Detection of companion galaxies around hot dust-obscured hyper-luminous galaxy W0410-0913.

The phase transition between galaxies and quasars is often identified with the rare population of hyper-luminous, hot dust-obscured galaxies. Galaxy formation models predict these systems to grow via mergers, that can deliver large amounts of gas toward their centers, induce intense bursts of star formation and feed their supermassive black holes. Here we report the detection of 24 galaxies emitting Lyman-α emission on projected physical scales of about 400 kpc around the hyper-luminous hot dust-obscured galaxy W0410-0913, at redshift z = 3.631, using Very Large Telescope observations. While this indicates that W0410-0913 evolves in a very dense environment, we do not find clear signs of mergers that could sustain its growth. Data suggest that if mergers occurred, as models expect, these would involve less massive satellites, with only a moderate impact on the internal interstellar medium of W0410-0913, which is sustained by a rotationally-supported fast-rotating molecular disk, as Atacama Large Millimeter Array observations suggest.

Structured education using Dose Adjustment for Normal Eating (DAFNE) reduces long-term HbA1c and HbA1c variability.

AIMS: Previous evidence has demonstrated that participation in the Dose Adjustment for Normal Eating (DAFNE) education programme can reduce HbA1c and severe hypoglycaemia in people with Type 1 diabetes. In a number of studies, increased HbA1c variability has been associated with higher diabetic morbidity and mortality. No studies have examined the impact of structured education on HbA1c variability in Type 1 diabetes. METHODS: People with Type 1 diabetes who had attended DAFNE were identified for inclusion from the Scottish Care Information-Diabetes dataset. HbA1c median and variability, expressed as coefficient of variation (CV) before and after DAFNE was calculated. RESULTS: Some 1061 individuals participated in DAFNE education and 687 met the inclusion criteria. A significant median reduction in HbA1c [-3.5 mmol/mol (-0.3%)] was seen at 12 months with a significant reduction [-1.5 mmol/mol (-0.1%)] still seen at 60 months of follow-up. HbA1c variability as measured by CV was significantly lower during the post-DAFNE period: 0.08 (IQR 0.05-0.12) reduced to 0.07 (IQR 0.05-0.10); P = 0.002. CONCLUSION: The data confirm that DAFNE participation improves glycaemic control in Type 1 diabetes with benefits being sustained for 5 years. This study is the first to demonstrate reduced HbA1c variability after completion of structured education. This is new evidence of the beneficial impact of DAFNE on glycaemic profile.

HbA1c variability is associated with increased mortality and earlier hospital admission in people with Type 1 diabetes.

AIM: Despite evidence of morbidity, no evidence exists on the relationship between HbA1c variability and mortality in Type 1 diabetes. We performed an observational study to investigate whether the association between HbA1c variability and mortality exists in a population of people with Type 1 diabetes. As a secondary outcome, we compared onset of first hospital admission between groups. METHODS: People with Type 1 diabetes were identified for inclusion from the Scottish Care Information - Diabetes data set. This database includes data of all people known to have diabetes who live within Scotland. A survival analysis was carried out over a 47-month period comparing two groups; group 1 with a HbA1c coefficient of variation (CV) above the median CV value, and group 2 with a CV below the median value. Time to death or first admission was also analysed. A Cox proportional hazard model was used to compare time to death, adjusting for appropriate covariables. RESULTS: Some 6048 individuals with Type 1 diabetes were included in the analysis. Median HbA1c CV was 7.9. The hazard ratio (HR) for mortality for those with an HbA1c CV above the median value is 1.5 over 47 months of follow-up (P < 0.001). HR for survival to either the first admission to hospital or death for those with an HbA1c CV above the median value was 1.35 (95% confidence interval 1.25-1.45) over 730 days of follow-up (P < 0.001). CONCLUSION: Our results show that people with greater HbA1c variability have a higher rate of mortality and earlier hospital admission in Type 1 diabetes.

Trends in recorded capillary blood glucose and hypoglycaemia in hospitalised patients with diabetes.

