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All evolutionary biological processes lead to a change in heritable traits over successive generations. The responsible genetic information encoded in DNA is altered, selected, and inherited by mutation of the base sequence. While this is well known at the biological level, an evolutionary change at the molecular level of small organic molecules is unknown but represents an important prerequisite for the emergence of life. Here, we present a class of prebiotic imidazolidine-4-thione organocatalysts able to dynamically change their constitution and potentially capable to form an evolutionary system. These catalysts functionalize their building blocks and dynamically adapt to their (self-modified) environment by mutation of their own structure. Depending on the surrounding conditions, they show pronounced and opposing selectivity in their formation. Remarkably, the preferentially formed species can be associated with different catalytic properties, which enable multiple pathways for the transition from abiotic matter to functional biomolecules., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The formation of peptide bonds is one of the most important biochemical reaction steps. Without the development of structurally and catalytically active polymers, there would be no life on our planet. However, the formation of large, complex oligomer systems is prevented by the high thermodynamic barrier of peptide condensation in aqueous solution. Liquid sulphur dioxide proves to be a superior alternative for copper-catalyzed peptide condensations. Compared to water, amino acids are activated in sulphur dioxide, leading to the incorporation of all 20 proteinogenic amino acids into proteins. Strikingly, even extremely low initial reactant concentrations of only 50 mM are sufficient for extensive peptide formation, yielding up to 2.9% of dialanine in 7 days. The reactions carried out at room temperature and the successful use of the Hadean mineral covellite (CuS) as a catalyst, suggest a volcanic environment for the formation of the peptide world on early Earth., (© 2021. The Author(s).)

The ectoparasitic nematode Xiphinema index transmits grapevine fanleaf virus (GFLV) during feeding on grapevine roots, causing fanleaf degeneration in the plant. Hence, resistance breeding is a key to develop novel rootstocks to overcome such threats. In past years, various grapevine species were screened, and a few candidates with partial resistance were identified. However, they were hardly sufficient for viticulture because of their many agronomical defects. To develop reliably resistant rootstocks applicable in viticulture, multiple Vitis spp. genotypes were analyzed using root inoculation with nematodes in glass vials as an early and easy evaluation test. Resistance levels were evaluated 35 days after inoculation based on nematode reproduction factors, focusing on juveniles and eggs. Infection of grapevines with GFLV was analyzed after inoculation with viruliferous X. index . With this fast screening system, putative candidates with resistances against X. index have been identified for future breeding programs. Particularly, genotypes with the genetic background of Vitis aestivalis and Vitis labrusca were found to be nematode-resistant.

Mechanisms leading to a molecular evolution and the formation of homochirality in nature are interconnected and a key to the underlying principles that led to the emergence of life. So far proposed mechanisms leading to a non-linear reaction behavior are based mainly on the formation of homochiral and heterochiral dimers. Since homochiral and heterochiral dimers are diastereomers of each other, the minor enantiomer is shifted out of equilibrium with the major enantiomer by dimer formation and thus a reaction or catalysis can be dominated by the remaining molecules of the major enantiomer. In this article a mechanism is shown that leads to homochirality by the formation of a highly catalytically active transient intermediate in a stereodynamically controlled reaction. This is demonstrated by Soai's asymmetric autocatalysis, in which aldehydes are transformed into the corresponding alcohols by addition of dialkylzinc reagents. The mechanism of chirogenesis proposed here shows that an apparently inefficient reaction is the best prerequisite for a selection mechanism. In addition, stereodynamic control offers the advantage that the minor diastereomeric intermediate can be interconverted into the major diastereomer and thus be stereoeconomically efficient. This is supported by computer simulation of reaction kinetics., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Trapp.)

Invited for the cover of this issue is Oliver Trapp and his co-workers at Ludwig-Maximilians-Universität München, the Max-Planck-Institute for Astronomy and Ruprecht-Karls-Universität Heidelberg. The image depicts a magic trick representing the autocatalytic process reported in the manuscript. Read the full text of the article at 10.1002/chem.202003260., (© 2020 Wiley-VCH GmbH.)

Ever since the discovery of nucleic acids 150 years ago, [1] major achievements have been made in understanding and decrypting the fascinating scientific questions of the genetic code. [2] However, the most fundamental question about the origin and the evolution of the genetic code remains a mystery. How did nature manage to build up such intriguingly complex molecules able to encode structure and function from simple building blocks? What conditions were required? How could the precursors survive the unhostile environment of early Earth? Over the past decades, promising synthetic concepts were proposed providing clarity in the field of prebiotic nucleic acid research. In this Minireview, we show the current status and various approaches to answer these fascinating questions., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

The formation of carbohydrates represents an essential step to provide building blocks and a source of chemical energy in several models for the emergence of life. Formaldehyde, glycolaldehyde and a basic catalyst are the initial components forming a variety of sugar molecules in the cascade-type multi-step formose reaction. While numerous side reactions and even deterioration can be observed in aqueous media, selective prebiotic sugar formation is feasible in solid-state, mechanochemical reactions and might have occurred in early geochemistry. However, the precise role of different basic catalysts and the influence of the atmospheric conditions in the solid-state formose reaction remain unknown. Here we show, that in a primordial scenario the mechanochemical formose reaction is capable to form monosaccharides with a broad variety of mineral classes as catalysts with only minute amounts of side products such as lactic acid or methanol, independent of the atmospheric conditions. The results give insight into recent findings of formose sugars on meteorites and offer a water-free and robust pathway for monosaccharides independent of the external conditions both for the early Earth or an extra-terrestrial setting., (© 2020. The Author(s).)

