An outbreak of hepatitis A virus infection in a secondary school in England with no undetected asymptomatic transmission among students.

In June 2019 the Health Protection Team in Yorkshire and Humber, England, was notified of cases of hepatitis A virus (HAV) infection in staff at a secondary school. Investigation revealed that an earlier case worked as a food handler in the school kitchen. Indirect transmission through food from the canteen was considered the most likely route of transmission. Cases were described according to setting of exposure. Oral fluid was obtained from students for serological testing. Environmental investigations were undertaken at settings where food handling was considered a potential transmission risk. Thirty-three confirmed cases were linked to the outbreak. All of those tested (n = 31) shared the same sequence with a HAV IB genotype. The first three cases were a household cluster and included the index case for the school. A further 19 cases (16 students, 3 staff) were associated with the school and consistent with indirect exposure to the food handler. One late onset case could not be ruled out as a secondary case within the school and resulted in vaccination of the school population. Five cases were linked to a bakery where a case from the initial household cluster worked as a food server. No concerns about hygiene standards were noted at either the school or the bakery. Oral fluid samples taken at the time of vaccination from asymptomatic students (n = 219, 11-16 years-old) showed no evidence of recent or current infection. This outbreak included household and foodborne transmission but limited (and possibly zero) person-to-person transmission among secondary school students. Where adequate hygiene exists, secondary transmission within older students may not occur.

On 'Is vitamin E the only lipid-soluble, chain-breaking antioxidant in human blood plasma and erythrocyte membranes?' by Graham W. Burton, Anne Joyce, Keith U. Ingold.

Application of a time-tested quantitative method of measuring peroxyl radical production in conjunction with the determination of the stoichiometry of the reaction of peroxyl radicals with α-tocopherol has permitted the conclusion that α-tocopherol is the major lipid-soluble chain-breaking antioxidant in human plasma and red cell membranes.

Social-ecological network analysis for sustainability sciences: a systematic review and innovative research agenda for the future.

Social-ecological network (SEN) concepts and tools are increasingly used in human-environment and sustainability sciences. We take stock of this budding research area to further show the strength of SEN analysis for complex human-environment settings, identify future synergies between SEN and wider human-environment research, and provide guidance about when to use different kinds of SEN approaches and models. We characterize SEN research along a spectrum specifying the degree of explicit network representation of system components and dynamics. We then systematically review one end of this spectrum, what we term "fully articulated SEN" studies, which specifically model unique social and ecological units and relationships. Results show more focus on methodological advancement and applied ends. While there has been some development and testing of theories, this remains an area for future work and would help develop SENs as a unique field of research, not just a method. Authors have studied diverse systems, while mainly focused on the problem of social-ecological fit alongside a scattering of other topics. There is strong potential, however, to engage other issues central to human-environment studies. Analyzing the simultaneous effects of multiple social, environmental, and coupled processes, change over time, and linking network structures to outcomes are also areas for future advancement. This review provides a comprehensive assessment of (fully articulated) SEN research, a necessary step that can help scholars develop comparable cases and fill research gaps.

Improving network approaches to the study of complex social-ecological interdependencies.

Achieving effective, sustainable environmental governance requires a better understanding of the causes and consequences of the complex patterns of interdependencies connecting people and ecosystems within and across scales. Network approaches for conceptualizing and analyzing these interdependencies offer one promising solution. Here, we present two advances we argue are needed to further this area of research: (i) a typology of causal assumptions explicating the causal aims of any given network-centric study of social-ecological interdependencies; (ii) unifying research design considerations that facilitate conceptualizing exactly what is interdependent, through what types of relationships, and in relation to what kinds of environmental problems. The latter builds on the appreciation that many environmental problems draw from a set of core challenges that re-occur across contexts. We demonstrate how these advances combine into a comparative heuristic that facilitates leveraging case-specific findings of social-ecological interdependencies to generalizable, yet context-sensitive, theories based on explicit assumptions of causal relationships.

Why are sec-alkylperoxyl bimolecular self-reactions orders of magnitude faster than the analogous reactions of tert-alkylperoxyls? The unanticipated role of CH hydrogen bond donation.

