A simple two pulse phase modulation (TPPM) scheme greatly reduces the residual linewidths arising from insufficient proton decoupling power in double resonance magic angle spinning (MAS) experiments. Optimization of pulse lengths and phases in the sequence produces substantial improvements in both the resolution and sensitivity of dilute spins (e.g., 13C) over a broad range of spinning speeds at high magnetic field. The theoretical complications introduced by large homo‐ and heteronuclear interactions among the spins, as well as the amplitude modulation imposed by MAS, are explored analytically and numerically. To our knowledge, this method is the first phase‐switched sequence to exhibit improvement over continuous‐wave (cw) decoupling in a strongly coupled homogeneous spin system undergoing sample spinning.

Heteronuclear decoupling in rotating solids

Computer-optimized decoupling scheme for wideband applications and low-level operation

Several recent studies have identified nuclear factor-κB as a key modulator in driving inflammation to cancers. Besides this transcription factor, essential in regulating inflammation and cancer development, an inflammatory microenvironment inhabiting various inflammatory cells and a network of signaling molecules are also indispensable for the malignant progression of transformed cells, which is attributed to the mutagenic predisposition of persistent infection-fighting agents at sites of chronic inflammation. As a subverted host response to inflammation-induced tumors, the inflammatory cells and regulators may facilitate angiogenesis and promote the growth, invasion, and metastasis of tumor cells. Thus far, research regarding inflammation-associated cancer development has focused on cytokines and chemokines as well as their downstream targets in linking inflammation and cancer. Moreover, other proteins with extensive roles in inflammation and cancer, such as signal transducers and activators of transcription, Nrf2, and nuclear factor of activated T cells, are also proposed to be promising targets for future studies. The elucidation of their specific effects and interactions will accelerate the development of novel therapeutic interventions against cancer development triggered by inflammation. (Mol Cancer Res 2006;4(4):221–33)

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Inflammation, a key event in cancer development.

Iterative schemes for bilinear operators; application to spin decoupling

Evaluation of a new broadband decoupling sequence: WALTZ-16

The ^(13)C chemical shifts for a number of norbornyl derivatives have been obtained in natural abundance. The compounds studied were the series of methylnorbornanes, methylnorbornenes, methyl-2-norbornanones, methyl-2,2-difluoronorbornanes, and a variety of exo- and endo-2-substituted norbornanes. The observed shifts have been interpreted in terms of inductive, bond length, and steric effects. The ɑ- and β-substituent effects are shown to be dependent on the extent of substitution at both the α and β carbon atoms
and changes in bond lengths have been used to rationalize the shift changes. Steric interactions between the endo-2 and endo-6 positions, and the exo-2 and syn-7 positions have been shown to generate important chemical-
shift changes and these changes can be used as a semiquantitative measure of steric interactions in norbornyl derivatives. Studies with electron-withdrawing groups have revealed a new long-range cmr y effect produced by
exo-2 substituents on C-6. These shifts appear to provide a sensitive and quantitative measure of the electronic demands of a neighboring group as a function of stereochemistry. The substituent shifts obtained from the monosubstituted derivatives have been used to predict the shifts of each of the 1- and 3-methyl-2-norbornanols. The agreement between observed and calculated values is generally good and supports the general approach. Several ^(13)C-^(13)C coupling constants for norbornane, nortricyclene, and quadricyclene are reported and interpreted in terms of the s character of the C-C bonds.

Nuclear magnetic resonance spectroscopy. Carbon-13 chemical shifts in norbornyl derivatives

Bicycloaromaticity. Stability and rearrangement of the bicyclo[3.2.2]nonatrienyl cation

Certain plant species belonging to the family Annonaceae produce Annonaceous acetogenins, which are a unique class of long-chain fatty acid derivatives with potent cytotoxicity. Putative protein targets of the acetogenins are membrane-associated proteins, including complex I. Asimicin and its analogues constitute a class of Annonaceous acetogenins containing two tetrahydrofuran (THF) rings with hydrocarbon chains tethered to each ring; an alpha,beta-unsaturated gamma-lactone ring is terminal to one of the alkyl chains. The compounds examined in this study differ in the length of the alkyl chain between the THF rings and the lactone ring. The positions of both the THF and the lactone rings within liposomal membranes were determined by proton (1H) nuclear magnetic resonance spectroscopy. The depth of membrane penetration of acetogenins, coupled to membrane diffusion, controls the conformation of acetogenins as they diffuse to an active site. Based on 1H intermolecular nuclear Overhauser effects (NOEs), the THF rings of all acetogenins studied reside near the polar interfacial head group region of the DMPC. This was corroborated by 1H two-dimensional NOE spectroscopy and differential scanning calorimetry studies. The 1H difference NOE spectra indicated that the lactone rings of asimicin and parviflorin, the latter of which has two fewer carbons in its alkyl chain, are located below the glycerol backbone in the membrane. In contrast with asimicin and parviflorin, the lactone ring of longimicin B, an asimicin analogue with an alkyl chain four carbons shorter, resides close to the midplane in the membrane. This was corroborated by manganese-induced broadening studies. Since the THF rings are located near the center of the acetogenin molecules and the lactone ring is terminal to a long alkyl chain, these observations indicate that an asimicin-type acetogenin can be in either sickle-shaped or U-shaped conformations, depending on the length of the alkyl chain between the THF rings and the lactone ring. Interestingly, longimicin B does not exhibit significant cytotoxicity, but parviflorin is as cytotoxic as asimicin. The cytotoxicity of the asimicin-type of acetogenins would seem to be strongly related to the membrane conformation. This is the first report elucidating the conformation of Annonaceous acetogenins in membranes.

John B. Grutzner

Papers

Nuclear magnetic resonance spectroscopy. Carbon-13 chemical shifts in norbornyl derivatives

Bicycloaromaticity. Stability and rearrangement of the bicyclo[3.2.2]nonatrienyl cation

Membrane conformations and their relation to cytotoxicity of asimicin and its analogues.

Magnetic resonance. X. Spectroscopy of carbanions and the effect of ion pairing on chemical shifts

Structure of allylic Grignard reagents