pH-sensitive Surfactants Research Articles

Development and analysis of pH-sensitive surfactants for enhancing foam drainage gas retrieval

In this study, a novel surfactant with pH-responsive properties was developed to address the challenges associated with balancing foaming and defoaming properties in traditional foam drainage gas recovery processes. The surfactant was created by employing primary amine and aldehyde monomers based on the principles of reversible dynamic covalent bonds. Optimal synthesis conditions were determined through an extensive analysis of foaming performance: a molar reaction ratio of primary amine to aldehyde at 10:0.8, a 20-minute reaction time, and a stirring speed of 300 r/min.The formation of dynamic imine bonds was confirmed through infrared spectroscopy. Surface tension measurements revealed that at pH = 8, the surfactant achieved a minimum surface tension of 31.1 mN/m, while at pH = 3, the surface tension exceeded 40 mN/m. Particle size analysis demonstrated a 26.5-fold reduction in particle size as the pH decreased from 8 to 3. Zeta potential tests indicated excellent dispersion stability within the pH range of 3–8, with Zeta potential consistently exceeding 25 mV.Furthermore, the surfactant displayed remarkable foaming and foam stabilizing effects at pH = 8, with initial and 5-minute foam heights reaching 168 mm and 132 mm, respectively. When the pH dropped below 6, the surfactant exhibited rapid defoaming. After six cycles of alternating acid-base environments, it maintained excellent foaming performance, achieving a 5-minute foam height of up to 138 mm. Importantly, it retained its foaming capabilities in formation water solutions with a mineralization degree of 200 g/L.These findings hold significant implications for the development of intelligent environmental response treatments for foam drainage and gas production, enhancing the overall efficiency of drainage and gas production operations.

Performance Evaluation and Mechanism Study of Seawater-Based Circulatory Fracturing Fluid Based on pH-Regulated WormLike Micelles.

In this article, a novel salt-resistant pH-sensitive surfactant N-carboxystearamido methanesulfonic acid (MSA) was designed and synthesized. The rheological properties of the MSA/CTAB mixed system prepared using seawater were evaluated, and the variation laws of the related rheological parameters were discussed. The relevant fracturing technical parameters of the MSA/CTAB mixed system were comprehensively evaluated. The wormlike micelles formed by the non-covalent binding of MSA and CTAB molecules can resist the electrostatic effect of inorganic salts in the seawater. Meanwhile, the MSA/CTAB mixed system has an excellent pH response and revealed that the change from wormlike micelles to spherical micelles leads to the decrease of the apparent viscosity and the transition from Maxwell fluid to Newton-type fluid. Furthermore, the MSA/CTAB mixed system has excellent cyclic fracturing performance, which can meet the dual requirements of fracturing fluid cost and performance of offshore oilfield, and has a good application prospect.

Stimuli-responsive polyelectrolyte surfactant complexes for the reversible control of solution viscosity

Interactions of polyelectrolytes with oppositely charged surfactants can give rise to a large variety of self-assembled structures. Some of these systems cause a drastic increase in solution viscosity, which is related to the surfactant forming aggregates interconnecting several polyelectrolyte chains. For these aggregates to form, the surfactant needs to be sufficiently hydrophobic. Here, we present a system consisting of the anionic surfactant sodium monododecyl phosphate and the cationic cellulose-based polyelectrolyte JR 400. The hydrophobicity of the surfactant can be controlled by the solution's pH. At pH > 12, the surfactant headgroup bears two charges. As a consequence, the solution viscosity decreases drastically by up to two orders of magnitude, while it can be as high as 10 Pa s at lower pH. In this paper, we investigate the changes of the mesoscopic structure of the system which lead to such drastic changes in viscosity using small angle neutron scattering and neutron spin-echo spectroscopy. Such systems are potentially interesting as they allow for a modular design where stimuli responsiveness is introduced by relatively small amounts of surfactant reusing the same simple polyelectrolyte.

