Reactivity Profile Research Articles

π-π stacking assisted regioselectivity regulation in palladium-catalyzed cyclization reactions: a theoretical study.

The regulation of regioselectivity is an objective often pursued by organic chemists, and the comprehension of its mechanisms is crucial for devising efficient synthetic pathways. In this report, we conducted theoretical calculations to explore the regioselectivity regulatory mechanisms of two palladium-catalyzed cyclization reactions. In these cyclization reactions, manipulating the structural differences in the reaction substrates leads to the formation of distinct products. A detailed reaction mechanism and reactivity profile for this reaction were revealed. Furthermore, a π-π stacking assisted regioselectivity regulatory mechanism was proven by distortion-interaction energy analysis and noncovalent interaction calculations. The calculated results presented herein provide a theoretical guide for further experimental investigations of regioselectivity regulation.

Ancestral Sequence Reconstruction Meets Machine Learning: Ene Reductase Thermostabilization Yields Enzymes with Improved Reactivity Profiles

Ancestral Sequence Reconstruction Meets Machine Learning: Ene Reductase Thermostabilization Yields Enzymes with Improved Reactivity Profiles

Analysis of Excited Species Formation across the Flame of Various Ammonia‐Hydrogen Fired Combustor Geometries

Although ammonia can be used as a fuel, it also presents drawbacks that require further investigation before the chemical can overtake fossil fuels in combustion systems. The main barriers are the low flammability in combination with high NOx emissions. Although the first barrier can be surpassed by doping ammonia with hydrogen, the second becomes more challenging under these conditions, as hydrogen increases NO emissions due to the increase in H radicals in the chemical pool of species. How the change in radicals impacts the stability of the flame, its reactivity, and emissions profile is of the greatest concern for the use of these net zero fuels. Thus, the work herein presented shows the trends of excited species such as NH*, NH2*, and OH* when using ammonia–hydrogen at 70%–30% (vol) blending. Various equivalence ratios are employed from lean to rich conditions. Results denote that there is a continuous displacement of radicals across the field, with NH2* relocating closer to the centerline of the burner as equivalence ratio increases, while NH* tends to raise its location while dislocating from the production/consumption of OH* radicals. The results can be used to target desirable radicals for the mitigation of emissions and flame control.

Scalable Thiol Reactivity Profiling Identifies Azetidinyl Oxadiazoles as Cysteine-Targeting Electrophiles.

Cysteine reactive groups are a mainstay in the design of covalent drugs and probe molecules, yet only a handful of electrophiles are routinely used to target this amino acid. Here, we report the development of scalable thiol reactivity (STRP), a method which enables the facile interrogation of large chemical libraries for intrinsic reactivity with cysteine. High throughput screening using STRP identified the azetidinyl oxadiazole as a moiety that selectively reacts with cysteine through a ring opening-based mechanism, capable of covalently engaging cysteine residues broadly across the human proteome. We show the utility of this reactive group with the discovery of an azetidinyl oxadiazole containing a small molecule that augments the catalytic activity of the deubiquitinase UCHL1 in vitro and in cells by covalently modifying a cysteine distal to its enzymatic active site. This study adds a novel cysteine targeting group to the electrophilic lexicon and provides robust methodology to rapidly surveil libraries for reactivity with cysteine.

Pd-W18O49 Nanowire MEMS Gas Sensor for Ultraselective Dual Detection of Hydrogen and Ammonia.

Demand for real-time detection of hydrogen and ammonia, clean energy carriers, in a sensitive and selective manner, is growing rapidly for energy, industrial, and medical applications. Nevertheless, their selective detection still remains a challenge and requires the utilization of diverse sensors, hampering the miniaturization of sensor modules. Herein, a practical approach via material design and facile temperature modulation for dual selectivity is proposed. A Pd nanoparticles-decorated W18O49 nanowire gas sensor is prepared for dual detection of hydrogen and ammonia. The sensor exhibits distinct operating temperatures for ultraselective detection of hydrogen (125°C) and ammonia (225°C), with high responses of 35.3 and 133.8, respectively. This dual selectivity with high sensitivity is attributed to enhanced oxygen adsorption, the chemical affinity of sensing materials for target gases, and distinct reactivity profiles of gases. The proposed sensor is further integrated into a microelectromechanical system, enabling its small size, low power consumption, and rapid temperature modulation. Moreover, the practical feasibility of this sensor platform for smart energy monitoring systems is demonstrated by assessing its sensing properties in electrochemical ammonia oxidation reaction systems. This work can provide a practical approach for developing a single gas sensor with multiple functionalities for application in electronic nose systems.

