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Lung cancer is one of the most common malignant tumors and emerged as one of the leading causes of cancer-related death worldwide. Surgical resection can be a curative treatment for early stage but the most of lung cancer patients are diagnosed at an advanced stage when the pulmonary tumor has been invaded beyond the respiratory system. Therefore, chemotherapy is suitable for curing metastasized tumor. Baicalin (BL) is a flavonoid which has been studied in the treatment of several types of cancer including lung cancer. However, its low solubility in water and non-specificity impede its practical utilization. Hence, we have reported a stearic acid and pluronic F68 conjugated nanomicelles (PF68-SA) system to improve therapeutic efficacy of BL. Solvent evaporation method was used to prepare the BL-loaded PF68-SA nanomicelles (BLNM). The designed BLNM were characterized for the particle size, surface charge, critical micelle concentration, colloidal stability, morphology, and total drug content. BLNM formulation showed improved toxicity of BL against A549 human lung cancer cells in cytotoxicity assay. Further, apoptosis study also depicted BLNM-induced cell death in A549 cells. Therefore, the synthesized fatty acid-modified polymeric nanomicellar system could be useful in overcoming the stability and low therapeutic efficacy issues of hydrophobic anticancer drugs like BL and delivering them to the cancer cells., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Epigallocatechin-gallate (EGCG) is a potent anti-cancer therapeutic which effectively controls the growth of cancerous cells through a variety of different pathways. However, its molecular structure is susceptible to modifications due to cellular enzymes affecting its stability, bioavailability and hence, overall efficiency. In this study, we have initially encapsulated EGCG in the matrix of solid lipid nanoparticles to provide a stable drug carrier. To confer additional specificity towards gastrin releasing peptide receptors (GRPR) overexpressed in breast cancer, EGCG loaded nanoparticles were conjugated with a GRPR-specific peptide. In-vitro cytotoxicity studies showed that the peptide-conjugated formulations possessed greater cytotoxicity to cancer cell lines compared to the non-conjugated formulations. Further, in-vivo studies performed on C57/BL6 mice showed greater survivability and reduction in tumour volume in mice treated with peptide-conjugated formulation as compared to the mice treated with non-conjugated formulation or with plain EGCG. These results warrant the potential of the system designed in this study as a novel and effective drug delivery system in breast cancer therapy., (Copyright © 2019. Published by Elsevier B.V.)