PH-responsive micellization of an amine oxide surfactant with branched hydrophobic tail

pH-sensitive surfactants find applications in many fields, including responsive drug delivery and smart material design. The rational design of the surfactant molecular structure leads to species presenting strong variations of the micellization parameter (e.g., critical micelle concentration, cmc, and aggregate dimension) in a controlled pH range.In the present work, the micellization of the branched amine oxide surfactant N,N-dimethyl-2-propylheptan-1-amine oxide (C10DAO-branched) is studied as a function of pH in dilute aqueous mixtures. Its behavior is compared with that of the linear isomer N,N-dimethyldecan-1-amine oxide (C10DAO-linear). The samples are investigated by potentiometric titrations, fluorescence spectroscopy, and Dynamic Light Scattering (DLS). With increasing pH, micellized C10DAO-branched presents a higher tendency to remain in the protonated/cationic form with respect to the linear isomer. As a consequence, the minimum cmc value, observed when the protonated and the deprotonated/zwitterionic forms of the surfactant coexist in the micelles, is shifted to higher pH values. The volume of these C10DAO-branched “mixed micelles” is more than one order of magnitude higher than that of completely protonated or deprotonated aggregates. This is a singularity of the branched surfactant, not observed for the linear isomer. Overall, the results highlight that the branched molecular architecture of the surfactant tail, favoring the formation of low-curvature aggregates, enhances H-bonding between the protonated and deprotonated headgroups, which synergistically stabilizes the flatter surface of bulkier aggregates.Taking into account the good biodegradability of surfactants with a limited number of short side chains, purposely designed branched surfactants appear as a suitable option to accurately tune supramolecular aggregation in pH-responsive formulations.

Neutralisation rate controls the self-assembly of pH-sensitive surfactants.

The degree of ionisation of a weakly acidic surfactant can be continuously modified from nonionic to ionic by adjusting the pH. This property can be used to control the curvature and therefore the morphology of the self-assembled aggregates it forms in solution. Herein, we report the surprising phenomenon, observed in the alkyl ether oligo(ethylene oxide) carboxylate (CH3(CH2)11/13OEO4.5CH2COOH), whereby it is not only the pH but also the neutralisation rate that affects the aggregate morphology. Specifically, when the pH is increased slowly, up to 40 wt% of the surfactant remains in a long-lived vesicle state at high pH. This phenomenon was characterised in detail by small-angle neutron scattering and light scattering techniques. The cause of this phenomenon is thought to be related to a combination of polydispersity and the formation of acid-carboxylate dimers close to the pKa. The transition of these vesicles to the thermodynamically favoured micelles at high pH is inhibited by a high activation energy barrier and therefore only occurs very slowly. Increasing the NaCl concentration eliminates the presence of vesicles at high pH, demonstrating that the activation energy for the vesicle-to-micelle transition depends strongly on electrostatic interactions. These experiments show that the preparation pathway can be used to obtain different self-assembled structures at identical conditions via kinetic control. This phenomenon provides a useful tool for devising formulations where the properties of the system can be altered without changing the composition.

Ion foam flotation of neodymium: From speciation to extraction

Ion foam flotation of neodymium (Nd3+) was studied using a pH-sensitive surfactant, the nonaoxyethylene oleylether carboxilic acid, which has the peculiarity of remaining water soluble in the presence of multivalent cations. The flotation efficiency factors were determined as a function of pH and for two different (surfactant/Nd) molar ratios, equimolar (1/1) or stoichiometric (3/1). An opposite trend was observed, showing low (<30%) and high (>95%) ion extraction yields respectively for equimolar and stoichiometric conditions. We show that i) the determination of the surfactant/Nd speciation solutions is essential to understand the very different behaviors between equimolar and stoichiometric experiments and ii) the ion extraction process is mainly driven by interfacial mechanisms. In terms of applications we show that once the ion extraction is efficiently performed for pH values between 5 and 7, the recovery of the surfactant is possible by performing a second flotation process at lower pH (2.5). Moreover ion foam flotation using this pH sensitive surfactant was shown to be highly efficient for the removal of traces and ultra-traces of metal ions. Therefore the results presented here suggest that the development of a continuous process, for example in the context of waste water treatment, is feasible.

