13C-2H correlation NMR spectroscopy studies of the in vivo transformations of natural products from Artemisia annua

13C-2H correlation NMR spectroscopy (13C-2H COSY) permits the identification of 13C and 2H nuclei which are connected to one another by a single chemical bond via the sizeable 1JCD coupling constant. The practical development of this technique is described using a 13C-2H COSY pulse sequence which is derived from the classical 13C-1H correlation experiment. An example is given of the application of 13C-2H COSY to the study of the biogenesis of natural products from the anti-malarial plant Artemisia annua, using a doubly-labelled precursor molecule. Although the biogenesis of artemisinin, the anti-malarial principle from this species, has been extensively studied over the past twenty years there is still no consensus as to the true biosynthetic route to this important natural product – indeed, some published experimental results are directly contradictory. One possible reason for this confusion may be the ease with which some of the metabolites from A. annua undergo spontaneous autoxidation, as exemplified by our recent in vitro studies of the spontaneous autoxidation of dihydroartemisinic acid, and the application of 13C-2H COSY to this biosynthetic problem has been important in helping to mitigate against such processes. In this in vivo application of 13C-2H COSY, [15-13C2H3]-dihydroartemisinic acid (the doubly-labelled analogue of the natural product from this species which was obtained through synthesis) was fed to A. annua plants and was shown to be converted into several natural products which have been described previously, including artemisinin. It is proposed that all of these transformations occurred via a tertiary hydroperoxide intermediate, which is derived from dihyroartemisinic acid. This intermediate was observed directly in this feeding experiment by the 13C-2H COSY technique; its observation by more traditional procedures (e.g., chromatographic separation, followed by spectroscopic analysis of the purified product) would have been difficult owing to the instability of the hydroperoxide group (as had been established previously by our in vitro studies of the spontaneous autoxidation of dihydroartemisinic acid). This same hydroperoxide has been reported as the initial product of the spontaneous autoxidation of dihydroartemisinic acid in our previous in vitro studies. Its observation in this feeding experiment by the 13C-2H COSY technique, a procedure which requires the minimum of sample manipulation in order to achieve a reliable identification of metabolites (based on both 13C and 2H chemical shifts at the 15-position), provides the best possible evidence for its status as a genuine biosynthetic intermediate, rather than merely as an artifact of the experimental procedure.

Correlation-type structure activity relationships for the kinetics of gas-phase RO2 self-reactions and reaction with HO2

Structure activity relationships (SARs) are presented for the gas-phase reactions of RO2 with HO2, and the self- and cross-reactions of RO2. For RO2+HO2 the SAR is based upon a correlation between the logarithm of the measured rate coefficient and a calculated ionisation potential for the molecule R-CH=CH2, R being the same group in both the radical and molecular analogue. The correlation observed is strong and only for one RO2 species does the measured rate coefficient deviate by more than a factor of two from the linear least-squares regression line. For the self- and cross-reactions of RO2 radicals, the SAR is based upon a correlation between the logarithm of the measured rate coefficient and the calculated electrostatic potential (ESP) at the equivalent carbon atom in the RH molecule to which oxygen is attached in RO2, again R being the same group in the molecule and the radical. For cases where R is a simple alkyl-group, a strong linear correlation observed. For RO2 radicals which contain lone pair-bearing substituents and for which the calculated ESP<-0.05 self-reaction rate coefficients appear to be insensitive to the value of the ESP. For RO2 of this type with ESP>-0.05 a linear relationship between log k and the ESP is again observed. Using the relationships, 84 out of the 85 rate coefficients used to develop the SARs are predicted to within a factor of three of their measured values. A relationship is also presented that allows the prediction of the Arrhenius parameters for the self-reactions of simple alkyl RO2 radicals. On the basis of the correlations, predictions of room-temperature rate coefficients are made for a number of atmospherically important peroxyl-peroxyl radical reactions. (C) 2003 Elsevier Ltd. All rights reserved.

