Molecular Aggregates in Aqueous Solutions of Bile Acid Salts. Molecular Dynamics Simulation Study

Abstract

The aggregation behavior of two bile acid salts (i.e., sodium cholate and sodium deoxycholate) has been studied in their aqueous solutions of three different concentrations (i.e., 30, 90,and 300 mM) by means of molecular dynamics computer simulations. To let the systems reach thermodynamic equilibrium, rather long simulations have been performed: the equilibration period, lasting for 20-50 ns, has been followed by a 20 ns long production phase, during which the average size of the bile aggregates (regarded to be the slowest varying observable) has already fluctuated around a constant value. The production phase of the runs has been about an order of magnitude longer than the average lifetime of both the monomeric bile ions and the bonds that link two neighboring bile ions together to be part of the same aggregate. This has allowed the bile ions belonging to various aggregates to be in a dynamic equilibrium with the isolated monomers. The observed aggregation behavior of the studied bile ions has been found to be in good qualitative agreement with experimental findings. The analysis of the results has revealed that, due to their molecular structure, which is markedly different from that of the ordinary aliphatic surfactants, the bile ions form rather different aggregates than the usual spherical micelles. In the lowest concentration solution studied, the bile ions only form small oligomers. In the case of deoxycholate, these oligomers, such as the ordinary micelles, are kept together by hydrophobic interactions, whereas in the sodium cholate system, small hydrogen-bonded aggregates (mostly dimers) are also present. In the highest concentration systems, the bile ions form large secondary micelles, which are kept together both by hydrophobic interactions and by hydrogen bonds. Namely, in these secondary micelles, small hydrophobic primary micelles are linked together via the formation of hydrogen bonds between their hydrophilic outer surfaces.

The generalized identification of truly interfacial molecules (ITIM) algorithm for nonplanar interfaces

“…Further, its applicability to nonplanar interfaces was shown for three systems previously simulated, namely, a quasi-spherical micelle of DPC, 55 several molecular models of soot, 58 and a secondary micellar aggregate of irregular shape composed of cholic acid molecules. 67 In addition, we proposed how to compute density profiles relative to intrinsic interfaces, irrespective of the latter being macroscopically planar or not, by using a simple Monte Carlo-based algorithm, which allows to estimate the volume of slabs at constant distance from the intrinsic surface, and normalize correctly the density histograms. This issue has been shown to be relevant not only in presence of complex interfaces, but also for macroscopically flat ones, because of the combined effect of capillary waves and of the finite width of fluid slabs.…”

“…At relatively low concentrations they form regular micelles with an aggregation number of 2-10, while above a second critical micellar concentration these primary micelles form larger secondary aggregates by establishing hydrogen bonds between the hydrophilic surface groups of the primary micelles. 66,67 These secondary micelles are of rather irregular shape, 67,68 which makes them an excellent test system for our purposes.…”

“…Here we analyze the surface of a secondary cholic acid micelle composed of 35 molecules, extracted from a previous simulation work 67 and simulated for the present purposes for 500 ps in aqueous environment. An instantaneous snapshot of the micelle is shown in Fig.…”

Supramolecular complexes formed by the association of poly(ethyleneimine) (PEI), sodium cholate (NaC) and sodium dodecyl sulfate (SDS)

“…Although they are comparable to common surfactants, the general conclusion is that biosurfactants self-assemble in a different way than the standard surfactants. [1][2][3][4][5][6][7][8][9][10][11][12][13] Poly(ethyleneimine) (PEI) is a member of a large family of water-soluble polyamines having different molecular weights (M w ) and polymer architectures. Polyamines are weak bases and exhibit a cationic character depending on the degree of protonation.…”

Study on Micelle Formation of Bile Salt Using Nuclear Magnetic Resonance Spectroscopy

“…However, there is not sufficient experimental evidence to corroborate this correlation. On the other hand, computer simulations by Pártay et al suggested that hydrogen bonding and hydrophobic interactions are important in the composition of primary micelles 10,11 . The molecular dynamics simulations also supported the theory that changes in the aggregate structure primary-secondary micelle contribute to micelle growth.…”