Organocatalysis is a powerful approach to extend and (enantio-) selectively modify molecular structures. Adapting this concept to the Early Earth scenario offers a promising solution to explain their evolution into a complex homochiral world. Herein, we present a class of imidazolidine-4-thione organocatalysts, easily accessible from simple molecules available on an Early Earth under highly plausible prebiotic reaction conditions. These imidazolidine-4-thiones are readily formed from mixtures of aldehydes or ketones in presence of ammonia, cyanides and hydrogen sulfide in high selectivity and distinct preference for individual compounds of the resulting catalyst library. These organocatalysts enable the enantioselective α-alkylation of aldehydes under prebiotic conditions and show activities that correlate with the selectivity of their formation. Furthermore, the crystallization of single catalysts as conglomerates opens the pathway for symmetry breaking., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

The hyphenation of capillary electrophoresis with high-resolution mass spectrometry, such as Orbitrap MS, is of broad interest for the unambiguous and exceptionally sensitive identification of compounds. However, the coupling of these techniques requires a robust ionization interface that does not influence the stability of the separation voltage while coping with oxidation of the emitter tip at large ionization voltages. Herein, we present the design of a sheath-flow CE-ESI-MS interface which combines a robust and easy to operate set-up with high-resolution Orbitrap MS detection. The sheath liquid interface is equipped with a gold coated electrospray emitter which increases the stability and overall lifetime of the system. For the characterization of the interface, the spray stability and durability were investigated in dependence of the sheath-flow rate, electrospray voltage, and additional gold coating. The optimized conditions were applied to a separation of angiotensin II and neurotensin resulting in LODs of 2.4 and 3.5 ng/mL., (© 2020 The Authors. Electrophoresis published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The acetate-initiated aliphatic isocyanate trimerization to isocyanurate was investigated by state-of-the-art analytical and computational methods. Although the common cyclotrimerization mechanism assumes the consecutive addition of three equivalents of isocyanate to acetate prior to product formation, we found that the underlying mechanism is more complex. In this work, we demonstrate that the product, in fact, is formed via the connection of two unexpected catalytic cycles, with acetate being only the precatalyst. The initial discovery of a precatalyst activation by quantum chemical computations and the resulting first catalysis cycle were corroborated by mass spectrometric and NMR experiments, thereby additionally revealing a catalyst migration to the second catalytic cycle. These results were further confirmed by computations, completing the full mechanistic understanding of this catalytic system. Identification of a side product with undesired properties for final coating applications allows for process optimization in the chemical industry.

Thiete dioxide units have been employed as a template for further functionalization through C-H activation strategies. Using simple thiete dioxide building blocks, a new library of axially chiral molecules has been synthesized that owe their stability to electrostatic interactions in the solid state. Similar starting materials were further engaged in the formation of cyclic trimeric structures, opening the pathway to unprecedented macrocyclic ring systems., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Intraoperative imaging has been advanced substantially over the last decades. It supports localization of the region of interest, verification of the preoperatively classified fracture pattern, identification of correct insertion point of the implant, placement of instruments and fixation material, and verification of correct fracture reduction and implant positioning. While conventional fluoroscopic 2D imaging remains the gold standard in intraoperative imaging, critical anatomical regions are predestined for intraoperative 3D imaging. Additional options such as perioperative virtual planning, simulation, and surgical training, 3D printing techniques and 3D augmented reality visualization may potentially open new windows to improve surgical results in fracture care. This manuscript presents an update on current and upcoming imaging techniques in orthopaedic and trauma surgery focusing on technical advances for decreasing malreduction, malalignment, and malposition, as well as tips and tricks for daily surgical practice in order to improve clinical outcomes and patients' and surgeons' safety., Competing Interests: Conflict of Competing Interest None of the authors received benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this manuscript., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Chirality plays a pivotal role in an uncountable number of biological processes, and nature has developed intriguing mechanisms to maintain this state of enantiopurity. The strive for a deeper understanding of the different elements that constitute such self-sustaining systems on a molecular level has sparked great interest in the studies of autoinductive and amplifying enantioselective reactions. The design of these reactions remains highly challenging; however, the development of generally applicable principles promises to have a considerable impact on research of catalyst design and other adjacent fields in the future. Here, we report the realization of an autoinductive, enantioselective self-inhibiting hydrogenation reaction. Development of a stereodynamic catalyst with chiral sensing abilities allowed for a chiral reaction product to interact with the catalyst and change its selectivity in order to suppress its formation, which caused a reversal of selectivity over time., (© 2019 The Authors. Chirality published by Wiley Periodicals, Inc.)

