scholarly journals Clotrimazole Fluidizes Phospholipid Membranes and Localizes at the Hydrophobic Part near the Polar Part of the Membrane

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1304
Author(s):  
Alessio Ausili ◽  
Illya Yakymenko ◽  
José A. Teruel ◽  
Juan C. Gómez-Fernández
Keyword(s):  
Hydrocarbon Chain ◽  
Imidazole Ring ◽  
Fatty Acyl ◽  
Phospholipid Membranes ◽  
Polar Group ◽  
Relaxation Rates ◽  
Aromatic Rings ◽  
Scanning Calorimetry ◽  
Acyl Chains ◽  
Dynamics Simulations

Clotrimazole (1-[(2-chlorophenyl)-diphenylmethyl]-imidazole) is an azole antifungal drug belonging to the imidazole subclass that is widely used in pharmacology and that can be incorporated in membranes. We studied its interaction with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) phospholipid vesicles by using differential scanning calorimetry and found that the transition temperature decreases progressively as the concentration of clotrimazole increases. However, the temperature of completion of the transition remained constant despite the increase of clotrimazole concentration, suggesting the formation of fluid immiscibility. 1H-NMR and 1H NOESY MAS-NMR were employed to investigate the location of clotrimazole in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) phospholipid membranes. In the presence of clotrimazole, all the resonances originating from POPC were shifted upfield, but mainly those corresponding to C2 and C3 of the fatty acyl, chains suggesting that clotrimazole aromatic rings preferentially locate near these carbons. In the same way, 2D-NOESY measurements showed that the highest cross-relaxation rates between protons of clotrimazole and POPC were with those bound to the C2 and C3 carbons of the fatty acyl chains. Molecular dynamics simulations indicated that clotrimazole is located near the top of the hydrocarbon-chain phase, with the nitrogen atoms of the imidazole ring of clotrimazole being closest to the polar group of the carbonyl moiety. These results are in close agreement with the NMR and the conclusion is that clotrimazole is located near the water–lipid interface and in the upper part of the hydrophobic bilayer.

scholarly journals Diethylstilbestrol Modifies the Structure of Model Membranes and Is Localized Close to the First Carbons of the Fatty Acyl Chains

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 220
Author(s):  
Alessio Ausili ◽  
Inés Rodríguez-González ◽  
Alejandro Torrecillas ◽  
José A. Teruel ◽  
Juan C. Gómez-Fernández
Keyword(s):  
Membrane Surface ◽  
Water Layer ◽  
Fatty Acyl ◽  
31P Nmr Spectroscopy ◽  
Relaxation Rates ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Acyl Chains ◽  
Dynamics Simulations

The synthetic estrogen diethylstilbestrol (DES) is used to treat metastatic carcinomas and prostate cancer. We studied its interaction with membranes and its localization to understand its mechanism of action and side-effects. We used differential scanning calorimetry (DSC) showing that DES fluidized the membrane and has poor solubility in DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) in the fluid state. Using small-angle X-ray diffraction (SAXD), it was observed that DES increased the thickness of the water layer between phospholipid membranes, indicating effects on the membrane surface. DSC, X-ray diffraction, and 31P-NMR spectroscopy were used to study the effect of DES on the Lα-to-HII phase transition, and it was observed that negative curvature of the membrane is promoted by DES, and this effect may be significant to understand its action on membrane enzymes. Using the 1H-NOESY-NMR-MAS technique, cross-relaxation rates for different protons of DES with POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) protons were calculated, suggesting that the most likely location of DES in the membrane is with the main axis parallel to the surface and close to the first carbons of the fatty acyl chains of POPC. Molecular dynamics simulations were in close agreements with the experimental results regarding the location of DES in phospholipids bilayers.

scholarly journals Effect of the Degree of Substitution on the Hydrophobicity, Crystallinity, and Thermal Properties of Lauroylated Amaranth Starch

