Pore structure and sorption properties of silica aerogels studied by magnetic resonance imaging and pulsed-field gradient spectroscopy.

Magnetic resonance imaging (MRI) has provided direct visualization of gaseous xenon and methane in the void spaces of aerogels, offering unique information and insights into the pore structure and molecular diffusivities of occluded sorbates. Nuclear magnetic resonance (NMR) pulsed-field gradient (PFG) techniques were used to characterize exchange and diffusive motion of sorbed xenon gas at equilibrium. PFG measurements showed evidence of anisotropic diffusion; nominal self-diffusivity coefficients of xenon on the order of D = 10(-7) m2/s were determined. Based on a mathematical relationship for the restricted diffusion of gases in confined environments, an expression for estimating the mean free path was derived, from which the average pore size could be obtained from the extrapolated value of the diffusion coefficient to low xenon pressures.

Two-dimensional structure of beta-amyloid(10-35) fibrils.

Beta-amyloid (Abeta) peptides are the main protein component of the pathognomonic plaques found in the brains of patients with Alzheimer's disease. These heterogeneous peptides adopt a highly organized fibril structure both in vivo and in vitro. Here we use solid-state NMR on stable, homogeneous fibrils of Abeta(10-35). Specific interpeptide distance constraints are determined with dipolar recoupling NMR on fibrils prepared from a series of singly labeled peptides containing (13)C-carbonyl-enriched amino acids, and skipping no more that three residues in the sequence. From these studies, we demonstrate that the peptide adopts the structure of an extended parallel beta-sheet in-register at pH 7.4. Analysis of DRAWS data indicates interstrand distances of 5.3 +/- 0.3 A (mean +/- standard deviation) throughout the entire length of the peptide, which is compatible only with a parallel beta-strand in-register. Intrastrand NMR constraints, obtained from peptides containing labels at two adjacent amino acids, confirm the secondary structural findings obtained using DRAWS. Using peptides with (13)C incorporated at the carbonyl position of adjacent amino acids, structural transitions from alpha-helix to beta-sheet were observed at residues 19 and 20, but using similar techniques, no evidence for a turn could be found in the putative turn region comprising residues 25-29. Implications of this extended parallel organization for Abeta(10-35) for overall fibril formation, stability, and morphology based upon specific amino acid contacts are discussed.

Propagating structure of Alzheimer's beta-amyloid(10-35) is parallel beta-sheet with residues in exact register.

The pathognomonic plaques of Alzheimer's disease are composed primarily of the 39- to 43-aa beta-amyloid (Abeta) peptide. Crosslinking of Abeta peptides by tissue transglutaminase (tTg) indicates that Gln15 of one peptide is proximate to Lys16 of another in aggregated Abeta. Here we report how the fibril structure is resolved by mapping interstrand distances in this core region of the Abeta peptide chain with solid-state NMR. Isotopic substitution provides the source points for measuring distances in aggregated Abeta. Peptides containing a single carbonyl 13C label at Gln15, Lys16, Leu17, or Val18 were synthesized and evaluated by NMR dipolar recoupling methods for the measurement of interpeptide distances to a resolution of 0.2 A. Analysis of these data establish that this central core of Abeta consists of a parallel beta-sheet structure in which identical residues on adjacent chains are aligned directly, i. e., in register. Our data, in conjunction with existing structural data, establish that the Abeta fibril is a hydrogen-bonded, parallel beta-sheet defining the long axis of the Abeta fibril propagation.

Dipolar recoupling NMR of biomolecular self-assemblies: determining inter- and intrastrand distances in fibrilized Alzheimer's beta-amyloid peptide.

We demonstrate a new method for investigating the structure of self-associating biopolymers using dipolar recoupling NMR techniques. This approach was applied to the study of fibrillar beta-amyloid (Abeta) peptides (the primary component of the plaques of Alzheimer's disease) containing only a single isotopic spin label (13C), by employing the DRAWS (dipolar recoupling with a windowless sequence) technique to measure 13C-13C distances. The 'single-label' approach simplified analysis of DRAWS data, since only interstrand contacts are present, without the possibility of any intrastrand contacts. As previously reported [T.L.S. Benzinger, D.M. Gregory, T.S. Burkoth, H. Miller-Auer, D.G. Lynn, R.E. Botto, S.C. Meredith, Proc. Natl. Acad. Sci. 95 (1998) 13407.], contacts of approximately 5 A were observed at all residues studied, consistent with an extended parallel beta-sheet structure with each amino acid in exact register. Here, we propose that our strategy is completely generalizable, and provides a new approach for characterizing any iterative, self-associating biopolymer. Towards the end of generalizing and refining our approach, in this paper we evaluate several issues raised by our previous analyses. First, we consider the effects of double-quantum (DQ) transverse relaxation processes. Next, we discuss the effects of various multiple-spin geometries on modeling of DRAWS data. Several practical issues are also discussed: these include (1) the use of DQ filtering experiments, either to corroborate DRAWS data, or as a rapid screening assessment of the proper placement of isotopic spin labels; and (2) the comparison of solid samples prepared by either lyophilization or freezing. Finally, data obtained from the use of single labels is compared with that obtained in doubly 13C-labeled model compounds of known crystal structure. It is shown that such data are obtainable in far more complex peptide molecules. These data,taken together, refine the DRAWS method, and demonstrate its precision and utility in obtaining high resolution structural data in complex biomolecular aggregates such as Abeta.

Three-dimensional magnetic resonance microscopy of materials.

Several aspects of magnetic resonance microscopy are examined employing three-dimensional (3D) back-projection reconstruction techniques in combination with either simple Bloch-decay methods or MREV-8 multiple-pulse line narrowing techniques in the presence of static field gradients. Applications to the areas of ceramic processing, catalyst porosity measurements and the characterization of polymeric materials are presented. The focus of the discussion centers on issues of sensitivity and resolution using this approach compared with other methods. Advantages and limitations of 3D microscopy over more commonly employed slice selection protocols are discussed, as well as potential remedies to some of the inherent limitations of the technique.

Substituent effects on the nitrogen-15 and carbon-13 shieldings of some N-arylguanidinium chlorides.

The (13)C and (15)N chemical shifts of five N-arylguanidinium chlorides carrying polar substituents, ranging in character from 4-methoxy to 4-nitro groups, have been determined by NMR spectroscopy at the natural-abundance level of (13)C and (15)N in dimethyl sulfoxide solution. Comparison of the (13)C shifts of these salts with those of monosubstituted benzenes shows that the guanidinium group induces an average downfield shift of -5.8 ppm of the resonance of the aryl carbon to which it is attached (C1), an average upfield shift of +4.2 ppm for C2 and C6, and a small upfield shift of +1.9 ppm for C4. The shifts of C3 and C5 are small and erratic relative to the corresponding carbons in monosubstituted benzenes. The (15)N resonances of the guanidinium nitrogens are quite sensitive to electric effects resulting from substitution of polar groups at C4. The (15)N shift of the [unk]NAr nitrogen relative to that of the salts suggests that the predominant tautomer for N-arylguanidines is (H(2)N)(2)C[unk]NAr. The (15)N shifts of the (NH(2))(2) nitrogens correlate rather well with sigma(p) (-) parameters, whereas the shifts of the -NHAr nitrogens seem to correlate only with R values derived from the sigma(p) (-) substituent constants.