Distinct Reactions Research Articles

A Case Study in Catalyst Generality: Simultaneous, Highly-Enantioselective Brønsted- and Lewis-Acid Mechanisms in Hydrogen-Bond-Donor Catalyzed Oxetane Openings.

Generality in asymmetric catalysis can be manifested in dramatic and valuable ways, such as high enantioselectivity across a wide assortment of substrates in a given reaction (broad substrate scope) or as applicability of a given chiral framework across a variety of mechanistically distinct reactions (privileged catalysts). Reactions and catalysts that display such generality hold special utility, because they can be applied broadly and sometimes even predictably in new applications. Despite the great value of such systems, the factors that underlie generality are not well understood. Here, we report a detailed investigation of an asymmetric hydrogen-bond-donor catalyzed oxetane opening with TMSBr that is shown to possess unexpected mechanistic generality. Careful analysis of the role of adventitious protic impurities revealed the participation of competing pathways involving addition of either TMSBr or HBr in the enantiodetermining, ring-opening event. The optimal catalyst induces high enantioselectivity in both pathways, thereby achieving precise stereocontrol in fundamentally different mechanisms under the same conditions and with the same chiral framework. The basis for that generality is analyzed using a combination of experimental and computational methods, which indicate that proximally localized catalyst components cooperatively stabilize and precisely orient dipolar enantiodetermining transition states in both pathways. Generality across different mechanisms is rarely considered in catalyst discovery efforts, but we suggest that it may play a role in the identification of so-called privileged catalysts.

Emotional and Cognitive Responses to COVID-19 Information Overload under Lockdown Predict Media Attention and Risk Perceptions of COVID-19

The present study examined positive and negative effects of health communication on the fight against the COVID-19 under lockdown, during the first wave of the pandemic in Greece. An online survey (N = 1,199) examined the relationships among media trust, emotional and cognitive reactions to COVID-19 information overload, media attention, and risk perceptions regarding COVID-19. Participants’ media attention (exposure and attention combined) to information about the pandemic was positively related to their risk perceptions (perceived susceptibility and severity) about the disease. Media attention was dependent on participants’ trust in the media as valid sources of information, but also on their cognitive and emotional reactions to COVID-19 information overload. In response to this overload, they produced negative thoughts and more negative (fear and anger) than positive (protection) emotions. These distinct reactions had differential effects on media attention and risk perceptions. Fear and protection were positively related to media attention and risk perceptions, while anger and negative thinking undermined attention and perceptions. Furthermore, all reactions depended on media trust, which mediated the effect on media attention. These findings highlighted desirable and some undesirable effects of health communication in the fight against COVID-19, which can be used to improve health communication in the future.

Emperor penguin reactions to UAVs: First observations and comparisons with effects of human approach

The use of UAVs has greatly increased in recent years, worldwide and in the Antarctic. Their use has recently increased even in very remote and pristine regions of the Antarctic. There is, however, very little information on the sensitivity of Antarctic species to such disturbance. In particular, there is nothing on the emperor penguin (Aptenodytes forsteri), a flagship species of the region. We therefore, during November 2019, tested the responses of emperor penguins at the Atka Bay colony (Queen Maud Land). We video recorded the behaviour of adults and chicks during multirotor UAV activity and human approach. There were, in general, only moderate responses with distinct reactions in fewer than 20% of individuals observed. Chicks increased vigilance behaviour during UAV activity but both adults and chicks did so during human approach. We saw the greatest reaction in chicks during vertical UAV approach. Adults showed intermediate reactions to vertical UAV approach but only very few reactions to horizontal flights.

Effects of Light Intensity and Reaction Temperature on Photoreactions in Commercial Photoreactors

AbstractIn the last decade, visible‐light photoredox catalysis has evolved into a versatile tool in organic synthesis. However, most reports have used homemade photoreactors in their design and optimisation of new methods, complicating the reproducibility of some transformations. To improve reproducibility and efficiency, laboratory photoreactors have been developed and commercialized. Herein we report a comparison of four commercially available photoreactors in six mechanistically distinct photoredox reactions focusing on the difference in product yields and kinetics as well as the factors which lead to these differences, including reaction temperature and light intensity.

