In this thesis we study the interactions of ions and cationic peptides with a negatively charged lipid bilayer in an ionic solution where the electrostatic interactions are screened. <br /><br /> We first examine the problem of charge renormalization and inversion of a highly charged bilayer with low dielectric constant. To be specific, we consider an asymmetrically charged lipid bilayer, in which only one layer is negatively charged. In particular, we study how dielectric discontinuities and charge correlations among lipid charges and condensed counterions influence the effective charge of the surface. When counterions are monovalent, e. g. , Na⁺, our mean-field approach implies that dielectric discontinuities can enhance counterion condensation. A simple scaling picture shows how the effects of dielectric discontinuities and surface-charge distributions are intertwined: Dielectric discontinuities diminish condensation if the backbone charge is uniformly smeared out while counterions are localized in space; they can, however, enhance condensation when the backbone charge is discrete. In the presence of asymmetric salts such as CaCl₂, we find that the correlation effect, treated at the Gaussian level, is more pronounced when the surface has a lower dielectric constant, inverting the sign of the charge at a smaller value of Ca²⁺ concentration. <br /><br /> In the last chapter we study binding of cationic peptides onto a lipid-bilayer membrane. The peptide not only interacts electrostatically with anionic lipids, rearranging their spatial distributions, but it can also insert hydrophobically into the membrane, expanding the area of its binding layer (i. e. , the outer layer). We examine how peptide charges and peptide insertion (thus area expansion) are intertwined. Our results show that, depending on the bilayer's surface charge density and peptide hydrophobicity, there is an optimal peptide charge yielding the maximum peptide penetration. Our results shed light on the physics behind the activity and selective toxicity of antimicrobial peptides, i. e. , they selectively rupture bacterial membranes while leaving host cells intact.

In this thesis we study the interactions of ions and cationic peptides with a negatively charged lipid bilayer in an ionic solution where the electrostatic interactions are screened. <br /><br /> We first examine the problem of charge renormalization and inversion of a highly charged bilayer with low dielectric constant. To be specific, we consider an asymmetrically charged lipid bilayer, in which only one layer is negatively charged. In particular, we study how dielectric discontinuities and charge correlations among lipid charges and condensed counterions influence the effective charge of the surface. When counterions are monovalent, e. g. , Na⁺, our mean-field approach implies that dielectric discontinuities can enhance counterion condensation. A simple scaling picture shows how the effects of dielectric discontinuities and surface-charge distributions are intertwined: Dielectric discontinuities diminish condensation if the backbone charge is uniformly smeared out while counterions are localized in space; they can, however, enhance condensation when the backbone charge is discrete. In the presence of asymmetric salts such as CaCl₂, we find that the correlation effect, treated at the Gaussian level, is more pronounced when the surface has a lower dielectric constant, inverting the sign of the charge at a smaller value of Ca²⁺ concentration. <br /><br /> In the last chapter we study binding of cationic peptides onto a lipid-bilayer membrane. The peptide not only interacts electrostatically with anionic lipids, rearranging their spatial distributions, but it can also insert hydrophobically into the membrane, expanding the area of its binding layer (i. e. , the outer layer). We examine how peptide charges and peptide insertion (thus area expansion) are intertwined. Our results show that, depending on the bilayer's surface charge density and peptide hydrophobicity, there is an optimal peptide charge yielding the maximum peptide penetration. Our results shed light on the physics behind the activity and selective toxicity of antimicrobial peptides, i. e. , they selectively rupture bacterial membranes while leaving host cells intact.