Molecular Organization of an Adsorbed Layer: A Zwitterionic, pH-Sensitive Surfactant at the Air/Water Interface.

Neutron and X-ray reflection measurements have been used to study the structure of the adsorbed layer of a chelating surfactant at the air/liquid interface. The chelating surfactant 2-dodecyldiethylenetriaminepentaacetic acid (C12-DTPA) has a large headgroup containing eight donor atoms that can participate in the coordination of metal ions. The donor atoms are also titrating, resulting in an amphoteric surfactant that can adopt a number of differently charged species depending on the pH. Very strong coordination complexes are formed with metal ions, where the metal ion can be considered as part of the surfactant structure, in contrast to monovalent cations that act as regular counterions to the negative net charge. Adsorption was investigated over a large concentration interval, from well below the critical micelle concentration (cmc) to five times the cmc. The most striking result is the maximum in the surface excess found around the cmc, which is consistent with previous indications from surface tension measurements. Adding divalent metal ions has a limited effect on the adsorption at the air/liquid interface. The reason is the coordination of the metal ion, resulting in compensating deprotonation of the complex. Small variations in the headgroup area of different metal complexes are found, correlating to the conditional stability constants. Adding sodium chloride has a significant effect on the adsorption behavior, and the results indicate that the protonation equilibrium is more important than the ionic strength effects. From combined fits of the neutron and X-ray data, a model that consists of a thick headgroup region and a relatively thin dehydrated tail region is found, and it indicates that the tails are not fully extended and that the limiting area per molecule is determined by the bulky headgroup.

Microfluidic comparative study of foam flow between a classical and a pH sensitive surfactant

Abstract Comparative study between foams made of a pH sensitive surfactant, nonaoxyethylene oleylether carboxylic acid (AKYPO ® RO 90 VG) and a classical foaming surfactant, sodium dodecyl sulphate (SDS) was realised using simple microfluidic devices in the scope of Enhanced Oil Recovery (EOR). The influence of injecting fluid parameters such as gas and foaming liquid pressure was investigated and discussed in terms of foam morphology, and lamellae stability and curvature radii. The increasing stability of AKYPO ® foam film lamellae by increasing pH is classically explained by the electrostatic repulsive interaction of the double layer in foam film. In other hand, the addition of dodecanol (DOH) on SDS solution seems to have no effect on foam regime and lamellae stability except for high DOH concentration where the foam film shape becomes double bump. The behaviour difference between AKYPO ® and SDS lays on the lamellae shape and stability domain. While SDS lamellae stay unchanged with increasing pressure ratio between the gas and the liquid, AKYPO ® lamellae curvature radius increases which could be related to surfactants solubilities and structure. These results pointed out the relevance of solution physicochemical parameters on foam stability and flowing and help the understanding of flowing foam in EOR context.

Inclusion of a pH-responsive amino acid-based amphiphile in methotrexate-loaded chitosan nanoparticles as a delivery strategy in cancer therapy.

The encapsulation of antitumor drugs in nanosized systems with pH-sensitive behavior is a promising approach that may enhance the success of chemotherapy in many cancers. The nanocarrier dependence on pH might trigger an efficient delivery of the encapsulated drug both in the acidic extracellular environment of tumors and, especially, in the intracellular compartments through disruption of endosomal membrane. In this context, here we reported the preparation of chitosan-based nanoparticles encapsulating methotrexate as a model drug (MTX-CS-NPs), which comprises the incorporation of an amino acid-based amphiphile with pH-responsive properties (77KS) on the ionotropic complexation process. The presence of 77KS clearly gives a pH-sensitive behavior to NPs, which allowed accelerated release of MTX with decreasing pH as well as pH-dependent membrane-lytic activity. This latter performance demonstrates the potential of these NPs to facilitate cytosolic delivery of endocytosed materials. Outstandingly, the cytotoxicity of MTX-loaded CS-NPs was higher than free drug to MCF-7 tumor cells and, to a lesser extent, to HeLa cells. Based on the overall results, MTX-CS-NPs modified with the pH-sensitive surfactant 77KS could be potentially useful as a carrier system for intracellular drug delivery and, thus, a promising targeting anticancer chemotherapeutic agent.