AIMS: To utilise whole-system analysis of capillary glucose measurement results to examine trends in timing of glucose monitoring, and to investigate whether these timings are appropriate based on observed patterns of hypoglycaemia. METHODS: Near-patient capillary blood glucose results from eight acute hospitals collected over 57 months were analysed. Analysis of frequency of measurement, and measurements in the hypoglycaemic (<4mmol/l) and severe hypoglycaemic (<2.5mol/l) range per time of day was made. RESULTS: 3345241 capillary glucose measurements were analysed. 1657594 capillary blood glucose values were associated with 106624 admissions in those categorised as having diabetes. Large peaks in frequency of glucose measurements occurred before meals, with the highest frequency of capillary glucose measurement activity being seen pre-breakfast. Overnight, an increase in measurement activity was seen each hour. This pattern was mirrored by frequency of measured hypoglycaemia. 27968 admissions (26.2%) were associated with at least one hypoglycaemic measurement. A greater proportion of measurements were within the hypoglycaemic range overnight with 61.7% of all hypoglycaemia between 2100 and 0900h, with peak risk of measured capillary glucose being hypoglycaemic between 0300 and 0400h. CONCLUSIONS: Hypoglycaemic is common with the greatest risk of hypoglycaemia overnight and a peak percentage of all readings taken being in the hypoglycaemic range between 0300 and 0400h. Measurement activity overnight was driven by routine, with patterns of proportion of measurements in the hypoglycaemic range indicating that there may be a significant burden of undiscovered hypoglycaemia in the patients not routinely checked overnight.

Reactive oxygen species generated in the presence of fine pyrite particles and its implication in thermophilic mineral bioleaching.

In the tank bioleaching process, maximising solid loading and mineral availability, the latter through decreasing particle size, are key to maximising metal extraction. In this study, the effect of particle size distribution on bioleaching performance and microbial growth was studied through applying knowledge based on medical geology research to understand the adverse effects of suspended fine pyrite particles. Small-scale leaching studies, using pyrite concentrate fractions (106-75, 75-25, -25 µm fines), were used to confirm decreasing performance with decreasing particle size (D 50 <40 µm). Under equivalent experimental conditions, the generation of the reactive oxygen species (ROS), hydrogen peroxide and hydroxyl radicals from pyrite was illustrated. ROS generation measured from the different pyrite fractions was found to increase with increasing pyrite surface area loading (1.79-74.01 m(2) L(-1)) and Fe(2+) concentration (0.1-2.8 g L(-1)) in solution. The highest concentration of ROS was measured from the finest fraction of pyrite (0.85 mM) and from the largest concentration of Fe(2+) (0.78 mM). No ROS was detected from solutions containing only Fe(3+) under the same conditions tested. The potential of ROS to inhibit microbial performance under bioleaching conditions was demonstrated. Pyrite-free Sulfolobus metallicus cultures challenged with hydrogen peroxide (0.5-2.5 mM) showed significant decrease in both cell growth and Fe(2+) oxidation rates within the concentration range 1.5-2.5 mM. In combination, the results from this study suggest that conditions of large pyrite surface area loading, coupled with high concentrations of dissolved Fe(2+), can lead to the generation of ROS, resulting in oxidative stress of the microorganisms.

Cyclic loading of tendon fascicles using a novel fatigue loading system increases interleukin-6 expression by tenocytes.

Repetitive strain or 'overuse' is thought to be a major factor contributing to the development of tendinopathy. The aims of our study were to develop a novel cyclic loading system, and use it to investigate the effect of defined loading conditions on the mechanical properties and gene expression of isolated tendon fascicles. Tendon fascicles were dissected from bovine-foot extensors and subjected to cyclic tensile strain (1 Hz) at 30% or 60% of the strain at failure, for 0 h (control), 15 min, 30 min, 1 h, or 5 h. Post loading, a quasi-static test to failure assessed damage. Gene expression at a selected loading regime (1 h at 30% failure strain) was analyzed 6 h post loading by quantitative real-time polymerase chain reaction. Compared with unloaded controls, loading at 30% failure strain took 5 h to lead to a significant decrease in failure stress, whereas loading to 60% led to a significant reduction after 15 min. Loading for 1 h at 30% failure strain did not create significant structural damage, but increased Collagen-1-alpha-chain-1 and interleukin-6 (IL6) expression, suggesting a role of IL6 in tendon adaptation to exercise. Correlating failure properties with fatigue damage provides a method by which changes in gene expression can be associated with different degrees of fatigue damage.

