Christa Trandum

Excess partial molar enthalpies, entropies, Gibbs energies, and volumes in aqueous dimethylsulfoxide

The excess partial molar enthalpies, the vapor pressures, and the densities of dimethylsulfoxide (DMSO)−H2O mixtures were measured and the excess partial molar Gibbs energies and the partial molar volumes were calculated for DMSO and for H2O. The values of the excess partial molar Gibbs energies for both DMSO and H2O are negative over the entire composition range. The results for the water-rich region indicated that the presence of DMSO enhances the hydrogen bond network of H2O. Unlike monohydric alcohols, however, the solute-solute interaction is repulsive in terms of the Gibbs energy. This was a result of the fact that the repulsion among solutes in terms of enthalpy surpassed the attraction in terms of entropy. The data in the DMSO-rich region suggest that DMSO molecules form clusters which protect H2O molecules from exposure to the nonpolar alkyl groups of DMSO.

Influence of Ethanol on Lipid Membranes: From Lateral Pressure Profiles to Dynamics and Partitioning.

We have combined experiments with atomic-scale molecular dynamics simulations to consider the influence of ethanol on a variety of lipid membrane properties. We first employed isothermal titration calorimetry together with the solvent-null method to study the partitioning of ethanol molecules into saturated and unsaturated membrane systems. The results show that ethanol partitioning is considerably more favorable in unsaturated bilayers, which are characterized by their more disordered nature compared to their saturated counterparts. Simulation studies at varying ethanol concentrations propose that the partitioning of ethanol depends on its concentration, implying that the partitioning is a nonideal process. To gain further insight into the permeation of alcohols and their influence on lipid dynamics, we also employed molecular dynamics simulations to quantify kinetic events associated with the permeation of alcohols across a membrane, and to characterize the rotational and lateral diffusion of lipids and alcohols in these systems. The simulation results are in agreement with available experimental data and further show that alcohols have a small but non-vanishing effect on the dynamics of lipids in a membrane. The influence of ethanol on the lateral pressure profile of a lipid bilayer is found to be prominent: ethanol reduces the tension at the membrane-water interface and reduces the peaks in the lateral pressure profile close to the membrane-water interface. The changes in the lateral pressure profile are several hundred atmospheres. This supports the hypothesis that anesthetics may act by changing the lateral pressure profile exerted on proteins embedded in membranes.

A Thermodynamic Study of the Effects of Cholesterol on the Interaction between Liposomes and Ethanol

The association of ethanol with unilamellar dimyristoyl phosphatidylcholine (DMPC) liposomes of varying cholesterol content has been investigated by isothermal titration calorimetry over a wide temperature range (8-45 degrees C). The calorimetric data show that the interaction of ethanol with the lipid membranes is endothermic and strongly dependent on the phase behavior of the mixed lipid bilayer, specifically whether the lipid bilayer is in the solid ordered (so), liquid disordered (ld), or liquid ordered (lo) phase. In the low concentration regime (<10 mol%), cholesterol enhances the affinity of ethanol for the lipid bilayer compared to pure DMPC bilayers, whereas higher levels of cholesterol (>10 mol%) reduce affinity of ethanol for the lipid bilayer. Moreover, the experimental data reveal that the affinity of ethanol for the DMPC bilayers containing small amounts of cholesterol is enhanced in the region around the main phase transition. The results suggest the existence of a close relationship between the physical structure of the lipid bilayer and the association of ethanol with the bilayer. In particular, the existence of dynamically coexisting domains of gel and fluid lipids in the transition temperature region may play an important role for association of ethanol with the lipid bilayers. Finally, the relation between cholesterol content and the affinity of ethanol for the lipid bilayer provides some support for the in vivo observation that cholesterol acts as a natural antagonist against alcohol intoxication.

