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.

Structure, and thermal, magnetic and chemical properties of copper(II)iodoacetate monohydrate

Reaction of iodoacetic acid with cupric carbonate in water in dimmed light yields green Cu(ICH2COO)(2 center dot)H2O (1). From X-ray crystallography, it is found to be a tetra-acetato bridged copper(II) dimer with the water molecules occupying the apical positions. In thermogravimetry, the coordinated water molecules are lost in the temperature range 50-100 degrees C. From magnetic susceptibility measurements in the temperature range 300-1.8 K, the exchange coupling constant J is found to be -142(1) cm(-1) and g = 2.18(2) with the spin Hamiltonian H = -2J{S-Cu1 center dot S-Cu2}. It reacts with 2,2'-bipyridine (bpy) to yield [Cu(bpy)(2)I]I. It oxidises thiophenol to Ph-S-S-Ph under dry N-2 atmosphere.

Structure and magnetic properties of an unprecedented syn-antiμ-nitrito-1κO:2κO′ bridged Mn(iii)-salen complex and its isoelectronic and isostructural formate analogue

The preparation, crystal structures and magnetic properties of two new isoelectronic and isomorphous formate-and nitrite-bridged 1D chains of Mn(III)-salen complexes, [Mn(salen)(HCOO)](n) (1) and [Mn(salen)(NO2)](n) (2), where salen is the dianion of N,N'-bis(salicylidene)-1,2-diaminoethane, are presented. The structures show that the salen ligand coordinates to the four equatorial sites of the metal ion and the formate or nitrite ions coordinate to the axial positions to bridge the Mn(III)-salen units through a syn-anti mu-1 kappa O:2 kappa O' coordination mode. Such a bridging mode is unprecedented in Mn(III) for formate and in any transition metal ion for nitrite. Variable-temperature magnetic susceptibility measurements of complexes 1 and 2 indicate the presence of ferromagnetic exchange interactions with J values of 0.0607 cm(-1) (for 1) and 0.0883 cm(-1) (for 2). The ac measurements indicate negligible frequency dependence for 1 whereas compound 2 exhibits a decrease of chi(ac)' and a concomitant increase of chi(ac)'' on elevating frequency around 2 K. This finding is an indication of slow magnetization reversal characteristic of single-chain magnets or spin-glasses. The mu-nitrito-1 kappa O:2 kappa O' bridge seems to be a potentially superior magnetic coupler to the formate bridge for the construction of single-molecule/-chain magnets as its coupling constant is greater and the chi(ac)' and chi(ac)'' show frequency dependence.

Eigenvalues of a one-dimensional Dirac operator pencil

We study the spectrum of a one-dimensional Dirac operator pencil, with a coupling constant in front of the potential considered as the spectral parameter. Motivated by recent investigations of graphene waveguides, we focus on the values of the coupling constant for which the kernel of the Dirac operator contains a square integrable function. In physics literature such a function is called a confined zero mode. Several results on the asymptotic distribution of coupling constants giving rise to zero modes are obtained. In particular, we show that this distribution depends in a subtle way on the sign variation and the presence of gaps in the potential. Surprisingly, it also depends on the arithmetic properties of certain quantities determined by the potential. We further observe that variable sign potentials may produce complex eigenvalues of the operator pencil. Some examples and numerical calculations illustrating these phenomena are presented.

Solar influences on dynamical coupling between the stratosphere and troposphere

We use a simplified atmospheric general circulation model (AGCM) to investigate the response of the lower atmosphere to thermal perturbations in the lower stratosphere. The results show that generic heating of the lower stratosphere tends to weaken the sub-tropical jets and the tropospheric mean meridional circulations. The positions of the jets, and the extent of the Hadley cells, respond to the distribution of the stratospheric heating, with low latitude heating displacing them poleward, and uniform heating displacing them equatorward. The patterns of response to the low latitude heating are similar to those found to be associated with solar variability in previous observational data analysis, and to the effects of varying solar UV radiation in sophisticated AGCMs. In order to investigate the chain of causality involved in converting the stratospheric thermal forcing to a tropospheric climate signal we conduct an experiment which uses an ensemble of model spin-ups to analyse the time development of the response to an applied stratospheric perturbation. We find that the initial effect of the change in static stability at the tropopause is to reduce the eddy momentum flux convergence in this region. This is followed by a vertical transfer of the momentum forcing anomaly by an anomalous mean circulation to the surface, where it is partly balanced by surface stress anomalies. The unbalanced part drives the evolution of the vertically integrated zonal flow. We conclude that solar heating of the stratosphere may produce changes in the circulation of the troposphere even without any direct forcing below the tropopause. We suggest that the impact of the stratospheric changes on wave propagation is key to the mechanisms involved.