Drug interaction and location in liposomes: correlation with polar surface areas

An important step in liposome characterization is to determine the location of a drug within the liposome. This work thus investigated the interaction of dipalmitoylphosphatidylcholine liposomes with drugs of varied water solubility, polar surface area (PSA) and partition coefficient using high sensitivity differential scanning calorimetry. Lipophilic estradiol (ES) interacted strongest with the acyl chains of the lipid membrane, followed by the somewhat polar 5-fluorouracil (5-FU). Strongly hydrophilic mannitol (MAN) showed no evidence of interaction but water soluble polymers inulin (IN) and an antisense oligonucleotide (OLG), which have very high PSAs, interacted with the lipid head groups. Accordingly, the drugs could be classified as: hydrophilic ones situated in the aqueous core and which may interact with the head groups; those located at the water-bilayer interface with some degree of penetration into the lipid bilayer; those lipophilic drugs constrained within the bilayer. (c) 2004 Elsevier B.V. All rights reserved.

Physical interpretation of the correlation between multi-angle spectral data and canopy height

Recent empirical studies have shown that multi-angle spectral data can be useful for predicting canopy height, but the physical reason for this correlation was not understood. We follow the concept of canopy spectral invariants, specifically escape probability, to gain insight into the observed correlation. Airborne Multi-Angle Imaging Spectrometer (AirMISR) and airborne Laser Vegetation Imaging Sensor (LVIS) data acquired during a NASA Terrestrial Ecology Program aircraft campaign underlie our analysis. Two multivariate linear regression models were developed to estimate LVIS height measures from 28 AirMISR multi-angle spectral reflectances and from the spectrally invariant escape probability at 7 AirMISR view angles. Both models achieved nearly the same accuracy, suggesting that canopy spectral invariant theory can explain the observed correlation. We hypothesize that the escape probability is sensitive to the aspect ratio (crown diameter to crown height). The multi-angle spectral data alone therefore may not provide enough information to retrieve canopy height globally.

Efficient on the fly calculation of time correlation functions in computer simulations

Time correlation functions yield profound information about the dynamics of a physical system and hence are frequently calculated in computer simulations. For systems whose dynamics span a wide range of time, currently used methods require significant computer time and memory. In this paper, we discuss the multiple-tau correlator method for the efficient calculation of accurate time correlation functions on the fly during computer simulations. The multiple-tau correlator is efficacious in terms of computational requirements and can be tuned to the desired level of accuracy. Further, we derive estimates for the error arising from the use of the multiple-tau correlator and extend it for use in the calculation of mean-square particle displacements and dynamic structure factors. The method described here, in hardware implementation, is routinely used in light scattering experiments but has not yet found widespread use in computer simulations.

Effects of beverage alcohol taxes and prices on drinking: a meta-analysis of 1003 estimates from 112 studies

Aims: We conducted a systematic review of studies examining relationships between measures of beverage alcohol tax or price levels and alcohol sales or self-reported drinking. A total of 112 studies of alcohol tax or price effects were found, containing 1003 estimates of the tax/price–consumption relationship. Design: Studies included analyses of alternative outcome measures, varying subgroups of the population, several statistical models, and using different units of analysis. Multiple estimates were coded from each study, along with numerous study characteristics. Using reported estimates, standard errors, t-ratios, sample sizes and other statistics, we calculated the partial correlation for the relationship between alcohol price or tax and sales or drinking measures for each major model or subgroup reported within each study. Random-effects models were used to combine studies for inverse variance weighted overall estimates of the magnitude and significance of the relationship between alcohol tax/price and drinking. Findings: Simple means of reported elasticities are -0.46 for beer, -0.69 for wine and -0.80 for spirits. Meta-analytical results document the highly significant relationships (P < 0.001) between alcohol tax or price measures and indices of sales or consumption of alcohol (aggregate-level r = -0.17 for beer, -0.30 for wine, -0.29 for spirits and -0.44 for total alcohol). Price/tax also affects heavy drinking significantly (mean reported elasticity = -0.28, individual-level r = -0.01, P < 0.01), but the magnitude of effect is smaller than effects on overall drinking. Conclusions: A large literature establishes that beverage alcohol prices and taxes are related inversely to drinking. Effects are large compared to other prevention policies and programs. Public policies that raise prices of alcohol are an effective means to reduce drinking.