Oleic (cis9-18:1), linoleic (cis9,cis12-18:2) and α-linolenic (cis9,cis12,cis15-18:3) acids are well described substrates of the Δ6-desaturase encoded by the mammalian fatty acid desaturase 2 (FADS2) gene. In addition, at least 9 other very structurally different fatty acids have been shown to be Δ6- or even Δ8-desaturated by the FADS2 protein. A better characterization of the substrate specificity of this enzyme is therefore needed. By using commercial cis9-18:1 and chemically synthesized cis12- and cis15-18:1 (sharing the n-6 double bond with 18:2 n-6 and the n-3 double bond with 18:3 n-3, respectively), we tried to decrypt the fatty acid structure driving the FADS2 substrate affinity. We first showed that both recombinant and native rat FADS2 were able to Δ6-desaturate not only the cis9- but also the cis12- and cis15-18:1 isomers. Next, the inhibitory effect of increasing concentrations of each 18:1 isomer was investigated in vitro on the Δ6-desaturation of α-linolenic acid. At equimolar inhibitor/substrate ratio (60 μM), the cis9-18:1 exhibited a significantly higher inhibition (25%) than the cis12- (8%) and cis15-18:1 (5%). This study shows that a single cis double bond in 12- or 15-position in 18:1 is enough to make them low Δ6-desaturable substrates. If a preexisting cis9-double bond is not absolutely required for the Δ6-desaturation of octadecenoic acids, its presence is however crucial to explain the higher enzyme affinity. Compared with oleic acid, the additional presence of a cis12-double bond in linoleic acid increased its inhibitory effect on the Δ6-desaturation of α-linolenic acid at low concentration (30 μM) but not at higher concentrations (60 and 120 μM). In this classification of the decreasing impact of the double bond when it comes closer to the methyl end of octadecenoic acids, the cis11-18:1 (cis-vaccenic acid) should be considered apart since it is itself not Δ6-desaturated but still a good competitive inhibitor of the α-linolenic acid Δ6-desaturation., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The phase diagram of mixed monolayers composed of dimyristoyl phosphatidylcholine (DMPC) and stearic acid (SA) on different subphases was previously reported. It was observed that on acid subphases, liquid-condensed domains with shapes that depend on the SA proportion are formed. For mixtures with 40-45mole% of SA, the domain shape changes from flower-like to circular domains. In this work, we carried out a detailed study of the driving force for the shape change. We find that it is related to the domain density which, in turn, is driven by the domain nucleation process and thus by oversaturation of the system leading to phase segregation. This could be a way of self-regulating the local electrostatics and mechanical properties in membrane surfaces with segregated phase domains., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The aim of this work is to study the phase diagram of mixed monolayers composed of dimyristoylphosphatidylcholine (DMPC) and stearic acid (SA) at different ionic strength and bulk pH of the aqueous subphase. In this way, the effect of ionization of SA on the interaction and thus on phase separation with the DMPC matrix can be analyzed. To this purpose, we first determined the ionization state of pure SA monolayers as a function of the bulk subphase pH. The SA monolayers are nearly fully ionized at pH 10 and essentially neutral at pH 4 and the mixture of DMPC and SA was studied at those two pHs. We found that the DMPC-enriched phase admits more SA if the SA monolayer is in a liquid-expanded state, which is highly related to the acid ionization state, and thus to the bulk pH and ionic strength. At pH 4 the molecules hardly mix while at pH 10 the mixed monolayer with DMPC can admit between 30 and 100% of SA (depending on the lateral pressure) before phase separation is established. The addition of calcium ions to the subphase has a condensing effect on SA monolayers at all pHs and the solubility of SA in the DMPC matrix does not depend on the bulk pH in these conditions. The observed phase diagrams are independent on the manner in which the state of the mixed film is reached and may thus be considered states of apparent equilibrium., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

To study the effect of membrane composition on the oxidation of liposomes, different systems were prepared by adding one component at time to phosphatidylcholine (Epikuron 200). In particular, the effect of cholesterol and its ester, cholesterol stearate, on membrane structure and oxidation was studied. A first screening of the structure and net charge of the different preparation was made by means of z-potential and size measurements. Then the liposomes were oxidized by using a hydrophilic radical initiator, the (2,2-azobis(2-amidinopropane) hydrochloride, AAPH, which thermally decomposes to give a constant radical flux in water. The oxidation of liposomes, monitored by following the absorbance of the primary products of oxidation at 234 nm, was shown to be dependent on the composition of the liposomal bilayer and so on its biophysical properties. In addition, size and z-potential measurements gathered in the time course of the peroxidation reaction, revealed that the oxidation induced a modification of the superficial characteristics of the membrane bilayer so as to change its charge at the shear plane (z-potential). This behaviour was shared by all liposomal preparations independent of the composition. The change in sizes of the different liposomal preparation, instead, followed different trends, being more stable both in control samples and in oxidized ones when cholesterol was present. From the analysis of the results, it can be concluded that cholesterol affects the oxidation induced by hydrophilic radical initiator of model membranes by changing the biophysical properties of the phospholipid bilayer. The rigidity induced by cholesterol at temperatures above the T(m) makes the membrane more resistant to radical attack from an external aqueous phase and this in turn delays the start of the reaction. The decrease of z-potential of the liposomal particles induced by the oxidation process can be an important clue to understand the mechanisms involved in the etiology of important diseases., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The phase behaviour of pure oleanolic acid (OLA) and in mixtures with stearic acid (SA) was characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and nuclear magnetic resonance (NMR). The crystalline OLA as received (OLA(ar)) becomes amorphous after being dissolved in chloroform and vacuum-dried at 50 degrees C (OLA(50)). Upon heating, both forms transform to the needle shape crystalline form (OLA(220)). Dimerization through H-bonding between COOH groups was detected both in OLA(ar) and OLA(220). Dimers are stronger in OLA(220), where H-bonding also involves the alcohol groups and plays a role in the crystalline organization. A eutectic type phase diagram was established for mixtures, with the eutectic composition close to pure SA. Mixtures rich in SA are miscible in the liquid and in the amorphous solid states, where the presence of SA-OLA co-dimers, formed through H-bonding between carboxyl groups, was detected. Miscibility and SA crystallinity decrease drastically with the OLA content., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