Neonatal Music Therapy and Cerebral Oxygenation in Extremely and Very Preterm Infants: a Pilot Study

Music therapy is a novel intervention that may minimize neonatal stress. The mechanism of action is still largely unknown. We hypothesized that one mechanism of action regards altered brain oxygenation (either due to altered cerebral perfusion or altered cerebral oxygen consumption). We measured cerebral oxygenation before, during and after music therapy sessions using Near-Infrared Spectroscopy (NIRS). We extracted data on cerebral oxygen saturation (rcSO2) and calculated cerebral fractional tissue oxygen extraction (cFTOE). In addition, we measured heart rate. We included 20 infants, receiving 44 music therapy sessions. Median gestational age was 27 weeks, the majority were males. We identified two distinct reactions: in one group rcSO2 increased and cFTOE decreased during therapy compared with before therapy, whereas in the other group rcSO2 decreased and cFTOE increased during therapy compared with before therapy. The first may indicate a sedative effect, whereas the second may reflect a hyperalert state. The observed changes in heart rate may contribute to these observations through altered cerebral perfusion. The clinical significance of these two distinct reactions for music processing and (future) neurological functioning in these infants warrants further investigation.

Into the Blue: Ketene Multicomponent Reactions under Visible Light.

For the first time, a detailed study on the photophysical properties of variously substituted diazoketones and on their photoreactivity under blue LED irradiation was carried out. Despite very limited absorbance in the visible region, we have demonstrated that, independently from their structure, α-diazoketones all undergo a very efficient Wolff rearrangement. Contrarily to the same UV-mediated reaction, where photons can give rise to side processes, in this case, almost all absorbed photons are selective and effective, and the quantum yield is close to 100%. If the rearrangement is carried out in the presence of isocyanides and carboxylic acids/silanols, the photoreactivity is not affected, and the resulting ketenes can afford α-acyloxy- and α-silyloxyacrylamides through two distinct multicomponent reactions, performed both in batch and under continuous flow, with improved selectivity and broader scope. These photoinduced multicomponent reactions can be coupled with other visible-light-mediated transformations, thus increasing the diversity of the molecules obtainable by this approach.

Improved understanding of dynamic water and mass budgets of high‐alpine karst systems obtained from studying a well‐defined catchment area

AbstractLarge areas of Europe, especially in the Alps, are covered by carbonate rocks and in many alpine regions, karst springs are important sources for drinking water supply. Because of their high variability and heterogeneity, the understanding of the hydrogeological functioning of karst aquifers is of particular importance for their protection and utilisation. Climate change and heavy rainfall events are major challenges in managing alpine karst aquifers which possess an enormous potential for future drinking water supply. In this study, we present research from a high‐alpine karst system in the UNESCO Biosphere Reserve Großes Walsertal in Austria, which has a clearly defined catchment and is drained by only one spring system. Results show that (a) the investigated system is a highly dynamic karst aquifer with distinct reactions to rainfall events in discharge and electrical conductivity; (b) the estimated transient atmospheric CO2 sink is about 270 t/a; (c) the calculated carbonate rock denudation rate is between 23 and 47 mm/1000a and (d) the rainfall‐discharge behaviour and the internal flow dynamics can be successfully simulated using the modelling package KarstMod. The modelling results indicate the relevance of matrix storage in determining the discharge behaviour of the spring, particularly during low‐flow periods. This research and the consequent results can contribute and initiate a better understanding and management of alpine karst aquifers considering climate change with more heavy rainfall events and also longer dry periods.

Molecular Rationale for Partitioning between C-H and C-F Bond Activation in Heme-Dependent Tyrosine Hydroxylase.