Elimination of the Greenland Ice Sheet in a High CO2 Climate

Projections of future global sea level depend on reliable estimates of changes in the size of polar ice sheets. Calculating this directly from global general circulation models (GCMs) is unreliable because the coarse resolution of 100 km or more is unable to capture narrow ablation zones, and ice dynamics is not usually taken into account in GCMs. To overcome these problems a high-resolution (20 km) dynamic ice sheet model has been coupled to the third Hadley Centre Coupled Ocean-Atmosphere GCM (HadCM3). A novel feature is the use of two-way coupling, so that climate changes in the GCM drive ice mass changes in the ice sheet model that, in turn, can alter the future climate through changes in orography, surface albedo, and freshwater input to the model ocean. At the start of the main experiment the atmospheric carbon dioxide concentration was increased to 4 times the preindustrial level and held constant for 3000 yr. By the end of this period the Greenland ice sheet is almost completely ablated and has made a direct contribution of approximately 7 m to global average sea level, causing a peak rate of sea level rise of 5 mm yr-1 early in the simulation. The effect of ice sheet depletion on global and regional climate has been examined and it was found that apart from the sea level rise, the long-term effect on global climate is small. However, there are some significant regional climate changes that appear to have reduced the rate at which the ice sheet ablates.

Development of smart variable stiffness actuators using polymer hydrogels

In this work, compliant actuators are developed by coupling braided structures and polymer gels, able to produce work by controlled gel swelling in the presence of water. A number of aspects related to the engineering of gel actuators were studied, including gel selection, modelling and experimentation of constant force and constant displacement behaviour, and response time. The actuator was intended for use as vibration neutralizer: with this aim, generation of a force of 10 N in a time not exceeding a second was needed. Results were promising in terms of force generation, although response time was still longer than required. In addition, the easiest way to obtain the reversibility of the effect is still under discussion: possible routes for improvement are suggested and will be the object of future work.

Atmospheric electricity coupling between earthquake regions and the ionosphere

We propose a mechanism to explain suggested links between seismic activity and ionospheric changes detected overhead. Specifically, we explain changes in the natural extremely low-frequency (ELF) radio noise recently observed in the topside ionosphere aboard the DEMETER satellite at night, before major earthquakes. Our mechanism utilises increased electrical conductivity of surface layer air before a major earthquake, which reduces the surface-ionosphere electrical resistance. This increases the vertical fair weather current, and (to maintain continuity of electron flow) lowers the ionosphere. Magnitudes of crucial parameters are estimated and found to be consistent with observations. Natural variability in ionospheric and atmospheric electrical properties is evaluated, and may be overcome using a hybrid detection approach. Suggested experiments to investigate the mechanism involve measuring the cut-off frequency of ELF “tweeks”, the amplitude and phase of very low frequency radio waves in the Earth–ionosphere waveguide, or medium frequency radar, incoherent scatter or rocket studies of the lower ionospheric electron density.

Anharmonic force constant calculations

The relationship of the anharmonic force constants in curvilinear internal coordinates to the observed vibration-rotation spectrum of a molecule is reviewed. A simplified method of setting up the required non-linear coordinate transformations is described: this makes use of an / tensor, which is a straightforward generalization of the / matrix used in the customary description of harmonic force constant calculations. General formulae for the / tensor elements, in terms of the familiar L matrix elements, are presented. The use of non-linear symmetry coordinates and redundancies are described. Sample calculations on the water and ammonia molecules are reported.

C-H and C-D interbond coupling in CHDCl2

Laser photoacoustic spectra of vapour phase CHDCl2 reveal the presence of an interaction which has been ascribed to interbond coupling between C-H and C-D local modes. The absolute value of the interbond coupling parameter for the CHD group, determined from a fit of a model local mode hamiltonian to the experimental data, is shown to be given approximately by the geometric mean of the interbond coupling parameters of the CH2 and CD2 groups recently derived from similar studies of CH2Cl2 and CD2Cl2. Such behaviour is understood in terms of a simple analysis in which kinetic coupling effects dominate. It is suggested that C-H stretch/bend Fermi resonance is responsible for some weaker features in the spectra and modelling calculations are described which allow an order of magnitude estimate of the size of the coupling parameter involved.

Effects of solar wind magnetosphere coupling recorded at different geomagnetic latitudes: Separation of directly-driven and storage/release systems

The effect on geomagnetic activity of solar wind speed, compared with that of the strength of the interplanetary magnetic field, differs with geomagnetic latitude. In this study we construct a new index based on monthly standard deviations in the H-component of the geomagnetic field for all geomagnetic latitudes. We demonstrate that for this index the response at auroral regions correlates best with interplanetary coupling functions which include the solar wind speed while mid- and low-latitude regions respond to variations in the interplanetary magnetic field strength. These results are used to isolate the responsible geomagnetic current systems.

ASYM20: a program for force constant and normal coordinate calculations, with a critical review of the theory involved

The theory of harmonic force constant refinement calculations is reviewed, and a general-purpose program for force constant and normal coordinate calculations is described. The program, called ASYM20. is available through Quantum Chemistry Program Exchange. It will work on molecules of any symmetry containing up to 20 atoms and will produce results on a series of isotopomers as desired. The vibrational secular equations are solved in either nonredundant valence internal coordinates or symmetry coordinates. As well as calculating the (harmonic) vibrational wavenumbers and normal coordinates, the program will calculate centrifugal distortion constants, Coriolis zeta constants, harmonic contributions to the α′s. root-mean-square amplitudes of vibration, and other quantities related to gas electron-diffraction studies and thermodynamic properties. The program will work in either a predict mode, in which it calculates results from an input force field, or in a refine mode, in which it refines an input force field by least squares to fit observed data on the quantities mentioned above. Predicate values of the force constants may be included in the data set for a least-squares refinement. The program is written in FORTRAN for use on a PC or a mainframe computer. Operation is mainly controlled by steering indices in the input data file, but some interactive control is also implemented.