For the first time, the solid-liquid phase diagrams of five binary mixtures of saturated fatty acids are here presented. These mixtures are formed of caprylic acid (C(8:0))+capric acid (C(10:0)), capric acid (C(10:0))+lauric acid (C(12:0)), lauric acid (C(12:0))+myristic acid (C(14:0)), myristic acid (C(14:0))+palmitic acid (C(16:0)) and palmitic acid (C(16:0))+stearic acid (C(18:0)). The information used in these phase diagrams was obtained by differential scanning calorimetry (DSC), X-ray diffraction (XRD), FT-Raman spectrometry and polarized light microscopy, aiming at a complete understanding of the phase diagrams of the fatty acid mixtures. All of the phase diagrams reported here presented the same global behavior and it was shown that this was far more complex than previously imagined. They presented not only peritectic and eutectic reactions, but also metatectic reactions, due to solid-solid phase transitions common in fatty acids and regions of solid solution not previously reported. This work contributes to the elucidation of the phase behavior of these important biochemical molecules, with implications in various industrial applications.

The crystallographic and thermal properties of milk fat and fractions were investigated on heating using the coupling of synchrotron X-ray diffraction with differential scanning calorimetry. We showed that re-crystallisations occurred during the heating of the stearin and the olein fractions with the formation of a beta' 2L (41.1-42.6A) structure and a beta' 3L (66A) structure, respectively. By creating a quantified solid-liquid phase behaviour versus temperature diagram, the amount of the solid and liquid phases and the relative proportion of each of the crystalline structures within the solid phase were determined.

The structural basis of immiscibility of stearic acid (SA) in two unsaturated lipids at room temperature was examined. A 5% SA mixture in octadec-9-enoic acid (OA) is cloudy; a 5% SA solution in the methyl ester of OA (MeOA) is fully miscible. At 10% SA in MeOA, a clear and immiscible phase formed. The composition of this immiscible phase however was not 10% SA, but 25% SA. Adding additional SA altered the amount of the second phase, not its stoichiometry. Molecular mechanics explains the molecular basis for the ratio of saturated and unsaturated lipids in the different phases. Packing order of lipids within a unit volume explains the discrete lipid composition ratio forming each of the observed miscible and immiscible phases. The smallest unit cell volume that explains the observed stoichiometry is a cube (not a sphere).

The first total synthesis for the sponge derived (5Z,9Z)-(+/-)-2-methoxy-5,9-octadecadienoic acid, an analog of taxoleic acid, was accomplished in seven steps and in a 10% overall yield. It was again corroborated that the best strategy to prepare these cis,cis dimethylene interrupted double bonds is the double-alkyne bromide coupling reaction of 1,5-hexadiyne, which provides the advantage of achieving a 100% cis stereochemical purity for both double bonds after hydrogenation under Lindlar conditions. The alpha-methoxy functionality was best prepared via the Mukaiyama reaction of (4Z,8Z)-heptadecadienal with trimethylsilyl cyanide and triethylamine followed by acid hydrolysis. Selective methylation of the hydroxyl group of (5Z,9Z)-(+/-)-2-hydroxy-5,9-octadecadienoic acid was achieved with sodium hydride/methyl iodide when tetrahydrofuran was used as solvent. Complete spectral data is presented, for the first time, for this unusual marine alpha-methoxylated fatty acid.

We have previously shown how the location of an intercalant within the lipid bilayer can be qualitatively determined by using the excellent correlation that exists between the 13C NMR chemical shift of a polarizable carbon (e.g., the carbonyl or nitronyl carbon) and the polarity (using the Dimroth-Reichardt's ET(30) parameter) of the microenvironment in which that carbon resides. In a companion paper, we have determined criteria for reporter molecules that will assist us in converting this qualitative polarity data into quantitative Angstrom values. In the present paper, we report on our initial success in quantitatively mapping of the DMPC bilayer by linking two or more vertical points within a bilayer by both distance (in Angstroms) and ET(30) polarity. The results correlated well with the values obtained using the "parallax method" of Erwin London.