Evaluation of ion separation coefficients by foam flotation using a carboxylate surfactant

Separation of metal cations of different charges, Na+, Li+, Ca2+, Sr2+, Cu2+, Nd3+ and Eu3+ was investigated through ion foam flotation using a pH sensitive surfactant, nonaoxyethylene oleyl ether carboxylic acid. We propose here a method to evaluate ion selectivity coefficients using mass and volume balances. This method yields selectivity coefficients in agreement with those obtained with the classical slope method. The ion selectivity obtained by the flotation experiments was found to correlate well with the apparent charge of the surfactant micelles (zeta potential values) in the presence of different salts and is therefore not influenced by the surface curvature. Consequently the ion specificity order has been established according to the surfactant–ion affinity at the air–water and micelle–water interfaces as Na+ < Li+ < Sr2+ < Ca2+ < Cu2+ < Nd3+ < Eu3+. It has been noticed that the selectivity coefficients between the different metal ions, obtained by ion flotation, differ from the ones predicted by using metal ion complexation constants of acetate, which is considered here as the non-surface active complexing part of the surfactant. This discrepancy was attributed to the surface complexation effects at the air–water interface in flotation experiments and at the micelle–water interface. For the separation of lithium and neodymium, a depletion phenomenon of lithium ions from the interface, hence from the foam, has been observed, i.e. once the flotation experiment was finished, the lithium concentration in the remaining foaming solution was indeed higher compared to the initial one. This phenomenon was explained by the strong adsorption of Nd3+ that leads Li+ to be repelled from the foam.

Synthesis of a novel class of mixed-type surfmers and their properties in water

Abstract Three new mixed-type surfmers were synthesized using poly(propylene oxide)/poly(ethylene oxide)/poly(propylene oxide) (PPO-PEO-PPO) having terminal tertiary amine group as the basic material: (1) PPO-PEO-PPO with a carboxyl group on one end (MTA); (2) PPO-PEO-PPO with a quaternary ammonium group on one end (JTA); (3) PPO-PEO-PPO with a quaternary ammonium group on one end and a carboxyl group on the other end (MJTA). These products were confirmed by 1H-NMR and FT-IR. Similar to PPO-PEO-PPO, the three surfmers have a cloud point (Tcp). Both MJTA and MTA have lower Tcp than JTA. However, the cloud points of both MJTA-Na+ and MTA-Na+ are much higher than JTA. Their different Tcp may be caused by their strength of dissociation in water. In addition, at a high temperature (T&gt;Tcp of MJTA), MJTA-Na+ can be considered a pH-sensitive surfactant. At neutral and alkaline conditions, it can be used as an emulsifier. However, at acidic conditions, it loses its emulsification property. MTA-Na+ has the same property.

Self-Assembly and Bilayer–Micelle Transition of Fatty Acids Studied by Replica-Exchange Constant pH Molecular Dynamics

Recent interest in the development of surfactant-based nanodelivery systems targeting tumor sites has sparked our curiosity in understanding the detailed mechanism of the self-assembly and phase transitions of pH-sensitive surfactants. Toward this goal, we applied a state-of-the-art simulation technique, continuous constant pH molecular dynamics (CpHMD) with the hybrid-solvent scheme and pH-based replica-exchange protocol, to study the de novo self-assembly of 30 and 40 lauric acids, a simple model titratable surfactant. We observed the formation of a gel-state bilayer at low and intermediate pH and a spherical micelle at high pH, with the phase transition starting at 20-30% ionization and being completed at 50%. The degree of cooperativity for the transition increases from the 30-mer to the 40-mer. The calculated apparent or bulk pKa value is 7.0 for the 30-mer and 7.5 for the 40-mer. Congruent with experiment, these data demonstrate that CpHMD is capable of accurately modeling large conformational transitions of surfactant systems while allowing the simultaneous proton titration of constituent molecules. We suggest that CpHMD simulations may become a useful tool in aiding in the design and development of pH-sensitive nanocarriers for a variety of biomedical and technological applications.

