Interaction of keratolytic drug,salicylic acid with dipalmitoyl phosphatidylethanolamine vesicles

Salicylic acid (SA), a keratolytic drug, is used to treat skin disorder like corns, warts, and acne. To understand the mechanism by which SA interacts with the cell membranes, we have investigated its interaction with dipalmitoyl phosphatidylethanolamine (DPPE) vesicles using DSC, ¹H NMR and Raman spectroscopy. Presence of drug asymmetrically broadened the acyl chain melting transition and shifted the transition temperature, T _m, to lower value. Both, NMR and DSC studies indicate that the drug molecules are located in the glycerol backbone region of the lipid bilayer and increase the membrane headgroup fluidity. At high drug concentration, additional transitions are observed whose intensity increases with increasing drug concentration. In cholesterol doped DPPE dispersion the interaction of SA with DPPE bilayer is more. The transformation of the gel phase of DPPE dispersion to a stable crystalline subgel phase(s) is accelerated by the presence of SA.     

Procain interaction with DPPC multilayers: an ESR spin label investigation

A spin label electron spin resonance (ESR) study has been carried out on the interaction between the local anesthetic procaine (PRC) and multilamellar dispersions of di-palmitoylphosphatidylcholine (DPPC). The investigation has been performed either in the gel or in the liquid crystal phase of DPPC varying the anesthetic/DPPC molar ratio as well as the pH of the dispersion medium and using spin labeled DPPC molecules (5- and 16-PCSL) and the di-tert-butyl nitroxide (DTBN) spin probe. On increasing the anesthetic concentration in the dispersion medium up to PRC/DPPC molar ratio of 33 mol.%, a lyotropic transition of the bilayer from the lamellar gel phase L_β, to the interdigitated L_βi one is observed either at pH 5.0 or at pH 10.0. At intermediate pH values, about pH 7.0, such a PRC concentration dependent transition is absent. A decrease of the partition of the DTBN molecules between the dispersion medium and the fluid hydrophobic phase of DPPC multilayers is observed at pH 5.0 with anesthetic concentration, while an opposite behaviour is evidenced at pH 10.0. The pre- and main-phase transition temperatures of the DPPC multilayers are also affected although to different extent. These results are interpreted in terms of adsorption of the PRC molecules at the surface of the model membrane at the extreme pH values investigated, while at about neutral pH values they intercalate among the DPPC molecules. The protonation state of procaine plays an important role as it determines the way of surface adsorption of the PRC molecules in the neutral form at the high pH value and in the charged cationic form at pH 5.0.     

31P NMR and FTIR studies on the interaction of phosphorylacetohydrazides with dipalmitoyl phosphatidylcholine model membranes

The effect of original synthetic nootropic drugs (phosphorylacetohydrazides) on the physical properties of the dipalmitoyl phosphatidylcholine (DPPC) membranes was studied by³¹P nuclear magnetic resonance and Fourier transform infrared spectroscopies. It has been shown that the tested preparations reduce the phase transition temperature, widen the transition interval, suppress pretransition, render some condensing effect on the gel phase and essentially disorder the lipid bilayer in the liquid-crystalline state. The obtained results are in agreement with the suggested mechanism of the primary pharmacological effect of nootropic preparations. According to this mechanism, the drug molecules penetrate into the hydrophilic region of the bilayer, interacting closely with the polar groups of DPPC, disturbing the bilayer organization and leading to polymorphism. By taking into account that the main property of nootropic preparations is to improve processes of training and memory, we suppose that the new lipid-drug organization of phospholipidic membranes and lipid polymorphism are the necessary steps of the nootropic activity. The similarity of molecular mechanisms of various nootropic drug effects on the lipid bilayer allows us to suppose that the positive effect of nootropics on the synaptic transmission may be governed by their influence on the phase transition of the lipid component of the synaptic membranes at the stage of the neurotransmitter release.     