Polymers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 2548
Author(s):  
Vicente Espinosa-Solis ◽  
Yunia Verónica García-Tejeda ◽  
Everth Jimena Leal-Castañeda ◽  
Víctor Barrera-Figueroa
Keyword(s):  
Photoelectron Spectroscopy ◽  
Thermal Characterization ◽  
Fatty Acyl ◽  
Degree Of Substitution ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Amaranthus Hypochondriacus ◽  
Two Samples ◽  
Acyl Chains

In this paper, we consider amaranth starch extracted from the seeds of Amaranthus hypochondriacus L. An amphiphilic character is conferred to the starch by a chemical modification, which involves an esterification by lauroyl chloride at three modification levels. The degree of substitution (DS) after the modification ranged from 0.06 to 1.16. X-ray photoelectron spectroscopy analysis confirmed the presence of fatty acyl chains on the surface of the esterified starches. The hydrophobicity of starches was confirmed by their adsorption isotherms, which showed a decrease in the moisture adsorption of lauroylated as DS increased. X-ray diffraction analysis revealed a higher crystallinity, which was observed in the two samples subjected to the highest levels of modification. A higher crystallinity is related to a higher gelatinization enthalpy. These results are in agreement with the thermal characterization obtained by differential scanning calorimetry (DSC). An inhibition of the retrogradation properties of lauroylated amaranth starches was also observed.

Temperature-induced changes in lecithin model membranes detected by novel covalent spin-labelled phospholipids

1977 ◽  
Vol 55 (2) ◽  
pp. 173-185 ◽  
Author(s):  
L. Stuhne-Sekalec ◽  
N. Z. Stanacev
Keyword(s):  
Transition Temperature ◽  
Fatty Acyl ◽  
Model Membranes ◽  
Head Group ◽  
Polar Head Group ◽  
Polar Group ◽  
Conformational Isomers ◽  
Hydrocarbon Chains ◽  
Acyl Chains ◽  
Induced Changes

Several spin-labelled phospholipids carrying covalently bound 5-doxylstearic acid (2-(3-carboxydecyl)-2-hexyl-4,4-dimethyl-3-oxazolidinoxyl) were intercalated in liposomes of saturated and unsaturated lecithins. Temperature-induced changes of these liposomes, detected by the spin-labelled phospholipids, were found to be in agreement with the previously described transitions of hydrocarbon chains of host lecithins detected by different probes and different techniques, establishing that spin-labelled phosopholipids are sensitive probes for the detection of temperature-induced changes in lecithin model membranes. In addition to the detection of already-known transitions in lecithin liposomes, the coexistence of two distinctly different environments was observed above the characteristic transition temperature. This phenomenon was tentatively attributed to the influence of the lecithin polar group on the fluidity of fatty acyl chains near the polar group. Combined with other results from the literature, the coexistence of two environments could be associated with the coexistence of two conformational isomers of lecithin, differing in the orientation of the polar head group with respect to the plane of bilayer. These findings have been discussed in view of the present state of knowledge regarding temperature-induced changes in model membranes.

Structure and Dynamics of Spherical and Rodlike Alkyl Ethoxylate Surfactant Micelles Investigated Using NMR Relaxation and Atomistic Molecular Dynamics Simulations

2019 ◽  
Author(s):  
Allison Edwards ◽  
Abdolreza Javidialesaadi ◽  
Katie Weigandt ◽  
George Stan ◽  
Charles Eads
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Nmr Relaxation ◽  
Cross Relaxation ◽  
Relaxation Rates ◽  
Surfactant Micelles ◽  
Cylindrical Micelles ◽  
Spherical Micelles ◽  
Dynamics Simulations ◽  
Relative Motions

