Nuclear Magnetic Resonance Studies of Bicontinuous Liquid Crystalline Phases of Cubic Symmetry: Transport Properties from 2H Nuclear Magnetic Resonance Relaxation Rates.

The ternary system didodecyltrimethylammonium bromide, 1-decanol, and water forms an extended reversed continuous phase of cubic symmetry at 25 °C. The cubic phase belongs to the space group Im3m, as shown by small-angle X-ray experiments. We present extensive deuterium NMR relaxation data from this cubic phase for 1-decanol, deuterated at the carbon adjacent to the hydroxyl carbon position. 2H spin-lattice (R1) and spin-spin (R2) relaxation rates were measured over the existence region of the cubic phase, which extends from 0.2 to 0.6 in volume fraction of the dividing bilayer surface of the cubic phase. The data are interpreted with an existing theoretical framework for NMR spin relaxation in bicontinuous cubic phases, which takes its starting point in the description of bicontinuous phases using periodic minimal surfaces. Specifically, we obtain the self-diffusion coefficient over the minimal surface in one unit cell for 1-decanol. We also present pulsed field gradient NMR-derived self-diffusion data for didodecyltrimethylammonium bromide and compare the two sets of data. The diffusion data for both components show a mild, if any, dependence on the volume fraction of the bilayer surface. Furthermore, we present diffusion data for the water component in the cubic phase. Finally, we discuss the influences of the choice of the value of the product of the deuterium quadrupole constant and the order parameter S. Within the framework of the model used to analyze the relaxation data, a value for this parameter is required. As an initial value, we rely on measurements of deuterium quadrupolar splittings from deuterated decanol in an anisotropic phase.

Molecular Assembly in Block Copolymer-Surfactant Nanoparticle Dispersions: Information on Molecular Exchange and Apparent Solubility from High-Resolution and PFG NMR.

Internally structured block copolymer-surfactant particles are formed when the complex salts of ionic-neutral block copolymers neutralized by surfactant counterions are dispersed in aqueous media. Here, we report the 1H NMR signal intensities and self-diffusion coefficients (D, from pulsed field gradient nuclear magnetic resonance, PFG NMR) of trimethyl alkylammonium surfactant ions and the poly(acrylamide)-block-poly(acrylate) (PAAm-b-PA) polyions forming such particles. The results reveal the presence of an "NMR-invisible" (slowly exchanging) fraction of aggregated surfactant ions in the particle core and an "NMR-visible" fraction consisting of surface surfactant ions in rapid exchange with the surfactant ions dissociated into the aqueous domain. They also confirm that the neutral PAAm blocks are exposed to water at the particle surface, while the PA blocks are buried in the particle core. The self-diffusion of the polyions closely agree with the self-diffusion of a hydrophobic probe molecule solubilized in the particles, showing that essentially all copolymer chains are incorporated in the aggregates. Through centrifugation, we prepared macroscopically phase-separated systems with a phase concentrated in particles separated from a clear dilute phase. D values for the surfactant and block copolymer indicated that the dilute phase contained small aggregates (ca. 5 nm) of surfactant ions and a few anionic-neutral block copolymer chains. Regardless of the overall concentration of the sample, the fraction of block copolymer found in the dilute phase was nearly constant. This indicates that the dilute fraction represented a tail of small particles created by the dispersion process rather than a true thermodynamic solubility of the complex salts.

NMR Studies of Bicontinuous Liquid Crystalline Phases of Cubic Symmetry: Interpretation of Frequency-Dependent Relaxation Rates.

Extensive deuterium NMR relaxation data are presented for two specifically deuterium labeled surfactants forming bicontinuous cubic phases with water. 2H spin-lattice (R1) and spin-spin (R2) relaxation rates were measured over an extended frequency range from 2 to 60 MHz. The data are interpreted with an existing theoretical framework for spin relaxation in bicontinuous cubic phases, which takes its starting point in the description of bicontinuous phases using periodic minimal surfaces. We show that the theory succeeds in accounting for the data and that the defining parameters of the theory, correlation times and order parameters, are in agreement with related data in other surfactant phase situations. Specifically, we obtain the surfactant self-diffusion coefficient over the minimal surface in one unit cell and show that it is in agreement with the corresponding macroscopic NMR diffusion data. By measuring two additional NMR relaxation parameters for each carbon on the surfactant hydrocarbon tail, we demonstrate how order parameter and correlation time profiles can be obtained. Finally, we analyze published molecular dynamics trajectories for a bicontinuous cubic phase. The analysis provides further support for the theoretical framework used to interpret relaxation data.