Categorical and latent profile approaches to temperamental infant reactivity and early trajectories of socioemotional adjustment.

This article examines the patterns, and consequences, of infant temperamental reactivity to novel sensory input in a large (N = 357; 271 in current analysis) and diverse longitudinal sample through two approaches. First, we examined profiles of reactivity in 4-month-old infants using the traditional theory-driven analytic approach laid out by Jerome Kagan and colleagues, and derived groups characterized by extreme patterns of negative reactivity and positive reactivity. We then used a theory-neutral, data-driven approach to create latent profiles of reactivity from the same infants. Despite differences in sample characteristics and recruitment strategy, we noted similar reactivity groups relative to prior cohorts. The current data-driven approach found four profiles: high positive, high negative, high motor, and low reactive. Follow-up analyses found differential predictions of internalizing, externalizing, dysregulation, and competence trajectories across 12, 18, and 24 months of life based on 4-month reactivity profiles. Findings are discussed in light of the initial formulation of early reactivity by Kagan and the four decades of research that has followed to refine, bolster, and expand on this approach to child-centered individual differences. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Rapid and Environmentally-Friendly Synthesis of Thiazolidinone Analogues in Deep Eutectic Solvent Complemented with Computational Studies.

A greener, safer, and more efficient methodology for the synthesis of (Z)-5-benzylidene-2-thioxothiazolidin-4-ones (3 a-u) and (Z)-5-benzylidenethiazolidine-2,4-diones (4 a-i) has been developed. The deep eutectic solvent (DES) ZnCl2/urea used as a greener solvent as well as a catalyst in this study accelerated the condensation of rhodanine and thiazolidine-2,4-dione with different aldehydes to afford the target scaffolds in excellent yields (88-98 %). The reaction methodology adopted offered significant advantages such as mild reaction conditions, functional group tolerance, quick reaction time, column-free isolation, catalytic recyclability, and applicability to gram-scale production. Moreover, density function theory calculations were carried out to investigate the global reactivity and stability profiles of these compounds. Finally, the green metrics analysis supported the greener nature of the present methodology.

Gold‐Catalyzed Heck and Suzuki‐Type Reactions: Challenges and Recent Advances

AbstractTransition metal‐catalyzed Suzuki and Heck reactions are two of the most common carbon‐carbon bond formation reactions. Gold, unlike other transition metals (Pd, Ni, and Cu), offers unique reactivity profiles, and has emerged as an efficient tool in the field of synthetic organic chemistry. This mini‐review focused on the recent work in gold‐catalyzed Heck and Suzuki‐type reactions, especially by photocatalysts or ligand design, which show reactivities and features distinct from other transition metals. These discoveries will further facilitate the development of gold redox catalysis as well as applications in organic synthesis, biochemistry, and medicinal chemistry.

A versatile inhibitory approach and molecular mechanism on cancer cells and cholinesterase enzymes: Synthesis, DFT, ADMET and molecular docking of thiadiazole and oxadiazole derivatives