AMP-activated protein kinase is activated in adipose tissue of individuals with type 2 diabetes treated with metformin: a randomised glycaemia-controlled crossover study.

AIMS/HYPOTHESIS: The hypoglycaemic actions of metformin have been proposed to be mediated by hepatic AMP-activated protein kinase (AMPK). As the effects of metformin and the role of AMPK in adipose tissue remain poorly characterised, we examined the effect of metformin on AMPK activity in adipose tissue of individuals with type 2 diabetes in a randomised glycaemia-controlled crossover study. METHODS: Twenty men with type 2 diabetes (aged 50-70 years) treated with diet, metformin or sulfonylurea alone were recruited from North Glasgow University National Health Service Trusts' diabetes clinics and randomised to either metformin or gliclazide for 10 weeks. Randomisation codes, generated by computer, were put into sealed envelopes and stored by the hospital pharmacist. Medication bottles were numbered, and allocation was done in sequence. The participants and investigators were blinded to group assignment. At the end of each phase of therapy adipose biopsy, AMPK activity (primary endpoint) and levels of lipid metabolism and signalling proteins were assessed. In parallel, the effect of metformin on AMPK and insulin-signalling pathways was investigated in 3T3-L1 adipocytes. RESULTS: Ten participants were initially randomised to metformin and subsequently crossed over to gliclazide, while ten participants were initially randomised to gliclazide and subsequently crossed over to metformin. No participants discontinued the intervention and the adipose tissue AMPK activity was analysed in all 20 participants. There were no adverse events or side effects in the study group. Adipose AMPK activity was increased following metformin compared with gliclazide therapy (0.057 ± 0.007 vs 0.030 ± 0.005 [mean ± SEM] nmol min(-1) [mg lysate](-1); p < 0.005), independent of AMPK level, glycaemia or plasma adiponectin concentrations. The increase was associated with reduced levels of acetyl-CoA carboxylase (ACC) protein and increased ACC Ser80 phosphorylation. In 3T3-L1 adipocytes, metformin reduced levels of ACC protein and stimulated phosphorylation of AMPK Thr172 and hormone-sensitive lipase Ser565. CONCLUSIONS: These results provide the first evidence that metformin activates AMPK and reduces ACC protein levels in human adipose tissue in vivo. Future studies are required to assess the role of adipose AMPK activation in the pharmacological effects of metformin. TRIAL REGISTRATION: ISRCTN51336867.

The multi-element content of the lichen Parmelia sulcata, soil, and oak bark in relation to acidification and climate.

Understanding how biodiversity is influenced by changing atmospheric conditions is important for conservation, public policy and environmental health. In a recent study, an impact on two of the most abundant lichens in Europe (Parmelia sulcata and Hypogymnia physodes) was recorded at Burnham Beeches lying 40 km west of London (UK) during unusual atmospheric conditions whilst other species remained unaffected. Bark and soil chemistry also influence lichen vitality and community composition. Correlations between element concentrations and element ratios in different samples help understand element cycling. To study this further, the multi-element content of the lichen P. sulcata and bark sampled in 2000 from 16 oak (Quercus robur) trees at Burnham Beeches was compared with the same elements determined in 24 surface soils sampled in 2005 from beneath the same trees. Soil pH ranged from 4.1 to 6.7. Highly significant correlations (p<0.001) for Mn/Ca ratios in lichen versus bark, soil versus bark and soil versus lichen samples confirmed cycling via the soil-tree-lichen system. Similar Mn/Ca ratios were reported in coniferous forests where high Mn concentrations were shown to limit epiphytic lichen abundance. Soil acidification influences element bioavailability and bark chemistry in Burnham Beeches with implications for lichen diversity and health. Recovery was recorded in P. sulcata, including regeneration within monitoring quadrats. Biological systems are well known to be influenced by pollution episodes.

