A Review on Progress in QSPR Studies for Surfactants

This paper presents a review on recent progress in quantitative structure-property relationship (QSPR) studies of surfactants and applications of various molecular descriptors. QSPR studies on critical micelle concentration (cmc) and surface tension (γ) of surfactants are introduced. Studies on charge distribution in ionic surfactants by quantum chemical calculations and its effects on the structures and properties of the colloids of surfactants are also reviewed. The trends of QSPR studies on cloud point (for nonionic surfactants), biodegradation potential and some other properties of surfactants are evaluated

Micellar chromatographic partition coefficients and their application in predicting skin permeability

The major goal for physicochemical screening of pharmaceuticals is to predict human drug absorption, distribution, elimination, excretion and toxicity. These are all dependent on the lipophilicity of the drug, which is expressed as a partition coefficient i.e. a measure of a drug’s preference for the lipophilic or hydrophilic phases. The most common method of determining a partition coefficient is the shake flask method using octanol and water as partitioning media. However, this system has many limitations when modeling the interaction of ionised compounds with membranes, therefore, unreliable partitioning data for many solutes has been reported. In addition to these concerns, the procedure is tedious and time consuming and requires a high level of solute and solvent purity. Micellar liquid chromatography (MLC) has been proposed as an alternative technique for measuring partition coefficients utilising surfactant aggregates, known as micelles. This thesis investigates the application of MLC in determining micelle-water partition coefficients (logPMW) of pharmaceutical compounds of varying physicochemical properties. The effect of mobile phase pH and column temperature on the partitioning of compounds was evaluated. Results revealed that partitioning of drugs solely into the micellar core was influenced by the interaction of charged and neutral species with the surface of the micelle. Furthermore, the pH of the mobile phase significantly influenced the partitioning behaviour and a good correlation of logPMW was observed with calculated distribution coefficient (logD) values. More interestingly, a significant change in partitioning was observed near the dissociation constant of each drug indicating an influence of ionised species on the association with the micelle and retention on the stationary phase. Elevated column temperatures confirmed partitioning of drugs considered in this study was enthalpically driven with a small change in the entropy of the system because of the change in the nature of hydrogen bonding. Finally, a quantitative structure property relationship was developed to evaluate biological relevance in terms of predicting skin permeability of the newly developed partition coefficient values. This study provides a better surrogate for predicting skin permeability based on an easy, fast and cheap experimental methodology, and the method holds the predictive capability for a wider population of drugs. In summary, it can be concluded that MLC has the ability to generate partition coefficient values in a shorter time with higher accuracy, and has the potential to replace the octanol-water system for pharmaceutical compounds

Fundamental Studies of Metal Ion Extraction into Ionic Liquids By Macrocyclic Polyethers

The liquid-liquid extraction (LLX) of metal ions from aqueous media into ionic liquids (ILs) by macrocyclic polyethers has proven to be an efficient and selective, but complex approach to their separation. Partitioning in these systems has previously been described using a so-called ‘three-path’ model comprising three distinct extraction pathways: neutral complex / ion pair extraction, exchange of the IL cation for a metal-extractant complex, and exchange of the metal ion for a hydronium ion bound to the extractant. The balance of these three paths has been reported to be affected by several characteristics of the LLX system, including the structure of the IL, the stereochemistry of the extractant, and the Lewis acidity of the metal ion, among others. Qualitative trends for many of these factors have been reported, but despite the tremendous number of anion-cation combinations yielding an ionic liquid (i.e., \u3e 108), only a single family (i.e., 1, 3-dialkylimidazolium) has been systematically studied. Evaluating the benefit (i.e., improved efficiency or selectivity), if any of employing other families of ILs as extraction solvents requires extensive partitioning studies. Consequently, the performance of most IL families remains largely unknown. Furthermore, a quantitative description of metal ion extraction from acidic media into ionic liquids is necessary before they can be considered useful extraction solvents. In general terms then, the objective of this work is to investigate several families of ionic liquids to determine whether qualitative trends reported previously represent a ‘generic’ description of metal ion extraction in IL-based systems and if these trends can be confirmed quantitatively. To this end, extraction studies employing quaternary ammonium- and N-alkylpyridinium-based ILs and alkali and alkaline earth cations have been conducted to determine if the ‘three-path’ model provides a satisfactory description of metal ion partitioning in these LLX systems. The results of these studies are consistent with those reported previously for systems employing 1, 3-dialkylimidazolium-based ILs, but they have also unexpectedly revealed a significant effect of the self-aggregation of the IL cation on extraction behavior. In an attempt to reduce the number of experimental measurements required to describe metal ion extraction into an ionic liquid, several parameters that define the hydrophobicity of an IL (e.g., hydrophilicity index, water solubility, and Dow) have been investigated and found to accurately predict extraction behavior. Lastly, a process by which to quantitatively describe the balance of pathways in an IL-based extraction system that can be used as a basis for future evaluation of ILs as extraction solvents has been developed