Intermolecular interactions play a role in the distribution and transport of charged contrast agents in a cartilage model.

The transport and distribution of charged molecules in polyelectrolyte solutions are of both fundamental and practical importance. A practical example, which is the specific subject addressed in the present paper, is the transport and distribution of charged species into cartilage. The charged species could be a contrast agent or a drug molecule involved in diagnosis or treatment of the widespread degenerative disease osteoarthritis, which leads to degradation of articular cartilage. Associated scientific issues include the rate of transport and the equilibrium concentrations of the charged species in the cartilage and the synovial fluid. To address these questions, we present results from magnetic resonance micro-imaging experiments on a model system of articular cartilage. The experiments yield temporally and spatially resolved data on the transport of a negatively charged contrast agent (charge = -2), used in medical examinations of cartilage, into a polyelectrolyte solution, which is designed to capture the electrostatic interactions in cartilage. Also presented is a theoretical analysis of the transport where the relevant differential equations are solved using finite element techniques as well as treated with approximate analytical expressions. In the analysis, non-ideal effects are included in the treatment of the mobile species in the system. This is made possible by using results from previous Monte Carlo simulations. The results demonstrate the importance of taking non-idealities into account when data from measurements of transport of charged solutes in a system with fixed charges from biological polyelectrolytes are analyzed.

Stability and behaviour in aqueous solutions of the anionic cubic silsesquioxane substituted with tetramethylammonium.

The aqueous behaviour of the anionic octa-tetramethylammonium substituted cubic silsesquioxane, [N(CH3)4]8[Si8O20], was studied with quantitative 29Si-NMR. This molecule partially fragments in aqueous solutions, forming several smaller entities. The most abundant silica species are the monomer, dimer, cyclic trimer, cyclic tetramer and double three-ring. Higher concentrations are required in order to prevent complete fragmentation of the cubic structure. Additives such as alcohols and tetraalkylammonium salts have a stabilising effect on the cubic silsesquioxane, unlike sodium salts that destabilise it. A high concentration solution, containing the non-fragmented molecule as well as entities resulting from fragmentations, was investigated with neutron scattering coupled with modelling, using empirical potential structure refinement (EPSR). The modelling reveals that TMA+ ions coordinates to all different silica species, with approximately three TMA+ per cube. These are located at the faces of the cube.

Phase behavior in the biologically important oleic acid/sodium oleate/water system.

The phase behavior in the oleic acid/sodium oleate/normal saline (0.15M NaCl aqueous solution) system has been determined. For this purpose visual inspection of samples between crossed polarizers, and Small Angle X-ray diffraction was used to identify the various phases and their unit cell dimensions. A rich phase behavior was observed for the ternary system, featuring reverse micellar, micellar cubic, hexagonal, and cubic phases, and large regions with lamellar phases. As expected the ratio the 'oleic acid/sodium oleate' determines the pH and as a consequence the phase behavior. The results could be modeled by an extended Henderson-Hasselbalch (HH) equation, which takes into account the electrostatic potential at the aqueous lipid interface. The knowledge obtained is important for understanding the lipolysis of triglycerides, as the phase behavior of the end-product of the reaction regulates how well the insoluble product can be dispersed and consequently the kinetics of the process.

NMR quantification of diffusional exchange in cell suspensions with relaxation rate differences between intra and extracellular compartments.

Water transport across cell membranes can be measured non-invasively with diffusion NMR. We present a method to quantify the intracellular lifetime of water in cell suspensions with short transverse relaxation times, T2, and also circumvent the confounding effect of different T2 values in the intra- and extracellular compartments. Filter exchange spectroscopy (FEXSY) is specifically sensitive to exchange between compartments with different apparent diffusivities. Our investigation shows that FEXSY could yield significantly biased results if differences in T2 are not accounted for. To mitigate this problem, we propose combining FEXSY with diffusion-relaxation correlation experiment, which can quantify differences in T2 values in compartments with different diffusivities. Our analysis uses a joint constrained fitting of the two datasets and considers the effects of diffusion, relaxation and exchange in both experiments. The method is demonstrated on yeast cells with and without human aquaporins.

