Calibrating ITC instruments: Problems with weak base neutralization.

Modern isothermal titration calorimetry instruments give great precision, but for comparable accuracy they require chemical calibration. For the heat factor, one recommended process is HCl into the weak base TRIS. In studying this reaction with a VP-ITC and two Nano-ITCs, we have encountered some problems, most importantly a titrant volume shortfall Δv ≈ 0.3 µL, which we attribute to diffusive loss of HCl in the syringe tip. This interpretation is supported by a mathematical treatment of the diffusion problem. The effect was discovered through a variable-v protocol, which thus should be used to properly allow for it in any reaction that similarly approaches completion. We also find that the effects from carbonate contamination and from OH- from weak base hydrolysis can be more significant that previously thought. To facilitate proper weighting in the least-squares fitting of data, we have estimated data variance functions from replicate data. All three instruments have low-signal precision of σ ≈ 1 µJ; titrant volume uncertainty is a factor of ∼2 larger for the Nano-ITCs than for the VP-ITC. The final heat factors remain uncertain by more than the ∼1 % precision of the instruments and are unduly sensitive to the HCl concentration.

The Impact of Phospholipid-Based Liquid Crystals' Microstructure on Stability and Release Profile of Ascorbyl Palmitate and Skin Performance.

The drug delivery potential of liquid crystals (LCs) for ascorbyl palmitate (AP) was assessed, with the emphasis on the AP stability and release profile linked to microstructural rearrangement taking place along the dilution line being investigated by a set of complementary techniques. With high AP degradation observed after 56 days, two stabilization approaches, i.e., the addition of vitamin C or increasing AP concentration, were proposed. As a rule, LC samples with the lowest water content resulted in better AP stability (up to 52% of nondegraded AP in LC1 after 28 days) and faster API release (~18% in 8 h) as compared to the most diluted sample (29% of nondegraded AP in LC8 after 28 days, and up to 12% of AP released in 8 h). In addition, LCs exhibited a skin barrier-strengthening effect with up to 1.2-fold lower transepidermal water loss (TEWL) and 1.9-fold higher skin hydration observed in vitro on the porcine skin model. Although the latter cannot be linked to LCs' composition or specific microstructure, the obtained insight into LCs' microstructure contributed greatly to our understanding of AP positioning inside the system and its release profile, also influencing the overall LCs' performance after dermal application.

Hydration and counterion binding of aqueous acetylcholine chloride and carbamoylcholine chloride.

The hydration and Cl- ion binding of the neurot†ransmitter acetylcholine (ACh+) and its synthetic analogue, carbamoylcholine (CCh+), were studied by combining dilute-solution conductivity measurements with dielectric relaxation spectroscopy and statistical mechanics calculations at 1D-RISM and 3D-RISM level. Chloride ion binding was found to be weak but not negligible. From the ∼30 water molecules coordinating ACh and CCh+ only ∼1/3 is affected in its rotational dynamics by the cation, with the majority - situated close to the hydrophobic moieties - only retarded by a factor of ∼2.5. At vanishing solute concentration cations and the ∼3-4 H2O molecules hydrogen bonding to the CO group of the solute exhibit similar rotational dynamics but increasing concentration and temperature markedly dehydrates ACh+ and CCh+.

Interplay between aggregation number, micelle charge and hydration of catanionic surfactants.

Catanionic mixtures are commonly used in applications due to synergetic properties of both cationic and anionic surfactants. To better understand the mechanism of the micellization process of salt-free catanionic surfactants, alkyltrimethylammonium alkanecarboxylates, [CxMe3N]+[Cy]-, with medium to long alkyl chains on both cation and anion (x,y = 6-10), were investigated in aqueous solution by density and zeta potential measurements, isothermal titration calorimetry (ITC), and dielectric relaxation spectroscopy (DRS). The obtained ITC data was analysed with the help of a two-step model equation, yielding the thermodynamic parameters, micelle charge and aggregation numbers. Comparison with the "parent" decyltrimethylammonium chloride and sodium decanoate reveals that combined dehydration of both alkyl chains increases entropy upon micellization. In the first step neutral smaller micelles with partly dehydrated alkyl chains are formed, while in the second step larger charged micelles with fully dehydrated alkyl chains are equally favourable. At low temperature both formations are thermodynamically equivalent, while with increasing temperature neutral micelles become more entropically favourable and charged micelles more enthalpically favourable. The resulting average micelle charge and average aggregation number are decreasing with temperature. From the DRS spectra, effective hydration numbers of the free monomers and micelles were deduced and are comparable to the "parent" cationic surfactant micelles.