This study develops analytical approaches using comprehensive heart-cut multidimensional gas chromatography (H/C MDGC) to experimentally investigate effects of concentration and temperature on peak shapes and on kinetic analysis of E/Z isomerisation of oximes which undergo various extents of interconversion on 1 D and 2 D separation columns. Different stationary phase combinations were investigated. An SLB-IL76 1 D column results in good separation of the isomers but with negligible interconversion ( 1 D sep ). Precise targeted heart-cuts (H/C; 3-15 s windows) and cryogenic trapping of selected sections eluting from this 1 D column allows well controlled E/Z isomer ratios to be delivered to a 2 D poly(ethyleneglycol) (PEG) phase column. This phase catalyses oxime interconversion, with separation; this is termed 2 D inter . This column set describes a 1 D sep  ×  2 D inter arrangement. The interconversion forward rate constant (k 1 UE , calculated by using DCXplorer) was found to be independent of the %E isomer (i.e. first order kinetics); k 1 UE increased at higher temperature (increased Gibbs activation energies, ΔG app ). In addition, a long 1 D SLB-IL111 column gave oxime separation with interconversion ( 1 D inter ). Comprehensive multiple H/C of the zone performed on the 2 D PEG ( 2 D inter ) at 40, 60 and 80 °C resulted in a 2D presentation ( 1 D inter  ×  2 D inter ) with a unique rectangular display of interconversion from each H/C pulse with varied isomer concentration ratios. Data for k 1 UE from 1DGC analysis suggests underestimation of k 1 UE on 1 D inter SLB-IL111 from the 2D result. The k 1 UE value on 2 D inter PEG column is more reliably evaluated by summation of all the 2 D inter profiles rather than that obtained from the average value for the individual H/C pulses., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In times of a warming climate due to excessive carbon dioxide production, catalytic conversion of carbon dioxide to formaldehyde is not only a process of great industrial interest, but it could also serve as a means for meeting our climate goals. Currently, formaldehyde is produced in an energetically unfavourable and atom-inefficient process. A much needed solution remains academically challenging. Here we present an algorithmic workflow to improve the ruthenium-catalysed transformation of carbon dioxide to the formaldehyde derivative dimethoxymethane. Catalytic processes are typically optimised by comprehensive screening of catalysts, substrates, reaction parameters and additives to enhance activity and selectivity. The common problem of the multidimensionality of the parameter space, leading to only incremental improvement in laborious physical investigations, was overcome by combining elements from machine learning, optimisation and experimental design, tripling the turnover number of 786 to 2761. The optimised conditions were then used in a new reaction setup tailored to the process parameters leading to a turnover number of 3874, exceeding by far those of known processes., (This journal is © The Royal Society of Chemistry 2019.)

Well-defined supramolecular interactions are a powerful tool to control the stereochemistry of a catalytic reaction. In this paper, we report a novel core motif for fluxional 2,2'-biphenyl ligands carrying (S)-amino acid-derived interaction sites in 5,5'-position that cause spontaneous enrichment of the R ax rotamer. The process is based on strong non-covalent interlocking between interaction sites, which causes diastereoselective formation of a supramolecular ligand dimer, in which the axial chirality of the two subunits is dictated by the stereochemical information in the amino acid residues. The detailed structure of the dimer was elucidated by NMR spectroscopy and single-crystal X-ray analysis. Three different phosphorus-based ligand types, namely a bisphosphine, a bisphosphinite and a phosphoramidite were synthesized and characterized. Whereas the first one was found to exist in a strongly weighted equilibrium, the two others each exhibited stereoconvergent behavior transforming into the diastereopure R ax rotamer. Enriched ligands were used in rhodium-mediated asymmetric hydrogenation reactions of prochiral olefins in which very high enantioselectivities of up to 96:4 were achieved., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: European grapevine cultivars (Vitis vinifera spp.) are highly susceptible to the downy mildew pathogen Plasmopara viticola. Breeding of resistant V. vinifera cultivars is a promising strategy to reduce the impact of disease management. Most cultivars that have been bred for resistance to downy mildew, rely on resistance mediated by the Rpv3 (Resistance to P. viticola) locus. However, despite the extensive use of this locus, little is known about the mechanism of Rpv3-mediated resistance., Results: In this study, Rpv3-mediated defense responses were investigated in Rpv3 + and Rpv3- grapevine cultivars following inoculation with two distinct P. viticola isolates avrRpv3 + and avrRpv3-, with the latter being able to overcome Rpv3 resistance. Based on comparative microscopic, metabolomic and transcriptomic analyses, our results show that the Rpv3-1-mediated resistance is associated with a defense mechanism that triggers synthesis of fungi-toxic stilbenes and programmed cell death (PCD), resulting in reduced but not suppressed pathogen growth and development. Functional annotation of the encoded protein sequence of genes significantly upregulated during the Rpv3-1-mediated defense response revealed putative roles in pathogen recognition, signal transduction and defense responses., Conclusion: This study used histochemical, transcriptomic and metabolomic analyses of Rpv3 + and susceptible cultivars inoculated with avirulent and virulent P. viticola isolates to investigate mechanism underlying the Rpv3-1-mediated resistance response. We demonstrated a strong correlation between the expressions of stilbene biosynthesis related genes, the accumulation of fungi-toxic stilbenes, pathogen growth inhibition and PCD.