Effect of Oligomerization of Counterions on Water Activity in Aqueous Cationic Surfactant Systems.

A sorption calorimetry study of cationic cetyltrimethyl ammonium surfactants with four different counterions was performed. The counterions were acetate, succinate, citrate, and butyl tetracarboxylate with formal charges ranging from 1 to 4, respectively. The counterions with 2-4 charges can be considered as oligomers. In all the cases, hydration experiments started with dry solid phases that upon water uptake went through solid-state phase transitions and hexagonal to micellar cubic phase transitions. It was found that in liquid-crystalline phases the activity of water increased with the degree of oligomerization or, equivalently, the formal charge of the counterions. The results are discussed in terms of the forces acting between the colloidal aggregates. It is argued that under the conditions investigated, the so-called strong-coupling theory can be used to describe the electrostatic forces between the charged colloidal objects. Therefore, we suggest that the observed dependence of water activity on the degree of polymerization is due to the entropy of mixing of the counterions in the water volume, which we describe using Flory-Huggins theory.

Electrostatic interactions are important for the distribution of Gd(DTPA)(2-) in articular cartilage.

PURPOSE: The delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) method can be used to assess the content of glycosaminoglycan in cartilage. In in vitro and model studies, the content of glycosaminoglycan is often expressed in terms of a fixed charge density (FCD). Values of the fixed charge density obtained using the dGEMRIC method differs from values obtained using other methods. The purpose of this work was to further clarify the origin of this discrepancy. METHODS: dGEMRIC experiments were performed in a µMRI setup on a custom-designed, well-defined model system capturing the relevant ionic features of cartilage. The model system allows for good control over and systematic variation of relevant parameters. The experimental data was compared with results from Monte Carlo simulations on a coarse-grained model. RESULTS: Application of ideal Donnan theory on data obtained from experiments as well as simulations lead to underestimation of the fixed charge density, in agreement with previous studies. CONCLUSION: To obtain more accurate estimates of the fixed charge density using the dGEMRIC method, interionic interactions need to be taken into account in the Donnan analysis. Furthermore, the results suggest that the combination of µMRI dGEMRIC experiments and Monte Carlo simulations are useful tools for an improved understanding of these effects. Magn Reson Med 76:500-509, 2016. © 2015 Wiley Periodicals, Inc.

Do Cyclodextrins Aggregate in Water? Insights from NMR Experiments.

One decade ago Bonini et al. [Langmuir 2006, 22, 1478-1484] reported the occurrence of aggregates of ß-cyclodextrin in aqueous solutions with sizes in the range from 90 nm to a few micrometers. The experimental technique used was cryo-TEM. This work followed a number of previous studies involving other physical parameters, such as viscosities and activity coefficients, the results of which were interpreted in terms of self-aggregation of cyclodextrins. Since then, the ability of cyclodextrins to self-assemble were often used to explain and rationalize the supramolecular mechanisms involving cyclodextrins. Here, the question of aggregation of native cyclodextrins (α-, ß-, and γ-) in aqueous solutions is addressed by using (1)H NMR techniques, including NMR diffusometry, relaxometry, and proton peak intensities. Within the detection limit of the NMR experiments, no aggregates of cyclodextrin were observed. If aggregates are present, the fraction of cyclodextrin in aggregates is quite small-less than 1%. However, we cannot exclude the presence of transient clusters involving several cyclodextrin molecules where the lifetime of the cluster is short.

The formation of host-guest complexes between surfactants and cyclodextrins.

Cyclodextrins are able to act as host molecules in supramolecular chemistry with applications ranging from pharmaceutics to detergency. Among guest molecules surfactants play an important role with both fundamental and practical applications. The formation of cyclodextrin/surfactant host-guest compounds leads to an increase in the critical micelle concentration and in the solubility of surfactants. The possibility of changing the balance between several intermolecular forces, and thus allowing the study of, e.g., dehydration and steric hindrance effects upon association, makes surfactants ideal guest molecules for fundamental studies. Therefore, these systems allow for obtaining a deep insight into the host-guest association mechanism. In this paper, we review the influence on the thermodynamic properties of CD-surfactant association by highlighting the effect of different surfactant architectures (single tail, double-tailed, gemini and bolaform), with special emphasis on cationic surfactants. This is complemented with an assessment of the most common analytical techniques used to follow the association process. The applied methods for computation of the association stoichiometry and stability constants are also reviewed and discussed; this is an important point since there are significant discrepancies and scattered data for similar systems in the literature. In general, the surfactant-cyclodextrin association is treated without reference to the kinetics of the process. However, there are several examples where the kinetics of the process can be investigated, in particular those where volumes of the CD cavity and surfactant (either the tail or in special cases the head group) are similar in magnitude. This will also be critically reviewed.

