Gold-Catalyzed Direct Arylation

Gently Coupled Linked aryl rings are found in a broad range of commercial chemical products. Currently, the most versatile synthetic route to this motif involves cross-coupling of one ring with a halide substituent to another ring with a boron or metal-based substituent. Recent research has focused on eliminating the need for one or both of these activating substituents, but for the most part, the emerging methods have required high temperatures and high concentrations of one coupling partner. Ball et al. (p. 1644 ) now present a gold catalyst that can couple silyl-activated arenes to unactivated arenes in comparable concentrations at room temperature. </jats:p

The Oral-Vascular-Pulmonary Infection Route:a Pathogenic Mechanism Linking Oral Health Status to Acute and Post-Acute COVID-19

Purpose of Review: In recent years, much attention has focused on the role of poor oral health in the development or worsening of systemic diseases, including COVID-19. The mouth is an important site of cellular infection early in the disease course of COVID-19. We review how oral pathology, and specifically viral infection within the oral cavity, may mediate the disease severity and duration of COVID-19. In particular, the previously reported model of SARS-CoV-2 vascular delivery from the mouth to the lungs via the bloodstream is revisited.Recent Findings: We previously proposed that an oral-vascular-pulmonary route of infection could facilitate severe lung disease in COVID-19. This pathway could also explain the vital link between periodontitis and COVID-19 severity, including higher mortality risk. This model of pathogenesis is reconsidered in light of recent findings regarding the involvement of the mouth as a viral reservoir, and pathological processes in the blood, pulmonary vasculature, and elsewhere in the body. Oral dysbiosis in COVID-19 and the effect of oral hygiene in mitigating disease severity are discussed. The evidence for viral persistence in the mouth and intravascular viral passage from the mouth to the rest of the body via blood is also discussed in the context of post-acute COVID (long COVID).Summary: High viral load in the mouth and poor oral health status are associated with COVID-19 disease severity, increasing the risk of death. Pathophysiological links between viral activity in the mouth, oral health status, and disease outcome in the lungs and blood provide a rationale for further evaluation of the oral-vascular-systemic pathway in patients with acute COVID-19 and long COVID. The potential benefits of oral hygiene protocols and periodontal procedures in COVID-19 also warrant further investigation

The Oral-Vascular-Pulmonary Infection Route:a Pathogenic Mechanism Linking Oral Health Status to Acute and Post-Acute COVID-19

Purpose of Review: In recent years, much attention has focused on the role of poor oral health in the development or worsening of systemic diseases, including COVID-19. The mouth is an important site of cellular infection early in the disease course of COVID-19. We review how oral pathology, and specifically viral infection within the oral cavity, may mediate the disease severity and duration of COVID-19. In particular, the previously reported model of SARS-CoV-2 vascular delivery from the mouth to the lungs via the bloodstream is revisited.Recent Findings: We previously proposed that an oral-vascular-pulmonary route of infection could facilitate severe lung disease in COVID-19. This pathway could also explain the vital link between periodontitis and COVID-19 severity, including higher mortality risk. This model of pathogenesis is reconsidered in light of recent findings regarding the involvement of the mouth as a viral reservoir, and pathological processes in the blood, pulmonary vasculature, and elsewhere in the body. Oral dysbiosis in COVID-19 and the effect of oral hygiene in mitigating disease severity are discussed. The evidence for viral persistence in the mouth and intravascular viral passage from the mouth to the rest of the body via blood is also discussed in the context of post-acute COVID (long COVID).Summary: High viral load in the mouth and poor oral health status are associated with COVID-19 disease severity, increasing the risk of death. Pathophysiological links between viral activity in the mouth, oral health status, and disease outcome in the lungs and blood provide a rationale for further evaluation of the oral-vascular-systemic pathway in patients with acute COVID-19 and long COVID. The potential benefits of oral hygiene protocols and periodontal procedures in COVID-19 also warrant further investigation

<i>In Situ </i>Studies of Arylboronic Acids/Esters and R₃SiCF₃ Reagents: Kinetics, Speciation, and Dysfunction at the Carbanion–Ate Interface

