Ian M. Brereton

Haliclonacyclamines A and B, cytotoxic alkaloids from the tropical marine sponge Haliclona sp

Abstract The structures of haliclonacyclamines A (1) and B (2), and their methiodide salts (3) and (4), were investigated by 1D- and 2D-NMR experiments, notably DQFCOSY, HMBC, HMQC-HOHAHA, and HOHAHA. The relative stereochemistry and position of alkene substituents were determined by single crystal x-ray study at low temperature. The parent haliclonacyclamines show pronounced cytotoxic, antibacterial and antifungal activity.

Heat treatment injury of mango fruit revealed by nondestructive magnetic resonance imaging

Abstract Proton magnetic resonance imaging (MRI) was used to observe disinfestation heat treatment-induced injury in the mesocarp of ripening mango cv. Kensington Pride. Injured areas were characterised by relatively low water levels (low signal intensity) corresponding to air filled cavities and “islands” of starchy mesocarp. Heat treatment-induced lesions started to develop on the day of treatment (day 0) and were maximally evident in fruit held at 22°C by day 4. Nondestructive proton MRI was shown to be a sensitive method for detecting and monitoring the progress of heat treatment-induced injury in mango fruit.

Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase: a target for anti-malarial chemotherapy

The malarial parasite, Plasmodium vivax (Pv), causes a serious infectious disease found primarily in Asia and the Americas. For protozoan parasites, 6-oxopurine phosphoribosyltransferases (PRTases) provide the only metabolic pathway to synthesize the purine nucleoside monophosphates essential for DNA/RNA production. We have purified the recombinant Pv 6-oxopurine (PRTase) and compared its properties with the human and Pf enzymes. The Pv enzyme uses hypoxanthine and guanine with similar catalytic efficiency to the Pf enzyme but xanthine is not a substrate, hence we identify this enzyme as PvHGPRT. Mass spectrometry suggests that PvHGPRT contains bound magnesium ions that are removed by EDTA resulting in loss of activity. However, the addition of Mg(2+) restores activity. Acyclic nucleoside phosphonates (ANPs) are good inhibitors of PvHGPRT having K(i) values as low as 3 microM. These compounds can form the basis for the design of new drugs aimed at combating malaria caused by Pv.

Ciguatoxin-2 Is a Diastereomer of Ciguatoxin-3

Ciguatoxin-2, a major ciguatoxin present in the flesh and viscera of ciguateric fishes, has been shown by 1H nuclear magnetic resonance studies (2-dimensional homonuclear Hartman Hahn, nuclear Overhauser effect and decoupling difference experiments) to be a diastereomer of ciguatoxin-3, differing only in stereochemistry at carbon 52 (a quaternary carbon). This difference accounts for the significant changes in the chemical shift of resonances for protons in this region of ciguatoxin-2. Differences between ciguatoxin-1, -2 and -3 involve modifications at only one end of the ciguatoxins (ring M) and modest differences in potency, indicating that this ring contributes to, but is not critical for, high affinity binding of the ciguatoxins to voltage-dependent sodium channels. It is proposed that ciguatoxin-2 originates from a different precursor to the precursor (presumably gambiertoxin-4b) for ciguatoxin-1 and -3, and that both precursors are produced by a common biosynthetic pathway in Gambierdiscus toxicus.

Coherence selection in gradient-enhanced, heteronuclear correlation spectroscopy

Abstract The gradient-enhanced, heteronuclear, chemical-shift correlation experiment, which provides F 1 quadrature detection in a single acquisition, is analyzed in terms of product operators. Spectral distortions due to eddy-current effects can be avoided by judicial placement of gradient episodes with respect to the incremented evolution period as illustrated by an alternative gradient sequence. The analysis demonstrates the gradient selection of coherences and shows that the relative value of the gradients for N-type or P-type selection now depends upon the value of the ratio of gyromagnetic ratios, rather than on its sign. The new sequence is experimentally demonstrated by the acquisition of a 2D heteronuclear 1 H 3 C correlation spectrum of strychnine.