Biogeochemical signatures in the lichen Hypogymnia physodes in the mid Urals.

Multi-element content and uranium (U) isotopes were investigated in the lichen Hypogymnia physodes (native and transplants) sampled across a 60-km transect, centred on Karabash smelter town, from Turgoyak Lake (SW) to Kyshtym (NE) to investigate the origin of U. Kyshtym was the site of a major nuclear accident in 1957. (234)U/(238)U activity ratios in native thalli sampled during July 2001 were within the natural isotopic ratio in minerals. Uranium/thorium (U/Th) ratios were higher in native thalli towards the NE (average 0.73) than those in the SW (average 0.57). Element signatures in native thalli and transplants suggest U was derived from fossil fuel combustion from Karabash and sources lying further to the east. Systematic and significant U enrichment indicative of a nuclear fuel cycle source was not detected in any sample. Element signatures in epiphytic lichen transplants and native thalli provide a powerful method to evaluate U deposition.

Biomonitoring using the lichen Hypogymnia physodes and bark samples near Zlatna, Romania immediately following closure of a copper ore-processing plant.

Lichen transplants were established along a 40km transect centred on a large mine waste dump close to Zlatna town centre, two weeks after closure of a major industrial source, to compare spatial patterns of element concentrations in lichen and bark samples. After 3 months of exposure, spatial patterns of 4 element concentrations (Pb, Cu, Zn and Fe) in transplants confirmed deposition due to a point source 'Zlatna influence'. Cu and Pb reached concentrations 8 and 4 times, respectively, higher than samples transplanted in the 'background' site, and over 200 (Cu) and 2000 (Pb) times higher relative to 'background' bark. Ten out of 15 elements analysed reached highest concentrations in bark. Spatial patterns confirmed long-term pollution for 6 elements (Pb, S, Fe, Cu, Zn and Ba). The study provides a model baseline to monitor recovery following closure of major industrial sources and highlights the importance of considering biogeochemical processes when interpreting metal concentrations.

Characterisation of airborne particulate pollution in the Cu smelter and former mining town of Karabash, South Ural Mountains of Russia.

Airborne total suspended particulates (TSP), dusts from smelter blast furnace and converter stacks, and filtrates of snow melt waters have been characterised in the Cu smelter and former mining town of Karabash, Russia. TSP was collected at sites up- and downwind of the smelter and large waste and tailings dumps (Oct. 2000 and July 2001). Methods for particle size, mineralogical and elemental determinations have been tested and described, and a new PSD-MicroSOURCE XRD technique developed for the mineralogical analysis of microsamples on filter substrates. TSP in downwind samples has a mean equivalent spherical diameter of 0.5 microm (s.d. = 0.2) and was found to be 100% respirable. The main element of human health/environmental concern, above Russian maximum permitted levels (1 microg m(-3), average over any time period), was Pb which was measured at 16-30 microg m(-3) in downwind samples. Individual particulates mainly consisted of complex mixtures of anglesite (PbSO4), Zn2SnO4 and poorly ordered Zn sulphates. From experimental and theoretical considerations, a high proportion of contained Pb, Zn, Cd and As in this material is considered to be in a readily bioavailable form. Chemical and mineralogical differences between the TSP, stack dusts and snow samples are discussed, as well as the implications for human and regional environmental health.

Which factors are responsible for the changing lichen floras of London?

SO(2) is no longer the principal factor influencing the vitality and composition of lichen assemblages in London. We provide direct evidence for an impact on lichen growth during episodic high exhaust emissions coupled with unusual climatic conditions. This suggests a combination of particles and nitrogen plays a major role in influencing lichen growth. Nitrogen from traffic emissions may be at least as important as agriculture in influencing the composition of lichen assemblages.

Structural and mechanistic studies on the activation and propagation of a cationic allylpalladium procatalyst in 1,6-diene cycloisomerization.