Excess Chemical Potentials, Excess Partial Molar Enthalpies, Entropies, Volumes, and Isobaric Thermal Expansivities of Aqueous Glycerol at 25°C

The vapor pressures p the excess partial molar enthalpies of glycerol HGlyE the densities d and the thermal expansivities αp of aqueous glycerol were measured at 25°C. From the vapor pressure data, the excess chemical potential of H2O µWE was calculated, assuming that the partial pressure of glycerol pGly is negligibly small. The excess chemical potential of glycerol µ GlyE was estimated by applying the Gibbs–Duhem relation and these data were used to calculate the excess partial molar entropies SGlyE. From the density data, the excess partial molar volumes of glycerol VGlyE and from the thermal expansivity data, the normalized cross fluctuations SVΔ, introduced by us earlier, were evaluated. While the detailed manner in which glycerol modifies the molecular arrangement of H2O in its immediate vicinity is yet to be elucidated, the hydrogen bond probability in the bulk H2O away from solute molecules is reduced gradually as the glycerol composition increases to the point where putative presence of icelike patches is no longer possible. Thereupon, a qualitatively different mixing scheme seems to set in.

A Thermodynamic Study of 1-Propanol–Glycerol–H2O at 25°C: Effect of Glycerol on Molecular Organization of H2O

The excess chemical potential, partial molar enthalpy, and volume of 1-propanol were determined in ternary mixtures of 1-propanol–glycerol–H2O at 25°C. The mole fraction dependence of all these thermodynamic functions was used to elucidate the effect of glycerol on the molecular organization of H2O. The glycerol molecules do not exert a hydrophobic effect on H2O. Rather, the hydroxyl groups of glycerol, perhaps by forming clusters via its alkyl backbone with hydroxyl groups pointing outward, interact with H2O so as to reduce the characteristics of liquid H2O. The global hydrogen bond probability and, hence, the percolation nature of the hydrogen bond network is reduced. In addition, the degree of fluctuation inherent in liquid H2O is reduced by glycerol perhaps by participating in the hydrogen bond network via OH groups. At infinite dilution, the pair interaction coefficients in enthalpy were evaluated and these data suggest a possibility that the interaction is mediated through H2O.

Association of ethanol with lipid membranes containing cholesterol, sphingomyelin and ganglioside: a titration calorimetry study.

The association of ethanol at physiologically relevant concentrations with lipid bilayers of different lipid composition has been investigated by use of isothermal titration calorimetry (ITC). The liposomes examined were composed of combinations of lipids commonly found in neural cell membranes: dimyristoyl phosphatidylcholine (DMPC), ganglioside (GM(1)), sphingomyelin and cholesterol. The calorimetric results show that the interaction of ethanol with fluid lipid bilayers is endothermic and strongly dependent on the lipid composition of the liposomes. The data have been used to estimate partitioning coefficients for ethanol into the fluid lipid bilayer phase and the results are discussed in terms of the thermodynamics of partitioning. The presence of 10 mol% sphingomyelin or ganglioside in DMPC liposomes enhances the partitioning coefficient by a factor of 3. Correspondingly, cholesterol (30 mol%) reduces the partitioning coefficient by a factor of 3. This connection between lipid composition and partitioning coefficient correlates with in vivo observations. Comparison of the data with the molecular structure of the lipid molecules suggests that ethanol partitioning is highly sensitive to changes in the lipid backbone (glycerol or ceramide) while it appears much less sensitive to the nature of the head group.

Binding of small alcohols to a lipid bilayer membrane: does the partitioning coefficient express the net affinity?

The total vapor pressures at 26 degreesC of binary (water-alcohol) and ternary (water-alcohol-vesicle) systems were measured for six short chain alcohols. The vesicles were unilamellar dipalmitoyl phosphatidylcholine (DMPC). The data was used to evaluate the effect of vesicles on the chemical potential of alcohols expressed as the preferential binding parameter of the alcohol-lipid interaction, gamma23. This quantity is a thermodynamic (model-free) measure of the net strength of membrane-alcohol interactions. For the smaller investigated alcohols (methanol, ethanol and 1-propanol) gamma23 was negative. This is indicative of so-called preferential hydration, a condition where the affinity of the membrane for water is higher than the affinity for the alcohol. For the longer alcohols (1-butanol, 1-pentanol, 1-hexanol) gamma23 was positive and increasing with increasing chain length. This demonstrates preferential binding, i.e. enrichment of alcohol in the membrane and a concomitant depletion of the solute in the aqueous bulk. The measured values of gamma23 were compared to the number of alcohol-membrane contacts specified by partitioning coefficients from the literature. It was found that for the small alcohols the number of alcohol-membrane contacts is much larger than the number of preferentially bound solutes. This discrepancy, which is theoretically expected in cases of very weak binding, becomes less pronounced with increasing alcohol chain length, and when the partitioning coefficient exceeds approximately 3 on the molal scale (10(2) in mole fraction units) it vanishes. Based on this, relationships between structural and thermodynamic interpretations of membrane partitioning are discussed.