Insight into the Hydration of Cationic Surfactants: A Thermodynamic and Dielectric Study of Functionalized Quaternary Ammonium Chlorides.

Hydrophobic interactions are one of the main thermodynamic driving forces in self-assembly, folding, and association processes. To understand the dehydration-driven solvent exposure of hydrophobic surfaces, the micellization of functionalized decyldimethylammonium chlorides, XC10Me2N+Cl-, with a polar functional group, X = C2OH, C2OMe, C2OC2OMe, C2OOEt, together with the "reference" compound decyltrimethylammonium chloride, C10Me3N+Cl-, was investigated in aqueous solution by density measurements, isothermal titration calorimetry (ITC), and dielectric relaxation spectroscopy (DRS). From the density data, the apparent molar volumes of monomers and micelles were estimated, whereas the ITC data were analyzed with the help of a model equation, yielding the thermodynamic parameters and aggregation number. From the DRS spectra, effective hydration numbers of the free monomers and micelles were deduced. The comprehensive analysis of the obtained results shows that the thermodynamics of micellization are strongly affected by the nature of the functional group. Surprisingly, the hydration of micelles formed by surfactant cations with a single alkyl chain on quaternary ammonium is approximately the same, regardless of the alkyl chain length or functionalization of the headgroup. However, notable differences were found for the free monomers where increasing polarity lowers the effective hydration number.

Hydration and ion association of aqueous choline chloride and chlorocholine chloride.

The choline ion (Ch+) is ubiquitous in nature and also its synthetic homologue, chlorocholine (ClCh+), is widely used. Nevertheless, surprisingly little information on the hydration and counter-ion binding of these cations can be found in the literature. In this contribution we report effective hydration numbers, determined by dielectric relaxation spectroscopy, and ion-pair association constants with Cl-, determined by dilute-solution conductivity measurements. In combination with RISM calculations the obtained data suggest that for Ch+ water is bound to the hydroxy group via hydrogen bonds whereas for ClCh+ a rather stiff clathrate-like shell around the chlorine atom seems to be formed. With Cl- both cations form contact ion pairs with association constants of only ∼2 to 3 M-1.

Total Description of Intrinsic Amphiphile Aggregation: Calorimetry Study and Molecular Probing.

Isothermal titration calorimetry (ITC) is an apt tool for a total thermodynamic description of self-assembly of atypical amphiphiles such as anionic boron cluster compounds (COSAN) in water. Global fitting of ITC enthalpograms reveals remarkable features that differentiate COSAN from classical amphiphiles: (i) strong enthalpy and weak entropy contribution to the free energy of aggregation, (ii) low degree of counterion binding, and (iii) very low aggregation number, leading to deviations from the ideal closed association model. The counterion condensation obtained from the thermodynamic model was compared with the results of 7Li DOSY NMR of Li[COSAN] micelles, which allows direct tracking of Li cations. The basic thermodynamic study of COSAN alkaline salt aggregation was complemented by NMR and ITC experiments in dilute Li/NaCl and acetonitrile aqueous solutions of COSAN. The strong affinity of acetonitrile molecules to COSAN clusters was microscopically investigated by all-atomic molecular dynamics simulations. The impact of ionic strength on COSAN self-assembling was comparable to the behavior of classical amphiphiles, whereas even a small amount of acetonitrile cosolvent has a pronounced nonclassical character of COSAN aggregation. It demonstrates that large self-assembling changes are triggered by traces of organic solvents.

Two-Step Micellization Model: The Case of Long-Chain Carboxylates in Water.

The micellization behavior of the long-chain carboxylates-sodium and potassium octanoate (NaC8 and KC8), sodium decanoate (NaC10), potassium decanoate (KC10), cesium decanoate (CsC10), choline decanoate (ChC10), and sodium dodecanoate (NaC12)-in aqueous solutions were studied using isothermal titration calorimetry (ITC) in the temperature range between 288.15 and 328.15 K. Experimental data were analyzed by help of an improved model treating the micellization process as a two-step process. Furthermore, consideration of the state of the stock and titrated solutions during the experiment allowed for the elimination of all usually used empirical parameters. The proposed approach represents thus an essential improvement of the thermodynamic analysis of the micellization process and turned out to be (only) effective for the description of the micellization at carboxylates with moderate alkyl chain length (C8 and C10). By fitting the model equation to the experimental data, all the thermodynamic parameters of micellization for both steps were estimated. It was found that the first step is endothermic and thus a solely entropy driven processes in the studied temperature range for all investigated systems. The same goes also for the second step, except for KC10, Cs10, and NaC12 where at temperatures above ∼320 K the micellization was detected as an exothermic process. The delicate balance between entropy and enthalpy results in weak temperature dependence of (negative) Gibbs free energy which turned out as almost counterion independent quantity. The carboxylic groups are namely able to form H-bonds with water molecules, and it is quite likely that they remain strongly hydrated even upon micellization. Thus, the interactions with counterions are less expressed in comparison to those observed by other ionic surfactants (alkyl sulfates and cationic surfactants), where the micellization process was found to be an exothermic process even below ∼300 K.

