Effects and Location of Coplanar and Noncoplanar PCB in a Lipid Bilayer: A Solid-State NMR Study.

Coplanar and noncoplanar polychlorinated biphenyls (PCBs) are known to have different routes and degree of toxicity. Here, the effects of noncoplanar PCB 52 and coplanar PCB 77 present at 2 mol % in a model system consisting of POPC liposomes (50% hydrated) are investigated by solid-state (13)C and (31)P NMR at 298 K. Both PCBs intercalate horizontally in the outer part of the bilayer, near the segments of the acyl chain close to the glycerol group. Despite similar membrane locations, the coplanar PCB 77 shows little effect on the bilayer properties overall, except for the four nearest neighboring lipids, while the effect of PCB 52 is more dramatic. The first ∼2 layers of lipids around each PCB 52 in the bilayer form a high fluidity lamellar phase, whereas lipids beyond these layers form a lamellar phase with a slight increase in fluidity compared to a bilayer without PCB 52. Further, a third high mobility domain is observed. The explanation for this is the interference of several high fluidity lamellar phases caused by interactions of PCB 52 molecules in different leaflets of the model bilayer. This causes formation of high curvature toroidal region in the bilayer and might induce formation of channels.

CoenzymeQ10 localizations in model membranes. A Langmuir monolayer study.

The interaction of coenzyme Q10 (CoQ10) in a monolayer of 1,2-dipalmitoyl-sn-glysero-3-phospho-L-choline (DPPC), in a monolayer of 1,2-dierucoyl-sn-glysero-3-phospho-L-choline (DEPC), in a monolayer of 1-palmitoyl-2-oleoyl-sn-glysero-3-phospho-L-serine (POPS) and in a monolayer of total lipid extract from pig brain (PB) has been investigated by using the Langmuir monolayer technique. Surface pressure (π)-mean molecular area (mma) isotherms have been measured for pure lipid monolayers and lipid monolayers with 0.5, 1.0, 2.0, 5.0 and 10.0 mol% CoQ10 concentrations. At the biological concentration (1.0-3.0 mol%) of CoQ10, intercalation of CoQ10 occurs in the lipid acyl chains of DPPC, POPS and PB monolayers. Above the biological concentration of CoQ10, the CoQ10 molecule induces domain formation in the monolayers of DPPC, POPS and PB lipids. The DEPC monolayer behavior deviates from the other lipids in this study. At 2.0 mol% the CoQ10 promotes very dense lipid packing, and the CoQ10 molecule is located parallel to the DEPC acyl chains at all concentrations.

Interaction of local anaesthetic articaine enantiomers with brain lipids: a Langmuir monolayer study.

The interactions of the racemic mixture of articaine as well as pure (R)-articaine and pure (S)-articaine with monolayers of glycerophospholipids and brain lipids have been studied using the Langmuir monolayer technique. Articaine was added to the glycerophospholipids dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylserine (DPPS), 1-palmitoyl-2-oleoylphosphatidylserine (POPS) and total lipid extract from pig brain (TLPB). The amount of articaine in the monolayers was 30 mol%. The intercalation of each of the two enantiomers of articaine into a glycerophospholipid/brain lipid monolayers composed of chiral phospholipids will be diastereoisomeric in nature, hence different intercalation pattern for the two enantiomers can be expected. All the articaine species are found to intercalate into the DPPC monolayer and to increase the monolayer stability, this is most pronounced for the (R)-enantiomer. Intercalation of the articaine species into the DPPS monolayer increases the MMA and hardly affects the stability of the DPPS monolayer. In this monolayer, the articaine species intercalates into the head group region of the small and negatively charged serine head group, this is pronounced for the (R)-enantiomer. Our results indicate that by introducing an unsaturated acyl chain in the monolayer as in POPS, the monolayer discriminates between the articaine species. The (R)-enantiomer is located deep in the acyl chain region, whereas the (S)-enantiomer is found at or close to the head group. The data also might indicate that the (R)-enantiomer in the racemic mixture forms dimers in the POPS monolayer. Both articaine species as well as the racemic mixture intercalate into the monolayer of TLPB. Intercalation into this monolayer did not show any distinct difference in intercalation mode of the articaine species, probably due to camouflaging effect of large head groups like gangliosides and/or formation of lipid rafts in the monolayer. However, the (R)-enantiomer appears to intercalate better into the TLPB monolayer than the (S)-enantiomer. With proper standardization the Langmuir monolayer technique is a powerful method to discriminate between (R)- and (S)-enantiomer articaine interaction with model membranes.