Thesis (PhD)--Stellenbosch University, 2011. / ENGLISH ABSTRACT: Several experiments [1, 2, 3, 4] have shown that e ective attractive interactions exist between con ned like-charged macromolecules. Theoretical approaches have not reached consensus as to precisely what the mechanism for the attraction is, but it is agreed that comprehending the role of the counterion arrangement around macromolecules is crucial for understanding the e ective macromolecule interactions. It is generally assumed that attraction only occurs in the limit of strong electrostatic coupling and is driven by correlation e ects that are neglible in a mean- eld approach, which is valid in the weak-coupling limit. However, in some experimental situations attraction occurs even in the limit of weak-coupling. We consider a eld-theoretic approach that includes uctuations to study the Coulomb interactions of con ned counterions with a single exible charged spherical macromolecule that can expand or collapse uniformly by changing its radius. We show how the linearised eld-theory (valid in the weak-coupling limit) is mapped onto the square-well potential of Quantum Mechanics. The con nement leads to bound states being present in the spectrum at all times. Bound states are non-perturbative and we investigate the role they play in the physics of the system. Some of the e ects are rather counter-intuitive. Firstly, upon expanding the macromolecule in a xed con nement volume, the uctuation part of the free energy favours a decrease in the free energy. Secondly, upon increasing the temperature to high but nite values, the uctuation contribution does not dominate the free energy as would be expected. The mathematical origins of these e ects are dicussed in detail and as part of the analysis we introduce a novel regularisation scheme for computing the functional determinant arising in the model considered where the cut-o is speci ed unambiguously in terms of physical parameters. / AFRIKAANSE OPSOMMING: Verskeie eksperimente [1, 2, 3, 4] toon dat makro-ione met gelyksoortige ladings, in `n eindige volume, `n e ektiewe aantrekkende krag ondervind. Alhoewel daar nog geen konsensus oor die presiese meganisme vir die aantrekking bereik is nie, is dit duidelik dat die rol van \counter-ion" rangskikking rondom die makro-ione belangrik is om die e ektiewe wisselwerkings te verstaan. Dit word algemeen aanvaar dat die aantrekkende krag slegs in die limiet van sterk elektrostatiese koppeling plaasvind en dat dit `n gevolg van \counter-ion" korrelasies is wat weglaatbaar is in `n gemiddelde veld benadering, wat geldig is in die limiet van swak elektrostatiese koppeling. Daar bestaan egter eksperimentele situasies waar die aantrekking in die limiet van swak elektrostatiese koppeling waargeneem word. Ons bestudeer die Coulomb wisselwerking tussen \counter-ions" en `n enkele rekbare sferiese makro-ioon vanuit `n veld-teoretiese beskouing wat uktuasies in ag neem. Die sferiese makro-ioon kan vergroot of verklein deur sy radius uniform te verander. Ons toon aan dat die gelineariseerde veldeteorie (geldig in die limiet van swak elektrostatiese koppeling) op die eindige-diepte put Kwantummeganiese model afgebeeld kan word. Die eindige volume van die sisteem het tot gevolg dat daar altyd gebonde toestande in die spektrum voorkom. Gebonde toestande is `n suiwer nie-steuringsteoretiese e ek en ons ondersoek die rol wat dit speel in die sika van die sisteem. Die teenwoordigheid van die gebonde toestande in die spektrum het `n paar teen-intuitiewe e ekte tot gevolg. Eerstens word die vrye energie verlaag soos die makro-ioon in `n eindige volume vergroot. Tweedens oorheers die uktuasie bydrae nie die vrye energie met toenemende temperatuur soos verwag sou word nie. Ons bespreek die wiskundige oorsprong van hierdie e ekte. As deel van die analise ontwikkel ons `n nuwe regulariseringstegniek vir die berekening van funksionaalintegrale waar die regulariseringsparameter ondubbelsinnig in terme van siese hoeveelhede uitgedruk kan word.