This study presents a multi-routed research design featuring thiadiazole/ oxadiazole based Schiff base derivatives as potential inhibitors, targeting cancer and Alzheimer. Among thiadiazole based Schiff base derivatives, the excellent inhibition was exhibited by compound 1 (IC50 = 20.10 ± 1.1, 22.21 ± 1.03 and 26.23 ± 2.2 µM for HepG2 (liver cancer), MCF-7 (breast cancer) and W138 (lung cancer), respectively) in comparison to the standard Doxorubicin. Oxadiazole based compound 9 was also found with spellbinding efficacy (IC50 =15.20 ± 2.5, 19.13 ± 2.2 and 12.33 ± 3.4 µM for HepG2, MCF-7 and W138, respectively). Both compounds 1(IC50=3.10 ± 0.20 and 3.70 ± 0.10 µM against AChE and BuChE) and 9 (IC50=2.20 ± 0.10 and 2.80 ± 0.50 µM against AChE and BuChE) were also found as excellent anti-Alzheimer agents in comparison to reference donepezil. The outcomes of in vitro biological activity were further studied in silico via molecular docking, DFT and ADMET to elucidate the binding interactions, stability, reactivity and pharmacokinetic profiles of potent compounds.

Randomized study of the effects of empagliflozin and topiramate dual therapy on anthropometric and metabolic indices in non-diabetic individuals with overweight/obesity on a calorie-restricted diet

ObjectivesThe objective of this study was to evaluate the effectiveness of the combined use of empagliflozin (EMPA) and topiramate (TPM) versus a placebo in overweight/obese individuals without diabetes on a calorie-restricted diet.MethodsIn this study, 44 non-diabetic and overweight/obese subjects who were on a calorie restricted diet were randomly assigned into 2 groups: (1) Participants received a 10 mg EMPA tablet daily plus TPM tablet (at the 1st week 25 mg once a day and from the second week 25 mg twice a day); (2) Participants received an empagliflozin placebo (daily) plus a topiramate placebo (as mentioned for topiramate tablet in group 1), for 12 weeks. At baseline and weeks 4, 8, 12, weight, height, body mass index (BMI), waist circumference (WC), and body composition were evaluated. Before and after the intervention, blood pressure, C reactive protein, and glucose and lipid profile parameters were measured.ResultsThe EMPA/TPM group, compared to placebo, had a greater percent change of weight at week 12 (− 8.92 ± 1.80 vs. − 4.93 ± 1.17). The intervention group had a greater percent change of fat mass and fat percent at week 12 (P < 0.05). However, there was no difference in the percent of change in fat-free percent between the two groups at week 12 (P = 0.577). Within-group analysis found a significant reduction in SBP, DBP, FBS, insulin, HOMA-IR, TC, LDL, HDL, TG, and CRP in both groups (P < 0.05). At week 12, no statistically significant difference was observed between the two groups in any of mentioned variables (P > 0.05).ConclusionIn non-diabetic overweight/obese individuals, the combination of EMPA/TPM and calorie restriction led to a notable decrease in body weight and was generally well-tolerated. Further research is required to evaluate the potential advantages of utilizing this combination for sustained weight management in the long run.Level I Randomized clinical trial.

Coadministration of PEGylated apohemoglobin and haptoglobin can limit vascular dysfunction in the microcirculation and prevent acute inflammation.

Unfortunately, during pathological conditions resulting in chronic hemolysis cell-free hemoglobin (Hb) is released into the circulation that releases free heme, resulting in several complications. One approach to prevent these toxicities is the administration of supplemental scavenger proteins, haptoglobin (Hp) and hemopexin (Hpx). The goal of this body of work is to objectively measure the levels of vascular reactivity and inflammatory profiles after an infusion of acellular hemoglobin in animals that were given a coadministration of PEGylated human apohemoglobin (PEG-apoHb), a hemopexin (Hpx)-mimetic that can scavenge free heme from hemoglobin, together with human plasma-derived Hp that can scavenge dimerized Hb. Using intravital microscopy, Golden Syrian hamsters instrumented with a dorsal window chamber were used to evaluate the in vivo effects of four experimental groups that were then challenged with a hypovolemic injection (10% of the animal's blood volume) of human Hb (hHb, 5 g/dL). The four experimental groups consisted of: 1) lactated Ringer's solution (control), 2) PEG-apoHb only, 3) Hp only, and 4) PEG-apoHb + Hp. The microvascular hemodynamics (diameter and flow) in arterioles and venules were recorded at baseline, 20 min after treatment, and 20 min after hHb challenge. Systemic parameters (blood pressure and heart rate), blood gases (pH, Pco2, and Po2), blood parameters (Hb concentration and hematocrit), and multiorgan functionality/inflammation were also measured. Our results suggest that coadministration of PEG-apoHb + Hp as a booster before the infusion of acellular hemoglobin significantly prevented vasoconstriction in the microcirculation, significantly increased the number of functional capillaries, and significantly reduced inflammation.NEW & NOTEWORTHY Coadministration of PEGylated human apohemoglobin (PEG-apoHb)-a hemopexin (Hpx) mimetic that can scavenge free heme-and human plasma-derived haptoglobin (Hp) that can scavenge hemoglobin (Hb), reduces microcirculatory dysfunction and cardiac and kidney inflammation in a Hb-challenge model.