Use of isothermal titration calorimetry to study the interaction of short-chain alcohols with lipid membranes

Abstract The molecular mechanisms by which ethanol and other short-chain alcohols exert their effect in biological systems have been suggested to involve specific interactions with proteins and/or non-specific interactions with the lipid bilayer part of the cell membrane. To gain insight into the effect of short-chain alcohols on lipid bilayers, isothermal titration calorimetry (ITC) has been used to determine the energy involved in the association of the alcohols with lipid bilayers. Pure unilamellar DMPC liposomes and DMPC liposomes incorporated with different amounts of cholesterol, sphingomyelin and ganglioside (GM 1 ) were investigated at temperatures above, and below, the main phase-transition temperature of DMPC. The alcohols used were ethanol, 1-propanol, and 1-butanol. The calorimetric results reveal that the interaction of short-chain alcohols with the lipid bilayer is endothermic and strongly dependent on the lipid bilayer composition. In the presence of high concentrations of cholesterol, the binding enthalpy of ethanol is decreased, whereas the presence of ceramides enhances the enthalpic response of the lipid bilayer to ethanol. Isothermal titration calorimetry offers a new methodology of investigating molecular interactions and for determining partitioning coefficients for alcohols into lipid bilayers. We have estimated the partitioning coefficients for the three alcohols between the aqueous phase and the lipid bilayers of various lipid composition on the basis of calorimetric results.

Mixing scheme of aqueous butan-1-ol in the water-rich region at 25°C: Excess chemical potential, partial molar enthalpy, entropy and volume, heat capacity compressibility and thermal expansivity

We determined excess chemical potential, partial molar enthalpy, entropy and volume, heat capacity, isothermal compressibility and thermal expansivity for aqueous butan-1-ol in the water-rich region up to the phase separation boundary at 25°C. The latter three response functions were used to calculate the mean-square fluctuation densities, which signifies the amplitude, or the intensity, of fluctuations in volume, entropy or cross (entropy–volume) fluctuations. Furthermore, we calculated the (mean-square) normalized fluctuations that are indicative of the wavelength, or the extensity, as well as the amplitude of respective fluctuations. The behaviour of these thermodynamic quantities were compared with those obtained earlier in this laboratory for aqueous methanol, ethanol, propan-1-ol, tert-butanol (tert-butyl alcohol), and 2-butoxyethanol. We conclude that in the water-rich region of aqueous butan-1-ol, mixing scheme I is operative as in other alcohols, whereby butan-1-ol molecules enhance the hydrogen bond network of H2O in their immediate vicinities with concomitant reduction of hydrogen bond probability in the bulk H2O away from solutes. However, before reaching the phase separation boundary there was no signature indicative of the transition of mixing scheme observed in other aqueous alcohols. Thus, in aqueous butan-1-ol phase separation occurs directly from mixing scheme I, without going through mixing scheme II, which we argued earlier to be a preparation stage for phase separation for the other alcohols.

Slow relaxation of the sub-main transition in multilamellar phosphatidylcholine vesicles.

The influence of ionic strength and equilibration time on the appearance of the sub-main transition in fully hydrated multilamellar vesicles composed of phosphatidylcholines has been investigated by means of calorimetry and densitometry. The heat capacity measurements show that the transition enthalpy of the sub-main transition is affected by both salt concentration (KCl) and equilibration time. The small heat capacity peak appearing in vesicles made in pure water is significantly increased upon addition of salt. Furthermore, equilibration of the multilamellar vesicles at low temperatures for several weeks results in a pronounced enhancement of the transition enthalpy of the sub-main transition. Neither salt concentration nor equilibration time affected the transition temperature of the sub-main transition. In the densitometry measurements a small volume change is detectable for high salt concentrations. In order to gain further insight into the physical mechanisms involved in the sub-main transition, a Monte Carlo computer simulation study has been carried out using a microscopic model. The combined experimental and simulation results suggest that the sub-main transition involves an acyl chain disordering of phospholipids in lipid bilayer regions that are characterized by a locally decreased lateral pressure most likely caused by a curvature stress.