Recently there has been a great deal of attention in the oilfield industry focused on the phenomenal properties of viscoelastic surfactants (VES). The interest is motivated by their applications as switchable smart fluids, their surface tension, and their thickening and rheology enhancement in aqueous solution. Surfactant molecules in solution are known for their ability to assemble spontaneously into complex structures. Under certain thermodynamic conditions, temperature and electrolyte concentrations, wormlike micelles are formed. These micelles share similar equilibrium and dynamic properties with polymer solutions, However, micellar chains can break and recombine spontaneously which make them part of the more general class of living polymers. It is vital to understand the properties of viscoelastic wormlike micelles with regard to their flow in porous media. The overall objective of this study is to establish a better understanding of counterion effect on behavior of VES. The dependence of macroscopic properties on intermolecular interactions of complex fluid systems such as VES is an enormous challenge. To achieve our objective, we use first-principle calculations and molecular dynamics (MD) simulations to resolve the full chemical details in order to study how the structure of the micellar and solution properties depends on the chemical structure of the surfactant head group (HG) and type of counterion. In particular, we run simulations for different structures in gas-phase and aqueous solutions together with their salt counterions at room temperature and atmospheric pressure. For this purpose, we consider four types of surfactant HG (anionic, cationic, betaine and amidoamine oxide) together with the most common ions present in the acidizing fluid of a carbonate reservoir such as Ca2+, Mg2+, Fe2+, Fe3+, Mn2+ and Zn2+, Cl-, OH- and HS-. Hydration of ions as well as interactions with surfactant the HG are studied using density functional theory (DFT). The results give important insight into the links between molecular details of VES HG structure and observed solution properties. This study proposes for the first time the possible mechanisms that explain the exotic behavior of VES at high Fe(III) concentration. Also, our MD simulation suggests that distribution of chloride ion around surfactant molecules is responsible for their viscosity behavior in HCl solution. We believe that our results are an important step to develop more systematic procedures for the molecular design and formulation of more effective and efficient VES systems.

Lipid bilayers are key components of biomembranes; they are self-assembled two-dimensional structures, primarily serving as barriers to the leakage of cell's contents. Lipid bilayers are typically charged in aqueous solution and may electrostatically interact with each other and with their environment. In this work, we investigate electrostatics of charged lipid bilayers with the main focus on the binding and bending of the bilayers. We first present a theoretical approach to charge-correlation attractions between like-charged lipid bilayers with neutralizing counterions assumed to be localized to the bilayer surface. In particular, we study the effect of nonzero ionic sizes on the attraction by treating the bilayer charges (both backbone charges and localized counterions) as forming a two-dimensional ionic fluid of hard spheres of the same diameter <i>D</i>. Using a two-dimensional Debye-H??ckel approach to this system, we examine how ion sizes influence the attraction. We find that the attraction gets stronger as surface charge densities or counterion valency increase, consistent with long-standing observations. Our results also indicate non-trivial dependence of the attraction on separations <i>h</i>: The attraction is enhanced by ion sizes for <i>h</i> ranges of physical interest, while it crosses over to the known <i>D</i>-independent universal behavior as <i>h</i> &rarr; &infin;; it remains finite as <i>h</i> &rarr; 0, as expected for a system of finite-sized ions. We also study the preferred curvature of an asymmetrically charged bilayer, in which the inner leaflet is negatively charged, while the outer one is neutral. In particular, we calculate the relaxed area difference &Delta; <i>A</i>₀ and the spontaneous curvature <i>C</i>₀ of the bilayer. We find &Delta; <i>A</i>₀ and <i>C</i>₀ are determined by the balance of a few distinct contributions: net charge repulsions, charge correlations, and the entropy associated with counterion release from the bilayer. The entropic effect is dominant for weakly charged surfaces in the presence of monovalent counterions only and tends to expand the inner leaflet, leading to negative &Delta; <i>A</i>₀ and <i>C</i>₀. In the presence of even a small concentration of divalent counterions, however, charge correlations counterbalance the entropic effect and shrink the inner leaflet, leading to positive &Delta; <i>A</i>₀ and <i>C</i>₀. We outline biological implications of our results.