Reactive astrocytes generated from human iPSC are pro-inflammatory and display altered metabolism

Astrocytes are the most abundant type of glial cell in the central nervous system and they play pivotal roles in both normal health and disease. Their dysfunction is detrimental to many brain related pathologies. Under pathological conditions, such as Alzheimer's disease, astrocytes adopt an activated reactive phenotype which can contribute to disease progression. A prominent risk factor for many neurodegenerative diseases is neuroinflammation which is the purview of glial cells, such as astrocytes and microglia. Human in vitro models have the potential to reveal relevant disease specific mechanisms, through the study of individual cell types such as astrocytes or the addition of specific factors, such as those secreted by microglia. The aim of this study was to generate human cortical astrocytes, in order to assess their protein and gene expression, examine their reactivity profile in response to exposure to the microglial secreted factors IL-1α, TNFα and C1q and assess their functionality in terms of calcium signalling and metabolism. The successfully differentiated and stimulated reactive astrocytes display increased IL-6, RANTES and GM-CSF secretion, and increased expression of genes associated with reactivity including, IL-6, ICAM1, LCN2, C3 and SERPINA3. Functional assessment of these reactive astrocytes showed a delayed and sustained calcium response to ATP and a concomitant decrease in the expression of connexin–43. Furthermore, it was demonstrated these astrocytes had an increased glycolytic capacity with no effect on oxidative phosphorylation. These findings not only increase our understanding of astrocyte reactivity but also provides a functional platform for drug discovery.

Characterization of monoclonal antibodies targeting SARS-CoV-2 spike glycoprotein: Reactivity against Delta and Omicron BA.1 variants

The cross-species transmissibility of SARS-CoV-2 infection has necessitated development of specific reagents for detecting infection in various animal species. The spike glycoprotein of SARS-CoV-2, which is involved in viral entry, is a highly immunogenic protein. To develop assays targeting this protein, we generated eight monoclonal antibodies (mAbs) against the S1 and seven against the S1/S2 protein (ectodomain) of SARS CoV-2. Based on neutralization capability and reactivity profile observed in ELISA, the mAbs generated against the S1/S2 antigen exhibited a broader spectrum of epitope specificity than those produced against the S1 domain alone. The full-length ectodomain induced antibodies that could neutralize the two most important variants of the virus encountered during the pandemic, namely Delta and Omicron. The availability of these reagents could greatly enhance the development of precise diagnostics for detecting COVID-19 infections in various host species and contribute to the advancement of mAb-based therapeutics.

Assessing the impact of corrosive acids on human bone integrity in forensic context.