High-level ab initio calculations are used to identify the mechanism of secondary (and primary) alkylperoxyl radical termination and explain why their reactions are much faster than their tertiary counterparts. Contrary to existing literature, the decomposition of both tertiary and non-tertiary tetroxides follows the same asymmetric two-step bond cleavage pathway to form a caged intermediate of overall singlet multiplicity comprising triplet oxygen and two alkoxyl radicals. The alpha hydrogen atoms of non-tertiary species facilitate this process by forming unexpected CHO hydrogen bonds to the evolving O2. For non-tertiary peroxyls, subsequent alpha hydrogen atom transfer then yields the experimentally observed non-radical products, ketone, alcohol and O2, whereas for tertiary species, this reaction is precluded and cage escape of the (unpaired) alkoxyl radicals is a likely outcome with important consequences for autoxidation.

Why are organotin hydride reductions of organic halides so frequently retarded? Kinetic studies, analyses, and a few remedies.

Kinetic data for reduction of organic halides (RX) by tri-n-butylstannane (SnH) reveal a serious flaw in the current view of the kinetic radical chain: the tacit but unproven assumption that the speed of reaction is determined by the slowest propagation step. Our results show this is rarely true for reductive chains and that the observed rate is in fact controlled by unseen side-reactions of propagating R(•) and Sn(•) radicals with the solvent (notably, benzene!) or solvent impurities (e.g., trace benzophenone dryness indicator in THF) or, crucially, with allylic-CH and conjugated unsaturated groups in substrates and products. Most R(•) and/or Sn(•) radicals are therefore converted into relatively inert delocalized species A(•) and/or B(•) that inhibit the chain. Retardation in the degraded chain is given by a simple sum of terms, each being the ratio of the chain-transfer rate divided by the rate of chain-return. The model kinetic equation is linear and easy to ratify, interpret, and apply: to calculate retarding rate constants, optimize reaction conditions, and identify additives or "remedies" that repair the chain and accelerate reaction. The present work is thus expected to have a helpful impact on the practice and design of SnH radical chain based (and related) syntheses.

New insights into the mechanism of amine/nitroxide cycling during the hindered amine light stabilizer inhibited oxidative degradation of polymers.

High-level ab initio molecular orbital theory calculations are used to identify the origin of the remarkably high inhibition stoichiometric factors exhibited by dialkylamine-based radical-trapping antioxidants. We have calculated the free energy barriers and reaction energies at 25, 80, and 260 °C in the gas phase and in aqueous solution for a broad range of reactions that might, potentially, be involved in amine/nitroxide cycling, as well as several novel pathways proposed as part of the present work, including that of N-alkyl hindered amine light stabilizer activation. We find that most of the literature nitroxide regeneration cycles should be discarded on either kinetic or thermodynamic grounds; some are even inconsistent with existing experimental observations. We therefore propose a new mechanistic cycle that relies on abstraction of a ß-hydrogen atom from an alkoxyamine (R(1)R(2)NOCHR(3)R(4)). Our results suggest that this cycle is energetically feasible for a range of substrates and provides an explanation for previously misinterpreted or unexplained experimental results. We also explore alternative mechanisms for amine/nitroxide cycling for cases where the alkoxyamines do not possess an abstractable ß-hydrogen.

Kinetics of the oxidation of quercetin by 2,2-diphenyl-1-picrylhydrazyl (dpph•).

In methanol/water, dpph(•) bleaching (519 nm) by quercetin, QH(2), exhibits biphasic kinetics. The dpph(•) reacts completely with the quercetin anion within 100 ms. Subsequent slower bleaching involves solvent and QH(2) addition to quinoid products. The fast reaction is first-order in dpph(•) but only ca. 0.38 order in [QH(2)]. This extraordinary nonintegral order is attributed to reversible formation of π-stacked {QH(-)/dpph(•)} complexes in which electron transfer to products, {QH(•)/dpph(-)}, is slow (k(ET) ≈ 10(5) s(-1)).

The frequently overlooked importance of solvent in free radical syntheses.

This tutorial review is designed to dispel the myth, still believed by many synthetic organic chemists, that radical-based syntheses are free from significant solvent effects. However, many synthetically valuable radical reactions do exhibit large kinetic solvent effects. It is therefore important to select the solvent for any proposed radical synthesis with considerable care if good product yields are to be achieved.

Accurate O-H bond dissociation energy differences of hydroxylamines determined by EPR spectroscopy: computational insight into stereoelectronic effects on BDEs and EPR spectral parameters.

