Reactions of hydroxyl radicals with trichloroethene and tetrachloroethene in argon matrices at 12 K

Irradiation of argon matrices at 12 K containing hydrogen peroxide and tetrachloroethene using the output from a medium-pressure mercury lamp gives rise to the carbonyl compound trichloroacetyl chloride (CCl3CClO). Similarly trichloroethene gives dichloroacetyl chloride ( CCl2HCClO) - predominantly in the gauche form - under the same conditions. It appears that the reaction is initiated by homolysis of the O-O bond of H2O2 to give OH radicals, one of which adds to the double bond of an alkene molecule. The reaction then proceeds by abstraction of the H atom of the hydroxyl group and Cl-atom migration. This mechanism has been explored by the use of DFT calculations to back up the experimental findings. The mechanism is analogous to that shown by the simple hydrocarbon alkenes.

In vivo transformations of dihydro-epi-deoxyarteannuin B in Artemisia annua plants

[15-(CH3)-C-13-H-2]-dihydro-epi-deoxyarteannuin B (4a) has been fed to intact Artemisia annua plants via the root and three labeled metabolites (17a-19a) have been identified by 1D- and 2D-NMR spectroscopies. The in vivo transformations of 4a in A. annua are proposed to involve enzymatically-mediated processes in addition to possible spontaneous autoxidation. In the hypothetical spontaneous autoxidation pathway, the tri-substituted double bond in 4a appears to have undergone 'ene-type' reaction with oxygen to form an allylic hydroperoxide, which subsequently rearranges to the allylic hydroxyl group in the metabolite 3 alpha-hydroxy-dihydro-epi-deoxyarteannuin B (17a). In the enzymatically-mediated pathways, compound 17a has then been converted to its acetyl derivative, 3 alpha-acetoxy-dihydro-epi-deoxyarteannuin B (18a), while oxidation of 4a at the 'unactivated' 9-position has yielded 9 beta-hydroxy-dihydro-epi-deoxyarteannuin B (19a). Although all of the natural products artemisinin ( 1), arteannuin K ( 7), arteannuin L ( 8), and arteannuin M ( 9) have been suggested previously as hypothetical metabolites from dihydro-epi-deoxyarteannuin B in A. annua, none were isolated in labeled form in this study. It is argued that the nature of the transformations undergone by compound 4a are more consistent with a degradative metabolism, designed to eliminate this compound from the plant, rather than with a role as a late precursor in the biosynthesis of artemisinin or other natural products from A. annua. (C) 2007 Elsevier Ltd. All rights reserved.

A synthetic route to fully substituted chiral cyclopentylamine derivatives: precursors of carbanucleosides

Removal of silyl protection from D-glucose derived substrate 6 afforded 7, which upon acetonide deprotection followed by reaction with N-benzylhydroxylamine furnished two isomeric isoxazolidinocyclopentane derivatives via spontaneous cyclization of an in situ generated nitrone. The methyl xanthate derivative of the tertiary hydroxyl group of one isomer was isolated and subjected to radical deoxygenation reaction to form epimeric products, while with the other isomer it underwent spontaneous 1,2-elimination to form a mixture of the two possible endocyclic olefins. Hydrogenolytic cleavage of the isoxazolidine rings of the purified products followed by insertion of 5-amino-4-chloropyrimidine moiety and purine ring construction smoothly afforded structurally unique carbanucleoside analogues. Various spectroscopic methods on the synthesized compounds and X-ray analysis on one important intermediate were used to assign the structures and stereochemistry of the products.

A ferromagnetic methoxido-bridged Mn(III) dimer and a spin-canted metamagnetic μ1,3-azido-bridged chain