Dissolving bodies is a contemporary method of disposing of human remains and has been practiced throughout the years. This research article discussed the impact of readily available corrosive chemicals, such as Hydrochloric acid (HCl), Sulfuric acid (H2SO4), and Expelz™ toilet cleaner, on human bone. Unfortunately, the existing literature on this subject is scarce, with only a few studies conducted on human bones. To address this gap, we conducted an experimental analysis using human sternum bone fragments. These samples were subjected to immersion in different acids, namely HCl and H2SO4, at two concentrations (10% and 37%), and Expelz™ toilet cleaner. This research aims to describe the impact of toilet cleaner, sulphuric acid, and hydrochloric acid on bone tissue deterioration at various time intervals. Further, the morphological alterations weight loss, and cytological analysis of bone tissue residue with various acid concentrations and immersion times (3.5, 9, 24, 36, 48, 60, and 72h) were analyzed. Among the chemicals examined, it is evident that 37% hydrochloric acid (HCl) and sulfuric acid (H2SO4), regardless of refreshment, exhibit the highest reactivity, resulting in the complete decomposition of hard tissue within a few hours. In contrast, the behaviour of 10% H2SO4 reveals a more intricate degradation process characterized by fluctuations in weight loss. These distinct reactivity profiles under different conditions are crucial in understanding the potential for rapid weight loss, signifying high reactivity and more gradual weight loss, indicating a faster decomposition rate. Notably, refreshment of the solution enhanced the reactivity of both HCl and H2SO4.

Characterization of the SARS-CoV-2 antibody landscape in Norway in the late summer of 2022: high seroprevalence in all age groups with patterns of primary Omicron infection in children and hybrid immunity in adults

BackgroundAccording to Norwegian registries, 91% of individuals ≥ 16 years had received ≥ 1 dose of COVID-19 vaccine by mid-July 2022, whereas less than 2% of children < 12 years were vaccinated. Confirmed COVID-19 was reported for 27% of the population, but relaxation of testing lead to substantial underreporting. We have characterized the humoral immunity to SARS-CoV-2 in Norway in the late summer of 2022 by estimating the seroprevalence and identifying antibody profiles based on reactivity to Wuhan or Omicron-like viruses in a nationwide cross-sectional collection of residual sera, and validated our findings using cohort sera.Methods1,914 anonymized convenience sera and 243 NorFlu-cohort sera previously collected from the Oslo-area with reported infection and vaccination status were analyzed for antibodies against spike, the receptor-binding domain (RBD) of the ancestral Wuhan strain and Omicron BA.2 RBD, and nucleocapsid (N). Samples were also tested for antibodies inhibiting RBD-ACE2 interaction. Neutralization assays were performed on subsets of residual sera against B.1, BA.2, XBB.1.5 and BQ.1.1.ResultsThe national seroprevalence estimate from vaccination and/or infection was 99.1% (95% CrI 97.0-100.0%) based on Wuhan (spike_W and RBD_W) and RBD_BA2 antibodies. Sera from children < 12 years had 2.2 times higher levels of antibodies against RBD_BA2 than RBD_W and their seroprevalence estimate showed a 14.4 percentage points increase when also including anti-RBD_BA2 antibodies compared to Wuhan-antibodies alone. 50.3% (95% CI 45.0-55.5%) of residual sera from children and 38.1% (95% CI 36.0-40.4%) of all residual sera were positive for anti-N-antibodies. By combining measurements of binding- and ACE2-RBD-interaction-inhibiting antibodies, reactivity profiles indicative of infection and vaccination history were identified and validated using cohort sera. Residual sera with a profile indicative of hybrid immunity were able to neutralize newer Omicron variants XBB.1.5 and BQ.1.1.ConclusionsBy late summer of 2022, most of the Norwegian population had antibodies to SARS-CoV-2, and almost all children had been infected. Antibody profiles indicated that children mostly had experienced a primary Omicron infection, while hybrid immunity was common among adults. The finding that sera displaying hybrid immunity could neutralize newer Omicron variants indicates that Wuhan-like priming of the immune response did not have a harmful imprinting effect and that infections induce cross-reacting antibodies against future variants.

Mechanochemical Synthesis of a Sodium Anion Complex [Na+(2,2,2-cryptand)Na-] and Studies of Its Reactivity: Two-Electron and One-Electron Reductions.