[Pd(eta3-C3H5)(MeCN)2]OTf acts as an efficient procatalyst for the cycloisomerisation of dimethyl hept-1,6-dienyl-4,4-dicarboxylate (1a) in CHCl3. The reaction displays a pronounced and variable induction period and gives dimethyl 3-methylene-4-methylcyclopentane-1,1-dicarboxylate (2a) as the kinetic product. The thermodynamically more favourable tri- and tetra-substituted alkenes dimethyl 3,4-dimethylcylopent-2-ene-1,1-dicarboxylate (3a) and dimethyl 3,4-dimethylcylopent-3-ene-1,1-dicarboxylate (4a) are also generated directly (3a) or by isomerisation (3a and 4a) of 2a. The mechanism of procatalyst activation and the ensuing cycloisomerisation reaction was investigated by NMR spectroscopy (1H, 2H, 13C) and GC analysis of the products arising from isotopically labelled substrates (13C, 2H). Three general mechanisms were considered: hydrometallation, cyclometallation and C-H insertion. These last two were shown to be incompatible with the results. The first, which involves generation and propagation of a palladium hydride species ("Pd-H"), was found to be consistent with both the isotopic distribution and stereochemistry of the reaction product and is supported by the observation of intermolecular transfer of a single 2H label. Due to the high catalytic activity of the palladium hydride and its slow generation, the cycloisomerisation process ultimately yields a mixture of alkene products (2a, 3a and 4a) with incomplete consumption of the procatalyst [Pd(eta3-C3H5)(MeCN)2]OTf. The mechanism by which the catalytically active palladium hydride is generated from the procatalyst was studied in detail by NMR spectroscopic analysis of stoichiometric reactions between diene 1a and [Pd(eta3-C3H5)(MeCN)2]OTf. This demonstrated that a carbopalladated complex, namely, [Pd[7,7-(CO2Me)2-(1,2,5,9,10-eta5)-dec-1,9-diene)](OTf)] (15a), is formed in small quantities by unfavourable displacement of acetonitrile by the diene, followed by a rapid and irreversible beta-migratory insertion reaction. Although attempts to isolate 15a from the reaction mixture were not successful (due to its slow decomposition, low concentration and competing cycloisomerisation), an alternative synthesis in the absence of acetonitrile allowed its isolation and characterisation. However, pure samples of 15a are completely ineffective as a procatalyst system for cycloisomerisation of 1a. Further investigation revealed that treatment of 15a with one equivalent of water results in quantitative beta-H elimination to generate triene 16a (C(1)-allylated 1a). Thus, addition of catalytic quantities of water to a solution of 1a in CHCl3 containing 5 mol% 15a and 10 mol% MeCN results in generation of an active "Pd-H" catalyst for cycloisomerisation. Although procatalyst activation is facilitated by traces of water, no exchange of protons is observed between "Pd-H" and H2O under catalytic turnover. The slow generation of 15a and the requirement for traces of water for beta-H elimination accounts for variability in the induction period when [Pd(eta3-C3H5)(MeCN)2]OTf is employed as procatalyst.

Synthesis and stereochemistry of some bicyclic gamma-lactones from parasitic wasps (Hymenoptera: Braconidae). Utility of hydrolytic kinetic resolution of epoxides and palladium(II)-catalyzed hydroxycyclization-carbonylation-lactonization of ene-diols.

A palladium(II)-catalyzed hydroxycyclization-carbonylation-lactonization sequence with appropriate pent-4-ene-1,3-diols provides efficient access to the bicyclic gamma-lactones, 5-n-butyl- and 5-n-hexyltetrahydrofuro-[3,2-b]furan-2(3H)-ones (3) and (4), respectively, in both racemic and enantiomeric forms. Some of the substrate pent-4-ene-1,3-diols of high enantiomeric excess (ee) have been derived from racemic terminal epoxides by hydrolytic kinetic resolution (HKR) using cobalt (III)-salen complexes. (9Z,12R)-(+)-Ricinoleic acid also serves as a "chiral pool" source of other pent-4-ene-1,3-diols. These syntheses and enantioselective gas chromatography confirm the structures and absolute stereochemistry of the lactones in some species of parasitic wasps (Hymenoptera: Braconidae). The highly abundant 5-n-hexyltetrahydrofuro-[3,2-b]furan-2(3H)-one (4) in Diachasmimorpha kraussii and D. longicaudata is of high ee (>99%) with (3aR,5R,6aR) stereochemistry.