The heme-dependent l-tyrosine hydroxylases (TyrHs) in natural product biosynthesis constitute a new enzyme family in contrast to the nonheme iron enzymes for DOPA production. A representative TyrH exhibits dual reactivity of C-H and C-F bond cleavage when challenged with 3-fluoro-l-tyrosine (3-F-Tyr) as a substrate. However, little is known about how the enzyme mediates two distinct reactions. Herein, a new TyrH from the thermophilic bacterium Streptomyces sclerotialus (SsTyrH) was functionally and structurally characterized. A de novo crystal structure of the enzyme-substrate complex at 1.89-Å resolution provides the first comprehensive structural study of this hydroxylase. The binding conformation of l-tyrosine indicates that C-H bond hydroxylation is initiated by electron transfer. Mutagenesis studies confirmed that an active site histidine, His88, participates in catalysis. We also obtained a 1.68-Å resolution crystal structure in complex with the monofluorinated substrate, 3-F-Tyr, which shows one binding conformation but two orientations of the fluorine atom with a ratio of 7:3, revealing that the primary factor of product distribution is the substrate orientation. During in crystallo reaction, a ferric-hydroperoxo intermediate (compound 0, Fe3+-OOH) was observed with 3-F-Tyr as a substrate based on characteristic spectroscopic features. We determined the crystal structure of this compound 0-type intermediate and refined it to 1.58-Å resolution. Collectively, this study provided the first molecular details of the heme-dependent TyrH and determined the primary factor that dictates the partitioning between the dual reactivities of C-H and C-F bond activation.

A “Solvent‐Free” Crystal Structure of [Fe{N(SiMe3)2}3] – Synthesis, Structure and Properties

AbstractFor the synthesis of the ferric bis(trimethylsilyl)amido complex [Fe{N(SiMe3)2}3] literature gives differing synthetic protocols based on crystallization from solution. In this report we present a ‘solvent‐free’ structural phase of [Fe{N(SiMe3)2}3] which was isolated by sublimation of the product obtained from the reaction of 2 eq FeCl3 with 3 eq LiN(SiMe3)2 in benzene. It could be characterized by single crystal as well as powder XRD and elemental analysis. However, 57Fe Mößbauer spectroscopy suggests a contamination of the main product with an Fe(II) species. Also, a part of the solid reaction byproducts from the reactions in solution were identified by powder XRD and 7Li MAS NMR which indicate distinct redox side reactions between oxidizing FeCl3 and reducing LiN(SiMe3)2, a fact which rationalizes the lower than expected yields and the observation of an Fe(II) impurity compound. AC magnetic measurements of [Fe{N(SiMe3)2}3] have been performed in an extended frequency range up to 104 s−1, allowing for a more precise evaluation of the magnetic relaxation parameters when compared to previously published measurements.

Recent advances in (hetero)dimetallic systems towards tandem catalysis

Abstract Combining multiple mechanistically distinct reactions in one-pot (tandem reaction) is a fascinating area in catalysis research. The tandem reaction becomes the subject of interest as it offers environmentally benign, green, and sustainable process with high atom economy, minimizing the loss of reagents, consumption of energy and chemical waste generation. Considering the advantages and usefulness of metal catalyzed tandem reaction, the present review focuses on highlighting the use of different metal complexes (monometallic, homodimetallic and mixture of multiple metal complexes) in conducting tandem reaction. Further, a special emphasis is given to the heterodimetallic systems, considering their usefulness in ease of modification of active centers, elimination of catalytic incompatibility and better activity and selectivity as compared to mono- and homodimetallic systems.

A pair of threonines mark ent-kaurene synthases for phytohormone biosynthesis

All land plants (embryophytes) must contain an ent-kaurene synthase (KS), as the ability to produce this olefin from ent-copalyl diphosphate (ent-CPP) is required for phytohormone biosynthesis. These KSs have frequently given rise to other class I diterpene synthases that catalyze distinct reactions for more specialized plant metabolism. Indeed, the prevalence of such gene duplication and neofunctionalization has obscured phylogenetic assignment of function. Here a pair of threonines is found to be conserved in all land plant KS involved in phytohormone biosynthesis, and their role in enzyme function investigated. Surprisingly, these threonines are not required, nor even particularly important for efficient production of ent-kaurene from ent-CPP. In addition, these threonines do not seem to affect protein structure or stability. Moreover, the absence of codon bias and positioning within an intron do not support a role in transcription or translation either. Despite their lack of apparent function, this pair of threonines are nevertheless completely conserved in all embryophyte KS from phytohormone biosynthesis. Thus, regardless of exact role, this serves as a diagnostic mark for such KS, enabling more confident distinction of these critical enzymes.