Differences in O-H bond dissociation enthalpies (ΔBDEs) between the hydroxylamine of (15)N-labeled TEMPONE and 10 N,N-di-tert-alkyl hydroxylamines were determined by EPR. These ΔBDEs, together with the g and a(N) values of the derived nitroxide radicals, are discussed in relation to various geometric, intramolecular dipole/dipole, and steric effects and in relation to the results from DFT calculations. We find that dipole/dipole interactions are the dominant factors in dictating a(N) values and O-H BDEs in all of these structurally similar nitroxides and hydroxylamines, respectively. The importance of including the Boltzmann distribution of conformations for each nitroxide in the a(N) calculations is emphasized.

Influence of "remote" intramolecular hydrogen bonds on the stabilities of phenoxyl radicals and benzyl cations.

Remote intramolecular hydrogen bonds (HBs) in phenols and benzylammonium cations influence the dissociation enthalpies of their O-H and C-N bonds, respectively. The direction of these intramolecular HBs, para --> meta or meta --> para, determines the sign of the variation with respect to molecules lacking remote intramolecular HBs. For example, the O-H bond dissociation enthalpy of 3-methoxy-4-hydroxyphenol, 4, is about 2.5 kcal/mol lower than that of its isomer 3-hydroxy-4-methoxyphenol, 5, although group additivity rules would predict nearly identical values. In the case of 3-methoxy-4-hydroxybenzylammonium and 3-hydroxy-4-methoxybenzylammonium ions, the CBS-QB3 level calculated C-N eterolytic dissociation enthalpy is about 3.7 kcal/mol lower in the former ion. These effects are caused by the strong electron-withdrawing character of the -O(*) and -CH(2)(+) groups in the phenoxyl radical and benzyl cation, respectively, which modulates the strength of the HB. An O-H group in the para position of ArO(*) or ArCH(2)(+) becomes more acidic than in the parent molecules and hence forms stronger HBs with hydrogen bond acceptors (HBAs) in the meta position. Conversely, HBAs, such as OCH(3), in the para position become weaker HBAs in phenoxyl radicals and benzyl cations than in the parent molecules. These product thermochemistries are reflected in the transition states for, and hence in the kinetics of, hydrogen atom abstraction from phenols by free radicals (dpph(*) and ROO(*)). For example, the 298 K rate constant for the 4 + dpph(*) reaction is 22 times greater than that for the 5 + dpph(*) reaction. Fragmentation of ring-substituted benzylammonium ions, generated by ESI-MS, to form the benzyl cations reflects similar remote intramolecular HB effects.

Intramolecular and intermolecular hydrogen bond formation by some ortho-substituted phenols: some surprising results from an experimental and theoretical investigation.

The effects produced by addition of various concentrations of the strong hydrogen bond (HB) acceptor, dimethyl sulfoxide (DMSO), on the OH fundamental stretching region of the IR spectra of several o-methoxy, o-nitro, and o-carbonyl phenols in CCl(4) are reported. In most of these phenols the intramolecular HB is not broken by the DMSO. Instead, the DMSO acts as a HB acceptor to the intramolecular HB forming a bifurcated intra/intermolecular HB. For o-methoxyphenols the bifurcated HBs are observed as new IR bands at much lower wavenumbers (Deltanu(OH) approximately -300 cm(-1)) than the band due to their intramolecular HB. The formation of bifurcated HBs and the large frequency shift of their OH bands in o-methoxyphenols are well reproduced by theoretical modeling. In contrast to the o-methoxyphenols DMSO has little effect (other than causing some broadening) on the intramolecular HB OH bands of o-nitro and o-carbonyl phenols, with the single exception of 2,4-dinitrophenol. In this case, but not for 2,4-diformylphenol, the intramolecular HB OH band decreases as the DMSO concentration increases and a new absorption grows in at lower wavenumbers, indicating that DMSO can break this intra-HB and form an inter-HB, a result well reproduced by theory. Although DMSO has little effect on the O-H stretching band of 2-nitrophenol, theory indicates extensive formation (90%) of bifurcated HBs with OH stretching bands at slightly higher wavenumbers (Deltanu(OH) approximately +20 cm(-1)) than that for the intramolecular HB OH group and 10% of a "simple" intermolecular HB in which the intramolecular HB has been broken. Theory also indicates that, with DMSO, 2-formylphenol also forms a bifurcated HB (Deltanu(OH) approximately +150 cm(-1)), whereas 2,4-diformylphenol forms both intermolecular HBs (Deltanu(OH) approximately -130 cm(-1)) and bifurcated HBs (Deltanu(OH) approximately +165 cm(-1)). The IR spectrum of 2-methoxymethylphenol shows that although an intramolecular HB conformer is dominant there is a small percentage of a "free" OH, non-HB conformer (2.1% in CCl(4), 1.5% in cyclohexane). These results are quantitatively reproduced by theory. We conclude that theory can provide important insights into the formation and structure of inter, intra, and bifurcated HBs, and into their OH stretching frequencies, that are not always revealed by IR studies alone.