The binary mixtures involving tristearin (TS), stearyl stearate (SS) and stearic acid (SA) were studied by surface pressure-area (pi-A) measurements and by Brewster angle microscopy (BAM), at the air-water interface, and the Langmuir-Blodgett (LB) monolayers, transferred onto mica substrates, were analysed by AFM. The thermodynamic analysis indicated miscibility in the whole composition range for the system SA/TS, and partial miscibility for systems SA/SS and TS/SS. This behaviour was further confirmed by BAM observation and AFM analysis of LB films. The AFM imaging of collapsed monolayers revealed domains with a multilayered structure varying with system and composition. The layers thickness determined by cross section analysis are consistent with estimated molecular lengths and conformations proposed for the molecules, assuming nearly perpendicular or tilted orientations of the hydrocarbon chains to the interface.

Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies are reported for combinations of cis-6-octadecenoic acid (also termed petroselinic acid, PSA) and octadecanoic acid (also termed stearic acid, SA) across a wide range of binary mole ratio combinations. The data are then used to plot the phase diagram which is found to be montotectic with the PSA reducing the melting temperature of SA at all compositions. The relevance of these experiments to stratum corneum (SC) biophysical behavior, particularly the influence and potential mechanisms of PSA on dermal permeation, is discussed. The potential role of cis-6-octadecenoic acid as a permeation enhancer is discussed in the context of these studies of its interaction with saturated fatty acids.

Monolayers of oleanolic acid (OLA) mixed with stearic acid (SA) were studied at the air-water interface. The surface pressure-area (pi-A) isotherms, measured over the whole composition range, and BAM observations were used to investigate the phase behaviour and self-organization of these components in a two-dimensional structure. Pure OLA forms a very compressible monolayer, and BAM observation revealed the coexistence of large and irregular solid domains of different thickness dispersed in a gas matrix, compatible with the two most probable orientations of the OLA molecule at the interface. Mixtures of OLA/SA form condensed monolayers from low surface pressures and the thermodynamic analysis indicates that OLA molecules, in the presence of the long-chain SA, orient with the major axis almost perpendicular to the interface. Langmuir-Blodgett (LB) monolayers of pure SA and mixtures were further characterized by atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR). AFM images of LB mixed monolayers evidenced microphase separation, not observable by BAM. The SA rich domains are 4-6A thicker than those rich in OLA. The FTIR spectra of mixed LB films on CaF2 substrates showed that OLA does not perturb the all-trans conformation of the SA long alkyl chains, up to a mole fraction of 0.4. The carbonyl-stretching band of OLA suggests that the carboxylic groups of neighbour OLA molecules are involved in hydrogen bonds, forming dimers, as in pure solid phase OLA. These interactions seem to prevail over the OLA-water hydrogen bonds.

We studied dibucaine's effects on specific locations of n-(9-anthroyloxy)palmitic acid or stearic acid (n-AS) within phospholipids of synaptosomal plasma membrane vesicles isolated from bovine cerebral cortex (SPMV) and model membranes. Giant unilamellar vesicles (GUVs) were prepared with total lipids (SPMVTL) and mixture of several phospholipids (SPMVPL) extracted from SPMV. Dibucaine.HCl increased rotational mobility (increased disordering) of hydrocarbon interior, but it decreased mobility (increased ordering) of membrane interface, in both native and model membranes. The degree of rotational mobility in accordance with the carbon atom numbers of phospholipids comprising neuronal and model membranes was in the order at the 16, 12, 9, 6 and 2 position of aliphatic chain present in phospholipids. The sensitivity of increasing or decreasing effect of rotational mobility of hydrocarbon interior or surface region by dibucaine.HCl differed depending on the neuronal and model membranes in the descending order of SPMV, SPMVPL and SPMVTL.

