The solution structure of a copper(II) compound of a new cyclic octapeptide by EPR spectroscopy and force field calculations

A new cyclic octapeptide, cyclo(Ile-Ser-(Gly)Thz-Ile-Thr-(Gly)Thz) (PatN), related to patellamide A, has been synthesized and reacted with copper(II) and base to form mono- and dinuclear complexes. The coordination environments around copper(TI) have been characterized by EPR spectroscopy. The solution structure of the thermodynamically most stable product, a purple dicopper(TI) compound, has been examined by simulating weakly dipole-dipole coupled EPR spectra based upon structural parameters obtained from force field (MM and MD) calculations. The MM-EPR method produces a saddle-shaped structure for [Cu-2(PatN)(OH2)(6)] that is similar to the known solution structure of patellamide A and the known solid-state structure of [Cu-2(AscidH(2))CO3(OH2)(2)]. Compared with the latter, [Cu-2(PatN)] has no carbonate bridge and a significantly flatter topology. The MM-EPR approach to solution-structure determination for paramagnetic metallopeptides may find wide applications to other metallopeptides and metalloproteins.

Synthesis of [Cu-2(Me-2[9]aneN(2)S)(2)(OH)(2)] (PF6)(2), a hydroxo-bridged copper(II) complex of N,N '-dimethyl-1-thia-4,7-diazacyclononane (Me-2[9]aneN(2)S). X-ray structural analysis, magnetic susceptibility, EPR and visible spectroscopy

The bis(mu-hydroxo) complex [Cu-2(Me-2[9]aneN(2)S)(2)(OH)(2)](PF6)(2) (Me-2[9]aneN(2)S = N,N'-dimethyl-1-thia-4,7-diazacyclononane) results after reaction of [Cu(Me-2[9]aneN(2)S)(MeCN)] (PF6) with dioxygen at -78 degrees C in acetonitrile. The complex has been characterized by X-ray crystallography: orthorhombic, space group Pnma, with a 18.710(3), b 16.758(2), c 9.593(2) Angstrom, and Z = 4. The structure refined to a final R value of 0.051. The complex contains two copper(II) ions bridged by two hydroxo groups with Cu ... Cu 2.866(1) Angstrom. The solid-state magnetic susceptibility study reveals ferromagnetic coupling, the fitting parameters being J = +46+/-5 cm(-1), g = 2.01+/-0.01 and theta = -0.58+/-0.03 K. The frozen-solution e.p.r. spectrum in dimethyl sulfoxide is characteristic of a monomeric copper(II) ion (g(parallel to) 2.300, g(perpendicular to) 2.063; A(parallel to) 156.2 x 10(-4) cm(-1), A(perpendicular to) 9.0 x 10(-4) cm(-1)) with an N2O2 donor set. Thioether coordination to the copper(II) in solution is supported by the presence of an intense absorption assigned to a sigma(S)-->Cu-II LMCT transition at c. 34000 cm(-1). The single-crystal spectrum of [Cu-2(Me-2[9]aneN(2)S)(2)(OH)(2)] (PF6)(2) (273 K) reveals d-->d transitions at 14500 and 18300 cm(-1) and a weak pi(S)-->Cu-II charge-transfer band at approximately 25000 cm(-1).

Detection of dimethyl sulfone in the human brain by in vivo proton magnetic resonance spectroscopy

We wish to report the detection of dimethyl sulfone (methylsulfonylmethane, C2H6O2S) in the brain of a normal 62-year-old male using in vivo proton magnetic resonance spectroscopy. The presence of this exogenous metabolite resulted from ingestion of a dietary supplement containing dimethyl sulfone. The concentration of this compound in the brain was measured to be 2.4 mmol, with a washout half life of approximately 7.5 days. The in vivo T-1 and T-2 relaxation times of dimethyl sulfone were measured to be 2180 ms and 385 ms, respectively. The concentration of major brain metabolites, namely N-acetylaspartate, total Creatine and Choline, and myo-Inositol were within normal limits. (C) 2000 Elsevier Science Inc. All rights reserved.