Lipid bilayers are key components of biomembranes; they are self-assembled two-dimensional structures, primarily serving as barriers to the leakage of cell's contents. Lipid bilayers are typically charged in aqueous solution and may electrostatically interact with each other and with their environment. In this work, we investigate electrostatics of charged lipid bilayers with the main focus on the binding and bending of the bilayers. We first present a theoretical approach to charge-correlation attractions between like-charged lipid bilayers with neutralizing counterions assumed to be localized to the bilayer surface. In particular, we study the effect of nonzero ionic sizes on the attraction by treating the bilayer charges (both backbone charges and localized counterions) as forming a two-dimensional ionic fluid of hard spheres of the same diameter <i>D</i>. Using a two-dimensional Debye-Hückel approach to this system, we examine how ion sizes influence the attraction. We find that the attraction gets stronger as surface charge densities or counterion valency increase, consistent with long-standing observations. Our results also indicate non-trivial dependence of the attraction on separations <i>h</i>: The attraction is enhanced by ion sizes for <i>h</i> ranges of physical interest, while it crosses over to the known <i>D</i>-independent universal behavior as <i>h</i> &rarr; &infin;; it remains finite as <i>h</i> &rarr; 0, as expected for a system of finite-sized ions. We also study the preferred curvature of an asymmetrically charged bilayer, in which the inner leaflet is negatively charged, while the outer one is neutral. In particular, we calculate the relaxed area difference &Delta; <i>A</i>₀ and the spontaneous curvature <i>C</i>₀ of the bilayer. We find &Delta; <i>A</i>₀ and <i>C</i>₀ are determined by the balance of a few distinct contributions: net charge repulsions, charge correlations, and the entropy associated with counterion release from the bilayer. The entropic effect is dominant for weakly charged surfaces in the presence of monovalent counterions only and tends to expand the inner leaflet, leading to negative &Delta; <i>A</i>₀ and <i>C</i>₀. In the presence of even a small concentration of divalent counterions, however, charge correlations counterbalance the entropic effect and shrink the inner leaflet, leading to positive &Delta; <i>A</i>₀ and <i>C</i>₀. We outline biological implications of our results.

<strong>Introduction – Dearomatisation of Heteroaromatic Compounds</strong> The introduction provides a survey of dearomatisation reaction of heteroaromatics, with a particular focus on pyridines/pyridinium salts and furans. The mechanism, scope, and limitations of various approaches are covered, along with the goals of this project. <strong>Results and Discussion – Dearomatisation of Electron-Deficient Heteroaromatics</strong> This chapter initially explores the asymmetric addition of organometallic nucleophiles to pyridinium salts bearing a chiral counterion. Unfortunately, this approach ultimately proved unsuccessful, due to low observed enantioselectivities, and the low solubility of such salts. The second part of this chapter concerns the attempted asymmetric addition of dicarbonyl nucleophiles to electron-deficient furans, under conditions of chiral phase-transfer catalysts, affording bicyclic products in moderate enantioselectivity. Various alternative routes were also explored for the dearomatisation of furans and benzenoid systems. <strong>Introduction – Hydrogen Borrowing Alkylation Reactions with Alcohols</strong> The introduction surveys the range of methods available for the alkylation of various nucleophiles with alcohols under transition metal-catalysed conditions. Related methodologies are also explored, along with methods for the dehydrogenation of methanol. <strong>Results and Discussion - Rhodium-catalysed Methylation of Ketones Using Methanol</strong> This chapter describes the development of a novel ketone α-methylation using methanol. The development of reaction conditions is explored, followed by expansion of the substrate scope, including limitations of the methylation reaction. Mechanistic investigations support a methanol oxidation, aldol reaction/elimination, conjugate reduction pathway. Investigations into the role of O2 in the methylation reaction proved inconclusive. The utility of the reaction was also expanded via one-pot dialkylation reactions (work by Di Shen), Baeyer-Villiger oxidation of the products, and an attempted asymmetric transfer-hydrogenation. <strong>Results and Discussion - Interrupted Hydrogen Borrowing Reactions of Methanol</strong> This chapter looks to intercept intermediates from the α-methylation reaction. The selective methylenation of ketones is described, and a range of nucleophiles are screened for further functionalisation of ketones. Finally, a number of nucleophiles, including nitroalkanes, amines, peroxides and boronic acids are applied to one pot methylenation/conjugate addition protocols, affording complex products after two steps in one reaction vessel. <strong>Experimental</strong> Full experimental procedures and spectroscopic characterisation of compounds are provided.