Group 1 metal molecular chemistry is dominated by a +1 oxidation state, while a 0 oxidation state is widespread in the metals. A more exotic, yet still available, oxidation state of group 1 metal is -1, i.e., alkalide. Reported as early as the 1970s, the alkalides appear in every modern inorganic chemistry textbook as an iconic chemical curiosity, yet their reactivity remains unexplored. This is due to their synthetic hurdles. In this work, we report the first facile synthesis of the archetypical alkalide complex, [Na+(2,2,2-cryptand)Na-], which allows us to unveil a versatile reactivity profile of this once exotic species.

Dual-Probe Activity-Based Protein Profiling Reveals Site-Specific Differences in Protein Binding of EGFR-Directed Drugs.

Comparative, dose-dependent analysis of interactions between small molecule drugs and their targets, as well as off-target interactions, in complex proteomes is crucial for selecting optimal drug candidates. The affinity of small molecules for targeted proteins is largely dictated by interactions between amino acid side chains and these drugs. Thus, studying drug-protein interactions at an amino acid resolution provides a comprehensive understanding of the drug selectivity and efficacy. In this study, we further refined the site-specific activity-based protein profiling strategy (ABPP), PhosID-ABPP, on a timsTOF HT mass spectrometer. This refinement enables dual dose-dependent competition of inhibitors within a single cellular proteome. Here, a comparative analysis of two activity-based probes (ABPs), developed to selectively target the epidermal growth factor receptor (EGFR), namely, PF-06672131 (PF131) and PF-6422899 (PF899), facilitated the simultaneous identification of ABP-specific binding sites at a proteome-wide scale within a cellular proteome. Dose-dependent probe-binding preferences for proteinaceous cysteines, even at low nanomolar ABP concentrations, could be revealed. Notably, in addition to the intrinsic affinity of the electrophilic probes for specific sites in targeted proteins, the observed labeling intensity is influenced by several other factors. These include the efficiency of cellular uptake, the stability of the probes, and their intracellular distribution. While both ABPs showed comparable labeling efficiency for EGFR, PF131 had a broader off-target reactivity profile. In contrast, PF899 exhibited a higher labeling efficiency for the ERBB2 receptor and bound to catalytic cysteines in several other enzymes, which is likely to disrupt their catalytic activity. Notably, PF131 effectively labeled ADP/ATP translocase proteins at a concentration of just 1 nm, and we found this affected ATP transport. Analysis of the effect of PF131 and its parent inhibitor Afatinib on murine translocase SLC25A4 (ANT1)-mediated ATP transport strongly indicated that PF131 (10 μM) partially blocked ATP transport. Afatinib was less efficient at inhibiting ATP transport by SLC25A4 than PF131, and the reduction of ATP transport by Afatinib was not significant. Follow-up analysis is required to evaluate the affinity of these inhibitors for ADP/ATP translocase SLC25A4 in more detail. Additionally, the analysis of different binding sites within the EGF receptor and the voltage-dependent anion channel 2 revealed secondary binding sites of both probes and provided insights into the binding poses of inhibitors on these proteins. Insights from the PhosID-ABPP analysis of these two ABPs serve as a valuable resource for understanding drug on- and off-target engagement in a dose- and site-specific manner.

Human stem cell-derived neurons and astrocytes to detect novel auto-reactive IgG response in immune-mediated neurological diseases.