Respiratory Triggered Imaging with An Optical Displacement Sensor

Motion of abdominal organs with respiration is a major problem in NMR spectroscopy and imaging thereof. Triggering each phase-encoding step with respiration or gating a number of phase-encoding steps is one approach to the problem. The design of a sensor for small animal experiments has not been as simple. An optical device, implemented with polymer optical fibres is described, along with associated hardware and electronics which can act as a trigger for small animal NMR experiments. A brief description of a similar device for human application is also given. 2DFT spin-echo and B0 susceptibility images, both triggered and untriggered, are presented to validate the technique.

Linewidth reduction in a large-smile laser diode array

We present theory and simulations for a spectral narrowing scheme for laser diode arrays (LDAs) that employs optical feedback from a diffraction grating. We calculate the effect of the so-called smile of the LDA and show that it is possible to reduce the effect by using a cylindrical lens set at an angle to the beam. The scheme is implemented on a 19-element LDA with smile of 7.6 microm and yields frequency narrowing from a free-running width of 2 to 0.15 nm. The experimental results are in good agreement with the theory.

Application of volume-selected, two-dimensional multiple-quantum editing in vivo to observe cerebral metabolites.

The volume selection technique SPACE has been combined with a two‐dimensional multiple‐quantum editing sequence to uniquely detect certain J‐coupled cerebral metabolites. In vivo results demonstrating edited glutamate/glutamine and lactate from 0.4 ml of a rats brain at 4.7 T are presented. The sequence was optimized to balance multiple‐quantum generation and signal loss due to T2 relaxation. Without due regard to T2 relaxation little signal is observed.

Preliminary studies on the potential of in vivo deuterium NMR spectroscopy

Natural abundance deuterium NMR spectroscopy can be used to characterise in vivo 2H signals arising from water and fat in mice, with acquisition times of less than two minutes. Administration of D(2)0 (10% V/V) in the drinking water enhances these signals so that excellent spectra can be obtained with one scan. Using these procedures the in vivo turnover of 2H in water and fat in mice has been determined. This procedure may be of particular importance in studies of fat turnover in obesity.

Gradient-induced water-suppression techniques for high-resolution NMR spectroscopy

Water-suppression techniques can be divided into two types, those that result in zero net excitation of the water resonance and those in which the water magnetization is randomized prior to observation of the spectrum of interest. The randomization mechanism may involve selective irradiation, use of natural spin relaxation, or application of a homospoil gradient pulse to dephase selectively excited transverse spin coherence. Destruction techniques considered in this paper will involve the latter of these processes. Nonexcitation methods usually involve a binomial-type pulse cluster which results in off-resonance excitation but zero net rotation on resonance ( 1). Although the water-suppression factor of these methods is usually high ( > 1000)) they suffer from the major limitation that the spectral response is either not flat and/ or there is a large linear phase distortion of the spectrum. Destruction techniques are attractive because the final read pulse can be a hard 90” pulse which ensures uniform excitation of the spectrum with minimal phase distortion. The aim of these methods is the establishment of (S,) = (3,) = (&) = 0 over some selective band in frequency space. For those that utilize a pulsed field gradient, selectivity is achieved by the application of a shaped RF pulse which generates transverse spin coherence over a narrow band and the coherence is dephased by the field gradient. In a previous paper (2) we discussed the difficulties of maintaining high-resolution conditions (Au < 1 Hz) during data acquisition following a field gradient pulse. The major problems can be overcome by preemphasis of the gradient pulse and by applying a correction current through the Z0 coil during data acquisition to ensure that the static magnetic field is stable. Decoupling of the gradient coils from the magnet, shim set, and bore tubes by shielding and isolation may also alleviate these induced eddy current problems. In this paper we consider the nature of the shaped pulse to achieve the optimum water suppression. As well, we introduce a new mechanism to achieve water suppression using a pulsed field gradient and a selective noise pulse. All spectra were obtained on a Bruker MSL-200 spectrometer interfaced to an Oxford Instruments 4.7 T, 13 cm vertical bore magnet. Gradient pulses and Z0 correction were controlled by a Bruker MSL preemphasis unit and were applied to the