Specific Salt and pH Effects on Foam Film of a pH Sensitive Surfactant

Steady state foams made of a pH sensitive surfactant, nonaoxyethylene oleylether carboxylic acid, with ion complexing properties was studied using small angle neutron scattering (SANS). The effect of pH variation and salt addition on the foam film thickness was investigated and discussed in terms of the influent parameters stabilizing the foam such as surface properties and electrostatic effects determined by tensiometry and zeta potential measurements. The decrease in the film thickness by adding mono (Na(+)) and divalent (Ca(2+)) salts is classically explained by screening of the double layer in foam films (transverse interactions). On the contrary, addition of acid or complexing ion (Nd(3+)) results in an increase in the film thickness and can be analyzed in terms of cohesive forces between surfactants at the liquid/gas interface (lateral interactions). pH and specific salt effects revealed that foams produced by nonaoxyethylene oleylether carboxylic acid are of interest in the potential use of this surfactant in ion separation process.

All Atom Molecular Dynamics Simulations of pH Dependent Surfactants

Molecular dynamics simulations have been widely applied to study surfactant systems. However, traditional methods do not capture the effect of changing pH, as all molecules have a fixed protonation state. Continuous constant pH molecular dynamics (CpHMD), however, allows for atomistic study of pH-coupled phenomena, and has been successfully applied to study proteins. In this work we use CpHMD with pH-based replica exchange to study pH-sensitive surfactants in aqueous solution. Lauric acid, a twelve-carbon fatty acid, self-assembles in a pH-dependent manner, with a bilayer to micelle transition seen near the aggregate's pKa. The calculated pKa of a 0.5 M lauric acid solution is 7.0, in good agreement with the experimental value of 7.5. Decreasing the tail length by four carbons decreases the pKa by ∼0.5 units, in qualitative agreement with experiment. The effect of aggregate size and concentration was also examined. We have also simulated the titration of fatty acids in fully-solvated detergent bilayers, which sets the stage for exploring proton-coupled biological processes in cellular environments.

Atomistic simulations of pH-dependent self-assembly of micelle and bilayer from fatty acids

Detailed knowledge of the self-assembly and phase behavior of pH-sensitive surfactants has implications in areas such as targeted drug delivery. Here we present a study of the formation of micelle and bilayer from lauric acids using a state-of-the-art simulation technique, continuous constant pH molecular dynamics (CpHMD) with conformational sampling in explicit solvent and the pH-based replica-exchange protocol. We find that at high pH conditions a spherical micelle is formed, while at low pH conditions a bilayer is formed with a considerable degree of interdigitation. The mid-point of the phase transition is in good agreement with experiment. Preliminary investigation also reveals that the effect of counterions and salt screening shifts the transition mid-point and does not change the structure of the surfactant assembly. Based on these data we suggest that CpHMD simulations may be applied to computational design of surfactant-based nano devices in the future.