Two new Mn(III) complexes of formulas [MnL1(N-3)(OMe)](2) (1) and [MnL2(N-3)(2)](n) (2) have been synthesized by using two tridentate NNO-donor Schiff base ligands HL1{(2-[(3-methylaminoethylimino)-methyl]-phenol)} and HL2 {(2-[1-(2-dimethylaminoethylimino)methyl]-phenol)}, respectively. Substitution of the H atom on the secondary amine group of the N-methyldiamine fragment of the Schiff base by a methyl group leads to a drastic structural change from a methoxido-bridged dimer (1) to a single mu(1,3)-azido-bridged 1D helical polymer (2). Both complexes were characterized by single-crystal X-ray structural analyses and variable-temperature magnetic susceptibility measurements. The magnetic properties of compound I show the presence of weak ferromagnetic exchange interactions mediated by double methoiddo bridges (J = 0.95 cm(-1)). Compound 2 shows the existence of a weak antiferromangetic coupling along the chain (J = -8.5 cm(-1)) through the single mu(1,3)-N-3 bridge with a spin canting that leads to a long-range antiferromagnetic order at T-c approximate to 9.3 K and a canting leading to a weak ferromagnetic long-range order at T-c approximate to 8.5 K. It also exibits metamagnetic behavior at low temperatures with a critical field of ca.1.2 T due to the weak antiferromagnetic interchain interactions that appear in the canted ordered phase.

Interaction of anthocyanins with human serum albumin: influence of pH and chemical structure on binding

The affinity of anthocyanins for human serum albumin (HSA) was determined by a fluorescence quenching method. The effects of pH and structure of anthocyanins on the binding constants were studied. The constants for binding of anthocyanins to HSA ranged from 1.08 x 10^5 M-1 to 13.16 x 10^5 M-1. A hydrophobic effect at acidic pH was shown by the relatively high positive entropy values under the conditions studied. Electrostatic interactions including hydrogen bonding contributed to the binding at pH 7.4. The effect of structure of anthocyanins on the affinity was pH dependent, particularly the effect of additional hydroxyl substituents. Hydroxyl substituents and glycosylation of anthocyanins decreased the affinity for binding to HSA at lower pH (especially pH 4), but increased the strength of binding at pH 7.4. In contrast, methylation of a hydroxyl group enhanced the binding at acidic pH, while this substitution reduced the strength of binding at pH 7.4. This paper has shown that changes in anthocyanin structure or reductions in pH, which may occur in the region of inflammatory sites, have an effect of the binding of anthocyanins to HSA.

Origin and evolution of 3'UTR of flaviviruses: long direct repeats as a basis for the formation of secondary structures and their significance for virus transmission

The 3' untranslated regions (3'UTRs) of flaviviruses are reviewed and analyzed in relation to short sequences conserved as direct repeats (DRs). Previously, alignments of the 3'UTRs have been constructed for three of the four recognized flavivirus groups, namely mosquito-borne, tick-borne, and nonclassified flaviviruses (MBFV, TBFV, and NCFV, respectively). This revealed (1) six long repeat sequences (LRSs) in the 3'UTR and open-reading frame (ORF) of the TBFV, (2) duplication of the 3'UTR of the NCFV by intramolecular recombination, and (3) the possibility of a common origin for all DRs within the MBFV. We have now extended this analysis and review it in the context of all previous published analyses. This has been achieved by constructing a robust alignment between all flaviviruses using the published DRs and secondary RNA structures as "anchors" to reveal additional homologies along the 3'UTR. This approach identified nucleotide regions within the MBFV, NKV (no-known vector viruses), and NCFV 3'UTRs that are homologous to different LRSs in the TBFV 3'UTR and ORF. The analysis revealed that some of the DRs and secondary RNA structures described individually within each flavivirus group share common evolutionary origins. The 3'UTR of flaviviruses, and possibly the ORF, therefore probably evolved through multiple duplication of an RNA domain, homologous to the LRS previously identified only in the TBFV. The short DRs in all virus groups appear to represent the evolutionary remnants of these domains rather than resulting from new duplications. The relevance of these flavivirus DRs to evolution, diversity, 3'UTR enhancer function, and virus transmission is reviewed.