It is assumed that RNA played a key role in the origin of life, and the transition to more complex but more stable DNA for continuous information storage and replication requires the development of a ribonucleotide reductase to obtain the deoxyribonucleotides from ribonucleotides. This step, as well as an alternative path from abiotic molecules to DNA-based life is completely unknown. Shown here is the formation of deoxyribonucleosides under relevant prebiotic conditions in water in high regio- and stereoselectivity, from all canonical purine and pyrimidine bases, by condensation with acetaldehyde and sugar-forming precursors. Thus, a continuous path to deoxyribonucleosides, starting from simple, prebiotically available molecules has been discovered. Furthermore, the deoxyapionucleosides (DApiNA) were identified as a potential DNA progenitor. The results suggest that the DNA world evolved much earlier than previously assumed., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The development of fast and precise measurement techniques for process analytical technology is important to operate chemical processes safely and efficiently. For quantitative measurements of multiple components at a trace level, often gas chromatographic methods are used which have a response time of several minutes or of up to one hour. For fast changing processes, this can be too slow for efficient control. For reducing the dead time of a control loop by increasing the measurement frequency, a multiplexing gas chromatography (mpGC) technique for a chromatographic system exhibiting a systematic non-linear response has been developed. For mpGC, superimposed chromatograms are measured by injecting consecutive samples before all components of previous samples have eluted from the column. The deconvolution of a superimposed chromatogram yields a computed chromatogram which is an average over the single chromatograms forming the superimposed chromatogram. Such a computed chromatogram typically shows so called correlation noise depending on the degree by which the single chromatograms forming the superimposed chromatogram will differ from each other (non-linear response). A technique is presented to calibrate the convolution matrix in order to suppress correlation noise introduced by systematic errors of the chromatographic system. The remaining correlation noise in the computed chromatogram is then exclusively caused by changing concentrations in the sample stream. For the method presented here, the sample is injected five times during the run time of a single chromatogram. The computed chromatogram is obtained three times within this timespan while representing each time an averaged chromatogram over the last five injections. Therefore, the sample throughput is increased by a factor of three compared to conventional GC., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Monosaccharides represent one of the major building blocks of life. One of the plausible prebiotic synthesis routes is the formose network, which generates sugars from C1 and C2 carbon sources in basic aqueous solution. We report on the feasibility of the formation of monosaccharides under physical forces simulated in a ball mill starting from formaldehyde, glycolaldehyde, DL-glyceraldehyde as prebiotically available substrates using catalytically active, basic minerals. We investigated the influence of the mechanic energy input on our model system using calcium hydroxide in an oscillatory ball mill. We show that the synthesis of monosaccharides is kinetically accelerated under mechanochemical conditions. The resulting sugar mixture contains monosaccharides with straight and branched carbon chains as well as decomposition products. In comparison to the sugar formation in water, the monosaccharides formed under mechanochemical conditions are more stable and selectively synthesized. Our results imply the possibility of a prebiotic monosaccharide origin in geochemical environments scant or devoid of water promoted by mechanochemical forces such as meteorite impacts or lithospheric activity.

Proteins of the Fanconi Anemia (FA) complementation group are required for crosslink (CL) repair in humans and their loss leads to severe pathological phenotypes. Here we characterize a homolog of the Fe-S cluster helicase FANCJ in the model plant Arabidopsis, AtFANCJB, and show that it is involved in interstrand CL repair. It acts at a presumably early step in concert with the nuclease FAN1 but independently of the nuclease AtMUS81, and is epistatic to both error-prone and error-free post-replicative repair in Arabidopsis. The simultaneous knock out of FANCJB and the Fe-S cluster helicase RTEL1 leads to induced cell death in root meristems, indicating an important role of the enzymes in replicative DNA repair. Surprisingly, we found that AtFANCJB is involved in safeguarding rDNA stability in plants. In the absence of AtRTEL1 and AtFANCJB, we detected a synergetic reduction to about one third of the original number of 45S rDNA copies. It is tempting to speculate that the detected rDNA instability might be due to deficiencies in G-quadruplex structure resolution and might thus contribute to pathological phenotypes of certain human genetic diseases., Competing Interests: The authors have declared that no competing interests exist.

The design of a new class of fluxional biphenyl bisphosphinite (BIBIPHOS) ligands decorated with amino acid-based diamide interaction sites is reported that undergo spontaneous desymmetrization. Hydrogenation of prochiral alkenes using Rh-BIBIPHOS results in enantiomeric ratios of up to 96:4 (R/S). This stereoconvergent behavior of the fluxional BIBIPHOS ligand is triggered by pronounced intermolecular interlocking of the recognition sites, leading to the formation of a supramolecular assembly, where the axial orientation of the biphenyl ligand backbone is governed by the chirality of the amino acid moieties. Stereoinduction during catalysis is decoupled from this process and occurs as an immediate consequence of the emergent behavior of the ligands. This supramolecular system is very robust and has the potential to be adopted for other ligand designs in enantioselective catalysis., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

DNA-protein crosslinks (DPCs) represent a severe threat to the genome integrity; however, the main mechanisms of DPC repair were only recently elucidated in humans and yeast. Here we define the pathways for DPC repair in plants. Using CRISPR/Cas9, we could show that only one of two homologs of the universal repair proteases SPARTAN/ weak suppressor of smt3 (Wss1), WSS1A, is essential for DPC repair in Arabidopsis ( Arabidopsis thaliana ). WSS1A defective lines exhibit developmental defects and are hypersensitive to camptothecin (CPT) and cis-platin. Interestingly, the CRISPR/Cas9 mutants of TYROSYL-DNA PHOSPHODIESTERASE 1 ( TDP1 ) are insensitive to CPT, and only the wss1A tdp1 double mutant reveals a higher sensitivity than the wss1A single mutant. This indicates that TDP1 defines a minor backup pathway in the repair of DPCs. Moreover, we found that knock out of the endonuclease METHYL METHANESULFONATE AND UV SENSITIVE PROTEIN 81 ( MUS81 ) results in a strong sensitivity to DPC-inducing agents. The fact that wss1A mus81 and tdp1 mus81 double mutants exhibit growth defects and an increase in dead cells in root meristems after CPT treatment demonstrates that there are three independent pathways for DPC repair in Arabidopsis. These pathways are defined by their different biochemical specificities, as main actors, the DNA endonuclease MUS81 and the protease WSS1A, and the phosphodiesterase TDP1 as backup., (© 2019 American Society of Plant Biologists. All rights reserved.)

The rotational spectrum of monodeutero-oxirane was analysed as measured using the Zurich Gigahertz (GHz) spectrometer and our highest resolution Fourier Transform Infrared (FTIR) spectrometer system coupled to synchrotron radiation at the Swiss Light Source (SLS). 112 distinct line frequencies have been newly assigned in the GHz range (extended to 120 GHz, compared to previous work extending to only 59 GHz) including rotational states up to J = 23. We have furthermore assigned 398 lines in the far infrared or Terahertz range (0.75-2.10 THz or 25-70 cm-1) including transitions with rotational quantum numbers up to J = 59. The results are discussed in relation to the possible first astrophysical observation of an isotopically chiral molecule and in relation to molecular parity violation.