[Image: see text] Reagent instability reduces the efficiency of chemical processes, and while much effort is devoted to reaction optimization, less attention is paid to the mechanistic causes of reagent decomposition. Indeed, the response is often to simply use an excess of the reagent. Two reaction classes with ubiquitous examples of this are the Suzuki–Miyaura cross-coupling of boronic acids/esters and the transfer of CF(3) or CF(2) from the Ruppert–Prakash reagent, TMSCF(3). This Account describes some of the overarching features of our mechanistic investigations into their decomposition. In the first section we summarize how specific examples of (hetero)arylboronic acids can decompose via aqueous protodeboronation processes: Ar–B(OH)(2) + H(2)O → ArH + B(OH)(3). Key to the analysis was the development of a kinetic model in which pH controls boron speciation and heterocycle protonation states. This method revealed six different protodeboronation pathways, including self-catalysis when the pH is close to the pK(a) of the boronic acid, and protodeboronation via a transient aryl anionoid pathway for highly electron-deficient arenes. The degree of “protection” of boronic acids by diol-esterification is shown to be very dependent on the diol identity, with six-membered ring esters resulting in faster protodeboronation than the parent boronic acid. In the second section of the Account we describe (19)F NMR spectroscopic analysis of the kinetics of the reaction of TMSCF(3) with ketones, fluoroarenes, and alkenes. Processes initiated by substoichiometric “TBAT” ([Ph(3)SiF(2)][Bu(4)N]) involve anionic chain reactions in which low concentrations of [CF(3)](−) are rapidly and reversibly liberated from a siliconate reservoir, [TMS(CF(3))(2)][Bu(4)N]. Increased TMSCF(3) concentrations reduce the [CF(3)](−) concentration and thus inhibit the rates of CF(3) transfer. Computation and kinetics reveal that the TMSCF(3) intermolecularly abstracts fluoride from [CF(3)](−) to generate the CF(2), in what would otherwise be an endergonic α-fluoride elimination. Starting from [CF(3)](−) and CF(2), a cascade involving perfluoroalkene homologation results in the generation of a hindered perfluorocarbanion, [C(11)F(23)](−), and inhibition. The generation of CF(2) from TMSCF(3) is much more efficiently mediated by NaI, and in contrast to TBAT, the process undergoes autoacceleration. The process involves NaI-mediated α-fluoride elimination from [CF(3)][Na] to generate CF(2) and a [NaI·NaF] chain carrier. Chain-branching, by [(CF(2))(3)I][Na] generated in situ (CF(2) + TFE + NaI), causes autoacceleration. Alkenes that efficiently capture CF(2) attenuate the chain-branching, suppress autoacceleration, and lead to less rapid difluorocyclopropanation. The Account also highlights how a collaborative approach to experiment and computation enables mechanistic insight for control of processes

Effect of work:rest ratio on cycling performance following sprint interval training: A randomised control trial

Sprint interval training (SIT) has been shown to improve performance measures in a range of individuals, and it is understood that different responses can be elicited from different training protocols. However, consideration of changes in work: rest ratios could offer important insight into optimising training programmes. The purpose of this study was to investigate the effect of three different work: rest ratios on exercise performance. Thirty-six male and female participants were randomly allocated to one of three training groups, or a non-training control group. Training consisted of 10x6 second ‘all-out’ sprints on a cycle ergometer, with a 1:8, 1:10 or 1:12 work: rest ratio. Performance data, including peak power output, performance decrement, and 10km time trial performance data were collected before and after 2-weeks of SIT. There were significant (p ≤ 0.05) improvements in all parameters for the training groups, but no changes in the control condition. Peak power increased by 57.2W, 50.7W and 53.7W in the 1:8, 1:10 and 1:12 groups respectively, with no significant differences in response between conditions. Time trial performance improved significantly in all three training conditions (29.4s, 8.7s, and 25.1s in the 1:8, 1:10 and 1:12 groups), while worsening in the control group. All training conditions resulted in significant improvements in performance, but there were no significant differences in improvement for any of the groups. Any of the three stated work: rest ratios would be appropriate for use with athletes and allow some level of personal preference for those interested in using the protocol

Self-control tames the coupling of reactive radicals

Highly reactive or unstable chemical reagents are challenging to prepare, store, and safely handle, so chemists frequently generate them in situ from convenient precursors. In an ideal case, the rate of release of the reagent would be matched to the rate of its “capture” in the desired chemical reaction, thereby preventing the reagent from accumulating and minimizing any opportunity for decomposition. However, this synchronization is rarely achieved or even attempted: The rate of release is usually dictated by the conditions of the reaction (1), rather than being regulated by capture of the reagent. In this issue, Tellis et al. (2) on page 433 and Zuo et al. (3) on page 437 independently report the use of iridium photocatalysis (4, 5) to supply highly reactive radical coupling partners (R⋅) to a nickel-catalyzed carbon-carbon bond-forming process (see the figure). Intriguingly, the two points of contact between the iridium and nickel cycles enforce autoregulated release of the radical, ensuring its efficient capture by nickel rather than its decomposition via other pathways

