Abstract:
X-Ray diffraction revealed the absolute configuration of 4aβ-methyl-4a-homo-7,19-dinor-5α,10α-androstane-3,17-dione. Detailed NMR analysis suggested that the 5α configuration existed in the starting material, 3β-acetoxy-4a-methylidene-4a-homo-7,19-dinor-5α-androst-9-en-17-one, and related compounds. Thus 5-methyl-5β-estr-9-ene derivatives with a leaving group in position 6β were found to react with nucleophiles to form rearranged 4a-homo-7,19-dinorandrostane derivatives with a 5α configuration.
Abstract:
Theoretical models of phospholipid systems have indicated that both intramolecular and intermolecular forces are important in governing their acyl chain order. Knowledge of the nature and magnitude of these interactions is central to understanding the balance of forces present in lipid lamellar phases, which in turn is related to their microscopic and macroscopic behavior. It is possible to explore the contribution of iniermolecular interactions using lipid systems with the same headgroup and acyl chain identity by variation of the ratio of the headgroups to acyl chains. In this paper, deuterium (2H) NMR spectroscopy has been used to gain information on the orientational order of an acyl chain perdeuterated lipid, 1-perdeuteriopalmitoyl-sn-glycero-3-phosphocholine (PaLPC-d31), in various molecular environments. The orientational order of PaLPC-d31, was studied in four different lamellar phases, including pure PaLPC-d31 (containing 10 wt % H2O), dipalmitoylphosphatidylcholine/PaLPC-d31 (3:1), palmitic acid/PaLPC-d31 (1:1), and cholesterol/PaLPC-d31 (1:1) (each containing 50 wt % H2O) 2H NMR spectra were obtained for the low-temperature and liquid-crystalline (Lα) states of each of these mixtures. In the low-temperature state, the first three systems yielded 2H NMR spectra characteristic of all-trans chains undergoing axial diffusion, with the methyl groups rotating about their C3 axes. The molecular order, as judged by the presence of spectral discontinuities and moment analysis, was found to be almost identical in the low-temperature phases. A different behavior was observed for the cholesterol/PaLPC-d31 (1:1) sample in that the maximum splitting was close to the all-trans rotating value, with a profile of quadrupolar splittings due to increased disorder near the chain ends. The first three systems underwent order-disorder phase transitions near the same midpoint temperature (range of Tm values 40-48°C), whereas the chotesterol/PaLPC-d31 (1:1) sample did not display a transition over the temperature range studied. In the Lα phase, where order profiles were determined as a function of acyl chain segment position, the segmental ordering differed significantly among the samples. The differences were interpreted using a simple diamond lattice model for the acyl chain configurational statistics, as a means of comparing the effective lengths, 〈L〉, projected along the bilayer normal and estimated chain cross-sectional areas, 〈A〉, of PaLPC-d31 in the various mixtures. The derived values of 〈L〉 and 〈A〉 can be understood qualitatively in terms of average packing parameters related to the balance of forces in the headgroup and acyl chain regions, or alternatively the curvature free energy of the membrane lipid-water interface. In lamellar phases of pure PaLPC-d31 the curvature stress is potentially large, and interdigitation of the acyl chains of the apposed monolayers may occur. However, in mixtures of PaLPC-d31 with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), the curvature elastic stress is apparently relieved by an increase in the cross-sectional acyl chain area, 〈A〉, i.e. corresponding to an increase in configurational freedom. The data were also compared to the results of statistical theories to yield additional knowledge of the intermolecular forces. These studies indicate how the segmental ordering reflects lute/molecular interactions within a given lamellar phase. Average properties of the entire system such as average cross-sectional area accessible to each acyl chain relative to the headgroup area can be modulated by these interactions. Such mfermolecular interactions may be related to the presence of lipid diversity in biological membranes. © 1992 American Chemical Society.
Abstract:
Magnetic resonance imaging (MRI) of atherosclerotic lipids using a stimulated-echo diffusion- weighted (STED) sequence is demonstrated. The STED sequence exploits the large difference in diffusion between lipid (primarily cholesteryl ester) and water. The optimization of the STED sequence is discussed. The results of lipid imaging are corroborated with nuclear magnetic resonance (NMR) spectroscopy. This technique is non-invasive, and therefore, it is potentially useful in following the progression of the disease in animal models and in humans.
Abstract:
Deuterium NMR spectroscopy is widely applicable to studies of the structure and dynamics of molecular solids, liquid crystals, and thin films of membrane lipids. The properties of soft nanomaterials are also accessible on the mesoscopic length scale intermediate between the molecular and bulk dimensions. For membrane lipids in the liquid-crystalline state, rapid axial averaging occurs about the director axis (the membrane normal). One can then relate the profiles of the order parameters |(CD)| of the individual C-2H labeled segments to average bilayer properties. These include the mean area per molecule and projected acyl chain length, the area compressibility modulus, and the radius of curvature for reverse hexagonal (H(II)) phase nanotubes. In addition, measurements of the relaxation rates for Zeeman order, R(1Z), and quadrupolar order, R(1Q), enable one to investigate the mean-squared amplitudes and time-scales of the fluctuations that underlie the thermodynamic properties. A unified interpretation is provided by a composite membrane deformation model, which fits simultaneously the frequency dependence and the angular anisotropy of the R(1Z) and R(1Q) relaxation rates. The results suggest the bilayer dynamics in the MHz regime can be modeled in terms of nematic-like deformations of the membrane hydrocarbon interior, together with axial rotations of the lipid acyl chains. A small contribution from internal segmental motions is found, which implies the bilayer microviscosity is comparable to that of a liquid hydrocarbon. Finally, the 2H-NMR relaxation rates of lipid bilayers containing cholesterol in the liquid-ordered phase suggest a dynamically more rigid bilayer, involving fast axial lipid rotations together with a reduction in collective bilayer deformations. Possible future applications include studies of liquid crystals and thin films of membrane lipids and surfactants, as well as lipid-protein systems.