Characterization of the sequential non-covalent and covalent interactions of the antitumour antibiotic hedamycin with double stranded DNA by NMR spectroscopy

Hedamycin, a member of the pluramycin class of antitumour antibiotics, consists of a planar anthrapyrantrione chromophore to which is attached two aminosugar rings at one end and a bisepoxide-containing sidechain at the other end, Binding to double-stranded DNA is known to involve both reversible and non-reversible modes of interaction. As a part of studies directed towards elucidating the structural basis for the observed 5'-pyGT-3' sequence selectivity of hedamycin, we conducted one-dimensional NMR titration experiments at low temperature using the hexadeoxyribonucleotide duplexes d(CACGTG)(2) and d(CGTACG)(2). Spectral changes which occurred during these titrations are consistent with hedamycin initially forming a reversible complex in slow exchange on the NMR timescale and binding through intercalation of the chromophore. Monitoring of this reversible complex over a period of hours revealed a second type of spectral change which corresponds with formation of a non-reversible complex. Copyright (C) 1999 John Wiley & Sons, Ltd.

Identification of initiation sites for T4 lysozyme folding using CD and NMR spectroscopy of peptide fragments

Using CD and 2D H-1 NMR spectroscopy, we have identified potential initiation sites for the folding of T4 lysozyme by examining the conformational preferences of peptide fragments corresponding to regions of secondary structure. CD spectropolarimetry showed most peptides were unstructured in water, but adopted partial helical conformations in TFE and SDS solution. This was also consistent with the H-1 NMR data which showed that the peptides were predominantly disordered in water, although in some cases, nascent or small populations of partially folded conformations could be detected. NOE patterns, coupling constants, and deviations from random coil Her chemical shift values complemented the CD data and confirmed that many of the peptides were helical in TFE and SDS micelles. In particular, the peptide corresponding to helix E in the native enzyme formed a well-defined helix in both TFE and SDS, indicating that helix E potentially forms an initiation site for T4 lysozyme folding. The data for the other peptides indicated that helices D, F, G, and H are dependent on tertiary interactions for their folding and/or stability. Overall, the results from this study, and those of our earlier studies, are in agreement with modeling and IID-deuterium exchange experiments, and support an hierarchical model of folding for T4 lysozyme.

U-q[(sl(2)over-cap vertical bar 1)] vertex operators, screen currents, and correlation functions at an arbitrary level

Bosonized q-vertex operators related to the four-dimensional evaluation modules of the quantum affine superalgebra U-q[sl((2) over cap\1)] are constructed for arbitrary level k=alpha, where alpha not equal 0,-1 is a complex parameter appearing in the four-dimensional evaluation representations. They are intertwiners among the level-alpha highest weight Fock-Wakimoto modules. Screen currents which commute with the action of U-q[sl((2) over cap/1)] up to total differences are presented. Integral formulas for N-point functions of type I and type II q-vertex operators are proposed. (C) 2000 American Institute of Physics. [S0022-2488(00)00608-3].

Variation in mortality rates in Australia: correlation with Indigenous status, remoteness and socio-economic deprivation