Kinetic analysis of bioorthogonal reaction mechanisms using Raman microscopy

Raman spectroscopy is well-suited to the study of bioorthogonal reaction processes because it is a non-destructive technique, which employs relatively low energy laser irradiation, and water is only very weakly scattered in the Raman spectrum enabling live cell imaging. In addition, Raman spectroscopy allows species-specific label-free visualisation; chemical contrast may be achieved when imaging a cell in its native environment without fixatives or stains. Combined with the rapid advances in the field of Raman imaging over the last decade, particularly in stimulated Raman spectroscopy (SRS), this technique has the potential to revolutionise our mechanistic understanding of the biochemical and medicinal chemistry applications of bioorthogonal reactions. Current approaches to the kinetic analysis of bioorthogonal reactions (including heat flow calorimetry, UV-vis spectroscopy, fluorescence, IR, NMR and MS) have a number of practical shortcomings for intracellular applications. We highlight the advantages offered by Raman microscopy for reaction analysis in the context of both established and emerging bioorthogonal reactions, including the copper(i) catalysed azide-alkyne cycloaddition (CuAAC) click reaction and Glaser-Hay coupling

Improved Exercise-Related Skeletal Muscle Oxygen Consumption Following Uptake of Endurance Training Measured Using Near-Infrared Spectroscopy

Skeletal muscle metabolic function is known to respond positively to exercise interventions. Developing non-invasive techniques that quantify metabolic adaptations and identifying interventions that impart successful response are ongoing challenges for research. Healthy non-athletic adults (18–35 years old) were enrolled in a study investigating physiological adaptations to a minimum of 16 weeks endurance training prior to undertaking their first marathon. Before beginning training, participants underwent measurements of skeletal muscle oxygen consumption using near-infrared spectroscopy (NIRS) at rest (resting muscleV˙O2) and immediately following a maximal exercise test (post-exercise muscleV˙O2). Exercise-related increase in muscleV˙O2 (ΔmV˙O2) was derived from these measurements and cardio-pulmonary peakV˙O2 measured by analysis of expired gases. All measurements were repeated within 3 weeks of participants completing following the marathon and marathon completion time recorded. MuscleV˙O2 was positively correlated with cardio-pulmonary peakV˙O2 (r = 0.63, p < 0.001). MuscleV˙O2 increased at follow-up (48% increase; p = 0.004) despite no change in cardio-pulmonary peakV˙O2 (0% change; p = 0.97). Faster marathon completion time correlated with higher cardio-pulmonary peakV˙O2 (rpartial = −0.58, p = 0.002) but not muscleV˙O2 (rpartial = 0.16, p = 0.44) after adjustment for age and sex [and adipose tissue thickness (ATT) for muscleV˙O2 measurements]. Skeletal muscle metabolic adaptions occur following training and completion of a first-time marathon; these can be identified non-invasively using NIRS. Although the cardio-pulmonary system is limiting for running performance, skeletal muscle changes can be detected despite minimal improvement in cardio-pulmonary function

Expansion of the ligand knowledge base for chelating P,P-donor ligands (LKB-PP)

[Image: see text] We have expanded the ligand knowledge base for bidentate P,P- and P,N-donor ligands (LKB-PP, Organometallics2008, 27, 1372–1383) by 208 ligands and introduced an additional steric descriptor (nHe(8)). This expanded knowledge base now captures information on 334 bidentate ligands and has been processed with principal component analysis (PCA) of the descriptors to produce a detailed map of bidentate ligand space, which better captures ligand variation and has been used for the analysis of ligand properties

Quantum search without entanglement

Entanglement of quantum variables is usually thought to be a prerequisite for obtaining quantum speed-ups of information processing tasks such as searching databases. This paper presents methods for quantum search that give a speed-up over classical methods, but that do not require entanglement. These methods rely instead on interference to provide a speed-up. Search without entanglement comes at a cost: although they outperform analogous classical devices, the quantum devices that perform the search are not universal quantum computers and require exponentially greater overhead than a quantum computer that operates using entanglement. Quantum search without entanglement is compared to classical search using waves.Comment: 9 pages, TeX, submitted to Physical Review Letter