Convergent Assembly of Highly Oxygenated Natural Products Enabled by Intermolecular Radical Reactions.

Natural products with a high ratio of sp3-hybridized atoms and oxygen-substituted stereogenic centers represent privileged structures for the development of pharmaceuticals and chemical probes. The multiple oxygen functionalities of these natural products endow their potent and selective biological activities, although they significantly heighten the challenge of their chemical assemblies. We focused on developing efficient strategies for the total syntheses of this biologically and chemically important class of molecules. A convergent strategy is more advantageous than a linear strategy for designing a shorter synthetic route because a convergent strategy enables direct coupling of functionalized fragments whereas a linear strategy involves stepwise construction of a molecule from its terminus. Radical reactions are preferred over polar reactions for the coupling of heavily functionalized and sp3-rich fragments, as they allow for C(sp3)-C(sp3) coupling without damaging diverse polar functional groups. With these considerations in mind, we designed radical-based convergent strategies for assembling highly oxygenated natural products. Here we summarize the concise total syntheses of asimicin (1, antibiotic activity), 1-hydroxytaxinine (2, cytotoxicity), polyoxins (3, antifungal activity), and hikizimycin (4, anthelmintic activity) as representative examples. Retrosynthetic disconnection at the central part of these molecules produces highly substituted α-alkoxy radicals as synthons. In the synthetic direction, the α-alkoxy radicals were generated from the corresponding α-alkoxyacyl tellurides in a unified fashion, and then utilized for four distinct coupling reactions. Formation of the Et radical from Et3B and O2 homolytically cleaves the C-Te bond of α-alkoxyacyl telluride, and the facile expulsion of carbon monoxide from the acyl radical leads to the α-alkoxy radical. Dimerization of the stabilized α-alkoxy radical resulted in the core structure of 1 with 10 contiguous stereocenters. The coupling adduct was derivatized to 1 through the attachment of two different carbon chains (17 steps as the longest linear sequence). Alternatively, intermolecular addition reactions of the α-alkoxy radicals to electron-deficient C═C, C═N, and C═O bonds, followed by Et3B-mediated radical termination, led to the core structures of 2, 3, and 4, respectively. Intermolecular coupling between the α-alkoxy radical and the cyclohexenone derivative and intramolecular pinacol coupling gave rise to the 6/8/6-fused ring system of 2, which was transformed to 2 (26 steps). The two amino acid moieties of 3 were prepared by combining the α-alkoxy radical and the oxime and were then condensed to complete the synthesis of 3 (11 steps). Furthermore, a combination of α-alkoxyacyl telluride and Et3B/O2 realized a novel addition reaction of α-alkoxy radicals to aldehydes. This method was incorporated in the construction of the core 4-amino-5-deoxyundecose with 10 contiguous stereocenters, which was fabricated with two appendage structures to deliver 4. The four total syntheses described here demonstrate the versatility and robustness of intermolecular radical reactions. These syntheses will also provide new insights for retrosynthetic analyses in the field of organic chemistry and streamline synthetic routes to various bioactive natural products with multiple oxygen functionalities.

Biolubricant Production from Several Oleaginous Feedstocks Using Lipases as Catalysts: Current Scenario and Future Perspectives

