Photoactivated Reactions without Traditional Photocatalysts: Electron-Donor Complexation of 1,2,3-Triazoles Initiates Denitrogenative Transformations.

We present a set of visible-light-promoted denitrogenative transformations of 1,2,3-triazoles that generate high product yields without the use of a traditional, external photocatalyst, with the reaction viable for both benzotriazole and benzotriazinone. Mechanistic studies using UV-vis absorption, H NMR spectroscopy, and density functional theory indicate that these reactions are initiated by an electron donor-acceptor (EDA) complex which forms between ,-diisopropylethylamine (DIPEA) and the 1,2,3-triazole. A comprehensive analysis of how irradiation wavelength impacts reactivity was obtained using an online photochemical reactor coupled mass spectrometer, indicating a lack of correlation between absorptivity and photoreactivity for the reaction between benzotriazinone and methyl acrylate.

Divergent Reactivity of 1,2,3-Benzotriazin-4(3)-ones: Photocatalytic Synthesis of 3-Substituted Isoindolinones Achieved through a Nitrogen-Mediated Hydrogen Atom Shift.

A regioselective visible-light-mediated denitrogenative alkene insertion of 1,2,3-benzotriazin-4(3)-ones was developed to access 3-substituted isoindolinones, an important structural motif present in many biologically active molecules and natural products. Notably, divergent reactivity was achieved by switching from reported nickel catalysis (where C3-substituted 3,4-dihydroisoquinolin-1(2)-ones form) to photocatalysis, where photocatalytic denitrogenation and a subsequent nitrogen-mediated hydrogen atom shift lead to exclusive 3-substituted isoindolinone formation. The developed photocatalytic reaction is compatible with activated terminal alkenes and cyclic α,β-unsaturated esters and ketones, with wide functional group tolerance for N-substitution of the 1,2,3-benzotriazin-4(3)-ones.

A Photoreactor-Interfaced Mass Spectrometer: An Online Platform to Monitor Photochemical Reactions.

An experimental platform is reported that allows for the online characterization of photochemical reactions by coupling a continuous flow photoreactor, equipped with LED light irradiation and a dual-tipped ESI source, directly to a mass spectrometer with electrospray ionization. The capabilities of this platform are demonstrated with two classes of photoreactions: (1) the photopolymerization of methyl methacrylate and (2) photocatalyzed alkyne insertion into a 1,2,3-benzotriazinone. The online technique provides rapid information to inform the underlying photochemical mechanism and evaluate the overall photochemistry.

Amplicon-Based High-Throughput Sequencing Method for Genotypic Characterization of Norovirus in Oysters.

Norovirus is a highly diverse RNA virus often implicated in foodborne outbreaks, particularly those associated with shellfish. Shellfish are filter feeders, and when harvested in bays exposed to wastewater overflow or storm overflows, they can harbor various pathogens, including human-pathogenic viruses. The application of Sanger or amplicon-based high-throughput sequencing (HTS) technologies to identify human pathogens in shellfish faces two main challenges: (i) distinguishing multiple genotypes/variants in a single sample and (ii) low concentrations of norovirus RNA.

An Investigation into the In Vitro Metabolic Stability of Aryl Sulfonyl Fluorides for their Application in Medicinal Chemistry and Radiochemistry.

Molecules that feature a sulfonyl fluoride (SOF) moiety have been gaining increasing interest due to their unique reactivity and potential applications in synthetic chemistry, medicinal chemistry, and other biological uses. A particular interest is towards F-radiochemistry where sulfonyl fluorides can be used as a method to radiolabel biomolecules or can be used as radiofluoride relay reagents that facilitate radiolabeling of other molecules. The low metabolic stability of sulfonyl fluoride S-F bonds, however, presents an issue and limits the applicability of sulfonyl fluorides.

Benchmarking Bioinformatic Tools for Amplicon-Based Sequencing of Norovirus.

In order to survey noroviruses in our environment, it is essential that both wet-lab and computational methods are fit for purpose. Using a simulated sequencing data set, denoising-based (DADA2, Deblur and USEARCH-UNOISE3) and clustering-based pipelines (VSEARCH and FROGS) were compared with respect to their ability to represent composition and sequence information. Open source classifiers (Ribosomal Database Project [RDP], BLASTn, IDTAXA, QIIME2 naive Bayes, and SINTAX) were trained using three different databases: a custom database, the NoroNet database, and the Human calicivirus database.

Impact of COVID-19 Nonpharmaceutical Interventions on the Extent of Norovirus Contamination in Oyster Production Areas in Ireland during Winter 2020 to 2021.

Abstract: A significant decrease in norovirus prevalence and concentration was observed in oyster production areas in Ireland during winter 2020 to 2021. Oyster production areas impacted by human wastewater discharges that had been undergoing norovirus surveillance since 2018 were investigated. Samples collected in the winter seasons of 2018 to 2019 and 2019 to 2020, prior to when the COVID-19 pandemic interventions were applied, showed a prevalence of 94.