The solid-liquid phase behaviour of stearic acid (SA) and stearonitrile (SN) in binary mixtures was investigated by differential scanning calorimetry (DSC), and the formation of SA-SN mixed monolayers at the air-water interface was followed by surface pressure-area (pi-A) measurements and by Brewster angle microscope (BAM) observation. The solid-liquid phase diagram is a eutectic type phase diagram, with the eutectic composition 0.90

The chemical composition and crystallisation properties of milk fat and its primary fractions, obtained by dry fractionation at 21 degrees C, were investigated. The solid fraction (stearin) and the liquid fraction (olein) displayed a different triacylglycerol (TG) composition. Stearin fraction was enriched in long-chain fatty acids, whereas olein fraction was enriched in short-chain and unsaturated fatty acids. Crystallisation properties of milk fat, and both the stearin and olein fractions were studied on cooling at |dT/dt|=1 degrees C min(-1) by differential scanning calorimetry and time-resolved synchrotron X-ray diffraction (XRD) at small and wide angles. Two main types of crystals corresponding to double chain length structures were characterised in the stearin fraction: alpha 2L(1) (47.5 Angstrom) and beta' 2L(2) (41.7 Angstrom). A triple chain length structure was formed in the olein fraction: alpha 3L (72.1 Angstrom). Crystallization of milk fat showed the formation of two 2L (47.3 and 41.6 Angstrom) and one 3L (72.1 Angstrom) lamellar structures with an hexagonal packing (alpha form). A schematic representation of the 3L packing of olein fraction was proposed to explain how a wide diversity of TG can accommodate to form a lamellar structure with a thickness of 72 Angstrom. Furthermore, the sharpness of the small-angle XRD lines associated to the alpha form was explained by the formation of liquid crystals of smectic type.

Stearic acid (SA) is highly soluble in structurally diverse solvents. SA/solvent packing within a (24.8 A)3 cubic volume explains the stoichiometry of SA solubility at multiple temperatures in multiple solvents. In the absence of solvent, the cubic volume contains 25 molecules at van der Waals distances from each other. At 55 degrees C, SA occupied half the cubic volume in saturated solution of four structurally diverse solvents. Below 4% SA/volume (e.g. in acetonitrile), the head and foot of each SA molecules on average is more than one solvent molecule away from the head and foot of a neighboring SA molecule. At 50% SA/cubic volume, -CH2- groups on SA molecules are separated from neighboring -CH2- groups on SA molecules by a monolayer of solvent molecules. Lowering the temperature from 55 to 25 degrees C, the volume fraction of SA decreased by a factor of 2 (or more) for every 6 degrees C. Lowering temperature increased the relative number of column of solvent molecules in the cubic phase, and correspondingly, the distance between SA molecules within the cubic volume increased. In three of five solvents, molecular mechanics calculations demonstrated the van der Waals stabilization that occurs from SA/SA affinity in the absence of solvent is similar in magnitude to the van der Waals stabilization from SA/solvent affinity. Methyl-t-butyl ether was less stabilized than hexane, acetone or methanol because the more bulky molecules packed less efficiently within the cubic volume. The most efficient/most stable packing however was still as columns of solvent between columns of SA. The efficiency and stability of SA and solvent packing optimal within the (24.8 A)3 cubic volume. Between 100 and 8% SA, multiple SA molecules present within the cubic volume function as SA aggregates. Both inter- and intra-cubic (phase) volume properties of SA aggregates coexist. Although acetonitrile and SA at the molecular level are both rod shaped, acetonitrile disrupted the packing of SA molecules within the cubic phase. The disrupted packing explains the much lower solubility of SA in acetonitrile than in the other solvents. The same molecular structures (e.g. methanol) can either stabilize or disrupt the packing of aggregated SA molecules, depending upon temperature. The mechanisms of aggregation within cubic volumes could also occur with structurally more complicated lipids. Aggregation and dispersion from such cubic phases could also be present in more complex chemical and/or macromolecular environments.