Background The aim of this study was to study ecological correlations between age-adjusted all-cause mortality rates in Australian statistical divisions and (1) the proportion of residents that self-identify as Indigenous, (2) remoteness, and (3) socio-economic deprivation. Methods All-cause mortality rates for 57 statistical divisions were calculated and directly standardized to the 1997 Australian population in 5-year age groups using Australian Bureau of Statistics (ABS) data. The proportion of residents who self-identified as Indigenous was obtained from the 1996 Census. Remoteness was measured using ARIA (Accessibility and Remoteness Index for Australia) values. Socioeconomic deprivation was measured using SEIFA (Socio-Economic index for Australia) values from the ABS. Results Age-standardized all-cause mortality varies twofold from 5.7 to 11.3 per 1000 across Australian statistical divisions. Strongest correlation was between Indigenous status and mortality (r = 0.69, p < 0.001). correlation between remoteness and mortality was modest (r = 0.39, p = 0.002) as was correlation between socio-economic deprivation and mortality (r = -0.42, p = 0.001). Excluding the three divisions with the highest mortality, a multiple regression model using the logarithm of the adjusted mortality rate as the dependent variable showed that the partial correlation (and hence proportion of the variance explained) for Indigenous status was 0.03 (9 per cent; p = 0.03), for SEIFA score was -0.17 (3 per cent; p = 0.22); and for remoteness was -0.22 (5 per cent; p = 0.13). Collectively, the three variables studied explain 13 per cent of the variability in mortality. Conclusions Ecological correlation exists between all-cause mortality, Indigenous status, remoteness and disadvantage across Australia. The strongest correlation is with indigenous status, and correlation with all three characteristics is weak when the three statistical divisions with the highest mortality rates are excluded. intervention targeted at these three statistical divisions could reduce much of the variability in mortality in Australia.

Spin states of C-60(3-) and C120On- (n=2, 3, 4) anions using electron spin transient nutation spectroscopy

Electron spin transient nutation (ESTN) experiments show that the spin multiplicity of the ground state of C-60(3-) in frozen solution is a doublet with S = 1/2. In purified samples, there is no evidence for excited states or other species with higher multiplicity. In the anions Of C120On- (n = 2, 3, 4), where the CW EPR experiments have shown that a mixture of species is present, ESTN experiments confirm that a doublet with S = 1/2 is associated with the 3- anion and triplets with S = 1 are associated with the 2- and 4- anions. A weak nutation peak attributable to m(s) = -1/2 1/2 transitions within a quartet state may arise from association of anions with spins of 1/2 and 1 in solute aggregates.

Event-related FMRI analysis with maximum correlation modelling

Functional magnetic resonance imaging (FMRI) analysis methods can be quite generally divided into hypothesis-driven and data-driven approaches. The former are utilised in the majority of FMRI studies, where a specific haemodynamic response is modelled utilising knowledge of event timing during the scan, and is tested against the data using a t test or a correlation analysis. These approaches often lack the flexibility to account for variability in haemodynamic response across subjects and brain regions which is of specific interest in high-temporal resolution event-related studies. Current data-driven approaches attempt to identify components of interest in the data, but currently do not utilise any physiological information for the discrimination of these components. Here we present a hypothesis-driven approach that is an extension of Friman's maximum correlation modelling method (Neurolmage 16, 454-464, 2002) specifically focused on discriminating the temporal characteristics of event-related haemodynamic activity. Test analyses, on both simulated and real event-related FMRI data, will be presented.

Correlation of business cycles in the euro zone

In this short article we use a simple differences-in-clifferences technique to investigate whether bilateral correlation of business cycles increased more amongst members of the European Monetary Union (EMU) after the implementation of the Euro than amidst other OECD economies. We present evidence suggesting this to be the case. (C) 2008 Elsevier B.V. All rights reserved.

Stereochemistry of cyclopentane derivatives from (2,3)J(CH) dependence on dihedral angle (theta H-C-C-X)

The (2,3)J(CH) dependence on dihedral angle (theta H-C-C-X) for cyclopentane derivatives was investigated. We observed that the combined use of experimentally obtained (2,3)J(CH) values and the theoretically determined dihedral angles between the corresponding nuclei can be used to infer the relative stereochemistry of the ring substituents in cyclopentane derivatives. There is a good correlation between the magnitude of (3)J(CH) and the dihedral angle between the hydrogen and the coupled carbon (R-2 = 0.88). Copyright (C) 2008 John Wiley & Sons, Ltd.