Synthesis of Long-Chain Alkanoyl Benzenes by an Aluminum(III) Chloride-Catalyzed Destannylative Acylation Reaction.

This paper describes the facile synthesis of haloaryl compounds with long-chain alkanoyl substituents by the destannylative acylation of haloaryls bearing tri--butyltin (BuSn) substituents. The method allows the synthesis of many important synthons for novel functional materials in a highly efficient manner. The halo-tri--butyltin benzenes are obtained by the lithium-halogen exchange of commercially available bis-haloarenes and the subsequent reaction with BuSnCl.

High Throughput Sequencing for the Detection and Characterization of RNA Viruses.

This review aims to assess and recommend approaches for targeted and agnostic High Throughput Sequencing of RNA viruses in a variety of sample matrices. HTS also referred to as deep sequencing, next generation sequencing and third generation sequencing; has much to offer to the field of environmental virology as its increased sequencing depth circumvents issues with cloning environmental isolates for Sanger sequencing. That said however, it is important to consider the challenges and biases that method choice can impart to sequencing results.

Evaluation of Norovirus Reduction in Environmentally Contaminated Pacific Oysters During Laboratory Controlled and Commercial Depuration.

Norovirus contamination of oysters is the lead cause of non-bacterial gastroenteritis and a significant food safety concern for the oyster industry. Here, norovirus reduction from Pacific oysters (Crassostrea gigas), contaminated in the marine environment, was studied in laboratory depuration trials and in two commercial settings. Norovirus concentrations were measured in oyster digestive tissue before, during and post-depuration using the ISO 15216-1 quantitative real-time RT-PCR method.

Base-Free Cross-Couplings of Aryl Diazonium Salts in Methanol: Pd -Alkoxy as Reactivity-Controlling Intermediate.

Pd-catalyzed cross-coupling reactions of aryl diazonium salts are generally assumed to proceed via cationic Pd intermediates which in turn would be highly reactive in the subsequent transmetalation step. Contrary to this belief, we herein report our observation and rationalization of opposing reactivities of ArN in Suzuki (=effective) and Stille (=ineffective) cross-couplings in MeOH. Our systematic experimental and computational studies on the roles of transmetalating agent, solvent, base and the likely involvement of in situ formed diazoether derivatives challenge the currently accepted mechanism.

Development of tethered dual catalysts: synergy between photo- and transition metal catalysts for enhanced catalysis.

While dual photocatalysis-transition metal catalysis strategies are extensively reported, the majority of systems feature two separate catalysts, limiting the potential for synergistic interactions between the catalytic centres. In this work we synthesised a series of tethered dual catalysts allowing us to investigate this underexplored area of dual catalysis. In particular, Ir(i) or Ir(iii) complexes were tethered to a BODIPY photocatalyst through different tethering modes.

Estimating the distribution of norovirus in individual oysters.

Norovirus in oysters is a significant food safety risk. A recent ISO detection method allows for reliable and repeatable estimates of norovirus concentrations in pooled samples, but there is insufficient data to estimate a distribution of copies per animal from this. The spread of norovirus accumulated across individual oysters is useful for risk assessment models.

Ion-Reagent Interactions Contributing to Ionic Liquid Solvent Effects on a Condensation Reaction.

Molecular dynamics simulations of solutions of hexan-1-amine or 4-methoxybenzaldehyde in acetonitrile, an ionic liquid/acetonitrile mixture (χ =0.2), and a number of different (neat) ionic liquids were performed, to further understand the solvent effects on the condensation reaction of these species. This work indicates that, in the presence of an ionic liquid, the amine group of hexan-1-amine is exclusively solvated by the components of the ionic liquid, and not by acetonitrile, and that the anion interacts with the aldehyde group of 4-methoxybenzaldehyde.

Modular Functionalization of Arenes in a Triply Selective Sequence: Rapid C(sp ) and C(sp ) Coupling of C-Br, C-OTf, and C-Cl Bonds Enabled by a Single Palladium(I) Dimer.

Full control over multiple competing coupling sites would enable straightforward access to densely functionalized compound libraries. Historically, the site selection in Pd -catalyzed functionalizations of poly(pseudo)halogenated arenes has been unpredictable, being dependent on the employed catalyst, the reaction conditions, and the substrate itself. Building on our previous report of C-Br-selective functionalization in the presence of C-OTf and C-Cl bonds, we herein complete the sequence and demonstrate the first general arylations and alkylations of C-OTf bonds (in <10 min), followed by functionalization of the C-Cl site (in <25 min), at room temperature using the same air- and moisture-stable Pd dimer.

The Impact of Winter Relocation and Depuration on Norovirus Concentrations in Pacific Oysters Harvested from a Commercial Production Site.

Oysters contaminated with norovirus present a significant public health risk when consumed raw. In this study, norovirus genome copy concentrations were determined in Pacific oysters (Magallana gigas) harvested from a sewage-impacted production site and then subjected to site-specific management procedures. These procedures consisted of relocation of oysters to an alternative production area during the norovirus high-risk winter periods (November to March) followed by an extended depuration (self-purification) under controlled temperature conditions.