Formaldehyde is an important precursor to numerous industrial processes and is produced in multimillion ton scale every year by catalytic oxidation of methanol in an energetically unfavorable and atom-inefficient industrial process. In this work, we present a highly selective one-step synthesis of a formaldehyde derivative starting from carbon dioxide and hydrogen gas utilizing a homogeneous ruthenium catalyst. Here, formaldehyde is obtained as dimethoxymethane, its dimethyl acetal, by selective reduction of carbon dioxide at moderate temperatures (90 °C) and partial pressures (90 bar H 2 /20 bar CO 2 ) in the presence of methanol. Besides the desired product, only methyl formate is formed, which can be transformed to dimethoxymethane in a consecutive catalytic step. By comprehensive screening of the catalytic system, maximum turnover numbers of 786 for dimethoxymethane and 1290 for methyl formate were achieved with remarkable selectivities of over 90% for dimethoxymethane.

Hadamard encoding, utilizing pseudo-random injection sequences with n-bit (2 n -1) elements, is applied in analytical sciences to enhance the signal-to-noise ratio (S/N) of weak analyte signals. We have developed a software approach that allows using Hadamard encoding on standard HPLC systems. This strategy is only limited by the number of instructions that can be transmitted to the autosampler and its performance degrades if an accumulation of chromatographic irregularities occurs while applying long modulation sequences. Here we demonstrate that such sequences (>4000 elements) can be subdivided into suitable subsequences, which can be independently executed. The measured subchromatograms are subsequently realigned and deconvoluted yielding a chromatogram with increased S/N. This opens an avenue to achieve unprecedented sensitivity gains. In the analysis of highly diluted nucleoside samples an S/N enhancement of up to 30-fold was observed. Furthermore, we applied the method to a sample containing the antibiotic drug fidaxomicin and found a significant sensitivity improvement that strongly depends on the applied elution conditions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We present rhodium catalysts that contain stereodynamic axially chiral biphenol-derived phosphinite ligands modified with non-stereoselective amides for non-covalent interactions. A chirality transfer was achieved with (R)- or (S)-acetylphenylalanine methyl amide, and the interaction mechanism was investigated by NMR measurements. These interactions at the non-stereoselective interaction sites and the formation of supramolecular complexes result in an enrichment of either the (R ax )- or (S ax ) enantiomer of the tropos catalysts, which in turn provide the (R)- or (S)-acetylphenylalanine methyl ester in the hydrogenation of (Z)-methyl-α-acetamidocinnamate., (© 2018 Wiley Periodicals, Inc.)

The separation and analysis of complex monosaccharide mixtures is highly challenging and requires typically carefully selected derivatization procedures to avoid changes in the sample composition. Here we present in a comparative study several single- and two-step derivatization approaches for LC and GC separations using a set of reference compounds ranging from C1 building block such as formaldehyde to C6 monosaccharides. Separation conditions have been optimized resulting in the simultaneous separation of 15 unbranched aldoses. By parallel derivatization using hydroxylamine hydrochloride (HACl)/ N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and O-ethylhydroxylamine hydrochloride (EtOx)/ N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and comparative GC measurements we developed a protocol for the unambiguous identification and separation of aldoses, ketoses, alditols and aldonic acids, which commonly occur in complex sugar mixtures as reaction by-products or decomposition products. In particular this procedure helps to deconvolute overlapping analytes and facilitates quantification. Additionally, the method presented here has been investigated in regard to storage life, detection limits, quantification and MS analysis. The broad applicability of this method to different sample matrices is shown for the analysis of food samples and complex aldol reaction mixtures in the formose reaction, which is of great relevance in the context of the origin of life., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Developing new catalysts is crucial for optimization of chemical processes. Thus, advanced analytical methods are required to determine the catalytic performance of new catalysts accurately. Usually, gas chromatographic methods are employed to analyze quantitatively the product distribution of volatile compounds generated by a specific catalyst. However, the characterization of rapidly changing catalysts, e.g., due to deactivation, still poses an analytical challenge because gas chromatographic methods are too slow for monitoring the change of the complex product spectra. Here, we developed a gas chromatographic technique based on the concept of multiplexing gas chromatography (mpGC) for fast and comprehensive analysis of the product stream from a catalytic testing unit. This technique is applied for the study of the catalytic reaction of methanol-to-olefins (MTO) conversion. For this method, the time distance between two measurements is chosen so that the chromatograms but not the peaks themselves are superimposed. In this way, stacked chromatograms are generated in which the components from successively injected samples elute baseline separated next to each other from the column. The peaks from different samples are interlaced, and for this reason, the method is referred to as time-division multiplexing gas chromatography (td-mpGC). The peaks are analyzed by direct peak integration not requiring a Hadamard transformation for deconvolution of the raw data as usual for many mpGC applications. Therefore, the sample can be injected equidistantly. The integrated peaks have to be allocated to the correct retention times. The time distance between two measurements for studying the reaction and regeneration cycles of MTO catalysts is 4.3 min and 38 s, respectively. Column switching techniques such as back-flush and heart-cut are introduced as general tools for multiplexing gas chromatography.