Structure and Stability of Long Rod-like Dodecyltrimethylammonium Chloride Micelles in Solutions of Hydroxybenzoates: A Molecular Dynamics Simulation Study.

The relative position of the hydroxylic and carboxylic groups in the isomeric hydroxybenzoate (HB) anions is experimentally known to have a large impact on the thermodynamics of micellization of cationic surfactants, such as dodecyltrimethylammonium chloride (DTAC), and on the structure of the resulting micelles. To understand the effect of the different isomers on the molecular level, we employed atomistic molecular dynamics simulations to study systems containing infinitely long cylindrical DTAC micelles in aqueous solutions of the sodium salts of all three isomers of HB at a temperature and a pressure of 298.15 K and 1 atm. In all studied systems, the number of DTAC unimers is identical to the number of HB anions. At this concentration, the initially cylindrical micelles remain stable, irrespective of the nature of the isomer, whereas micelles rapidly disintegrated in the absence of HB anions. The HB isomers decrease the line density of unimers along the micellar axis and its concomitant thickness in the order o-HB > m-HB > p-HB. It is further observed that o-HB anions penetrate more deeply into the micellar core, induce a more ordered internal structure of the micelle, and are oriented more strongly than the other two isomers. In addition, the ortho isomer shows two different preferential orientations with respect to the radial direction of the cylindrical micelle; it can either be incorporated almost completely into the micelle or it can be attached through hydrogen bonding to one of those o-HB anions that are already incorporated into the micelle, and thus stick out of the micellar surface.

Mobility and association of ions in aqueous solutions: the case of imidazolium based ionic liquids.

The mobility and the mechanism of ion pairing of 1,1 electrolytes in aqueous solutions were investigated systematically on nine imidazolium based ionic liquids (ILs) from 1-methylimidazolium chloride, [MIM][Cl], to 1-dodecyl-3-methylimidazolium chloride, [1,3-DoMIM][Cl], with two isomers 1,2-dimethylimidazolium chloride, [1,2-MMIM][Cl], and 1,3-dimethylimidazolium chloride, [1,3-MMIM][Cl]. Molecular dynamics (MD) simulations, statistical mechanics calculations in the framework of the integral equation theory using one-dimensional (1D-) and three-dimensional (3D-) reference interaction site model (RISM) approaches as well as conductivity measurements were applied. From experiment and MD simulations it was found that the mobility/diffusion coefficients of cations in the limit of infinite dilution decrease with an increasing length of the cation alkyl chain, but not linearly. The aggregation tendency of cations with long alkyl chains at higher IL concentrations impedes their diffusivity. Binding free energies of imidazolium cations with the chloride anion estimated by RISM calculations, MD simulations and experiments reveal that the association of investigated ILs as model 1,1 electrolytes in water solutions is weak but evidently dependent on the molecular structure (alkyl chain length), which also strongly affects the mobility of cations.

Thermodynamics of micellization from heat-capacity measurements.

Differential scanning calorimetry (DSC), the most important technique for studying the thermodynamics of structural transitions of biological macromolecules, is seldom used in quantitative thermodynamic studies of surfactant micellization/demicellization. The reason for this could be ascribed to an insufficient understanding of the temperature dependence of the heat capacity of surfactant solutions (DSC data) in terms of thermodynamics, which leads to problems with the design of experiments and interpretation of the output signals. We address these issues by careful design of DSC experiments performed with solutions of ionic and nonionic surfactants at various surfactant concentrations, and individual and global mass-action model analysis of the obtained DSC data. Our approach leads to reliable thermodynamic parameters of micellization for all types of surfactants, comparable with those obtained by using isothermal titration calorimetry (ITC). In summary, we demonstrate that DSC can be successfully used as an independent method to obtain temperature-dependent thermodynamic parameters for micellization.

Ion mobility and clustering of sodium hydroxybenzoates in aqueous solutions: a molecular dynamics simulation study.