Kinetics and mechanism of electron transfer reaction of single and double chain surfactant cobalt(III) complex by Fe2+ ions in liposome (dipalmitoylphosphotidylcholine) vesicles: effects of phase transition

In this study, we report the kinetics of reduction reactions of single and double chain surfactant cobalt(III) complexes of octahedral geometry, cis-[Co(en)₂(4AMP)(DA)](ClO₄)₃ and cis-[Co(dmp)₂(C₁₂H₂₅NH₂)₂](ClO₄)₃ (en = ethylenediamine, dmp = 1,3-diaminopropane, 4AMP = 4-aminopropane, C₁₂H₂₅NH₂ = dodecylamine) by Fe²⁺ ion in dipalmitoylphosphotidylcholine (DPPC) vesicles at different temperatures under pseudo first-order conditions. The kinetics of these reactions is followed by spectrophotometry method. The reactions are found to be second order and the electron transfer is postulated as outer sphere. The remarkable findings in the present investigation are that, below the phase transition temperature of DPPC, the rate decreases with an increase in the concentration of DPPC, while above the phase transition temperature the rate increases with an increase in the concentration of DPPC. The main driving force for this phenomenon is considered to be the intervesicular hydrophobic interaction between vesicles surface and hydrophobic part of the surfactant complexes. Besides, comparing the values of rate constants of these outer-sphere electron transfer reactions in the absence and in the presence of DPPC, the rate constant values in the presence of DPPC are always found to be greater than in the absence of DPPC. This is ascribed to the double hydrophobic fatty acid chain in the DPPC that gives the molecule an overall tubular shape due to the intervesicular hydrophobic interaction between vesicles surface and hydrophobic part of the surfactant complexes more suitable for vesicle aggregation which facilitates lower activation energy, and consequently higher rate is observed in the presence of DPPC. The activation parameters (ΔS^# and ΔH^#) of the reactions at different temperatures have been calculated which corroborate the kinetics of the reaction.     

Theory of XMCD spectra at the L2,3 absorption edges of mixed valence Ce and Yb compounds in high magnetic fields

We examine the structure of aggregates formed due to DNA interaction with dipalmitoylphosphatidylcholine (DPPC) in presence of Ca²⁺ and Zn²⁺ using small-angle synchrotron X-ray diffraction (SAXD) and neutron scattering (SANS). SAXD shows structural heterogeneity as a function of the cation concentration and temperature: At low cation concentration (∼1 mM), aggregates show two DPPC phases, one with a lateral segregation of DNA and cation, while higher cation concentration improves the DNA packing and the condensed lamellar phase is observed in DNA+DPPC+20mMion²⁺ aggregates. The SANS detected the dissolution of the condensed lamellar phase into unilamellar DPPC+Zn²⁺ vesicles due to gel ↦ liquid-crystal phase transition in DNA+DPPC+20mM Zn²⁺ aggregates with the short fragmented salmon sperm DNA.     

变温拉曼光谱和DSC探讨人参皂苷Rb1分子与DPPC双层膜的作用

研究人参皂苷分子与生物膜的作用对于深入了解中药人参的药理活性及其生物学功效至关重要。DPPC作为具有双分子层结构的脂质分子,常被许多国内外学者作为模拟膜的模型来研究药物分子与细胞膜的作用;Rb1作为中药人参中的重要皂苷成分,具有显著的药理学功效和生物性能。拉曼光谱是探讨分子间作用的有力工具,差示扫描量热技术（differential scanning calorimetry, DSC）是研究脂双层分子单体及其与药物分子作用的常用技术,而将两者结合研究药物分子对细胞膜作用的研究的报道较少。本文采用变温拉曼光谱和DSC探讨了在温度变化条件下人参皂苷Rb1单体分子与DPPC双层膜的作用。通过拉曼光谱测试,在Rb1作用前后,DPPC分子极性头部O—C—C—N+和C—C伸缩振动区域以及烷基链部分C—H键的伸缩振动区域的变化表明,随着温度的增加,含有一定浓度Rb1的DPPC磷脂极性头部旁氏构象没有发生变化,脂酰链的无序性构象增多,侧向排列的无序性增强,DPPC脂双层的流动性增加。由DSC实验得到的几个热力学常数[相变温度（T_m）、半峰宽（ΔT_1/2）及相转变焓值（ΔH）]的变化表明,DSC进一步验证了变温拉曼实验结果,随着Rb1浓度的增大,DPPC双层膜的相变温度显著下降,流动性增强,说明Rb1对DPPC双层膜的影响较大。     

