On Tetramethylammonium Ion Role in Glycodeoxycholate Micellar Aggregate Formation

Previously, fiber and crystal structural models were proposed for bile acid salt micellar aggregates and verified in aqueous solutions. Electromotive force (emf) measurements on sodium salts versus ionic strength, pH, and bile salt concentration provided micellar aggregate compositions that supported the models. Ionic strength was varied by adding tetramethylammonium chloride (TMACl), although tetramethylammonium (TMA(+)) and Na+ ions could interfere in the aggregate formation and structure. In this case emf results cannot be used for sodium salts. Tetramethylammonium (TMAGDC) and sodium glycodeoxycholate (NaGDC), which forms helical aggregates constituted by trimers, are studied to clarify this point. TMAGDC crystal structure is solved, and circular dichroism (CD), quasi-elastic light-scattering (QELS), electrolytic conductance, and dielectric measurements on TMAGDC and NaGDC aqueous solutions are compared for determining similarities and dissimilarities in their behavior. TMA(+) and Na+ coordinations in TMAGDC and NaGDC crystals show that Na+ potential energy is lower than that of TMA(+), thus suggesting a stronger Na+ binding to glycodeoxycholate anion (GDC(-)) aggregates. Bilirubin-Ma (Bn) chiral recognition is sensitive to aggregate structures. BR CD spectra suggest similar structures for TMAGDC and NaGDC anion aggregates. QELS measurements indicate that GDC(-) aggregates have a greater affinity for Na+ ions than for TMA(+) ions and that TMA(+) ions form TMAGDC aggregates that are smaller than those formed by NaGDC and could interrupt NaGDC aggregate growth. From conductance data TMA(+) seems to be bound to anion aggregates less than Na+, enhances its interactions when micellar size increases, could be included together with Cl-, coming from TMACl, into micellar aggregates, and could be bound through hydrophobic forces with the apolar lateral surface of anion aggregates. High TMAGDC values of the average electric dipole moment per monomer mu can be justified by cation and anion hydration. Probably, aggregate composition, population, and structure change slightly or do not change at all within the range 15-45 degreesC, where mu is nearly constant. The high single monomer mu (more than 70 D) suggests that TMA(double dagger) is anchored to GDC(-) in dilute solution, thus forming an ion pair. TMAGDC and NaGDC mu trends are both interpreted assuming a two-structure model and an equilibrium between dimeric and trimeric species. In conclusion, TMAGDC and NaGDC bigger aggregates have similar structures, even though the TMAGDC micellar size is smaller than that of NaGDC.