We report the first successful implementation of a multiplexing method on a standard capillary electrophoresis system with UV detection that is independent of additional hardware. This was achieved using the Hadamard transform approach and employing vial exchange and voltage suspensions for translation of pseudorandom binary sequence elements into sample and background electrolyte injections of a capillary zone electrophoresis separation. Sequences exceeding peak capacity of the capillary were subdivided into shorter subsequences measured successively and realigned afterward based on EOF marker or analyte peaks. This way, we realized and deconvoluted modulation sequences as long as 8-bit (255 injections) for two systems containing either AMP or a mixture of the nucleotides (A,C,G,U)MP resulting in electropherograms of considerably improved signal-to-noise ratio. We achieved factors of intensity enhancement of around 6.9 and 5.2, respectively (theoretical maximum 8.0). This contribution, further, presents experimental and simulation studies on the effects on zones during injection and separation when experiencing voltage suspensions. Besides analysis of EOF behavior and influence of diffusion dispersion, we also provide data on the significance of specific electrophoretic errors such as peak position shift, inconsistent sample injection, and peak broadening on the quality of the inverse Hadamard transform. Moreover, the application of our approach to the practical analysis of a milk sample is described. The results demonstrate the applicability of multiplexing on unmodified standard CE instrumentation and establish a new suitable methodology to enhance the low sensitivity of on-column UV detection in capillary electrophoresis.

The Cu-free 1,3-dipolar cycloaddition of cyclooctynes and azides is an up-and-coming method in bioorganic chemistry and other disciplines. However, broad application is still hampered by major drawbacks such as poor solubility of the reactants in aqueous media and low reaction rates. It is thus of high demand to devise a fast and user-friendly strategy for the optimization of reaction conditions and reagent design. We describe a capillary electrophoresis (CE) study of reaction kinetics in strain-promoted azide-alkyne cycloadditions (SPAAC) using substrates with acidic or basic functionalities. This study reveals that the pH value has a significant effect on reaction rates as a result of changes in the reactants' charge state via protonation or deprotonation, and the concomitant changes of electronic properties. This novel experimental setup also enables the study of even more challenging conditions such as reactions in micelles and we did indeed observe much faster SPAAC reactions in the presence of surfactants. Careful combination of the above-mentioned parameters resulted in the identification of conditions enabling remarkable rate enhancement by a factor of 80. This electrophoretic method may thus serve as a versatile, fast and reliable tool for screening purposes in all research areas applying SPAAC reactions.

The asymmetric ruthenium-catalyzed reductive amination employing ammonia and hydrogen to primary amines is described. Here we demonstrate the capability of our catalyst to perform a chemo- and enantioselective process while using simple ammonia gas as a reagent, one of the most attractive and industrially relevant nitrogen sources. The presence of a catalytic amount of ammonium iodide was essential for obtaining good yields and enantioselectivities. The mechanism of this reaction was investigated by DFT and we found a viable pathway that also explains the trend and magnitude of enantioselectivity through the halide series in good agreement with the experimental data. The in-depth investigation of substrate conformers during the reaction turned out to be crucial in obtaining an accurate prediction of the enantioselectivity. Furthermore, we report the crystallographic data of the chiral [Ru(I)H(CO)((S,S)-f-binaphane)(PPh 3 )] complex, which we identified as the most efficient catalyst in our investigation.

Background: The weaning target in tracheotomised patients is not extubation, but spontaneous breathing without the support of a ventilator. Overloading the respiratory pump during such spontaneous breathing trials is unfavorable, prolongs weaning time, and increases morbidity and mortality. The goal of this study was to evaluate the electrical activity of the diaphragm during a t-piece trial in non-communicative neurological patients and the comparison to clinical parameters of exhaustion., Methods: During multiple t-piece trials, the electrical activity of the diaphragm was obtained before, during and after the end of the trial. T-piece trials were grouped based on the reason for stopping the trial (exhaustion or allotted time period)., Results: Twenty-nine tracheotomised patients in prolonged weaning (29 ± 22 days ventilated at the start of the study) were included in a prospective observational study. T-piece trials (n = 152; 5 ± 2 per patient) were grouped based on the reason for stopping the trial (n = 91 because of exhaustion; n = 61 because of the allotted time period). We found that the electrical activity of the diaphragm exhibits an earlier increase than protocol-based clinical parameters in patients who failed the trial due to exhaustion. The electrical activity of the diaphragm shows no relevant difference during the t-piece trial in patients in whom the trial was stopped due to the allotted time period per protocol., Conclusions: Monitoring the electrical activity of the diaphragm in non-communicative neurological patients in prolonged weaning allows earlier detection of exhaustion than protocol-based parameters.

Multiple pathways exist to repair DNA damage induced by methylating and crosslinking agents in Arabidopsis thaliana. The SWI2/SNF2 translocase RAD5A, the functional homolog of budding yeast Rad5 that is required for the error-free branch of post-replicative repair, plays a surprisingly prominent role in the repair of both kinds of lesions in Arabidopsis. Here we show that both the ATPase domain and the ubiquitination function of the RING domain of the Arabidopsis protein are essential for the cellular response to different forms of DNA damage. To define the exact role of RAD5A within the complex network of DNA repair pathways, we crossed the rad5a mutant line with mutants of different known repair factors of Arabidopsis. We had previously shown that RAD5A acts independently of two main pathways of replication-associated DNA repair defined by the helicase RECQ4A and the endonuclease MUS81. The enhanced sensitivity of all double mutants tested in this study indicates that the repair of damaged DNA by RAD5A also occurs independently of nucleotide excision repair (AtRAD1), single-strand break repair (AtPARP1), as well as microhomology-mediated double-strand break repair (AtTEB). Moreover, RAD5A can partially complement for a deficient AtATM-mediated DNA damage response in plants, as the double mutant shows phenotypic growth defects., (© 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.)

