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.

The variation of solar wind correlation lengths over three solar cycles

We present the results of a study of solar wind velocity and magnetic field correlation lengths over the last 35 years. The correlation length of the magnetic field magnitude λ | B| increases on average by a factor of two at solar maxima compared to solar minima. The correlation lengths of the components of the magnetic field λ_{B_{XYZ}} and of the velocity λ_{V_{YZ}} do not show this change and have similar values, indicating a continual turbulent correlation length of around 1.4×106 km. We conclude that a linear relation between λ | B|, VB 2, and Kp suggests that the former is related to the total magnetic energy in the solar wind and an estimate of the average size of geoeffective structures, which is, in turn, proportional to VB 2. By looking at the distribution of daily correlation lengths we show that the solar minimum values of λ | B| correspond to the turbulent outer scale. A tail of larger λ | B| values is present at solar maximum causing the increase in mean value.

Correlation of magnetic field intensities and solar wind speeds of events observed by ACE

The relationship between the magnetic field intensity and speed of solar wind events is examined using ∼3 years of data from the ACE spacecraft. No preselection of coronal mass ejections (CMEs) or magnetic clouds is carried out. The correlation between the field intensity and maximum speed is shown to increase significantly when |B| > 18 nT for 3 hours or more. Of the 24 events satisfying this criterion, 50% are magnetic clouds, the remaining half having no ordered field structure. A weaker correlation also exists between southward magnetic field and speed. Sixteen of the events are associated with halo CMEs leaving the Sun 2 to 4 days prior to the leading edge of the events arriving at ACE. Events selected by speed thresholds show no significant correlation, suggesting different relations between field intensity and speed for fast solar wind streams and ICMEs.

Neocolonialism and international law, with specific reference to customary counterterrorism obligations and the principle of self-defence

Has international law ever, and, if it has not, can it ever, truly freed itself from the strictures of neocolonialism and the drive by a privileged elite to dominate the world scene? This article begins by inquiring into the nature of neocolonialism and, in so doing, pays particular attention to the writings of former Ghanaian President Kwame Nkrumah. It then proceeds to determine how neocolonialist designs surface in international law today by briefly looking at two aspects of international law in particular, namely customary international law, with specific reference to the counterterrorism context, and the principle of self-defence. In the final analysis, this article argues for a necessary and eternal scepticism of international law and the agendas of its privileged gatekeepers. Like classic State power, it opens itself to, and often operates as, neocolonial overreach, and to quote Nkrumah, “[t]he cajolement, the wheedlings, the seductions and the Trojan horses of neo-colonialism must be stoutly resisted, for neo-colonialism is a latter-day harpy, a monster which entices its victims with sweet music.”