In recent years, biolubricants have been gaining further prominence than conventional petroleum-based lubricants. This trend is observed in almost all sectors relying on these products, regardless of their applications. Environmental problems caused by coventional lubricants and the depletion of oil reserves that have led to the need for renewable and biodegradable lubricants are among the factors that contribute to such growing trend. Biolubricants have several advantages over mineral oil lubricants such as high biodegradability, low toxicity, excellent lubricating performance, and minimal impact on the environment and human health. In addition, they can be produced using several types of oleaginous feedstocks and distinct chemical reactions that can be efficiently catalyzed by lipases, which make them quite attractive in the context of Green Chemistry. Thereby, this review describes different aspects of biolubricants by detailing their main applications, properties, uses, and potential feedstocks such as vegetable oils. In this review, chemical modification of their structures using different routes has been highlighted in order to overcome a few limitations for direct application of oleaginuous feedstocks as biolubricants. It also depicts the progress of enzymatic catalysis and immobilization protocols for preparing heterogenous biocatalysts (immobilized lipases), once it is a promising route to obtain a variety of biolubricants based on recent studies described in available literature. Furthermore, future prospects and challenges for enzymatic biolubricant production on an industrial scale are also reviewed.

Active learning accelerates ab initio molecular dynamics on reactive energy surfaces

<h2>Summary</h2> Modeling dynamical effects in chemical reactions typically requires <i>ab initio</i> molecular dynamics (AIMD) simulations due to the breakdown of transition state theory (TST). Reactive AIMD simulations are limited to lower-accuracy electronic structure methods and weak statistics because quantum mechanical energies and forces must be evaluated at femtosecond time resolution over many replicas. We report a data-driven pipeline that allows for the treatment of dynamical effects with the same level of theory and overall cost as that of TST approaches. High-throughput <i>ab initio</i> calculations and autonomous data acquisition are coupled to graph convolutional neural-network interatomic potentials, allowing for inexpensive reactive AIMD simulations at quantum mechanical accuracy. We demonstrate the approach by accurately simulating post-TS dynamical effects in three distinct pericyclic reactions, including a challenging trispericyclic reaction with a complex bifurcating potential energy surface. This approach is broadly applicable to understanding dynamical effects and predicting reaction outcomes in large, previously intractable systems.

TfOH catalysed domino-double annulation of arenes with propargylic alcohols: a unified approach to indene polycyclic systems

TfOH catalysed domino-double annulation of arenes with propargylic alcohols is developed for the generation of indene based polycyclic systems. Three distinct reactions, dehydration–intramolecular hydroarylation–cationic cyclization were promoted.

Structural change induced by electrochemical sodium extraction from layered O′3-NaMnO2

Synergizing ex situ synchrotron and operando XRD analysis, the structural change of O′3-NaMnO2 is found to proceed via 6 distinct two-phase reactions involving 7 different O′3 phases during charging up to the optimum cut-off voltage of 3.476 V.

Polymeric dimethylytterbium and the terminal methyl complex (TptBu,Me)Yb(CH3)(thf).

Divalent ytterbium bis(trimethylsilyl)amides [Yb{N(SiMe3)2}2]2 and Yb[N(SiMe3)2]2(thf)2 react with purified methyllithium to amorphous dimethylytterbium [YbMe2]n. The characterisation was performed by 171Yb and 13C CP/MAS NMR spectroscopy as well as by conducting protonolysis reactions with HC5Me5 and HTptBu,Me, affording known (C5Me5)2Yb(OEt2) and new (TptBu,Me)Yb(CH3)(thf).

Programmable photoresponsive materials based on a single molecule via distinct topochemical reactions.

Engineering the preorganization of photoactive units remains a big challenge in solid-state photochemistry research. It is of not only theoretical importance in the construction of topochemical reactions but also technological significance in the fabrication of advanced materials. Here, a cyanostilbene derivative, (Z)-2-(3,5-bis(trifluoromethyl)phenyl)-3-(naphthalen-2-yl) acrylonitrile (BNA), was crystallized into two polymorphs under different conditions. The two crystals, BNA-α and BNA-β, have totally different intra-π-dimer and inter-π-dimer hierarchical architectures on the basis of a very simple monomer, which provides them with distinct reactivities, functions and photoresponsive properties. Firstly, two different types of solid-state [2 + 2] photocycloaddition reaction: (i) a typical olefin–olefin cycloaddition reaction within the symmetric π-dimers of BNA-α and (ii) an unusual olefin-aromatic ring cycloaddition reaction within the offset π-dimers of BNA-β have been observed, respectively. Secondly, the crystal of BNA-α can be bent to 90° without any fracture, exhibiting outstanding flexibility upon UV irradiation, while the reversible photocycloaddition/thermal cleavage process (below 100 °C) accompanied by unique fluorescence changes can be achieved in the crystal of BNA-β. Finally, micro-scale photoactuators and light-writable anti-counterfeiting materials have been successfully fabricated. This work paves a simple way to construct smart materials through a bottom-up way that is realized by manipulating hierarchical architectures in the solid state.