The relative position of the hydroxylic and the carboxylic group in the isomeric hydroxybenzoate (HB) anions is known to have a large impact on transport properties of this species. It also influences crucially the self-organisation of cationic surfactants. In this article a systematic investigation of aqueous solutions of the ortho, meta, and para isomers of the HB anion is presented. Molecular dynamics simulations of all three HB isomers were conducted for two different concentrations at 298.15 K and using two separate water models. From the resulting trajectories we calculated the self-diffusion coefficient of each isomer. According to the calculated self-diffusion coefficients, isomers were ranked in the order o-HB > m-HB > p-HB at both concentrations for both the used SPC and SPC/E water models, which agrees very well with the experiment. The structural analysis revealed that at lower concentration, where the tendency for dimerisation or cluster formation is low, hydrogen bonding with water determines the mobility of the HB anion. o-HB forms the least hydrogen bonds and is therefore the most mobile, and p-HB, which forms the most hydrogen bonds with water, is the least mobile isomer. At higher concentration the formation of clusters also needs to be considered. The ortho isomer predominantly forms dimers with 2 hydrogen bonds per dimer between one OH and one carboxylate group of each anion. m-HB mostly forms clusters of sizes around 5 and p-HB forms clusters of sizes even larger than 10, which can be either rings or chains.

Ageing of water or dissolution of glass: an electrical conductivity study.

Water and water based solutions are often stored in glass vessels. There are many studies in the literature dealing with solubility of glass-strictly speaking leaching of its components-in water. In present work the leaching process was investigated by measuring the electrical resistance/conductivity of water in a gas tight closed cell under nitrogen atmosphere during three weeks in the temperature range from 5 °C to 40 °C. From obtained results it was concluded, that the observed increase in electrical conductivity of water-actually extremely diluted solution of ions released form glass - in the used time period, can be ascribed to the leaching of ions from the glass solely.

An Investigation of Ion-Pairing of Alkali Metal Halides in Aqueous Solutions Using the Electrical Conductivity and the Monte Carlo Computer Simulation Methods.

The ion pairing is, in very dilute aqueous solutions, of rather small importance for solutions' properties, which renders its precise quantification quite a laborious task. Here we studied the ion pairing of alkali halides in water by using the precise electric conductivity measurements in dilute solutions, and in a wide temperature range. The low-concentration chemical model was used to analyze the results, and to estimate the association constant of different alkali halide salts. It has been shown that the association constant is related to the solubility of salts in water and produces a 'volcano relationship', when plotted against the difference between the free energy of hydration of the corresponding individual ions. The computer simulation, using the simple MB+dipole water model, were used to interprete the results, to find a microscopic basis for Collins' law of matching water affinities.

Salicylate isomer-specific effect on the micellization of dodecyltrimethylammonium chloride: large effects from small changes.

Specific effects of the sodium salts of m- and p-hydroxybenzoates (m-HB and p-HB) on the aggregation process of dodecyltrimethylammonium chloride have been investigated by isothermal titration calorimetry, electrical conductivity, and (1)H NMR and compared with already reported data for the sodium salt of o-hydroxybenzoate (o-HB). For p-HB, it has been found that the aggregate is only formed by spherical micelles at all p-HB concentrations. On the other side, the situation is more complex for o-HB, where two distinct states of aggregation can be involved, depending on the concentration of o-HB. At high salt concentration, rodlike micelles are formed, whereas at lower concentration spherical aggregates are predominant. The transition from the cylinder to the sphere increases the mobility of the surfactant because the core of the rodlike micelles is more closely packed due to the expulsion of water from the interior of the aggregate. m-HB exhibits an intermediate behavior between these two extreme situations. The effect of the position of hydrophilic substituents on the aromatic ring on the insertion of the hydroxybenzoate anion in the micellar aggregate has been discussed.

Closo-dodecaborate-based dianionic surfactants with distorted classical morphology: Synthesis and atypical micellization in water.

HYPOTHESIS: To challenge the classical concept of step-like micellization of ionic surfactants with singular critical micelle concentration, novel amphiphilic compounds with bulky dianionic head and the alkoxy tail connected via short linker, which can complex sodium cations, were synthesized in the form of disodium salts. EXPERIMENT: The surfactants were synthesized by opening of a dioxanate ring attached to closo-dodecaborate by activated alcohol, which allows for attachment of alkyloxy tails of desired length to boron cluster dianion. The synthesis of the compounds with high cationic purity (sodium salt) is described. Self-assembly of the surfactant compound at air/water interface and in bulk water was studied by tensiometry, light and small angle X-ray scattering, electron microscopy, NMR spectroscopy, MD simulations and by isothermal titration calorimetry, ITC. The peculiarities in the micelle structure and formation were revealed by thermodynamic modelling and MD simulations of the micellization process. FINDINGS: In an atypical process, the surfactants self-assemble in water to form relatively small micelles, where the aggregation number is decreasing with the surfactant concentration. The extensive counterion binding is a key characteristic of the micelles. The analysis strongly indicates complex compensation between the degree of bound sodium ions and the aggregation number. For the first time, a three-step thermodynamic model was used to estimate the thermodynamic parameters associated with micellization process. Diverse micelles differing in size and counterion binding can (co-)exist in the solution over the broad concentration and temperature range. Thus, the concept of step-like micellization was found inappropriate for these types of micelles.