A comparative electron spin resonance investigation on the effects of barbital and tetracaine on DPPC multilayers

We have performed a comparative spin label ESR investigation of the effects of tetracaine and barbital on DPPC multilamellar vesicles (MLV). The investigation has been carried out both at pH 5.0 and 9.0, by using the spin labels 5-SASL, 5-PCSL and DTBN as magnetic probes. Information on the thermotropic properties of the multilamellae, such as molecular orientational degree of order, packing density and permeability has been obtained. The results show that tetracaine induces fluidization of the phospholipid bilayers, reduction of the molecular packing density and downward shift of the main phase transition temperature of the multilayers of DPPC. Moreover, increasing concentrations of tetracaine are able to induce the lyotropic gel → liquid-crystal phase transition at a fixed temperature, in particular at pH 5.0. Barbital, instead, is much less effective than tetracaine in perturbing the membrane properties. In fact, the most important effect observed is only a progressive fluidization of the DPPC bilayers especially at pH 9.0. The dependence on pH of the effects observed suggests that the anesthetic molecules locate at different position in the lipid bilayers depending on the protonation state of both molecules.     

Some structural and dynamical properties of multilamellar vesicles incorporated with propranolol

Summary Spin labelling ESR, calorimetry and³¹P NMR have been used to investigate dipalmitoyl phosphatidylcholine dispersions incorporated with propranolol which is a β-adrenoceptor blocking drug, widely used in the treatment of arrhythmy. The drug appears to enter the lipid bilayer also at the lowest concentrations and to induce a progressive fluidification of multilamellar vesicles. In fact, the presence of drug reduces the temperature of chain melting transition and the corresponding cooperation number. Furthermore the phase transitionL _β′ −P _β′ is not observable also at the lowest drug concentrations. Work presented at the First USSR-Italy Bilateral Meeting on Liquid Crystals held in Portonovo, Ancona (Italy), September 30–October 2, 1987.     

Interaction of dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin

Insulin, a peptide that has been used for decades in the treatment of diabetes, has well-defined properties and delivery requirements. Liposomes, which are lipid bilayer vesicles, have gained increasing attention as drug carriers which reduce the toxicity and increase the pharmacological activity of various drugs. The molecular interaction between (uncharged lipid) dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin has been characterized by using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction. The characteristic protein absorption band peaks, Amide I (at about 1660?cm^?1) and Amide II band (at about 1546?cm^?1) are potentially reduced in the liposome insulin complex. Wide-angle x-ray scattering measurements showed that the association of insulin with DPPC lipid of liposomes still maintains the characteristic DPPC diffraction peaks with almost no change in relative intensities or change in peak positions. The absence of any shift in protein peak positions after insulin being associated with DPPC liposomes indicates that insulin is successfully forming complex with DPPC liposomes with possibly no pronounced alterations in the structure of insulin molecule.     