Water structure and dynamics at a silica surface: Pake doublets in 1H NMR spectra.

Detailed knowledge about the dynamics and structure of liquids in the vicinity of a solid surface is important in several fields of research. In this study a homogeneous model system of colloidal and nonporous silica particles with a narrow particle size distribution was used to examine such properties of adsorbed water and 1-heptanol. Doublet (1)H water resonances ("Pake doublets") indicate a preferred spatial orientation for the water molecules, as well as a lower molecular density in the surface-induced water structures compared to bulk water. These surface-induced structures are found to extend at least 8 nm from the silica surface. T(1) relaxation measurements at several temperatures indicate weaker H-bonding in the adsorbed water compared to bulk water. T(2) relaxation measurements at several temperatures reveal the presence of two water phases and give quantitative information on the mobility of water molecules and proton exchange processes. The presence of 1-heptanol changes the water characteristics, primarily in the water phase closer to the surface, where water molecules experience decreased translational and increased rotational freedom. In the absence of water, adsorbed 1-heptanol forms surface aggregates encompassing several molecular layers, where the first adsorbed layer shows severe restrictions in mobility and subsequent layers are more mobile.

pH-dependent interaction of psychotropic drug with glycerophospholipid monolayers studied by the Langmuir technique.

We have earlier investigated the interaction of the antipsychotic drugs chlorpromazine(CPZ) and olanzapine(OLP) with glycerophospholipid monolayers. These experiments were carried out at high and low temperatures and showed that OLP had a more pronounced effect on the packing of the phospholipid (PL) monolayers than CPZ. At pH 7.36, where OLP consists of one positive and one neutral species. In the present work we have studied the interaction of the drugs with monolayers of PLs by the Langmuir technique at pH 6.00 and 10.00 at 37°C. The PLs were palmitoylphosphatidyl-choline(DPPC), 1-stearoyl-2-arachinodonoylphoshatidylcholine(SAPC),dipalmitoylphosphatidyl-serine(DPPS) and 1-palmitoyl-2-oleoylphosphatidylserine(POPS). OLP has a pKa around 7.4, with one neutral and one positive species at pH 6.00 and pH 10.00, respectively. CPZ has pKa value around 9.4, and is positively charged at pH 6.00 and neutral at pH 10.00. Our studies revealed that the surface area of DPPC with CPZ in the subphase did not change at pH 6.00. In contrast, OLP increased the mean molecular area(MMA) of DPPC at pH 6.00, while CPZ caused distinct increase in MMA on the monolayer packing of all the other PLs, including monolayers of DPPC at pH 10.00. OLP, increased MMA of all PLs at both pHs. Further, OLP increased MMA of DPPC (pH 10.00), SAPC (pH 10.00), DPPS (pH 6.00) and POPS (pH 6.00) at 30mN/m, the expected MMA of biological membranes. CPZ had the more pronounced effect at lift-off and gave an effect of the monolayers with negatively charged head groups in accordance our earlier experiments. However, CPZ affected the packing of the SAPC monolayer both at pH 6.00 and 10.00, and DPPC at pH 10.00. Both these PLs have neutral choline head group. Our results suggest that both drugs intercalate in the PL monolayers, and that the intercalation might involve electrostatic interaction with the head groups or hydrophobic interaction with the acyl chains of the PLs, or both. Probably the drugs intercalate to different extents depending on charge of both the drugs and the PL head groups. Our investigation may suggest that the interaction of CPZ and OLP with membrane PLs could be linked to both the psychotropic and the side effects.

The psychotropic drug olanzapine (Zyprexa) increases the area of acid glycerophospholipid monolayers.

The typical antipsychotics chlorpromazine (CPZ) and trifluoperazine (TFP) increase the mean molecular area (mma) of acidic, but not neutral, glycerophospholipids in monolayers at pH 7.36 measured by the Langmuir technique. The atypical antipsychotic olanzapine (OLP(1)) is structurally similar to TFP. We have therefore studied the effects of OLP on glycerophospholipid monolayers and in comparison with CPZ. Olanzapine (10 microM, in subphase, pH 7.36) influenced the isotherms (surface pressure versus mma) in monolayers of the neutral dipalmitoyl phosphatidylcholine (DPPC) and the acidic dipalmitoyl phosphatidylserine (DPPS) or 1-palmitoyl-2-oleoylphosphatidylserine (POPS) in the increasing order of mma: DPPS