In vitro assays for characterization of distinct multiple catalytic activities of thyroid peroxidase using LC-MS/MS

A diverse set of environmental contaminants have raised a concern about their potential adverse effects on endocrine signaling. Robust and widely accepted battery of in vitro assays is available to assess the disruption of androgenic and estrogenic pathways. However, such definitive systems to investigate effects on the disruption of thyroid pathways by the xenobiotics are not yet well established. One of the major “Molecular Initiating Events” (MIEs) in thyroid disruption involves targeting of thyroid peroxidase (TPO), a key enzyme involved in thyroid hormone synthesis. TPO catalyzes mono- and diiodination of L-Tyrosine (L-Tyr) to generate 3-Iodo-l-tyrosine (MIT) and 3,5-Diiodo-l-tyrosine (DIT), respectively, followed by the coupling of iodinated tyrosine rings to generate thyroid hormones, 3,3’5-Triiodo-l-thyronine (T3) and Levothyroxine (T4).We sought to develop a robust, sensitive, and rapid in vitro assay systems to evaluate the effects of test chemicals on the multiple catalytic activities of thyroid peroxidase. Simple in vitro assays were designed to study TPO mediated distinct reactions using a single LC-MS/MS method.Herein, we describe a battery of assays to investigate the iodination of L-Tyr to MIT and DIT, MIT to DIT as well as, T3 to T4 catalyzed by rat thyroid TPO. Importantly, two sequential reactions involving mono- and diiodination of L-Tyr could be analyzed in a single assay. The assay that monitors in vitro conversion of DIT to T4 was developed to study the coupling of tyrosine rings. Enzyme kinetics studies revealed distinct characteristics of multiple reactions catalyzed by TPO. Further, the known TPO inhibitors were used to assess their potency towards individual TPO substrates and reactions. The resultant half maximum inhibitory concentration (IC50) values highlighted differential targeting of TPO catalyzed reactions by the same inhibitor. Overall results underscore the need to develop more nuanced approaches that account for distinct multiple catalytic activities of TPO.

More fuel to the fire: some patients with non-celiac self-reported wheat sensitivity exhibit adaptive immunological responses in duodenal mucosa

BackgroundIn contrast to the well-characterized Celiac Disease (CD), the clinical scenarios encompassed by the non-celiac self-reported wheat sensitivity (NCSRWS) might be related to different antigens that trigger distinct immune-inflammatory reactions. Although an increased number of intestinal intraepithelial lymphocytes is observed at the inception of both diseases, the subsequent immunopathogenic pathways seem to be different. We aimed to describe the cytokine profile observed in the duodenal mucosa of patients with NCSRWS.MethodsIn a blind, cross-sectional study, we included duodenal biopsies from 15 consecutive untreated patients with active CD, 9 individuals with NCSRWS and 10 subjects with dyspepsia without CD and food intolerances. Immunohistochemistry and flow-cytometry were used to determine the presence of pro-inflammatory cytokine expressing monocytes and monocyte-derived dendritic cells involved in innate immune activation, cytokine-driven polarization and maintenance of Th1 and Th17/Th 22, and anti-inflammatory/profibrogenic cytokines.ResultsThe percentage of cells expressing all tested cytokines in the lamina propria and the epithelium was higher in CD patients than in the control group. Cytokines that induce and maintain Th1 and Th17 polarization were higher in CD than in NCSRWS and controls, also were higher in NCSRWS compared to controls. Similar differences were detected in the expression of IL-4 and TGF-1, while IL-10-expressing cells were lower in NCSRWS patients than in controls and CD subjects.ConclusionsNCSRWS patients exhibit components of both, innate and adaptive immune mechanisms but to a lesser extent compared to CD.