Palladium-Catalyzed Decarbonylative Trifluoromethylation of Acid Fluorides.

While acid fluorides can readily be made from widely available or biomass-feedstock-derived carboxylic acids, their use as functional groups in metal-catalyzed cross-coupling reactions is rare. This report presents the first demonstration of Pd-catalyzed decarbonylative functionalization of acid fluorides to yield trifluoromethyl arenes (ArCF ). The strategy relies on a Pd/Xantphos catalytic system and the supply of fluoride for transmetalation through intramolecular redistribution to the the Pd center.

Investigating Solvent Effects of an Ionic Liquid on Pericyclic Reactions through Kinetic Analyses of Simple Rearrangements.

Simple Cope and Claisen rearrangements were investigated in an ionic liquid and a range of molecular solvents through a series of kinetic studies. Analysis of the solvent effects on the Cope rearrangement of 3-phenyl-1,5-hexadiene indicated that a solvophobic effect was responsible for the observed rate enhancement in the ionic liquid, and that this was due to preferential solvation of the transition state. A similar solvophobic effect contributes to the ionic liquid solvent effect on the Claisen rearrangement of allyl vinyl ether, although the ability of the ionic liquid to stabilise the incipient charges in the transition state also likely contributes to the rate increase observed in the ionic liquid solvent.

Understanding the Effect of Solvent Structure on Organic Reaction Outcomes When Using Ionic Liquid/Acetonitrile Mixtures.

The rate constant for the reaction between hexan-1-amine and 4-methoxybenzaldehyde was determined in ionic liquids containing an imidazolium cation. The effect on the rate constant of increasing the length of the alkyl substituent on the cation was examined in a number of ionic liquid/acetonitrile mixtures. In general it was found that there was no significant effect of changing the alkyl substituent on the rate constant of this process, suggesting that any nanodomains in these mixtures do not have a significant effect on the outcome of this process.

NMR Diffusion Measurements as a Simple Method to Examine Solvent-Solvent and Solvent-Solute Interactions in Mixtures of the Ionic Liquid [Bmim][N(SO CF ) ] and Acetonitrile.

The self-diffusion coefficients of each component in mixtures of 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([Bmim][N(SO CF ) ]) and acetonitrile were determined. The results suggest that the hydrodynamic boundary conditions change from "stick" to "slip" as the solvent composition transitions from "ionic liquid dissolved in acetonitrile" (χ <0.4) to "acetonitrile dissolved in ionic liquid" (χ >0.

The effects of an ionic liquid on unimolecular substitution processes: the importance of the extent of transition state solvation.

The reaction of bromodiphenylmethane and 3-chloropyridine, which proceeds concurrently through both unimolecular and bimolecular mechanisms, was examined in mixtures of acetonitrile and an ionic liquid. As predicted, the bimolecular rate constant (k2) gradually increased as the amount of ionic liquid in the reaction mixture increased, as a result of a minor enthalpic cost offset by a more significant entropic benefit. Addition of an ionic liquid had a substantial effect on the unimolecular rate constant (k1) of the reaction, with at least a 5-fold rate enhancement relative to acetonitrile, which was found to be due to a significant decrease in the enthalpy of activation, partially offset by the associated decrease in the entropy of activation.

Ionic liquid effects on a multistep process. Increased product formation due to enhancement of all steps.

The reaction of a series of substituted benzaldehydes with hexylamine was examined in acetonitrile and an ionic liquid. In acetonitrile, as the electron withdrawing nature of the substituent increases, the overall addition-elimination process becomes faster as does the build-up of the aminol intermediate. Under equivalent conditions in an ionic liquid, less intermediate build up is observed, and the effect on the rate on varying the substituent is different to that in acetonitrile.

Developing principles for predicting ionic liquid effects on reaction outcome. The importance of the anion in controlling microscopic interactions.

A series of ionic liquids containing anions of differing coordination strength were investigated as solvents for the condensation reaction of an alkyl amine and an aromatic aldehyde. As predicted, the rate constant of the process was found to increase with the proportion of the ionic liquid in the reaction mixture. Temperature-dependent kinetic analyses demonstrated that by varying the ability of the anion to interact with the cation the magnitude of both the enthalpy and entropy of activation could be controlled in a predictable manner, with the activation parameters being linearly dependent on the ionic liquid basicity.

Developing principles for predicting ionic liquid effects on reaction outcome. A demonstration using a simple condensation reaction.

The effects of a series of ionic liquids, with systematic variations in the cation, on the condensation of an alkyl amine with an aromatic aldehyde were investigated, and the outcomes compared with those predicted based on related reactions. The addition of ionic liquids increased the observed rate constant; the mole fraction dependence of this increase was qualitatively consistent with predictions. Temperature-dependent kinetic analyses were used to demonstrate that the microscopic origins of the effects were as forecast, though the relative weighting of enthalpic and entropic contributions was dependent on the salt used.