Lyotropic model membrane structures of hydrated DPPC: DSC and small-angle X-ray scattering studies of phase transitions in the presence of membranotropic agents

Multibilayer structures of hydrated phospholipids, often considered as model biological membranes, are, from the physical viewpoint, lyotropic liquid crystalline systems undergoing temperature-induced mesomorphic phase transitions. Effects of silver nitrate and urocanic acid on lyotropic phase states of hydrated L-α-dipalmitoylphosphatidylcholine (DPPC) have been studied by small-angle X-ray scattering and differential scanning calorimetry (DSC). Both methods show increase of the main phase-transition temperature (T_m) of hydrated DPPC upon introduction of AgNO₃ or urocanic acid, decrease of pre-transition temperature (T_p) in the presence of urocanic acid and its increase in the presence of AgNO₃. Thus, urocanic acid widened the ripple-phase temperature region. Silver nitrate caused the appearance of an additional high-temperature peak on DSC thermograms, evidencing phase separation in the system. Both agents caused minor effects on DPPC lipid bilayer repeat distance (D) in gel phase, but resulted in noticeable increase of D in the liquid crystal phase with temperature as compared to undoped DPPC structures.     

Electrolyte interaction with DPPC vesicles: An ESR study

Summary The partition of the spin probe TEMPO between the fluid lipid phase of single-walled vesicles of dipalmitoylphosphatidylcholine and the aqueous bulk solution have been used to investigate the interaction of monovalent ions with polar head of neutral phospholipids. The study has been performed by electron spin resonance (ESR) spectroscopy in the temperature range of (20÷60)°C and in the presence of (0÷3) M 1∶1 electrolyte. In the absence of electrolyte the spin probe TEMPO reveals the characteristic order→disorder DPPC main phase transition atT _m≈37°C, while the pretransition occurs atT _p≈27.5°C. On increasing the ionic strength of the dispersion medium it results for the partition coefficient,P _C, that, at each temperature,P _C(3)>P _C(2)>P _C(1)>P _C(0). Correspondingly, the pretransition disappears and theT _m value downshifts from ≈37°C with 0 M electrolyte to ≈34°C with 3M salt in the order:T _m(3)>T _m(2)>T _m(1)>T _m(0). The results suggest an increase in the net surface charge density of vesicles due to high ionic-strength values. The alteration of the electric interactions occurring into the polar zone of DPPC bilayer reduces the hindrances which, in turn, favour the enhancement of TEMPO partitioning in the hydrophobic core of phospholipid bilayers. The authors of this paper have agreed to not receive the proofs for correction.     

Effect of temperature on the photobehavior of Rose Bengal associated with dipalmitoylphosphatidyl choline liposomes

The association and photobehavior of Rose Bengal (RB) in the presence of dipalmitoylphosphatidyl choline (DPPC) small unilamellar liposomes is determined by the temperature. At temperatures above the main phase transition of the bilayer, the incorporation of the dye is ca. 2.5 times more efficient than that taking place when the bilayer is in the gel state. In both temperature ranges, adsorption isotherms show a noticeable anti-cooperativity that can be related to electrostatic repulsion between bound molecules. The photophysics and the photochemistry of the bound dye molecules also depend on the bilayer status. In particular, in the liquid crystalline state the surrounding of the dye is more polar and production of singlet oxygen is less efficient (Φ∼0.1). This reduced singlet oxygen production is partially due to a low triplet yield (Φ_T=0.35) and triplet self-quenching due to a high local RB concentration. In spite of these, tryptophan is efficiently photobleached when RB is associated to liposomes in the liquid crystalline state, probably due to a Type I mechanism favored by its high local concentration in the sensitized surroundings.     

Lipid chain mobility in interdigitated DPPC systems

The segmental lipid chain mobility in the gel phase of dipalmitoylphosphatidylcholine (DPPC) multilayers dispersed in buffer and in the interdigitated gel phase induced by glycerol, ethylene glycol, ethanol and chaotropic salt NaClO₄ was compared by using conventional electron spin resonance (ESR) spectroscopy. The stearic acids bearing the nitroxide moiety at different positions down the acyl chain (n-NSA,n-5, 7, 10, 12 and 16) were used to characterized the chain motion, and the outer hyperfine splittings of the spectra, 2A _max, were taken as indices of the rotational mobility of the chain in the gel phase. The ESR measurements revealed a gradient of increased mobility on proceeding towards the terminal methyl end in the fully hydrated gel phase of DPPC bilayers. This gradient was reduced in the interdigitated gel phase induced by ethanol and chaotropic salt NaClO₄, whereas the rotational mobility throughout the length of the chain was comparable to that near the polar/apolar interface in the interdigitated gel phase in glycerol and ethylene glycol. Moreover, the motional anisotropy was much less affected by temperature in the interdigitated gel state of DPPC in glycerol and ethylene glycol as compared both to normal bilayer gel phase and to the other interdigitated DPPC systems. Finally, there was no evidence for chain interdigitation in the fluid phase of DPPC dispersions in any medium.     