X-band electron paramagnetic resonance (EPR) spectroscopy has been employed to investigate the dynamic properties of magnetically-aligned phospholipid bilayers (bicelles) based on the molecular order parameters (S(mol)), the hyperfine splitting values and the line shapes of the EPR spectra. For the first time, a series of EPR spectra of n-doxylstearic acid spin-labels (n = 5, 7, 12, and 16) incorporated into Tm3+-doped parallel-aligned, Dy3+-doped perpendicular-aligned, and randomly dispersed 1,2-dimyristoyl-sn-glycero-3-phosphocholine/1,2-dihexanoyl-sn-glycero-3-phosphocholine (DMPC/DHPC) bicelles with respect to the direction of the static magnetic field have been investigated as a function of cholesterol content and temperature variation to characterize the orientational aspects along the hydrocarbon acyl chains. Important general observations are that under conditions for which the bicelle is poised in the liquid crystalline phase, the degree of ordering decreases as the nitroxide moiety is transferred toward the end of the stearic acid acyl chains. The addition of cholesterol increases the phase transition temperature and alignment temperature of the DMPC/DHPC phospholipid bilayers and increases the chain order. However, increasing the temperature of the bicelle system decreases the chain order. This report reveals that the dynamic properties of DMPC/DHPC bicelles agree well with other biological and model membrane systems. The results indicate that magnetically-aligned phospholipid bilayers are an excellent model membrane system.

Dimer structure and liquid structure of fatty acids in their binary mixtures such as decanoic acid (DA)/octadecanoic acid (SA) and DA/dodecanoic acid (LA) were studied through the measurements of self-diffusion coefficient (D), differential scanning calorimetry (DSC), density and viscosity. The obtained phase diagrams showed that DA and SA form a eutectic in the solid state but partly a solid solution in the SA-rich region; DA and LA form an incongruent-melting compound which forms a eutectic with DA. In the liquid mixture of DA and SA, the D of DA is larger than that of SA over the entire range of compositions and tends to approach the D of SA with increasing SA-mole fraction; the D of DA in the DA/LA system is also larger than that of LA especially in the LA-poor region and steeply approaches that of LA with increasing LA-mole fraction. These D values and phase diagrams were compared with those for the binary mixtures of n-alkanes (C14/C20, C19/C20 and C20/C24); it is concluded that the two kinds of fatty acids always form their individual homodimers in their liquid mixtures regardless of their compositions and temperatures.

The behaviour of dipalmitoylphosphatidylcholine (DPPC), mixed with stearonitrile (SN), was investigated at the air-water interface by surface pressure-area (pi-A) measurements and by direct visualisation of monolayers by Brewster angle microscopy (BAM). The pi-A-X diagram of system DPPC/SN was compared with the corresponding diagrams of systems DPPC/stearic acid (SA) and DPPC/octadecanol (OD) at 20 degrees C. Monolayers of the three systems reach the closest packing of alkyl chains in the 0.4-0.6 range of XDPPC. Thermodynamic analysis indicates miscibility in the three binary systems with negative deviations from the ideal behaviour. Morphological features of system DPPC/SN change significantly with XDPPC and temperature in the range 10-30 degrees C. At 10 and 20 degrees C mixed monolayers form condensed states from low pi all over the composition range. At 30 degrees C, the liquid-expanded (LE)--liquid-condensed (LC) phase transition occurs at increasing pi with XDPPC. The shape and size of condensed domains change with XDPPC and pi. Contrarily to the behaviour of pure components, mixed monolayers of DPPC/SN exhibit orientational order in the 0.2-0.6 mol fraction range of DPPC. BAM observation confirmed the partial miscibility indicated by GE data in a limited range of compositions at 30 degrees C.

Oxidation of triacylglycerols (TAGs) containing oleic acid leads to the formation of several products. This study characterizes hydroperoxy- and epoxy-TAGs including their regio-isomers. For this purpose, epoxy- and hydroperoxy-TAGs, formed by oxidation of 1,2-dipalmitoyl-3-oleoyl-glycerol (PPO) and 1,3-dipalmitoyl-2-oleoyl-glycerol (POP) under air and 18O2, were analysed by reverse phase liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS) using a triple quadrupole mass analyser, in positive ion mode. Post-column infusion of ammonium formiate was used to obtain intense molecular ion adducts. Pure 1,2-dipalmitoyl-3-epoxystearoyl-glycerol (PPEs) and 1,3-dipalmitoyl-2-epoxystearoyl-glycerol (PEsP), synthesized by epoxidation of the corresponding monounsaturated TAGs, were used to confirm MS/MS identification. The use of 18O2 oxidation experiments permitted unambiguous identification of MS/MS fragmentation pathways of both hydroperoxide and epoxy-TAGs. Fragmentation of hydroperoxy-TAGs are very distinct from their epoxy-TAGs homologues and consist of simultaneous losses of hydrogen peroxide (34 a.m.u.) and water (18 a.m.u.).

