Self-Assembled Structures and pK_a Value of Oleic Acid in Systems of Biological Relevance

Abstract

In the human digestion process, triglycerides are hydrolyzed by lipases to monoglycerides and the corresponding fatty acids. Here we report the self-assembly of structures in biologically relevant, emulsified oleic acid-monoolein mixtures at various pH values and oleic acid concentrations. Small-angle X-ray scattering, cryogenic transmission electron microscopy, and dynamic light scattering were used to investigate the structures formed, and to follow their transitions while these factors were varied. The addition of oleic acid to monoolein-based cubosomes was found to increase the critical packing parameter in the system. Structural transitions from bicontinuous cubosomes through hexosomes and micellar cubosomes (Fd3m symmetry) to emulsified microemulsions occur with increasing oleic acid concentration. At sufficiently high oleic acid concentration, the internal particle structure was also found to strongly depend on the pH of the aqueous phase: transformations from emulsified microemulsion through micellar cubosomes, hexosomes, and bicontinuous cubosomes to vesicles can be observed as a function of increasing pH. The reversible transition from liquid crystals to vesicles occurs at intestinal pH values (between pH 7 and 8). The hydrodynamic radius of the particles decreases from around 120 nm for internally structured particles to around 60 nm for vesicles. All transitions with pH are reversible. Finally, the apparent pK(a) for oleic acid in monoolein could be determined from the change of structure with pH. This value is within the physiological pH range of the intestine and depends somewhat on composition.

Interaction forces and membrane charge tunability: Oleic acid containing membranes in different pH conditions

“…The magnitude of adhesion between the membranes was 0.6 ± 0.1 mN/m and no electrostatic repulsion was observed. The lack of electrostatic repulsion is consistent with a very low-degree of deprotonated oleic acid at pH of 5.8 (pKa of oleic acid N 6.1) [24].…”

“…For example, the pKa of pure oleic acid vesicles is 8.0- 9.5 [27,42,43]. While when mixed with monoolein, the pKa was 6.0-7.0 [24]. A similar pKa of 6.5 was found for 4:6 oleic acid-DPPE vesicles [25].…”

“…The interaction between oleic acid and DPPC molecules is also likely to affect the deprotonation of the oleic acid's carboxyl headgroup. The pKa of an isolated carboxyl group in water is~4.8 [23], while the apparent pKa of oleic acid's carboxyl headgroup tends to be higher depending on the type of co-existing molecules in the mixture and structure of the assembly (i.e., pKa of~6.1 in the hexagonal phase of oleic acid and monoolein mixtures [24]; pKa of~6.5 in 4:6 oleic acid-DPPE vesicles [25]; pKa of~8.0-8.5 in pure oleic acid vesicles [23]; and, an even higher pKa of~9.85 for oleic acid monolayers at air-water interface [26]). The deprotonation of oleic acid in the system consequently alters molecular level lateral interactions and phase behavior of the mixture [23,27].…”

Structure and growth behavior of centimeter-sized helical oleate assemblies formed with assistance of medium-length carboxylic acids

“…15 Therefore, in alkaline aqueous solutions (pH 7-10), fatty-acid assemblies are composed of two types of amphiphiles: a neutral carboxylic acid form and a carboxylate anion form. [16][17][18][19] The higher pK a app values of assembled fatty acids are due to the interaction between carboxylates 14,15,17 and the characteristic dielectric properties and proton activities around the self-assembly surface. 17 These properties change temporally during the nonequilibrium self-assembly process; thus, the acid dissociation of fatty acids fluctuates greatly.…”

“…[16][17][18][19] The higher pK a app values of assembled fatty acids are due to the interaction between carboxylates 14,15,17 and the characteristic dielectric properties and proton activities around the self-assembly surface. 17 These properties change temporally during the nonequilibrium self-assembly process; thus, the acid dissociation of fatty acids fluctuates greatly. For instance, Sugawara et al reported that several 10 micrometer-sized helical assemblies of oleates in aqueous solution showed spontaneous winding-rewinding motions during helical structure formation, probably owing to fluctuation of the ratio of neutral oleic acid to oleate anion in the assembly.…”