等静压下0.75Pb（Mg1/3Nb2/3）O3-0.25PbTiO3陶瓷的介电性能研究

研究了等静压对0.75Pb（Mg_1/3Nb_2/3）O₃-0.25PbTiO₃（PMN-25PT）陶瓷介电温谱的影响,PMN-25PT剩余极化随等静压变化和等静压压致相变.结果表明,随着压力增加,PMN-25PT的介电峰值温度T_m降低,/+{dT_m}/-{dP}≈-4℃/kbar,极化弛豫增强;剩余极化随压力增加连续减小;介电常数对压力的依赖关系与对温度场的依赖相似,压力诱导PMN-25PT发生弛豫铁电—顺电相变,相变为宽化的渐变过程,频率色散和极化弛豫更加强烈和普遍. 关键词： 铌镁酸铅-钛酸铅 等静压 介电弛豫 压致相变     

Influence of general-inhalation anesthetics on DPPC vesicles: a spin label study

Summary Electron spin resonance spectroscopy has been used to investigate the effects of three inhalation anesthetics,i.e. halothanechloroform-diethyl ether, on the thermomotropic behaviour of the polar interface and hydrophobic region as well as of DPPC-sonicated unilamellar vesicles. The study performed in the temperature range (25÷45)°C and for DPPC-to-anesthetic molar-concentration ratios of 4∶1, 2∶1 and 1∶1 shows that anesthetics, for their mechanisms of action, can be grouped in two classes: halothane and chloroform belong to one class, while diethyl ether to the other one. The former two downshift the main phase transition temperature,T _t, of DPPC in a remarkable way, whilst the latter one influences the gel→liquid crystalline-transition temperature in a less extent. TheT _t downshift depends on anesthetic concentration and the effectiveness in perturbing the bilayer order results halothane>chloroform≫ diethyl ether. Two microenvironments with a different degree of anisotropic motion are found in the hydrophobic region of vesicles in the absence of anesthetics. Halothane and chloroform affect the region more or less in a similar way which, in turn, results to be different from the action exerted on the microenvironments by diethyl ether. To speed publication, the authors of this paper have agreed to not receive the proofs for correction.     

Diffusion in supported lipid bilayers: Influence of substrate and preparation technique on the internal dynamics

The diffusion law of DMPC and DPPC in Supported Lipid Bilayers (SLB), on different substrates, has been investigated in details by Fluorescence Recovery After Patterned Photobleaching (FRAPP). Over micrometer length scales, we demonstrate the validity of a purely Brownian diffusive law both in the gel and the fluid phases of the lipids. Measuring the diffusion coefficient as a function of temperature, we characterize the gel-to-liquid phase transition of DMPC and DPPC. It is shown that, depending on the type of substrate and the method used for bilayer preparation, completely different behaviours can be observed. On glass substrates, using the Langmuir-Blodgett deposition technique, both leaflets of the bilayer have the same dynamics. On mica, the dynamics of the proximal leaflet is slower than the dynamics of the distal leaflet, although the transition temperature is the same for both layers. Preparing bilayers from vesicle fusion in same conditions leads to more random behaviours and shifted transition temperatures.     