The rapid and direct determination of enantiomeric ratios is of increasing interest due to the significantly reduced effort compared to chromatographic methods and the large number of analytes, for instance in enantioselective catalysis. Current strategies include colorimetric assays, (a)chiral solvating reagents for NMR spectroscopy and metal complexes for CD sensing. We report the determination of enantiomeric ratios based on the self-induced diastereomeric anisochronism (SIDA) effect. Alanine derivatives that represent chiral products of enantioselective catalysis, such as the well-established hydrogenation of dehydroamino acids, were investigated. The SIDA effect was significantly enhanced by attachment of 3,5-dinitrobenzoyl π-π interactions sites. This simple modification enabled simultaneous determination of enantiomeric ratios and conversions by NMR spectroscopy., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The analysis of impurities at a trace level in chemical products, nutrition additives, and drugs is highly important to guarantee safe products suitable for consumption. However, trace analysis in the presence of a dominating component can be a challenging task because of noncompatible linear detection ranges or strong signal overlap that suppresses the signal of interest. Here, we developed a technique for quantitative analysis using multiplexing gas chromatography (mpGC) for continuous and completely automated process trace analytics exemplified for the analysis of a CO 2 stream in a production plant for detection of benzene, toluene, ethylbenzene, and the three structural isomers of xylene (BTEX) in the concentration range of 0-10 ppb. Additional minor components are methane and methanol with concentrations up to 100 ppm. The sample is injected up to 512 times according to a pseudorandom binary sequence (PRBS) with a mean frequency of 0.1 Hz into a gas chromatograph equipped with a flame ionization detector (FID). A superimposed chromatogram is recorded which is deconvoluted into an averaged chromatogram with Hadamard transformation. Novel algorithms to maintain the data acquisition rate of the detector by application of Hadamard transformation and to suppress correlation noise induced by components with much higher concentrations than the target substances are shown. Compared to conventional GC-FID, the signal-to-noise ratio has been increased by a factor of 10 with mpGC-FID. Correspondingly, the detection limits for BTEX in CO 2 have been lowered from 10 to 1 ppb each. This has been achieved despite the presence of detectable components (methane and methanol) with a concentration about 1000 times higher than the target substances. The robustness and reliability of mpGC has been proven in a two-month field test in a chemical production plant.

Several vanadium(V) complexes with either dipic-based or Schiff base ligands were synthesized. The complexes were fully characterized by elemental analysis, IR, 1 H, 13 C, and 51 V NMR spectroscopy, as well as mass spectrometry and X-ray diffraction. Furthermore, they were tested toward their catalytic deperoxidation behavior and a significant difference between 4-heptyl hydroperoxide and cyclohexyl hydroperoxide was observed. In the case of 4-heptyl hydroperoxide, the selectivity toward the corresponding ketone was higher than with cyclohexyl hydroperoxide. DFT calculations performed on the vanadium complex showed that selective decomposition of secondary hydroperoxides with vanadium(V) to yield the corresponding ketone and water is indeed energetically feasible. The computed catalytic path, involving cleavage of the O-O bond, hydrogen transfer, release of ketone/water, and finally addition of hydroperoxide, can proceed without the generation of radical species.

The synthesis of enantiomerically pure compounds is of great importance in pharmaceuticals, fragrances and biological applications, and functions as a key to many processes in nature. Asymmetric catalysis using enantiomerically pure catalysts represents an efficient synthetic method to achieve this goal. The enantiomeric excess of the reaction product correlates with the enantiomeric purity of the catalysts, except for nonlinear behaviour, therefore the use of stereochemically flexible catalysts seems to complicate the control of stereoselectivity. Self-amplifying catalytic reactions are attractive, but a general rational design is highly challenging. Here we show that product interaction with chiral recognition sites attached to structurally flexible phoshoramidite-type catalysts can sense the chirality and induce enantioselectivity in the catalyst. Structural flexibility along with sensing of the chirality of the product molecules results in a rapid increase of enantioselectivity of the dynamic catalysts (Δe.e. of up to 76%) and a shift out of equilibrium. In contrast to stereodynamic catalysts controlled with cleavable chiral auxiliaries, the enantioselectivity does not decrease.

Stereodynamic ligands and complexes bearing functional groups to attach chiral or achiral binding sites and auxiliaries are highly attractive due to the interesting opportunities for controlling the stereochemical outcome of enantioselective transformations. In this study we report the preparation of a 3,3'-functionalized biphenol (BIPOL) phosphoramidite ligand (P Am ) bearing 3,5-dichlorobenzoyl (3,5-DCB) amide binding sites for noncovalent interactions. Upon coordination to [Rh(COD) 2 ]BF 4 this substitution pattern directs one of the 3,5-DCB binding sites in close proximity of the metal center resulting in liberation of both COD ligands and the formation of a [Rh(P Am ) 2 ]BF 4 complex. Coordination of the amide carbonyl unit was found to be reversible, since the complex acted as an active catalyst in the hydrogenation of dehydroamino acid derivatives. X-ray crystallographic investigation revealed that the second 3,5-DCB unit is capable of forming noncovalent π-π interactions connecting both phosphoramidite ligands., (© 2016 Wiley Periodicals, Inc.)