Solid-liquid phase behavior of binary fatty acid mixtures was investigated by means of differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) for the mixture composed of oleic acid (OA) and stearic acid (SA) and that composed of OA and behenic acid (BA). The DSC results provided a monotectic type T-X phase diagram for these mixtures, from which it was suggested that the two fatty acid species are completely immiscible in a solid phase regardless of the two polymorphs of OA, i.e., alpha-form or gamma-form. The solid phase immiscibility was confirmed by the FT-IR observation that the spectra obtained for the mixtures correspond to the superposition of the two spectra for respective components. Thermodynamic analysis of liquidus line demonstrated that OA and SA form an ideal mixture in a liquid phase, whereas the mixing of OA and BA in a liquid phase is slightly non-ideal.

Based on a series of physicochemical properties (differential scanning calorimetry, powder X-ray crystallographic studies and Fourier-transform infra red spectroscopic analysis) determined for N-stearoylethanolamine (NSEA) (C18:0) at different temperatures, evidence has been given that this compound can exist in (at least) three polymorphic forms. Powder X-ray crystallography clearly demonstrates the presence of three distinct molecular packings at distinct temperatures while spectral changes in the vibrational spectra reveal that the geometry of the CH(2)z.sbnd;CO functional group of the molecule is affected during the polymorphic transitions. Rationalization of the thermal physicochemical behavior of NSEA in terms of molecular packing is also proposed. It supposes rearrangement of the hydrocarbon chains upon heating of the molecule.

To elucidate the interaction among the molecules which constitute intercellular lipids of stratum corneum, the phase diagrams in the binary mixtures of N-octadecanoyl-phytosphingosine (CER)/stearic acid (SA) and CER/cholesterol (CHOL) were studied by differential scanning calorimetry and by small- and wide-angle X-ray diffraction. These phase diagrams are mostly expressed by a eutectic type one. However, from their detailed analyses, it was revealed that in the phase diagram of CER/SA a new solid structure is formed just above the eutectic temperature. The lamellar spacing of the new structure is nearly equal to the length given by the sum of the two molecules of CER and/or SA, that is, in the lipid bilayer the hydrocarbon chains of CER and SA lie almost perpendicular to the lipid bilayer surface and the two kinds of molecules distribute homogeneously. On the other hand, in the binary mixture of CER/CHOL, CHOL molecules are apt to be isolated from the mixture. In a ternary mixture composed of equimolar lipids of CER, CHOL and SA, it was found that a pseudo-hexagonal structure takes place even in the solid state. This fact indicates that the three components are miscible and the hydrocarbon chains lie perpendicular to the lipid bilayer surface. We can draw the conclusion that the multi-component mixtures containing ceramide are apt to form the lamellar structure where even in the solid state the hydrocarbon chains lie perpendicular to the lipid bilayer surface and the components with hydrocarbon chains distribute homogeneously.

One of the contributions to the surface potential in charged phospholipid monolayers at air-water interfaces is the double layer potential. In this note several misconceptions found in the literature concerning the relationship between the double layer potential and the degree of dissociation of the lipid polar headgroups are critically analyzed. The deviations of the double layer potential measurements from the Gouy-Chapman theory observed by several authors are explained by taking into account the dependence of the degree of dissociation with concentration, area per lipid molecule and pH.

