of bacterial pathogens both individually, and within a multiplex system, offering opportunities for future point of care devices and advancements in bio-medical applications.

The Friedel–Crafts reaction ( 1 ), named after its respective French and American pioneers, has long been used to attach alkyl groups to aromatic rings. This reaction is an electrophilic aromatic substitution. Electrophiles are electron-poor species, whereas nucleophiles are electron-rich species. Electron-rich aromatic molecules such as benzene can use their surplus of electrons to react with electron-poor, positively charged species, enabling benzene to exchange one of its hydrogen atoms for the electrophilic group to make a new, substituted benzene. Because “like species repel,” electron-rich species should not react with other electron-rich species, so benzene should never undergo direct nucleophilic alkylation. Nonetheless, on page [1168][1] of this issue, Wilson et al. ( 2 ) report the facile nucleophilic alkylation of benzene accomplished through highly reactive alkylcalcium nucleophiles. [1]: /lookup/doi/10.1126/science.aao5923