Averaging of chromatograms can lead to enhancement of signal to noise ratio (S/N) in proportion to the square root of the number of measurements. Although the general principle has been known for decades, chromatogram averaging is almost never used in current pharmaceutical research. In this study we explore the utility of this approach, showing it to be a simple and easily accessible method for boosting sensitivity for quantification of minor components and trace impurities, where current techniques deliver insufficient S/N., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Stereodynamic ligands offer intriguing possibilities in enantioselective catalysis. "NU-BIPHEPs" are a class of stereodynamic diphosphine ligands which are easily accessible via rhodium-catalyzed double [2 + 2 + 2] cycloadditions. This study explores the preparation of differently functionalized "NU-BIPHEP(O)" compounds, the characterization of non-covalent adduct formation and the quantification of enantiomerization barriers. In order to explore the possibilities of functionalization, we studied modifications of the ligand backbone, e.g., with 3,5-dichlorobenzoyl chloride. Diastereomeric adducts with Okamoto-type cellulose derivatives and on-column deracemization were realized on the basis of non-covalent interactions. Enantioselective dynamic HPLC (DHPLC) allowed for the determination of rotational barriers of ΔG (‡) 298K = 92.2 ± 0.3 kJ mol(-1) and 99.5 ± 0.1 kJ mol(-1) underlining the stereodynamic properties of "NU-BIPHEPs" and "NU-BIPHEP(O)s", respectively. These results make the preparation of tailor-made functionalized stereodynamic ligands possible and give an outline for possible applications in enantioselective catalysis.

A straightforward phosgene-free synthesis of aromatic isocyanates and diisocyanates is disclosed. Theoretical investigations suggested that the insertion of carbon dioxide (CO2 ) by dialkyltin(IV) dialkoxides could be used to convert aromatic amines into aromatic mono- and dicarbamates. Here we show, that methyl phenylcarbamate (MPC) from aniline using organotin(IV) dimethoxide and CO2 can be formed in high yield of up to 92 %, experimentally corroborating the predictions of density functional theory (DFT) calculations. MPC was then separated from the tin oxide residues and converted into phenyl isocyanate. Furthermore, organotin(IV) alkoxides could be regenerated from the tin oxide residues and reused, paving the way for a continuous industrial process. Extension of the scope to the synthesis of diurethanes from toluene 2,4-diamine and 4,4'-methylenedianiline could potentially allow the efficient production of industrially relevant diisocyanates., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Increasing sensitivity without further preconcentration steps is a major challenge in separation sciences. In this study a macro control approach that allows the implementation of Hadamard encoding on standard HPLC instrumentation was applied to the analysis of polysiloxane and polystyrene polymers by gel permeation chromatography. Here, the use of pseudo-random modulation sequences with 1023 elements (512 sample injections) improved the signal-to-noise ratio (S/N) by up to an order of magnitude. Comparison with conventional single injection confirmed the linearity and accuracy of the deconvolution process for the whole mass range of the column., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The CMC is one of the fundamental characteristics of surfactants and its determination is crucial for detail understanding of micelles formation. In this study the CMC of SDS in presence of ACN was determined by two independent experimental techniques, capillary electrophoresis and fluorescence correlation spectroscopy (FCS). Yet, studies of SDS micellization in solutions containing ACN as organic modifier are sparse and inconsistent in literature. The measurements were performed for various ACN contents in the range of 0-50% v/v. At ACN contents of up to 10% v/v the CMC is lower when compared to the aqueous solution, while increasing ACN content causes a significant increase of the CMC. Formation of micelles was observed up to ACN concentrations of 35% v/v, which is in contrast to most of the reports in literature. Based on the results of the FCS experiments, we were able to confirm that presence of ACN causes a gradual increase of the size of the micelles with increasing concentration of SDS. Simultaneously, we proved that the classical conductivity approach for the determination of the CMC does not yield reliable results in the presence of higher content of an organic modifier such as ACN., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A series of different unsymmetrically substituted naphthyl-based diynes were synthesized. These substrates formed the foundation for the assembly of novel biaryls containing pyridine moieties with differently substituted five-membered rings in the backbone of the newly formed heterobiaryl system. The key step for their efficient construction was the photo- and cobalt-catalyzed [2 + 2 + 2] cycloaddition reaction between the corresponding naphthyldiyne and aceto- or benzonitrile. The heterobiaryl products have been isolated and investigated with respect to the configurational stability of their biaryl axis using dynamic chiral HPLC; subtle effects of the substitution pattern on the stability of the axis were observed. For several compounds the activation barriers (ΔG(‡)) of racemization were determined. Suitable substitution of the five-membered ring backbone exemplarily allowed the Co-catalyzed enantioselective cyclization to yield the enantiomerically enriched heterobiaryl.

On-column reaction gas chromatography (ocRGC) was successfully utilized as high-throughput platform for monitoring of the conversion and selectivity of hydrogenation of 5-methylfurfural catalyzed by polymer-stabilized Ru and Pd nanoparticles. We were able to elucidate the effect of various reaction conditions, mainly together with the catalyst loading on the conversion rate and the selectivity of the reaction. Our strategy yields significant improvements in reaction analysis times and cost effectiveness in comparison to standard methods. We are able to demonstrate that ocRGC approach provides valuable information about the reaction system that gives scientists a tool to design suitable catalytic systems for enhanced sustainable chemistry in the future., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Enantiomerization of allylic trifluoromethyl sulfoxides occurs spontaneously at room temperature through the corresponding allylic trifluoromethanesulfenates via a [2,3]-sigmatropic rearrangement. Dynamic enantioselective high-performance liquid chromatography (HPLC) analysis revealed the stereodynamics of these sulfoxides ranging from chromatographic resolution to peak coalescence at temperatures between 5 and 53 °C. The rate constant of enantiomerization and activation parameters were determined and compared with Density Functional Theory (DFT) calculations., (© 2015 Wiley Periodicals, Inc.)