Effect of pH on the Binding of Sodium, Lysine, and Arginine Counterions to l‐Undecyl Leucinate Micelles

Abstract

Micelle formation by the amino acid‐based surfactant undecylenyl l‐leucine was investigated as a function of solution pH with NMR, dynamic light scattering, and fluorescence spectroscopy. NMR and dynamic light scattering showed that 50 mM undecylenyl l‐leucine and 50 mM NaHCO3 solutions contained micelles approximately 20 Å in diameter and that micelle radius and the mole fraction of surfactant molecules associated with micelles changed very little with solution pH. The binding of the amino acids arginine and lysine to the anionic micelles was also investigated from pH 7.0 to 11.5. Below pH 9.0, the mole fraction of arginine cations bound to the micelles was approximately 0.4. Above pH 9.0, the arginine counterions became zwitterionic, and the mole fraction of bound arginine molecules decreased steadily to less than 0.1 at pH 11. When arginine dissociated from the micelles, their radii decreased from 14 to 10 Å. Similar behavior was observed with lysine; however, when lysine dissociated from the micelle surface, little change in micelle radius was observed. Two‐dimensional NMR experiments suggested that below pH 9.0, l‐arginine bound perpendicular to the micelle surface primarily though its side chain amine while l‐lysine bound parallel to the surface through both of its amine functional groups. Finally, the rate at which the amide protons on the surfactant headgoup exchanged with solvent was investigated with NMR spectroscopy. The exchange reaction was faster in solutions containing only surfactant monomers and slower when the surfactants were in micellar form and the headgoup amide protons were less exposed to solvent.

Nuclear Magnetic Resonance Investigation of the Effect of pH on Micelle Formation by the Amino Acid‐Based Surfactant Undecyl l‐Phenylalaninate

“…Typical G values ranged from 5 to 50 G cm −1 . The intensity of NMR resonances in these experiments decayed exponentially with a rate proportional to the quantity, ( γ ⋅ G ⋅ δ ) 2 ⋅(Δ − δ /3 − τ /3), where γ is the magnetogyric ratio, δ is the duration of the magnetic field gradient pulses, τ is the short delay between the bipolar gradient pulses, and Δ is the diffusion time (Lewis et al, ; Wu et al, ). The Δ, δ , and τ values used in this study were 250, 4.0, and 0.20 ms, respectively.…”

“…The radii of the und‐Phe micelles and the binding of cationic counterions to the anionic micelle surface were investigated with NMR diffusion experiments. These experiments are described in detail by Lewis et al (). To summarize, a series of NMR spectra were collected with increasing magnetic field gradient strength, G , using the bipolar pulse pair longitudinal encode–decode pulse sequence (Wu, Chen, & Johnson, ).…”

“…The Δ, δ , and τ values used in this study were 250, 4.0, and 0.20 ms, respectively. A plot of the natural log of peak intensity versus ( γ ⋅ G ⋅ δ ) 2 ⋅(Δ − δ /3 − τ /3) produced a straight line with a slope equal to – D (Lewis et al, ; Wu et al, ). Figure shows a representative diffusion plot for each component in a sample containing 50 mM und‐Phe, 50 mM l ‐arginine, and TMS at pH 8.0.…”

Probe Molecules for Pulsed‐Field‐Gradient Diffusion Nuclear Magnetic Resonance Experiments on Micelles

“…The diffusion coefficients of the surfactant are often used to determine micellar size through the Stokes‐Einstein equation. A knowledge of micellar size (or relative changes in size) is important for many purposes, such as gauging the suitability for drug delivery, determining the aggregation number of the micelle (Hajy Alimohammadi et al, ; Javadian et al, ; Pérez et al, ), and identifying the effect of external conditions (Javadian et al, ; Lewis et al, ) or inclusion of a solubilizate (Fan et al, ; Fischer et al, ; Stilbs, ) on micellar structure. PFG NMR also has the advantage of spectral resolution of components in a mixture, allowing for the quantification of partitioning between the aqueous and micellar phases (Fan et al, ; Fischer et al, ; Krudopp et al, ; Stilbs, ) or studies of ion binding (Jansson and Stilbs, ).…”

“…NMR diffusion measurements of the probe molecule would then give D mic directly. The most common probe molecule is tetramethylsilane (TMS) (Annunziata et al, ; Hajy Alimohammadi et al, ; Javadian et al, ; Lewis et al, ; Stilbs, ; Stilbs and Lindman, ), but other molecules such as hexamethyldisiloxane (HMDS) (Jansson et al, ; Jansson and Stilbs, , ; Tehrani‐Bagha et al, ), decanol (Lindman et al, , ), isooctane (Lindman et al, ), and ferrocene (Bachofer and Lingwood, ) have been used. Unfortunately, the probe molecule also experiences rapid exchange between the micelle and bulk solution according to the same two‐site model described in Eq.…”