Reaction of phenols with the 2,2-diphenyl-1-picrylhydrazyl radical. Kinetics and DFT calculations applied to determine ArO-H bond dissociation enthalpies and reaction mechanism.

The formal H-atom abstraction by the 2,2-diphenyl-1-picrylhydrazyl (dpph(*)) radical from 27 phenols and two unsaturated hydrocarbons has been investigated by a combination of kinetic measurements in apolar solvents and density functional theory (DFT). The computed minimum energy structure of dpph(*) shows that the access to its divalent N is strongly hindered by an ortho H atom on each of the phenyl rings and by the o-NO(2) groups of the picryl ring. Remarkably small Arrhenius pre-exponential factors for the phenols [range (1.3-19) x 10(5) M(-1) s(-1)] are attributed to steric effects. Indeed, the entropy barrier accounts for up to ca. 70% of the free-energy barrier to reaction. Nevertheless, rate differences for different phenols are largely due to differences in the activation energy, E(a,1) (range 2 to 10 kcal/mol). In phenols, electronic effects of the substituents and intramolecular H-bonds have a large influence on the activation energies and on the ArO-H BDEs. There is a linear Evans-Polanyi relationship between E(a,1) and the ArO-H BDEs: E(a,1)/kcal x mol(-1) = 0.918 BDE(ArO-H)/kcal x mol(-1) - 70.273. The proportionality constant, 0.918, is large and implies a "late" or "product-like" transition state (TS), a conclusion that is congruent with the small deuterium kinetic isotope effects (range 1.3-3.3). This Evans-Polanyi relationship, though questionable on theoretical grounds, has profitably been used to estimate several ArO-H BDEs. Experimental ArO-H BDEs are generally in good agreement with the DFT calculations. Significant deviations between experimental and DFT calculated ArO-H BDEs were found, however, when an intramolecular H-bond to the O(*) center was present in the phenoxyl radical, e.g., in ortho semiquinone radicals. In these cases, the coupled cluster with single and double excitations correlated wave function technique with complete basis set extrapolation gave excellent results. The TSs for the reactions of dpph(*) with phenol, 3- and 4-methoxyphenol, and 1,4-cyclohexadiene were also computed. Surprisingly, these TS structures for the phenols show that the reactions cannot be described as occurring exclusively by either a HAT or a PCET mechanism, while with 1,4-cyclohexadiene the PCET character in the reaction coordinate is much better defined and shows a strong pi-pi stacking interaction between the incipient cyclohexadienyl radical and a phenyl ring of the dpph(*) radical.

Absolute rate constants for some intermolecular reactions of alpha-aminoalkylperoxyl radicals. Comparison with alkylperoxyls.

Seven alpha-aminoalkylperoxyl radicals have been generated by 355 nm laser flash photolysis (LFP) of oxygen-saturated di-tert-butyl peroxide containing mono-, di-, and trialkylamines and a dialkylarylamine. All these peroxyls possess absorptions in the near-UV (strongest for the trialkylamine-derived peroxyls) which permits direct monitoring of the kinetics of their reactions with many substrates. The measured rate constants for hydrogen atom abstraction from some phenols and oxygen atom transfer to triphenylphosphine demonstrated that all seven alpha-aminoalkylperoxyls have similar reactivities toward each specific substrate. More importantly, a comparison with literature data for alkylperoxyls shows that alpha-aminoalkylperoxyls and these alkylperoxyls have essentially the same reactivities. The combination of LFP and alkylamines provides a quick, reliable method for determining absolute rate constants for alkylperoxyl radical reactions, an otherwise laborious task.

A meta effect in nonphotochemical processes: the homolytic chemistry of m-methoxyphenol.