Perturbations induced by ethylazinphos on the physical organization of dipalmitoylphosphatidylcholine (DPPC) and DPPC/cholesterol membranes were studied by differential scanning calorimetry (DSC) and fluorescence polarization of 2-, 6-, 12-(9-anthroyloxy) stearic acids and 16-(9-anthroyloxy) palmitic acid. Ethylazinphos (50 and 100 microM) increases the fluorescence polarization of the probes, either in the gel or in the fluid phase of DPPC bilayers, and this concentration dependent effect decreases from the surface to the bilayer core. Additionally, the insecticide displaces the phase transition to a lower temperature range and broadens the transition profile of DPPC. A shifting and broadening of the phase transition is also observed by DSC. Furthermore at insecticide/lipid molar ratios higher than 1/7, DSC thermograms, in addition to the normal transition centered at 41 degrees C, also display a new phase transition centered at 45.5 degrees C. The enthalpy of this new transition increases with insecticide concentration, with a corresponding decrease of the main transition enthalpy. Ethylazinphos in DPPC bilayers with low cholesterol (< or = 20 mol%) perturbs the membrane organization as described above for pure DPPC. However, cholesterol concentrations higher than 20 mol% prevent insecticide interaction, as revealed by fluorescence polarization and DSC data. Apparently, cholesterol significantly modulates insecticide interaction by competition for similar distribution domains in the membrane. The present results strongly support our previous hypothesis that ethylazinphos locates in the cooperativity region, i.e. the region of C1-C9 atoms of the acyl chains, and extends to the lipid-water interface, where it increases lipid packing order sensed across all the thickness of the bilayer. Additionally, and, on the basis of DSC data, a lateral regionalization of ethylazinphos is here tentatively suggested.

Tuberculostearic acid, (R)-10-methyloctadecanoic acid, is a characteristic component of pathogenic mycobacteria and related organisms. Sensitive detection of this acid in infected material allows rapid detection of mycobacterial disease. A novel, convergent synthesis of tuberculostearic acid and key chiral intermediates is described in this communication, to provide a reference compound. Racemic and (R)- and (S)-1-iodo-2-methyldecanes were synthesised from 1-octanal and 1-carboethoxyethylidenetriphenylphosphorane as initial starting materials. 1-Hydroxyoct-7-yne was made from 1,6-hexanediol by two alternative methods and coupled with the above racemic iodide. Hydrogenation and oxidation of the resulting (R,S)-10-methyloctadec-7-yn-1-ol gave racemic tuberculostearic acid.

The influence of acyl chain length, double bond number and position on the structural and dynamic properties of phosphatidylcholine bilayers in the liquid crystalline state was studied. The range and rate of the rotation of 1,6-diphenyl-1,3,5-hexatriene and a set of n-(9-anthroyloxy)stearates(n = 2, 7 and 12), which are located at different depths in the lipid bilayers, were measured using differential polarized phase fluorometry in multilamellar liposomes of several unsaturated synthetic phosphatidylcholines. For the anthroyloxy-stearate probes, two rotational modes, 'in' and 'out' of the plane of the anthroyl aromatic ring, were partially resolved by measuring at different excitation wavelengths. The data obtained here indicate that in lecithins containing the same acyl chain in sn-1 and sn-2, the introduction of double bonds towards the deep interior of the lipid bilayer decreases the order in the external region of the bilayer and the viscous resistance to the rotation of all the probes tested. On the contrary, double bonds located towards the external region of the bilayer increase order and viscous resistance to the rotation of probes located in the external region. Increasing acyl chain length has different effects depending on the probe and on the rotational mode considered. Measurements in mixed chain lecithins indicate that the influence of increasing unsaturation in sn-2 has different consequences depending on the acyl group that is present in sn-1. Similarly, increasing acyl chain length in sn-1 influences differently the bilayer properties depending on the fatty acid that is present in sn-2.

GM1 ganglioside containing a hydroxylated fatty acid moiety, GM1(OH), was synthesized starting from lyso-GM1 and D-(+)-2-hydroxystearic acid. The aggregative, geometrical and distribution properties of GM1(OH) were compared with those of stearic acid containing GM1 ganglioside; laser light scattering measurements, differential scanning calorimetry and fluorescence spectroscopy were used. GM1 and GM1(OH) are present in solution as micelles with a hydrodynamic radius of 58.7 and 60.0 A, and molecular mass of 470 and 570 kDa, respectively. The surface area occupied by the monomer of GM1(OH) at the lipid-water interface of the aggregate was calculated to be 117 A2, which is 3 A2 lower than that determined for GM1. Proton NMR analyses of GM1 and GM1(OH) suggest different three-dimensional structures at the ganglioside lipid-water interface. Both GM1(OH) and GM1 inserted into dipalmitoylphosphatidylcholine (DPPC) vesicles undergo segregation phenomena, with the formation of ganglioside-enriched microdomains, but GM1(OH) shows a higher degree of dispersion in the DPPC matrix and exerts a lower rigidifying effect than does GM1.