Thermodynamic characterization of 3-[(3-cholamidopropyl)-dimethylammonium]-1-propanesulfonate (CHAPS) micellization using isothermal titration calorimetry: temperature, salt, and pH dependence.

A systematic investigation of the micellization process of a biocompatible zwitterionic surfactant 3-[(3-cholamidopropyl)-dimethylammonium]-1-propanesulfonate (CHAPS) has been carried out by isothermal titration calorimetry (ITC) at temperatures between 278.15 K and 328.15 K in water, aqueous NaCl (0.1, 0.5, and 1 M), and buffer solutions (pH = 3.0, 6.8, and 7.8). The effect of different cations and anions on the micellization of CHAPS surfactant has been also examined in LiCl, CsCl, NaBr, and NaI solutions at 308.15 K. It turned out that the critical micelle concentration, cmc, is only slightly shifted toward lower values in salt solutions, whereas in buffer media it remains similar to its value in water. From the results obtained, it could be assumed that CHAPS behaves as a weakly charged cationic surfactant in salt solutions and as a nonionic surfactant in water and buffer medium. Conventional surfactants alike, CHAPS micellization is endothermic at low and exothermic at high temperatures, but the estimated enthalpy of micellization, ΔHM0, is considerably lower in comparison with that obtained for ionic surfactants in water and NaCl solutions. The standard Gibbs free energy, ΔGM0, and entropy, ΔSM0, of micellization were estimated by fitting the model equation based on the mass action model to the experimental data. The aggregation numbers of CHAPS surfactant around cmc, obtained by the fitting procedure also, are considerably low (nagg ≈ 5 ± 1). Furthermore, some predictions about the hydration of the micelle interior based on the correlation between heat capacity change, Δcp,M0, and changes in solvent-accessible surface upon micelle formation were made. CHAPS molecules are believed to stay in contact with water upon aggregation, which is somehow similar to the micellization process of short alkyl chain cationic surfactants.

Global thermodynamic analysis of conductivity data.

Conductivity can serve as a tool to study ion properties in different solvents. In the current study, principles of the global modelling of the conductivity data measured at different concentrations and temperatures are demonstrated. Global model was developed on the basis of two modern conductivity theories; the low concentration chemical model and the Quint-Viallard model. It was tested on three different systems; NaCl in water, NaCl in water-1,4 dioxane mixture and MgSO4 in water. It turned out, that such approach successfully describes all the measured experimental data simultaneously. The applied global analysis of the experimental data allows determination of the thermodynamic profile of ion pairing process and the transport properties of ions at the same time.

Method and apparatus for determination of relative permittivity of solvents.

In this work a modification of an existing coaxial cylindrical capacitor cell is described, that is compatible with a system built recently for precise measuring of temperature dependent data in electrolyte solutions. The method and apparatus, presented in detail in this technical paper, turned out to be a reliable and easy procedure for determination of the relative permittivity of diverse solvents. It will be used further in our laboratory for collecting these data which are indispensable for conductivity studies.

What affects the degree of micelle ionization: conductivity study of alkyltrimethylammonium chlorides.

The critical micelle concentration, cmc, and the degree of micelle ionization, ß, of decyltrimethylammonium chloride (DeTAC), dodecyltrimethylammonium chloride (DTAC) and tetradecyltrimethylammonium chloride (TTAC) in water, 0.01 M, and 0.1 M NaCl solution were determined from the electrical conductivity data in the temperature range from 278.15 to 328.15 K. It has been found that cmc is decreasing with increasing surfactant chain length and increasing concentration of added NaCl, whereas the temperature dependence of cmc shows the typical U-shaped form with a minimum around (306 ± 3) K. Further, ß is decreasing with lengthening the alkyl chain of surfactant and increasing with increasing temperature, but no distinct influence of added salt has been found actually. It can be concluded that the effect of electrolyte on micelle ionization is quite complex.