Endothelium-derived hyperpolarizing factor and potassium use different mechanisms to induce relaxation of human subcutaneous resistance arteries.

This investigation examined the hypothesis that release of K(+) accounts for EDHF activity by comparing relaxant responses produced by ACh and KCl in human subcutaneous resistance arteries. Resistance arteries (internal diameter 244+/-12 microm, n=48) from human subcutaneous fat biopsies were suspended in a wire myograph. Cumulative concentration-response curves were obtained for ACh (10(-9) - 3x10(-5) M) and KCl (2.5 - 25 mM) following contraction with noradrenaline (NA; 0.1 - 3 microM). ACh (E(max) 99.07+/-9.61%; -LogIC(50) 7.03+/-0.22; n=9) and KCl (E(max) 74.14+/-5.61%; -LogIC(50) 2.12+/-0.07; n=10)-induced relaxations were attenuated (P<0.0001) by removal of the endothelium (E(max) 8.21+/-5.39% and 11.56+/-8.49%, respectively; n=6 - 7). Indomethacin (10 microM) did not alter ACh-induced relaxation whereas L-NOARG (100 microM) reduced this response (E(max) 61.7+/-3.4%, P<0.0001; n=6). The combination of ChTx (50 nM) and apamin (30 nM) attenuated the L-NOARG-insensitive component of ACh-induced relaxation (E(max): 15.2+/-10.5%, P<0.002, n=6) although these arteries retained the ability to relax in response to 100 microM SIN-1 (E(max) 127.6+/-13.0%, n=3). Exposure to BaCl(2) (30 microM) and Ouabain (1 mM) did not attenuate the L-NOARG resistant component of ACh-mediated relaxation (E(max), 76.09+/-8.92, P=0.16; n=5). KCl-mediated relaxation was unaffected by L-NOARG+indomethacin (E(max); 68.1+/-5.6%, P=0.33; n=5) or the combination of L-NOARG/indomethacin/ChTx/apamin (E(max); 86.61+/-14.02%, P=0.35; n=6). In contrast, the combination of L-NOARG, indomethacin, ouabain and BaCl(2) abolished this response (E(max), 5.67+/-2.59%, P<0.0001, n=6). The characteristics of KCl-mediated relaxation differed from those of the nitric oxide/prostaglandin-independent component of the response to ACh, and were endothelium-dependent, indicating that K(+) does not act as an EDHF in human subcutaneous resistance arteries.

Understanding the role of glucocorticoids in obesity: tissue-specific alterations of corticosterone metabolism in obese Zucker rats.

The role of glucocorticoids in obesity is poorly understood. Observations in obese men suggest enhanced inactivation of cortisol by 5alpha-reductase and altered reactivation of cortisone to cortisol by 11betahydroxysteroid dehydrogenase type 1 (11betaHSD1). These changes in glucocorticoid metabolism may influence corticosteroid receptor activation and feedback regulation of the hypothalamic-pituitary-adrenal axis (HPA). We have compared corticosterone metabolism in vivo and in vitro in male obese and lean Zucker rats, aged 9 weeks (n = 8/group). Steroids were measured in 72-h urine and 0900 h trunk blood samples. 5alpha-Reductase type 1 and 11betaHSD activities were assessed in dissected tissues. Obese animals were hypercorticosteronemic and excreted more total corticosterone metabolites (2264+/-623 vs. 388+/-144 ng/72 h; P = 0.003), with a greater proportion being 5alpha-reduced or 11-oxidized. 11-Dehydrocorticosterone was also elevated in plasma (73+/-9 vs. 18+/-2 nM; P = 0.001) and urine (408+/-111 vs. <28 ng/72 h; P = 0.01). In liver of obese rats, 5alpha-reductase type 1 activity was greater (20.6+/-2.7% vs. 14.1+/-1.5%; P<0.04), but 11betaHSD1 activity (maximum velocity, 3.43+/-0.56 vs. 6.57+/-1.13 nmol/min/mg protein; P = 0.01) and messenger RNA levels (0.56+/-0.08 vs. 1.03+/-0.15; P = 0.02) were lower. In contrast, in obese rats, 11betaHSD1 activity was not different in skeletal muscle and sc fat and was higher in omental fat(36.4+/-6.2 vs. 19.2+/-6.6; P = 0.01), whereas 11betaHSD2 activity was higher in kidney (16.7+/-0.6% vs. 11.3+/-1.5%; p = 0.01). We conclude that greater inactivation of glucocorticoids by 5alpha-reductase in liver and 11betaHSD2 in kidney combined with impaired reactivation of glucocorticoids by 11betaHSD1 in liver may increase the MCR of glucocorticoids and decrease local glucocorticoid concentrations at these sites. By contrast, enhanced 11betaHSD1 in omental adipose tissue may increase local glucocorticoid receptor activation and promote obesity.

