High-affinity small molecule-phospholipid complex formation: binding of siramesine to phosphatidic acid

Siramesine (SRM) is a sigma-2 receptor agonist which has been recently shown to inhibit growth of cancer cells. Fluorescence spectroscopy experiments revealed two distinct binding sites for this drug in phospholipid membranes. More specifically, acidic phospholipids retain siramesine on the bilayer surface due to a high-affinity interaction, reaching saturation at an apparent 1:1 drug-acidic phospholipid stoichiometry, where after the drug penetrates into the hydrocarbon core of the membrane. This behavior was confirmed using Langmuir films. Of the anionic phospholipids, the highest affinity, comparable to the affinities for the binding of small molecule ligands to proteins, was measured for phosphatidic acid (PA, mole fraction of X(PA) = 0.2 in phosphatidylcholine vesicles), yielding a molecular partition coefficient of 240 +/- 80 x 10(6). An MD simulation on the siramesine:PA interaction was in agreement with the above data. Taking into account the key role of PA as a signaling molecule promoting cell growth our results suggest a new paradigm for the development of anticancer drugs, viz. design of small molecules specifically scavenging phospholipids involved in the signaling cascades controlling cell behavior.     

Biotechnology and polymer chemistry: a growing relationship

DuPont is using biotechnology to make chemical compounds and materials, especially polymers and polymer intermediates ‐ demonstrating that biotechnology can lead to more effective and productive manufacturing processes for traditional chemical businesses as well as pharmaceuticals, agricultural products, and new products for improved nutrition and health.     

Naturally-occurring nitro compounds

Naturally-occurring nitro compounds display great structural diversity, and a wide range of biological activities. This review summarizes current information on the structures of naturally-occurring nitro compounds and on the biosynthesis of the nitro group.     

Geometrical Structure of Two-Dimensional Crystals with Non-Constant Dislocation Density

We outline mathematical methods which seem to be necessary in order to discuss crystal structures with non-constant dislocation density tensor (ddt) in some generality. It is known that, if the ddt is constant (in space), then material points can be identified with elements of a certain Lie group, with group operation determined in terms of the ddt—the dimension of the Lie group equals that of the ambient space in which the body resides, in that case. When the ddt is non-constant, there is also a relevant Lie group (given technical assumptions), but the dimension of the group is strictly greater than that of the ambient space. The group acts on the set of material points, and there is a non-trivial isotropy group associated with the group action. We introduce and discuss the requisite mathematical apparatus in the context of Davini’s model of defective crystals, and focus on a particular case where the ddt is such that a three dimensional Lie group acts on a two dimensional crystal state—this allows us to construct corresponding discrete structures too.     

Signatures of non locality for short-ranged wetting at curved substrates

The binding potential for wetting near planes, spheres, and cylinders in systems with short-ranged forces is shown to have a universal geometrical structure. This arises from the nonlocal nature of the interfacial interactions and is exactly described by a recently proposed binding potential functional, which provides a systematic framework for studying wetting at arbitrarily shaped substrates. The corrections to the equilibrium wetting layer thickness induced by nonlocality are comparable to those arising from a Tolman length and lead to diverging terms in the total mass adsorption.     

Impact of reductive cleavage of an intramolecular disulfide bond containing cationic gemini surfactant in monolayers and bilayers

The properties of a novel disulfide-bond-containing gemini surfactant bis[N,N-dimethyl-N-hexadecyl-N-(2-mercaptoethyl)ammonium bromide] disulfide (DSP) were studied using a Langmuir balance, supported monolayers, differential scanning calorimetry, giant vesicles, and LUVs. In 150 mM NaCl the cmc for DSP was 7.5 microM whereas that of the monomer N,N-dimethyl-N-hexadecyl-N-(2-mercaptoethyl)ammonium bromide (MSP) was 12.1 microM. Both surfactants exhibited single endotherms upon DSC, with peak temperatures Tm at 21.7 and 20.1 degrees C for DSP and MSP, respectively. The endotherm for MSP was significantly broader indicating less cooperative melting. Both in monolayers and in vesicles reductive cleavage of the disulfide bond of DSP could be obtained by glutathione (GSH). For Langmuir films of DSP the addition of GSH into the subphase led to a decrease in surface pressure pi as well as surface dipole potential psi. Although the cleavage by GSH was significantly slower in the presence of a charge saturating concentration of DNA, it did not prevent the reaction. The resulting monomers detached from supported monolayers, leading to loss of affinity of the surface for DNA. Disruption of giant vesicles containing DSP within approximately 30 s following a local injection of GSH was observed, revealing membrane destabilization.     

Wetting of a plane with a narrow solvophobic stripe

ABSTRACT

We present a numerical study of a simple density functional theory model of fluid adsorption occurring on a planar wall decorated with a narrow deep stripe of a weaker adsorbing (relatively solvophobic) material, where wall-fluid and fluid-fluid intermolecular forces are considered to be dispersive. Both the stripe and outer substrate exhibit first-order wetting transitions with the wetting temperature of the stripe lying above that of the outer material. This geometry leads to a rich phase diagram due to the interplay between the pre-wetting transition of the outer substrate and an unbending transition corresponding to the local evaporation of liquid near the stripe. Depending on the width of the stripe, the line of unbending transitions merges with the pre-wetting line inducing a two-dimensional wetting transition occurring across the substrate. In turn, this leads to the continuous pre-drying of the thick pre-wetting film as the pre-wetting line is approached from above. Interestingly we find that the merging of the unbending and pre-wetting lines occurs even for the widest stripes considered. This contrasts markedly with the scenario where the outer material has the higher wetting temperature, for which the merging of the unbending and pre-wetting lines only occurs for very narrow stripes.     

Four-quasiparticle high-K band in 130Ce

High-spin states have been populated in ¹³⁰Ce, using the ¹⁰⁰Mo(³⁴S, 4n??) reaction at 155 MeV. A new strongly coupled structure has been found and is interpreted as based on a mixed neutron-proton high-K four-quasiparticle configuration.