Micellization and Partition Equilibria in Mixed Nonionic/Ionic Micellar Systems: Predictions with Molecular Models.

In practical applications, surfactant solutions are mostly used in mixtures of nonionic and ionic surfactants because they have improved characteristics compared to those of single surfactant solutions. By adjusting the composition of the micelles and the pH value, the solubilization of solutes can be enhanced. Nevertheless, the partitioning of solutes between nonionic/ionic mixed micelles and the aqueous phase is studied to a much lesser extent than for single surfactant solutions. Theoretical methods to predict partition equilibria in mixed micelles are of interest for screening studies. For those, the composition of the mixed micelle has to be known. Here we investigate mixtures of TX-114 (Triton X-114), Brij35 (C12E23), SDS (sodium dodecyl sulfate), and CTAB (cetyltrimethylammonium bromide). First, to investigate the surfactant compositions in the micelles, molecular dynamics (MD) self-assembly simulations were applied. Thereafter, the predictive COSMO-RS model, which applies the pseudophase approach, and its extension to anisotropic systems termed COSMOmic were compared for the prediction of partition equilibria in mixed micelles, where various molar ratios of the surfactants were considered. It could be demonstrated that both methods are applicable and lead to reasonable predictions for neutral molecules. However, taking into account the three-dimensional structure of the micelle is beneficial because the calculations with COSMOmic are in better agreement with experimental results. Because the partitioning behavior of ionizable molecules in mixed micelles is of particular interest, the partitioning of ionized isovanillin in mixed Brij35/CTAB micelles at different micelle compositions was calculated with COSMOmic. Using a thermodynamic cycle, the position-dependent pKa of isovanillin within the micelle is calculated on the basis of COSMOmic free energy profiles. As a result, the protolytic equilibrium of isovanillin within the micelles can be taken into account, which is crucial for the reliable prediction of partition coefficients.

Solute Partitioning in Micelles: Combining Molecular Dynamics Simulations, COSMOmic, and Experiments.

The partition equilibria of solutes between micelles and an aqueous phase is a key factor in many applications. Depending on the task, many micelle-solute combinations are possible. Therefore, theoretical methods to predict the partition behavior in micellar systems are needed. Here, two predictive methods are evaluated and compared. First, it is shown how molecular dynamics simulations (MD) with the umbrella sampling method can be used to calculate free energy profiles in micellar systems. The second applied method is an extension of the COSMO-RS theory to anisotropic systems termed COSMOmic. Both methods are compared by means of free energy profiles and experimental micelle/water partition coefficients. A particular focus is on the partitioning of ionized solutes. As experimental data for partitioning in micelles especially for charged solutes is rare, partition coefficients were also determined experimentally. To get a general understanding of micelles examples of all micelle classes (classified by headgroup charge) are studied: nonionic Triton X-114 (TX114), zwitterionic miltefosine (HePC), anionic sodium dodecyl sulfate (SDS), and cationic cetyltrimethylammonium bromid (CTAB). The free energy profiles of neutral solutes obtained from MD simulations and COSMOmic are in an overall good agreement, and partition coefficients from both methods are in good agreement with experimental data. Depending on the system, the results for charged solutes show some deviations between the methods and experimental data.

Molecular Modeling of Triton X Micelles: Force Field Parameters, Self-Assembly, and Partition Equilibria.

Nonionic surfactants of the Triton X-series find various applications in extraction processes and as solubilizing agents for the purification of membrane proteins. However, so far no optimized parameters are available to perform molecular simulations with a biomolecular force field. Therefore, we have determined the first optimized set of CHARMM parameters for the Triton X-series, enabling all-atom molecular dynamics (MD) simulations. In order to validate the new parameters, micellar sizes (aggregation numbers) of Triton X-114 and Triton X-100 have been investigated as a function of temperature and surfactant concentration. These results are comparable with experimental results. Furthermore, we have introduced a new algorithm to obtain micelle structures from self-assembly MD simulations for the COSMOmic method. This model allows efficient partition behavior predictions once a representative micelle structure is available. The predicted partition coefficients for the systems Triton X-114/water and Triton X-100/water are in excellent agreement with experimental results. Therefore, this method can be applied as a screening tool to find optimal solute-surfactant combinations or suitable surfactant systems for a specific application.

[The pregnancy outcome in patients WITH ß-thalassemia minor].

UNLABELLED: Thalassemia syndromes are heterogenic group hereditary hemoglobinopathies, provoking chronic hemolytic anemia. They affect approximately 100 million people, mostly in the Mediterranean (including Bulgaria), South-eastern Asia and Africa. Thalassemia syndromes are the second reason for hypochromic anemia and anemia in pregnancy after iron deficiency. OBJECTIVE: To determine pregnancy outcome of women with ß-thalassemia minor. MATERIALS AND METHODS: It is an ambispective study in University Hospital of Obstetrics and Gynecology" Maichin dom", Sofia, for a year. Patients are divided in two groups regarding the presence of ß-thalassemia minor. Preeclampsia, gestational diabetes mellitus, olygo- and polyhydramnion, preterm labor intrauterine growth retardation (IUGR), Cesarean section delivery are recorded in study groups. RESULTS: Cases with ß-thalassemia minor have significantly higher prevalence of oligohydramnion and Cesarean section delivery. There is no significant difference regarding Apgar score in 1st and 5th minute, IUGR, gestational diabetes mellitus and preeclampsia between two study groups. CONCLUSION: ß-Thalassemia minor does not significantly influence the pregnancy in negative way.