Entropy-driven hydrogen bonding: stereodynamics of a protonated, N,N-chiral "proton sponge".

The C2-symmetric ("[DL]") and achiral ("[meso]") diastereoisomers of the hydrogen iodide salt of 1,8-bis-(N-benzyl-N-methylamino)naphthalene ([2H]-[I] ) interconvert in solution. Direct interconversion of the diastereoisomers of [2H]+ must involve hydrogen bond fission (to give "[nonHB-2H+]") and rotation-inversion of the non-protonated nitrogen centre. The global activation parameters (deltaH++ and deltaS++) for diastereoisomer interconversion in [D7]DMF have been determined from rate data obtained by temperature-drop and magnetisation-transfer 13C NMR spectroscopy over a temperature range of 170 degrees C. The process is found to have a high entropy of activation in both directions (deltaS++=163(+/-4) and 169(+/-4) JK(-1)mol(-1)) and this is suggested to arise through hydrogen bonding of the ammonium centre in [nonHB-2H+] with the solvent ([D7]DMF). Comparison of the enthalpy of activation (deltaH++) with that earlier found for diastereoisomer interconversion of the free-base form 2 suggests that the intramolecular hydrogen bond in [2H]+ is roughly equal in enthalpic strength (deltaH) with that made with the solvent ([D7]DMF) in the non-hydrogen-bonded intermediate [nonHB-2H+]. As such, the hydrogen bonding in [2H]+ may be considered as predominantly an entropically driven process, without any unusual enthalpic strength.

Diastereoisomeric cationic pi-allylpalladium-(P,C)-MAP and MOP complexes and their relationship to streochemical memory effects in allylic alkylation.

The axially chiral ligands 2-(diphenylphosphanyl)-2'-methoxy-1,1'-binaphthalene (MOP; 6) and 2'-dimethylamino-2-(diphenylphosphanyl)-1,1'-binaphthalene (MAP; 7) coordinate to a cationic allylpalladium fragment in an unusual bidentate (P,C)-mode through the triarylphosphane and ipso-carbon atom (C1'). The readily prepared MAP and MOP complexes [Pd[(P,C)-(L)](n3-allyl)][OTf] (9 (L = 7) and 10 (L = 6)) have been characterised in solution (NMR), in which two diastereoisomeric rotamers are observed. The stereochemical identity of the rotamers is established by one- and two-dimensional NMR spectroscopy experiments. In both the solid state and in solution, the allyl unit is shown to coordinate in a slightly distorted n3-mode that results in a more alkene-like character at the allyl terminus trans to phosphane ligand. The opposite allyl terminus, which is trans to the ipsocarbon atom (C1'), is more strongly bound and the dominant allyl stereodynamic process involves C-C bond rotation in an n'-allyl intermediate bound through this carbon. Palladium complexes of MAP and MOP are very efficient catalysts for allylic alkylation of racemic cyclopentenyl pivalate with [NaCH(CO2Me)2] in THF. Isotopic desymmetrisation revealed that the reaction occurs with powerful stereochemical memory effects and consequently with low global ee values. The memory effect is suggested to arise through selective generation of diastereoisomeric [Pd[(P,C)-L](n3-cyclopentenyl)]+ ions (L = MAP or MOP) and subsequent capture by nucleophile before ion-pair collapse or equilibration occurs.