Correlation between regioselectivity and site charge in propene polymerisation catalysed by metallocene

The reactions of propene with [Zr(cyclopentadienyl)(2)Me](+) have been investigated using density functional theory in order to study the correlation between regioselectivity and site charge in propene polymerisation. The reaction paths of the 1,2 and 2,1 additions of the methyl group to propene have been established. The geometries and energies of the reactants, transition states and products have been obtained using both PBEPBE/LANL2DZ and B3LYP/LANL2DZ methodologies. The results with both density functionals show that the activation energy for 1,2-insertion is lower than that for 2,1-insertion (Fig. 5) and this is consistent with the experiment results. Also for both density functionals, the difference of the thermal dynamic driving forces between the 2,1 product named 2-21 and the 1,2 product named 2-12 is significantly lower than the difference between the energy barriers. It is noted that in the reactants, the Mulliken partial charge on the central carbon atom C2 is positive and it can be concluded that 1,2-insertion is favoured because it can proceed via a cationic reaction.

Assessment of projected changes in upland environments using simple climatic indices

Climate controls upland habitats, soils and their associated ecosystem services; therefore, understanding possible changes in upland climatic conditions can provide a rapid assessment of climatic vulnerability over the next century. We used 3 different climatic indices that were optimised to fit the upland area classified by the EU as a Severely Disadvantaged Area (SDA) 1961–1990. Upland areas within the SDA covered all altitudinal ranges, whereas the maximum altitude of lowland areas outside of the SDA was ca. 300 m. In general, the climatic index based on the ratio between annual accumulated temperature (as a measure of growing season length) and annual precipitation predicted 96% of the SDA mapped area, which was slightly better than those indices based on annual or seasonal water deficit. Overall, all climatic indices showed that upland environments were exposed to some degree of change by 2071–2100 under UKCIP02 climate projections for high and low emissions scenarios. The projected area declined by 13 to 51% across 3 indices for the low emissions scenario and by 24 to 84% for the high emissions scenario. Mean altitude of the upland area increased by +11 to +86 m for the low scenario and +21 to +178 m for the high scenario. Low altitude areas in eastern and southern Great Britain were most vulnerable to change. These projected climatic changes are likely to affect upland habitat composition, long-term soil carbon storage and wider ecosystem service provision, although it is not yet possible to determine the rate at which this might occur.

A study of the antioxidant capacity of oak wood used in wine ageing and the correlation with polyphenol composition

The antioxidant capacity of oak wood used in the ageing of wine was studied by four different methods: measurement of scavenging capacity against a given radical (ABTS, DPPH), oxygen radical absorbance capacity (ORAC) and the ferric reducing antioxidant power (FRAP). Although, the four methods tested gave comparable results for the antioxidant capacity measured in oak wood extracts, the ORAC method gave results with some differences from the other methods. Non-toasted oak wood samples displayed more antioxidant power than toasted ones due to differences in the polyphenol compositon. A correlation analysis revealed that ellagitannins were the compounds mainly responsible for the antioxidant capacity of oak wood. Some phenolic acids, mainly gallic acid, also showed a significant correlation with antioxidant capacity.

Monetary integration and real estate markets: an investigation of the impact of the introduction of a single currency on real estate performance

This paper assesses the impact of the monetary integration on different types of stock returns in Europe. In order to isolate European factors, the impact of global equity integration and small cap factors are investigated. European countries are sub-divided according to the process of monetary convergence. Analysis shows that national equity indices are strongly influenced by global market movements, with a European stock factor providing additional explanatory power. The global and European factors explain small cap and real estate stocks much less well –suggesting an increased importance of ‘local’ drivers. For real estate, there are notable differences between core and non-core countries. Core European countries exhibit convergence – a convergence to a European rather than a global factor. The non-core countries do not seem to exhibit common trends or movements. For the non-core countries, monetary integration has been associated with increased dispersion of returns, lower correlation and lower explanatory power of a European factor. It is concluded that this may be explained by divergence in underlying macro-economic drivers between core and non-core countries in the post-Euro period.