Homogeneous length scale of shear-induced multilamellar vesicles studied by diffusion NMR.

A recently developed protocol for pulsed gradient spin echo (PGSE) NMR is applied for the size determination of multilamellar vesicles (MLVs). By monitoring the self-diffusion behavior of water, the technique yields an estimate of the homogeneous length scale λ(hom), i.e. the maximum length scale at which there is local structural heterogeneity in a globally homogeneous material. A cross-over between local non-Gaussian to global Gaussian diffusion is observed by varying the experimentally defined length- and time-scales. Occasional observation of a weak Bragg peak in the PGSE signal attenuation curves permits the direct estimation of the MLV radius in favorable cases, thus yielding the constant of proportionality between λ(hom) and radius. The microstructural origin of the Bragg peak is verified through Brownian dynamics simulations and a theoretical analysis based on the center-of-mass diffusion propagator. λ(hom) is decreasing with increasing shear rate in agreement with theoretical expectations and results from (2)H NMR lineshape analysis.

Anisotropic dynamic changes in the pore network structure, fluid diffusion and fluid flow in articular cartilage under compression.

A compression cell designed to fit inside an NMR spectrometer was used to investigate the in situ mechanical strain response, structural changes to the internal pore structure, and the diffusion and flow of interstitial water in full-thickness cartilage samples as it was deforming dynamically under a constant compressive load (pressure). We distinguish between the hydrostatic pressure acting on the interstitial fluid and the pore pressure acting on the cartilage fibril network. Our results show that properties related to the pore matrix microstructure such as diffusion and hydraulic conductivity are strongly influenced by the hydrostatic pressure in the interstitial fluid of the dynamically deforming cartilage which differ significantly from the properties measured under static i.e. equilibrium loading conditions (when the hydrostatic pressure has relaxed back to zero). The magnitude of the hydrostatic fluid pressure also appears to affect the way cartilage's pore matrix changes during deformation with implications for the diffusion and flow-driven fluid transport through the deforming pore matrix. We also show strong evidence for a highly anisotropic pore structure and deformational dynamics that allows cartilage to deform without significantly altering the axial porosity of the matrix even at very large strains. The insensitivity of the axial porosity to compressive strain may be playing a critical function in directing the flow of pressurized interstitial fluid in the compressed cartilage to the surface, to support the load, and provide a protective interfacial fluid film that 'weeps' out from the deforming tissue and thereby enhances the (elasto)hydrodynamic efficacy of sliding joints. Our results appear to show a close synergy between the structure of cartilage and both the hydrodynamic and boundary lubrication mechanisms.

An improved method to validate the relative humidity generation in sorption balances.

Sorption balances are instruments in which samples are weighed as they are exposed to a programmed relative humidity (RH). Such instruments are used to measure sorption isotherms and to study solid-vapour interaction. There are different methods to validate the performance of the RH generation in such instruments by charging them with saturated salt solutions and ramping/stepping the RH past the deliquescence RH of the salts. In this paper, an improved approach to perform validation is presented, where the RH is kept stepwise constant at a quasi-randomly chosen set of RH-values above and below the deliquescence RH. From the rates of change of mass as a function of RH, it is possible to calculate the RH at which deliquescence takes place. This alternative method gives similar results as the slow ramp method, but it is less sensitive to disturbances and is less time consuming.

Changes in pore morphology and fluid transport in compressed articular cartilage and the implications for joint lubrication.