Up to 46% of patients with presumed autoimmune limbic encephalitis are seronegative for all currently known central nervous system (CNS) antigens. We developed a cell-based assay (CBA) to screen for novel neural antibodies in serum and cerebrospinal fluid (CSF) using neurons and astrocytes derived from human-induced pluripotent stem cells (hiPSCs). Human iPSC-derived astrocytes or neurons were incubated with serum/CSF from 99 patients [42 with inflammatory neurological diseases (IND) and 57 with non-IND (NIND)]. The IND group included 11 patients with previously established neural antibodies, six with seronegative neuromyelitis optica spectrum disorder (NMOSD), 12 with suspected autoimmune encephalitis/paraneoplastic syndrome (AIE/PNS), and 13 with other IND (OIND). IgG binding to fixed CNS cells was detected using fluorescently-labeled antibodies and analyzed through automated fluorescence measures. IgG neuronal/astrocyte reactivity was further analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were used as CNS-irrelevant control target cells. Reactivity profile was defined as positive using a Robust regression and Outlier removal test with a false discovery rate at 10% following each individual readout. Using our CBA, we detected antibodies recognizing hiPSC-derived neural cells in 19/99 subjects. Antibodies bound specifically to astrocytes in nine cases, to neurons in eight cases, and to both cell types in two cases, as confirmed by microscopy single-cell analyses. Highlighting the significance of our comprehensive 96-well CBA assay, neural-specific antibody binding was more frequent in IND (15 of 42) than in NIND patients (4 of 57) (Fisher's exact test, p = 0.0005). Two of four AQP4+ NMO and four of seven definite AIE/PNS with intracellular-reactive antibodies [1 GFAP astrocytopathy, 2 Hu+, 1 Ri+ AIE/PNS)], as identified in diagnostic laboratories, were also positive with our CBA. Most interestingly, we showed antibody-reactivity in two of six seronegative NMOSD, six of 12 probable AIE/PNS, and one of 13 OIND. Flow cytometry using hiPSC-derived CNS cells or PBMC-detected antibody binding in 13 versus zero patients, respectively, establishing the specificity of the detected antibodies for neural tissue. Our unique hiPSC-based CBA allows for the testing of novel neuron-/astrocyte-reactive antibodies in patients with suspected immune-mediated neurological syndromes, and negative testing in established routine laboratories, opening new perspectives in establishing a diagnosis of such complex diseases.

Synthesis and Electrophilic Trifluoromethylthiolation Properties of 1-Methyl-4-(trifluoromethylthio)piperazine (MTTP).

A cyclic diamine, 1-methyl-4-(trifluoromethylthio)piperazine (MTTP, 1), prepared by a one-step reaction from commercial materials, is a shelf-stable and powerful electrophilic trifluoromethylthiolating (CF3S) reagent with wide reactivity profile. Activation of 1 with triflic acid (TfOH) yields two reactive species A and B, depending on the molar ratios of TfOH/1. B showed unprecedented high reactivity, making possible the trifluoromethylthiolation of electron-deficient aromatic systems. In addition, B accomplished the trifluoromethylthiolation of active methylene compounds under acidic conditions.

Evaluation of SARS-CoV-2-Specific IgY Antibodies: Production, Reactivity, and Neutralizing Capability against Virus Variants.

The emergence of SARS-CoV-2 in late 2019 initiated a global pandemic, which led to a need for effective therapeutics and diagnostic tools, including virus-specific antibodies. Here, we investigate different antigen preparations to produce SARS-CoV-2-specific and virus-neutralizing antibodies in chickens (n = 3/antigen) and rabbits (n = 2/antigen), exploring, in particular, egg yolk for large-scale production of immunoglobulin Y (IgY). Reactivity profiles of IgY preparations from chicken sera and yolk and rabbit sera were tested in parallel. We compared three types of antigens based on ancestral SARS-CoV-2: an inactivated whole-virus preparation, an S1 spike-protein subunit (S1 antigen) and a receptor-binding domain (RBD antigen, amino acids 319-519) coated on lumazine synthase (LS) particles using SpyCather/SpyTag technology. The RBD antigen proved to be the most efficient immunogen, and the resulting chicken IgY antibodies derived from serum or yolk, displayed strong reactivity with ELISA and indirect immunofluorescence and broad neutralizing activity against SARS-CoV-2 variants, including Omicron BA.1 and BA.5. Preliminary in vivo studies using RBD-lumazine synthase yolk preparations in a hamster model showed that local application was well tolerated and not harmful. However, despite the in vitro neutralizing capacity, this antibody preparation did not show protective effect. Further studies on galenic properties seem to be necessary. The RBD-lumazine antigen proved to be suitable for producing SARS-CoV-2 specific antibodies that can be applied to such therapeutic approaches and as reference reagents for SARS-CoV-2 diagnostics, including virus neutralization assays.