<p>The aim of this thesis was to investigate amphiphilic molecules in aqueous solution. The work was divided into two parts. In the first part the effects of different counterions on phase behavior was investigated, while the second part concerns the 1-monooleoyl-rac-glycerol (MO)/n-octyl-β-D-glucoside (OG)/2H2O-system. </p><p>The effects of mixing monovalent and divalent counterions were studied for two surfactant systems, sodium/calcium octyl sulfate, and piperidine/piperazine octanesulfonate. It was found that mixing monovalent and divalent counterions resulted in a large decrease in cmc already at very low fractions of the divalent counterion. Moreover, the degree of counterion binding for piperidine in the piperidine/piperazine octanesulfonate system was much higher than predicted, probably due to the larger hydrophobic moiety of piperidine.</p><p>The effects of hydrophobic counterions were studied for eight alkylpyridinium octanesulfonates (APOS). The results were discussed in terms of packing constraints. The anomalous behavior of the 2H2O quadrupolar splittings in the lamellar phases was explained by the presence of two or more binding sites at the lamellae surface. </p><p>The MO/OG/water system was studied in general and the MO-rich cubic phases in particular. When mixing MO and OG it was found that OG-rich structures (micelles, hexagonal and cubic phase of space group Ia3d) could solubilize quite large amounts of MO, while the MO-rich cubic structures where considerable less tolerant towards the addition of OG. The micelles in the OG-rich L1 phase were found to remain rather small and discrete in the larger part of the L1 phase area, but at low water concentration and high MO content a bicontinuous structure was indicated. Only small fractions of OG was necessary to convert the MO-rich cubic Pn3m structure to an Ia3d structure, and upon further addition of OG a lamellar (La) phase formed. Since the larger part of the phase diagram contains a lamellar structure (present either as a single La phase or as a dispersion of lamellar particles together with other phases), the conclusion was that introducing OG in the MO structures, forces the MO bilayer to become more flat. Upon heating the cubic phases, structures with more negative curvature were formed. The transformation between the cubic structures required very little energy, and this resulted in the appearance of additional peaks in the diffractograms.</p>

The aim of this thesis was to investigate amphiphilic molecules in aqueous solution. The work was divided into two parts. In the first part the effects of different counterions on phase behavior was investigated, while the second part concerns the 1-monooleoyl-rac-glycerol (MO)/n-octyl-β-D-glucoside (OG)/2H2O-system. The effects of mixing monovalent and divalent counterions were studied for two surfactant systems, sodium/calcium octyl sulfate, and piperidine/piperazine octanesulfonate. It was found that mixing monovalent and divalent counterions resulted in a large decrease in cmc already at very low fractions of the divalent counterion. Moreover, the degree of counterion binding for piperidine in the piperidine/piperazine octanesulfonate system was much higher than predicted, probably due to the larger hydrophobic moiety of piperidine. The effects of hydrophobic counterions were studied for eight alkylpyridinium octanesulfonates (APOS). The results were discussed in terms of packing constraints. The anomalous behavior of the 2H2O quadrupolar splittings in the lamellar phases was explained by the presence of two or more binding sites at the lamellae surface. The MO/OG/water system was studied in general and the MO-rich cubic phases in particular. When mixing MO and OG it was found that OG-rich structures (micelles, hexagonal and cubic phase of space group Ia3d) could solubilize quite large amounts of MO, while the MO-rich cubic structures where considerable less tolerant towards the addition of OG. The micelles in the OG-rich L1 phase were found to remain rather small and discrete in the larger part of the L1 phase area, but at low water concentration and high MO content a bicontinuous structure was indicated. Only small fractions of OG was necessary to convert the MO-rich cubic Pn3m structure to an Ia3d structure, and upon further addition of OG a lamellar (La) phase formed. Since the larger part of the phase diagram contains a lamellar structure (present either as a single La phase or as a dispersion of lamellar particles together with other phases), the conclusion was that introducing OG in the MO structures, forces the MO bilayer to become more flat. Upon heating the cubic phases, structures with more negative curvature were formed. The transformation between the cubic structures required very little energy, and this resulted in the appearance of additional peaks in the diffractograms.

No description available.