Mitogens-DPPC-vesicles interaction: A spin label ESR study

Summary The electron spin resonance spectroscopy with the spin labelling technique has been used to investigate the interaction of sonicated di-palmitoyl-phosphatidylcholine (DPPC) small unilamellar vesicles with concanavalin A (Con A), phytohemagglutinin (PHA) and staphylococcal enterotoxin B (SEB) in the temperature range 0–50°C. Conventional ESR measurements show that the addition of mitogens to the vesicles suspensions up to the number of mitogens/number of vesicles ratio of 60 increases the orientational degree of order of the lipid molecules in the gel phase and the gel→liquid-crystalline phase transition temperature. No effects on the liquid-crystalline phase have been observed, also no matter for the mitogen used. The effectiveness results in the order: ConA>SEB>PHA. Saturation transfer-ESR measurements evidence more restricted rotation of the DPPC molecules in the gel phase in the presence of Con A and SEB than in the presence of PHA if compared to pure DPPC-vesicles. The effective rotational correlation time, σ_c, of the spin label 5-SASL results about one order of magnitude higher in the presence of 60 mitogen molecules/vesicle. The ESR findings suggest a mitogen-induced increase in the packing density of lipid bilayers which is attributed to a morphological change from sonicated vesicles, with a small radius of curvature, to a more planar mesophase. Con A is more effective than SEB and PHA in inducing this process. The authors of this paper have agreed to not receive the proofs for correction.     

Effect of γ irradiation on the heat capacity of (CH3)2NH2Al(SO4)2 · 6H2O crystals near the ferroelectric phase transition

The heat capacity of dimethyl ammonium-aluminum sulfate crystals (DMAAS), both nonirradiated and γ-irradiated to fluences of 10⁷, 5×10⁷, and 10⁸ R, has been measured by the adiabatic method near the ferroelectric phase transition (PT) within the 80–300 K temperature range. The C _p =f(T) curve exhibits a λ-shaped anomaly near the phase-transition point T _C =152 K. The PT temperature and the magnitude of the anomaly are shown to decrease with increasing γ-irradiation fluence. It has been established that the ferroelectric PT at T _C =152 K, which lies close to the tricritical point, shifts progressively more under γ irradiation toward the second-order PT, and that the behavior of the anomalous part of the heat capacity in the ferroelectric phase is described by the thermodynamic theory of Landau. The experimental heat-capacity data have been used to calculate the variation of the thermodynamic functions of the DMAAS crystal.     

A comparative Raman study of 0.65(PbMg<Subscript>1/3</Subscript>Nb<Subscript>2/3</Subscript>O<Subscript>3</Subscript>) -0.35(PbTiO<Subscript>3</Subscript>) single crystal and thin film

We report a comparative Raman study of 0.65(PbMg_1/3Nb_2/3O₃)-0.35(PbTiO₃) (PMN-0.35PT) single crystal and thin film. Raman spectra investigation indicates a change in bulk from the high temperature cubic to the tetragonal phase and then to the low temperature Mc monoclinic phase. The transition temperatures are in good agreement with the ones previously observed by dielectric measurements on the same sample. In contrast, we observe no phase transition to the monoclinic phase in the PMN-0.35PT 4000 Å thick film and only a cubic to tetragonal diffuse transition has been determined at high temperature. The enhanced stability of the tetragonal phase and the absence of low temperature monoclinic phase have been attributed to the in plane strain.     

Dielectric and ultrasonic investigation of phase transition in cuinp2s6 crystals

Investigation results of dielectric and ultrasonic properties of layered CuInP₂S₆ crystals are presented. At low frequencies, dielectric spectra are highly influenced by the high ionic conductivity with the activation energy of 7357.4?K (0.635?eV). The high-frequency part of the spectra is determined by relaxational soft mode. The critical slowing down and Debye-type dispersion show the order–disorder type of the phase transition. The temperature dependence of the relaxational soft mode and dielectric contribution show a quasi-one-dimensional behaviour. Ultrasonic velocity exhibits critical slowing down which is accompanied by attenuation peaks in the phase transition region. Layered CuInP₂S₆ crystals have extremely large elastic nonlinearity in the direction perpendicular to layers. The nonlinear elastic parameters substantially increases at the PT temperature.