Phospholipid Bilayer-Perturbing Properties Underlying Lysis Induced by pH-Sensitive Cationic Lysine-Based Surfactants in Biomembranes

Amino acid-based surfactants constitute an important class of natural surface-active biomolecules with an unpredictable number of industrial applications. To gain a better mechanistic understanding of surfactant-induced membrane destabilization, we assessed the phospholipid bilayer-perturbing properties of new cationic lysine-based surfactants. We used erythrocytes as biomembrane models to study the hemolytic activity of surfactants and their effects on cells' osmotic resistance and morphology, as well as on membrane fluidity and membrane protein profile with varying pH. The antihemolytic capacity of amphiphiles correlated negatively with the length of the alkyl chain. Anisotropy measurements showed that the pH-sensitive surfactants, with the positive charge on the α-amino group of lysine, significantly increased membrane fluidity at acidic conditions. SDS-PAGE analysis revealed that surfactants induced significant degradation of membrane proteins in hypo-osmotic medium and at pH 5.4. By scanning electron microscopy examinations, we corroborated the interaction of surfactants with lipid bilayer. We found that varying the surfactant chemical structure is a way to modulate the positioning of the molecule inside bilayer and, thus, the overall effect on the membrane. Our work showed that pH-sensitive lysine-based surfactants significantly disturb the lipid bilayer of biomembranes especially at acidic conditions, which suggests that these compounds are promising as a new class of multifunctional bioactive excipients for active intracellular drug delivery.

PH-Sensitive Surfactants from Lysine: Assessment of Their Cytotoxicity and Environmental Behavior

The toxicity and environmental behavior of new pH-sensitive surfactants from lysine are presented. Three different chemical structures are studied: surfactants with one amino acid and one alkyl chain, surfactants with two amino acids on the polar head and one alkyl chain, and gemini surfactants. The pH sensitivity of these compounds can be tuned by modifying their chemical structures. Cytotoxicity has been evaluated using erythrocytes and fibroblast cells. The toxic effects against these cells depend on the hydrophobicity of the molecules as well as their cationic charge density. The effect of hydrophobicity and cationic charge density on toxicity is different for each type of cells. For erythrocytes, the toxicity increases as hydrophobicity and charge density increases. Nevertheless, for fibroblasts cationic charge density affects cytotoxicity in the opposite way: the higher charge density, the lower the toxicity. The effect of the pH on hemolysis has been evaluated in detail. The aquatic toxicity was established using Daphnia magna . All surfactants yielded EC(50) values considerably higher than that reported for cationic surfactants based on quaternary ammonium groups. Finally, their biodegradability was evaluated using the CO(2) headspace test (ISO 14593). These lysine derivatives showed high levels of biodegradation under aerobic conditions and can be classified as "readily biodegradable compounds".

The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants

Surfactants are among the most versatile and widely used excipients in pharmaceuticals. This versatility, together with their pH-responsive membrane-disruptive activity and low toxicity, could also enable their potential application in drug delivery systems. Five anionic lysine-based surfactants which differ in the nature of their counterion were studied. Their capacity to disrupt the cell membrane was examined under a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model for endosomal membranes. The surfactants showed pH-sensitive hemolytic activity and improved kinetics at the endosomal pH range. Low concentrations resulted in negligible hemolysis at physiological pH and high membrane lytic activity at pH 5.4, which is in the range characteristic of late endosomes. With increasing concentration, the surfactants showed an enhanced capacity to lyse cell membranes, and also caused significant membrane disruption at physiological pH. This observation indicates that, at high concentrations, surfactant behavior is independent of pH. The mechanism of surfactant-mediated membrane destabilization was addressed, and scanning electron microscopy studies were also performed to evaluate the effects of the compounds on erythrocyte morphology as a function of pH. The in vitro cytotoxicity of the surfactants was assessed by MTT and NRU assays with the 3T3 cell line. The influence of different types of counterion on hemolytic activity and the potential applications of these surfactants in drug delivery are discussed. The possibility of using pH-sensitive surfactants for endosome disruption could hold great promise for intracellular drug delivery systems in future therapeutic applications.