Modeling the Behavior of Amphiphilic Aqueous Solutions

Two types of predictive models based on artificial neural networks (ANN) and quadratic regression model developed in our laboratory will be summarized in this book chapter. Both models were developed to predict the density, speed of sound, kinematic viscosity and surface tension of amphiphilic aqueous solutions. These models were developed taking into account the concentration, the number of carbons and the molecular weight values. The experimental data were compiled from literature and included different surfactants: i) hexyl, ii) octyl, iii) decyl, iv) tetradecyl and v) octadecyl trimethyl ammonium bromide. Neural models present better adjustment values, with R2 values above 0.902 and AAPD values under 2.93% (for all data), than the quadratic regression models. Finally, it is concluded that the quadratic regression and the neural models can be powerful prediction tools for the physical properties of surfactants aqueous solutions

Characterization of hybrid micellar chromatography system with cationic surfactant cetyltrimethylammonium bromide

Примјена раствора сурфактанта, као мобилне фазе, у концентрацији већој од критичне мицеларне концентрације (КМК) у смјеши воде и органског растварача, омогућила је настанак хибридне мицеларне течне хроматографије (HMLC). У систему HMLC сурфактант се адсорбује на стационарну фазу, а у мобилној фази егзистира у облику мономера и мицела тако да се у овом хроматографском систему аналит расподјељује између водене фазе, мицеларне псеудофазе и сурфактантом модификоване стационарне фазе, што предвиђање ретеционог понашања аналита чини веома комплексним. Примјена мицеларних раствора катјонских сурфактаната као мобилних фаза интересантна је за изучавање јер се, за разлику од анјонског сурфактанта, мономери катјонског сурфактанта адсорбују на стационарну фазу двојако: тако да им је хидрофилни дио молекула оријентисан ка мобилној фази, али и тако да им је хидрофобни дио молекула оријентисан ка мобилној фази, што додатно усложњава систем HMLC. Поред тога, цетилтриметиламонијум бромид (СТАВ) ријетко је примјењиван у HMLC системима, тако да је процес мицелизације у мобилним фазама и утицај на ретенцију недовољно истражен. Како је процес формирања мицела од кључног значаја за ретенционе механизме у систему HMLC, циљ ове докторске дисертације био је истраживање физичкохемијских аспеката мицелизације одабраног сурфактанта СТАВ-а у води и у бинарним смјешама ацетонитрил-вода одређивањем параметара мицелизације (КМК, степена јонизације мицеле (α), Крафтове температуре (TK), термодинамичких параметара (промјене стандардне моларне Гибсове слободне енергије ( ), енталпије ( ) и ентропије мицелизације ( ), ентропијског доприноса Гибсовој слободној енергији ( ), слободне енергије трансфера ( ) и компензацијске температуре (TC)), агрегационог броја (Nag), структурних параметара мицеле (површине по глави мономера сурфактанта (a0) и параметра паковања (P)). Познавање КМК сурфактанта је од кључног значаја за примјену мицеларних раствора као мобилних фаза, а бројне математичке методе за одређивање КМК презентоване су до сада у научним истраживањима...Hybrid micellar liquid chromatography (HMLC) emerged as a result of application of mobile phases consisting of surfactant solutions in mixture of water and organic solvent, with concentration higher than surfactant critical micelle concentration (CMC). In HMLC system, surfactant is adsorbed onto the stationary phase, while in mobile phase it exists in form of monomers and micelles, so in this chromatographic system, analyte is distributed between water, micellar pseudophase and surfactant-modified stationary phase, which makes retention behavior prediction very complex. Use of cationic surfactants micellar solutions as mobile phases is interesting to study because, unlike anionic surfactants, monomers of cationic surfactant adsorb onto stationary phase in two ways: with hydrophilic part of molecule oriented towards mobile phase, as well as with hydrophobic part of molecule oriented towards mobile phase, which makes HMLC system even more complex. Also, CTAB has been rarely employed in HMLC systems, and thus micellization process in mobile phases and effect to retention has not been investigated sufficiently. Considering that micelles are key factor to retention mechanisms in HMLC system, the purpose of this doctoral dissertation was to investigate physicochemical aspects of micellization of chosen surfactant CTAB in water and in binary mixtures acetonitrile-water, by determinating micellization parameters (CMC, micelle ionization degree (α), Krafft temperature (TK), thermodynamic parameters (changes of the standard Gibbs free energy ( ), enthalpy ( ) and entropy of micellization ( ), entropic contribution to the Gibbs free energy ( ), free energy of transfer ( ) and compensation temperature (TC)), micelle aggregation number (Nagg), structural micelle parameters (surface area per head group (a0) and packing parameter (P)). Knowing CMC is of key importance for application of micellar solutions as mobile phases, and so far there have been numerous mathematical methods for CMC determination presented in scientific research. In order to make the best choice of mathematical method for precise CMC determination, comparatory analysis was conducted for CMC values obtained by applying different mathematical methods to conductometry experimental data for CTAB in water and CTAB in binary mixture acetonitrile-water..