Cartilage sections were cut from the middle zone of pig knee articular cartilage and attached to substrates in two different kinds of newly designed 'pressure cells', one for fluorescence the other for NMR measurements. The fluorescence cell was filled with buffer solution containing fluorescently marked 70 kDa dextran which was allowed to diffuse into the cartilage pores. A second glass surface was then pressed down onto the thin cartilage sample under different loads (pressures), and the resulting compression (strain) and change in pore volume were measured as a function of time, simultaneously with measurements of the lateral diffusion and flow pattern of the dextran molecules using Fluorescence Recovery After Photobleaching (FRAP). Complementary experiments were made on the normal diffusion coefficients of pure electrolyte solutions (no dextran) in thicker cartilage sections with pulse-gradient NMR using a new pressure cell suitable for such measurements. Taken together our results show that the highly anisotropic structure of cartilage has a strong effect on the way fluid diffuses laterally and normally at different stages of compression. Our results also show how geometric constraints on a cartilage network and trapped high MW polymer such as HA during normal compressions are likely to affect both the normal and the lateral mobilities of polyelectrolytes and water.

Thermodynamic and kinetic characterization of host-guest association between bolaform surfactants and alpha- and beta-cyclodextrins.

The thermodynamics and kinetics of formation of host-guest complexes between a series of bolaform surfactants of type C n Me 6 (2+)2Br (-) ( n = 8, 10, and 12) and alpha-cyclodextrin and beta-cyclodextrin were studied with the aid of isothermal titration calorimetry (ITC) at 298.15 and 308.20 K. The association constant, the enthalpy, and the entropy of formation were determined. The obtained thermodynamic parameters are compared with parameters for the micelle formation of a related cationic surfactant. The difference in magnitude and sign between the parameters of the alpha-CD and beta-CD complexes is discussed based on the curvature of the cavity of the CD. We suggest that the water molecules inside the alpha-CD cavity are not able to maintain their hydrogen bond network. Upon complex formation these water molecules are expelled and reform their hydrogen bond network. The situation is different in the larger beta-CD cavity where water has the possibility of a more extensive hydrogen bonding. The kinetics for alpha-CD is slow, associated with high activation energies for both association and dissociation of the complex. The rates increased with a decrease in the number of methylene groups in the hydrocarbon chain. The slow kinetics is argued to originate from the fact that the charged headgroup needs to be pushed through a relative nonpolar cavity. A comparison is made with the Born energy.

Spontaneous vesicle formation in catanionic mixtures of amino acid-based surfactants: chain length symmetry effects.

The use of amino acids for the synthesis of novel surfactants with vesicle-forming properties potentially enhances the biocompatibility levels needed for a viable alternative to conventional lipid vesicles. In this work, the formation and characterization of catanionic vesicles by newly synthesized lysine- and serine-derived surfactants have been investigated by means of phase behavior mapping and PFG-NMR diffusometry and cryo-TEM methods. The lysine-derived surfactants are double-chained anionic molecules bearing a pseudogemini configuration, whereas the serine-derived amphiphile is cationic and single-chained. Vesicles form in the cationic-rich side for narrow mixing ratios of the two amphiphiles. Two pairs of systems were studied: one symmetric with equal chain lengths, 2C12/C12, and the other highly asymmetric with 2C8/C16 chains, where the serine-based surfactant has the longest chain. Different mechanisms of the vesicle-to-micelle transition were found, depending on symmetry: the 2C12/C12 system entails limited micellar growth and intermediate phase separation, whereas the 2C8/C16 system shows a continuous transition involving large wormlike micelles. The results are interpreted on the basis of currently available models for the micelle-vesicle transitions and the stabilization of catanionic vesicles (energy of curvature vs mixing entropy).

Diffusion NMR for determining the homogeneous length-scale in lamellar phases.

The size of the anisotropic domains in a lyotropic liquid crystal is estimated using a new protocol for diffusion NMR. Echo attenuation decays are recorded for different durations of the displacement-encoding gradient pulses, while keeping the effective diffusion time and the range of the wave vectors constant. Deviations between the sets of data appear if there are non-Gaussian diffusion processes occurring on the time-scale defined by the gradient pulse duration and the length-scale defined by the wave vector. The homogeneous length-scale is defined as the minimum length-scale for which the diffusion appears to be Gaussian. Simulations are performed to show that spatial variation of the director orientation in an otherwise homogeneous system is sufficient to induce non-Gaussian diffusion. The method is demonstrated by numerical solutions of the Bloch-Torrey equation and experiments on a range of lamellar liquid crystals with different domain sizes.