Kinetics of formation of supramolecular tubules of a sodium cholate derivative

Abstract

We report a kinetic study of the supramolecular tubule formation of the bile salt derivative [3 beta, 5 beta, 7 alpha, 12 alpha]-3-(4-t-butylbenzoilamine)-7,12-dihydroxycholan-24-oic acid sodium salt (Na-tbutPhC). At high bicarbonate buffer concentration (pH similar to 10) this salt shows gelator properties. Starting from gels or viscous solutions, the tubule formation is triggered by increasing the temperature beyond the critical value of 34-36 degrees C. For gels, when the process takes place, the transition to sols occurs. The process is easily triggered and can be followed by several techniques. We used static light scattering (SLS), circular dichroism (CD), small angle X-ray scattering (SAXS) along with transmission electron (TEM) and optical microscopies. The CD results show that fibrils with a clockwise arrangement of the bile salt derivative are present in the samples at room temperature. When the tubule formation starts, evolutions of the CD and SLS profiles are observed indicating that the formation process begins with the aggregation of the fibrils accompanied by a simultaneous peculiar reciprocal reorientation of the surfactant molecules. After that, as pointed out by the long time evolution of the curves, a slow transformation towards the final well defined tubules occurs, involving an adjustment of the molecular packing. In the meanwhile, the slow ordering of the tubule walls in well spaced layers takes place, as inferred by SAXS. The TEM images show that short disordered tubules are formed, because of the aggregation of fibrils, in the beginning. Moreover they highlight a final elongation of the tubules taking place without a further aggregation of fibrils. Optical microscopy frames, collected during the process, point out that the tubules grow singly even at quite a high concentration, thus supporting the data interpretation

Self-assembly in aqueous bile salt solutions

“…In aqueous solutions of bile salt derivatives further types of aggregates can be observed [71][72][73]. For example, the reversible formation of fibrils and, through the aggregation of these fibrils, tubules can be observed and result in a viscous or gel-like solution [73].…”

“…For example, the reversible formation of fibrils and, through the aggregation of these fibrils, tubules can be observed and result in a viscous or gel-like solution [73]. Furthermore, bile salts show a very rich and interesting phase behaviour in mixtures with other amphiphiles, a classical example are lipid-bile salt mixtures [74][75][76][77][78][79][80][81][82] which have important implications for the solubilization of proteins and other materials [82][83][84].…”

Bile acid alkylamide derivatives as low molecular weight organogelators: Systematic gelation studies and qualitative structural analysis of the systems

“…Aggregation, and in a wider sense, self-assembling potential of natural-and modified-bile salts, as well as neutral bile acid derivatives, lead to a diverse library of structures at the nano-and micro-scale in water and organic solvents [32][33][34][35][36][37][38][39][40][41][42][43][44]. Examples of reported structures in solution-, sol-, gel-, or solid-state include various types of micelles [32,33], ribbon-or rod-like fibers [34][35][36][37][38], twisted ribbons [39], vesicles or spherical aggregates [29,40], lamellae [41], and tubules or nanotubes [42][43][44].…”

A tryptophan-substituted cholic acid: Expanding the family of labelled biomolecules

“…For example, the functionalization of both the side chain and the tetracyclic system is observed to lead to efficient gelators in organic solvents as well as in aqueous solutions [22], and the possibility to enhance their efficiency by using catanionic mixtures of the derivatives was demonstrated [23], whereas the BAs functionalized in their rigid backbone, selfassemble into lamellae or tubules [24][25][26][27][28][29][30]. In particular, the selective substitution of one of the steroid hydroxyl groups by an adamantly group gives derivatives that self-organize in lamellar arrays [24], whereas the introduction of an aromatic residue gives compounds able to self-associate into tubular structures [26][27][28][29][30][31][32][33][34] showing sometimes unique features such as extremely narrow cross sections [27,28], thermo- [33,34] or pH-responsive aggregations [32] and catanionic controlled Page 3 of 25 A c c e p t e d M a n u s c r i p t 4 compositions [31]. Tubular structures are also formed by BA molecules substituted with monosaccharide residues through an unusual mechanism involving scrolls as intermediates [25], whereas vesicles are given by some Gemini derivatives [35].…”