Estudo de partição de biomoléculas em sistemas anfífilicos: desenvolvimento de uma estratégia recorrendo a dinâmica molecular

Amphiphilic molecules are interesting building blocks of self-assembled structures for a variety of biotechnological purposes, due to their hydrophobic and hydrophilic moieties. Some of them are deemed as biocompatible, capable of carrying biomolecules, while being highly tuneable and controlled with external cues. Such properties are advantageous in drug delivery applications. Ionic liquids have gained relevance since their discovery as not only responsive and adjustable, but also as promising alternatives to conventionally used solvents. This project aims to use molecular dynamics to the study of ammonium-based ionic liquids in the extraction and delivery of biomolecules, specifically gallic acid and ibuprofen. A multiscale strategy was followed to simulate systems using the GROMACS package for classical molecular dynamics simulations. High-resolution descriptions were used to create a novel coarse-grained model to reproduce the phase behaviour and partition studies. The partition of gallic acid and ibuprofen in the studied ionic liquid solutions was assessed, as well as the particular orientation of the biomolecule in the supramolecular structure of the ionic liquids, as well as the interactions generating each outcome. A pH-driven effect was verified as the main parameter affecting the studied systems. This work has the potential to pave the way for a transferable, transversal platform to analyse and test different biomolecule-IL combinations in aqueous solutions in order to save time and experimental resources in diverse applications.As moléculas anfifílicas são elementos de elevado potencial de estruturas auto-organizadas para vários fins biotecnológicos, devido às suas componentes hidrofóbica e hidrofílica. Parte destas são biocompatíveis, capazes de transportar biomoléculas e altamente ajustáveis e controláveis por fatores externos. Estas propriedades são particularmente relevantes em aplicações de libertação controlada de fármacos. Os líquidos iónicos são cada vez mais utilizados desde a descoberta da sua sensibilidade a estímulos, ajustabilidade e possível uso como alternativas sustentáveis a solventes convencionais. Este trabalho teve como objetivo utilizar dinâmica molecular para estudar líquidos iónicos à base de iões amónio para extração e libertação de biomoléculas, particularmente ácido gálico ou ibuprofeno. Foi utilizada uma estratégia de simulação em várias escalas com o pacote de simulação em dinâmica molecular clássica GROMACS, onde modelos com alta resolução foram usados para criar modelos de grão-grosso novos, mais eficientes em estudos de partição e comportamento de fases. Foi averiguada a partição de ácido gálico e ibuprofeno nas soluções de líquido iónico em questão, bem como a orientação da biomolécula na estrutura supramolecular do líquido iónico e as interações que levaram à mesma. Foi verificado um efeito à base do pH como o principal fator a afetar os sistemas estudados. Este trabalho tem o potencial de dar origem a uma plataforma transversal e transferível para analisar e testar várias combinações de biomoléculas e líquidos iónicos em soluções aquosas de forma a poupar tempo e recursos experimentais em diversas aplicações.Mestrado em Biotecnologi