The m-methoxy group is normally electron-withdrawing (EW), sigma(m) = +0.12, sigma(m+) = +0.05. The strong EW activity of a phenoxyl radical's O* atom causes the m-methoxy group to become electron-donating (ED), sigma(m)(+) = -0.14. In valence bond terms, this can be ascribed to the nonclassical resonance structures 1c-e. Although it has long been known that m-methoxy is ED in photoexcited states, it has now been found to be ED for homolytic O-H bond breaking in ground-state 3-methoxyphenol.

Solvent effects on the rates and mechanisms of reaction of phenols with free radicals.

The rates of formal abstraction of phenolic hydrogen atoms by free radicals, Y* + ArOH --> YH + ArO*, are profoundly influenced by the hydrogen-bond-accepting and anion-solvation abilities of solvents, by the electron affinities and reactivities (Y-H bond dissociation enthalpies) of radicals, and by the phenol's ring substituents. These apparently simple reactions can occur by at least three different, nonexclusive mechanisms: hydrogen atom transfer, proton-coupled electron transfer, and sequential proton-loss electron transfer. The delicate balance among these mechanisms depends on both the environment and the reactants. The main features of these mechanisms are described, together with some interesting kinetic consequences.

The unexpected desulfurization of 4-aminothiophenols.

Thermolysis of 4-aminophenyl benzyl sulfide at 523 K in the hydrogen donor solvent (HDS), 9,10-dihydroanthracene (AnH2), gave 4-aminothiophenol and toluene as the predominant products of the homolytic S-C bond cleavage. Under these conditions, a portion of the 4-aminothiophenol was desulfurized to aniline with first-order kinetics and with a rate constant estimated by kinetic modeling to be 7.0x10(-6) s-1. Starting with 4-NH2C6H4SH at 523 K, it was found that sulfur loss was more efficient in the non-HDSs, anthracene and hexadecane, than in AnH2. Under similar (competitive) reaction conditions, YC6H4SHs with Y=H, 4-CN, and 3-CF3 were completely inert; with Y=4-CH3O, there was some very minor desulfurization, whereas with Y=4-N(CH3)2 and 4-N(CH3)(H), the sulfur extrusions were as fast as that for Y=4-NH2. We tentatively suggest that this apparently novel reaction is a chain process initiated by the bimolecular formation of diatomic sulfur, S2, followed by a reversible addition of ground state, triplet 3S2 to the thiol sulfur atom, 4-NH2C6H4S upward arrow(SS upward arrow)H, and insertion into the S-H bond, 4-NH2C6H4SSSH. In a cascade of reactions, aniline and S8 are formed with the chains being terminated by reaction of 4-NH2C6H4S upward arrow(SS upward arrow)H with 4-NH2C6H4SH. Such a reaction mechanism is consistent with the first-order kinetics. That this reaction is primarily observed with 4-YC6H4SH having Y=N(CH3)2, N(CH3)(H), and NH2 is attributed to the fact that these compounds can exist as zwitterions.

Bond strengths: the importance of hyperconjugation.

[Structure: see text] Gronert (J. Org. Chem. 2006, 71, 1209) has challenged the importance of hyperconjugation in determining C-H bond dissociation enthalpies (BDEs) in alkanes. Electron paramaganetic resonance spectra of H3CCH2*, (H3C)2CH*, and (H3C)3C* show significant positive spin on their beta-H3C groups' hydrogens. A 55%/45% partitioning of these spins between hyperconjugation and spin polarization mechanisms linearly correlates with the C-H BDEs in methane, ethane, propane, isobutane and propene. Hyperconjugation is an important factor determining alkane C-H BDEs.

Isomerization of triphenylmethoxyl and 1,1-diphenylethoxyl radicals. Revised assignment of the electron-spin resonance spectra of purported intermediates formed during the ceric ammonium nitrate mediated photooxidation of aryl carbinols.

Grossi and Strazzari have reported (J. Org. Chem. 2000, 65, 2748-2754) that the ceric ammonium nitrate modulated photooxidation of triphenylmethanol and 1,1-diphenylethanol yielded ESR spectra of the putative spiro-cyclohexadienyl intermediates in the O-neophyl rearrangements of the corresponding alkoxyl radicals, Ph2(R)CO* (R = Ph, CH3), to the phenoxymethyl radicals, Ph(R)C*OPh. Both ESR spectra are reassigned to the phenoxyl radical, C6H5O*, and the probable mechanism by which phenoxyl is formed in these systems is presented.