We study molecular arrangements and dynamics in alkyl ethoxylate nonionic surfactant micelles by combining high field (600 and 700 MHz) NMR relaxation measurements with large-scale atomistic molecular dynamics simulations. For spherical micelles, but not for cylindrical micelles, cross relaxation rates are positive only for surfactant alkyl tail atoms connected to the hydrophilic head group. All cross relaxation rates are negative for cylindrical micelles. This effect is reproducible either by changing composition (ratios of the nonionic surfactants) or changing temperature of a single surfactant in order to change the micelle shape. We validate the micelle shape by SANS and use the results as a guide for our simulations. We calculate parameters that determine relaxation rates directly from simulated trajectories, without introducing specific functional forms. Results indicate that relative motions of nearby atoms are liquid-like, in agreement with 13C T1 measurements, though constrained by micelle morphology. Relative motions of distant atoms have slower components because the relative changes in distances and angles are smaller when the moving atoms are further apart. The slow, long-range motions appear to be responsible for the predominantly negative cross relaxation rates observed in NOESY spectra. The densities of atoms from positions 1 and 2 in the boundary region are lower in spherical micelles compared to cylindrical micelles. Correspondingly, motions in this region are less constrained by micelle morphology in the spherical compared to the cylindrical cases. The two effects of morphology lead to the unusual occurrence of positive cross relaxation involving positions 1 and 2 for spheres.

scholarly journals Structure and Interdigitation of Chain-Asymmetric Phosphatidylcholines and Milk Sphingomyelin in the Fluid Phase

Symmetry ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1441
Author(s):  
Moritz P. K. Frewein ◽  
Milka Doktorova ◽  
Frederick A. Heberle ◽  
Haden L. Scott ◽  
Enrico F. Semeraro ◽  
...  
Keyword(s):  
Chain Length ◽  
Hydration Shell ◽  
Fluid Phase ◽  
Hydrocarbon Chain ◽  
Specific Model ◽  
Glycerol Backbone ◽  
Membrane Composition ◽  
Membrane Structures ◽  
Hydrocarbon Chain Length ◽  
Dynamics Simulations

We addressed the frequent occurrence of mixed-chain lipids in biological membranes and their impact on membrane structure by studying several chain-asymmetric phosphatidylcholines and the highly asymmetric milk sphingomyelin. Specifically, we report trans-membrane structures of the corresponding fluid lamellar phases using small-angle X-ray and neutron scattering, which were jointly analyzed in terms of a membrane composition-specific model, including a headgroup hydration shell. Focusing on terminal methyl groups at the bilayer center, we found a linear relation between hydrocarbon chain length mismatch and the methyl-overlap for phosphatidylcholines, and a non-negligible impact of the glycerol backbone-tilting, letting the sn1-chain penetrate deeper into the opposing leaflet by half a CH2 group. That is, penetration-depth differences due to the ester-linked hydrocarbons at the glycerol backbone, previously reported for gel phase structures, also extend to the more relevant physiological fluid phase, but are significantly reduced. Moreover, milk sphingomyelin was found to follow the same linear relationship suggesting a similar tilt of the sphingosine backbone. Complementarily performed molecular dynamics simulations revealed that there is always a part of the lipid tails bending back, even if there is a high interdigitation with the opposing chains. The extent of this back-bending was similar to that in chain symmetric bilayers. For both cases of adaptation to chain length mismatch, chain-asymmetry has a large impact on hydrocarbon chain ordering, inducing disorder in the longer of the two hydrocarbons.

Probing of the combined effect of bisquaternary ammonium antimicrobial agents and acetylsalicylic acid on model phospholipid membranes: differential scanning calorimetry and mass spectrometry studies

2014 ◽  
Vol 10 (12) ◽  
pp. 3155-3162 ◽  
Author(s):  
N. A. Kasian ◽  
V. A. Pashynska ◽  
O. V. Vashchenko ◽  
A. O. Krasnikova ◽  
A. Gömöry ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Differential Scanning Calorimetry ◽  
Acetylsalicylic Acid ◽  
Antimicrobial Agents ◽  
Combined Effect ◽  
Phospholipid Membranes ◽  
Scanning Calorimetry ◽  
Combined Use ◽  
The Individual

Qualitatively different membranotropic effects of the individual drugs and complexes formed in their combined use were demonstrated by differential scanning calorimetry.

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