Novel N,N ′-diacyl-1,3-diaminopropyl-2-carbamoyl bivalent cationic lipids for gene delivery - synthesis, in vitro transfection activity, and physicochemical characterization

Novel N,N'-diacyl-1,3-diaminopropyl-2-carbamoyl bivalent cationic lipids were synthesized and their physicochemical properties in lamellar assemblies with and without plasmid DNA were evaluated to elucidate the structural requirements of these double-chained pH-sensitive surfactants for potent non-viral gene delivery and expression. The highest in vitro transfection efficacies were induced at +/-4:1 by the dimyristoyl, dipalmitoyl and dioleoyl derivatives 1,3lb2, 1,3lb3 and 1,3lb5, respectively, without inclusion of helper lipids. Transfection activities were reduced in the presence of either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine alone or in combination with cholesterol for all derivatives except 1,3lb5, which maintained reporter gene expression levels at +/-4:1 and yielded increased lipofection activity at a lower charge ratio of +/-2:1. Ethidium bromide displacement indicated efficient plasmid DNA binding and compaction by the transfection-competent analogs. Dynamic light-scattering and electrophoretic mobility studies revealed lipoplexes of the active lipids with large particle sizes (mean diameter>or=500 nm) and zeta potentials with positive values (low ionic strength) or below neutrality (high ionic strength). Langmuir film balance studies showed high in-plane elasticity of these derivatives in isolation. In agreement with the monolayer experiments, fluorescence polarization studies verified the fluid nature of the highly transfection-efficient amphiphiles, with gel-to-liquid crystalline phase transitions below physiological temperature. The active compounds also interacted with endosome-mimicking vesicles to a greater extent than the poorly active derivative 1,3lb4, as revealed by fluorescence resonance energy transfer experiments. Taken together, the results suggest that well-hydrated and highly elastic cationic lipids with increased acyl chain fluidity and minimal cytotoxicity elicit high transfection activity.

Molecular-Thermodynamic Theory of Micellization of Multicomponent Surfactant Mixtures: 2. pH-Sensitive Surfactants

In article 1 of this series, we developed a molecular-thermodynamic (MT) theory to model the micellization of mixtures containing an arbitrary number of conventional (pH-insensitive) surfactants. In this article, we extend the MT theory to model mixtures containing a pH-sensitive surfactant. The MT theory was validated by examining mixtures containing both a pH-sensitive surfactant and a conventional surfactant, which effectively behave like ternary surfactant mixtures. We first compared the predicted micellar titration data to experimental micellar titration data that we obtained for varying compositions of mixed micelles containing the pH-sensitive surfactant dodecyldimethylamine oxide (C12DAO) mixed with either a cationic surfactant (dodecyltrimethylammonium bromide, C12TAB), a nonionic surfactant (dodecyl octa(ethylene oxide), C12E8), or an anionic surfactant (sodium dodecyl sulfate, SDS) surfactant. The MT theory accurately modeled the titration behavior of C12DAO mixed with C12E8. However, C12DAO was observed to interact more favorably with SDS and with C12TAB than was predicted by the MT theory. We also compared predictions to data from the literature for mixtures of C12DAO and SDS. Although the pH values of solutions with no added acid were modeled with only qualitative accuracy, the MT theory resulted in quantitatively accurate predictions of solution pH for mixtures containing added acid. In addition, the predicted degree of counterion binding yielded a lower bound to the experimentally measured value. Finally, we predicted the critical micelle concentration (cmc) of solutions of two pH-sensitive surfactants, tetradecyldimethylamine oxide (C14DAO) and hexadecyldimethyl betaine (C16Bet), at varying solution pH and surfactant composition. However, at the pH values considered, the pH sensitivity of C16Bet could be neglected, and it was equivalently modeled as a zwitterionic surfactant. The cmc's predicted using the MT theory agreed well with the experimental cmc's and were found to be comparable to and sometimes better than the cmc's determined using the regular solution theory (RST), even though the empirical RST utilizes experimentally measured cmc's as an input. The MT theory presented here represents the first molecular-based quantitative description of the micellization behavior of mixtures of pH-sensitive surfactants and conventional surfactants, and allows qualitative and quantitative predictions of the micellization behavior of a variety of surfactant systems.