Truancy in secondary pupils: prevalance, trajectories and pupil perspectives

School absenteeism and particularly unauthorized absenteeism or truancy has been the focus of a number of, so far largely unsuccessful, recent policy initiatives. The paper draws upon two sources of data, the British Household Panel Survey and detailed interviews with a group of persistent truants, to consider the extent, consequences and explanations for truancy from secondary schools. Truancy increases steadily across the years of secondary school and, especially in the later years of compulsory schooling there is evidence that patterns of truancy established in one year carry on into the next. Truancy is strongly associated with negative outcomes in terms of not staying in education post-16, GCSE results and becoming unemployed. Coming from families of low socio-economic status, parents not monitoring homework, negative attitudes towards teachers and the value of education are all associated with higher levels of truancy. However, the majority of young people in these situations do not truant and there are many truants who do not have these characteristics. A major explanation given by young people themselves for their non-attendance is poor relationships with teachers, including teachers failing to match their expectations. Other factors mentioned by young people include bullying but also a more general dislike of the atmosphere of the school, sometimes associated with a change of school. There was little evidence of negative responses to the curriculum leading to truancy. It is suggested that we can distinguish between socio-economic and attitudinal factors which make young people vulnerable to truancy and precipitating events or processes which result in truanting behaviour.

Intensive case management for severe psychotic illness: is there a general benefit for patients with complex needs? A secondary analysis of the UK700 trial data

The UK700 trial failed to demonstrate an overall benefit of intensive case management (ICM) in patients with severe psychotic illness. This does not discount a benefit for particular subgroups, and evidence of a benefit of ICM for patients of borderline intelligence has been presented. The aim of this study is to investigate whether this effect is part of a general benefit for patients with severe psychosis complicated by additional needs. In the UK700 trial patients with severe psychosis were randomly allocated to ICM or standard case management. For each patient group with complex needs the effect of ICM is compared with that in the rest of the study cohort. Outcome measures are days spent in psychiatric hospital and the admission and discharge rates. ICM may be of benefit to patients with severe psychosis complicated by borderline intelligence or depression, but may cause patients using illicit drugs to spend more time in hospital. There was no convincing evidence of an effect of ICM in a further seven patient groups. ICM is not of general benefit to patients with severe psychosis complicated by additional needs. The benefit of ICM for patients with borderline intelligence is an isolated effect which should be interpreted cautiously until further data are available.

Influence of a non-ionic amphiphilic copolymer on the self-assembly of a peptide amphiphile that forms nanotapes

The influence of a non-ionic polymeric surfactant on the self-assembly of a peptide amphiphile (PA) that forms nanotapes is investigated using a combination of microscopic, scattering and spectroscopic techniques. Mixtures of Pluronic copolymer P123 with the PA C16-KTTKS in aqueous solution were studied at a fixed concentration of the PA at which it is known to self-assemble into extended nanotapes, but varying P123 concentration. We find that P123 can disrupt the formation of C16- KTTKS nanotapes, leading instead to cylindrical nanofibril structures. The spherical micelles formed by P123 at room temperature are disrupted in the presence of the PA. There is a loss of cloudiness in the solutions as the large nanotape aggregates formed by C16-KTTKS are broken up, by P123 solubilization. At least locally, b-sheet structure is retained, as confirmed by XRD and FTIR spectroscopy, even for solutions containing 20 wt% P123. This indicates, unexpectedly, that peptide secondary structure can be retained in solutions with high concentration of non-ionic surfactant. Selfassembly in this system exhibits slow kinetics towards equilibrium, the initial self-assembly being dependent on the order of mixing. Heating above the lipid chain melting temperature assists in disrupting trapped non-equilibrium states.

A brief cognitive-behavioural intervention for pain reduces secondary hyperalgesia

Repeated exposure to pain can result in sensitization of the central nervous system, enhancing subsequent pain and potentially leading to chronicity. The ability to reverse this sensitization in a top-down manner would be of tremendous clinical benefit, but the degree that this can be accomplished volitionally remains unknown. Here we investigated whether a brief (~5 min) cognitive-behavioural intervention could modify pain perception and reduce central sensitization (as reflected by secondary hyperalgesia). In each of 8 sessions, 2 groups of healthy human subjects received a series of painful thermal stimuli that resulted in secondary hyperalgesia. One group (regulate) was given brief pain-focused cognitive training at each session, while the other group (control) received a non-pain-focused intervention. The intervention selectively reduced pain unpleasantness but not pain intensity in the regulate group. Furthermore, secondary hyperalgesia was significantly reduced in the regulate group compared with the control group. Reduction in secondary hyperalgesia was associated with reduced pain catastrophizing, suggesting that changes in central sensitization are related to changes in pain-related cognitions. Thus, we demonstrate that central sensitization can be modified volitionally by altering pain-related thoughts.