CHOLESTEROL SOLUBILITY BY BILE-SALTS IN PURE AND MIXED STATES WITH VARIOUS ADDITIVES

Results of a study of cholesterol solubility in aqueous solution of sodium salts of cholic, deoxycholic, and dehydrocholic acids and their mutual binary mixtures as well as mixtures with sodium salicylate (NaS), sodium ascorbate (NaA), glucose, fructose, poly(ethylene glycol) (PEG), urea, and cetyltrimethylammonium bromide (CTAB) are presented. Both in pure and mixed states sodium deoxycholate (NaDC) solubilized more sterol than sodium cholate (NaC), whereas the solubility is insignificant in sodium dehydrocholate (NaDHC). Although individually NaDHC and CTAB are poor cholesterol solubilizers, their equimolar mixture (50 mmol.dm-3 each) can appreciably solubilize the sterol (1.80 mmol.dm-3 at 306 K). A mixture of NaC and CTAB at equal concentrations (50 mmol.dm-3 each) also shows appreciable solubility (8.57 mmol.dm-3 at 306 K). All the additives as well as the individual bile salts have shown distinct solubility behaviors at lower and higher concentrations. The number of bile salt molecules required to solubilize a single molecule of cholesterol under different environments is reported. The order in NaC is CTAB < fructose < NaS < glucose < NaA < PEG < urea almost-equal-to NaDHC; in NaDC the order is fructose < urea < glucose < NaA < PEG < NaS < NaDHC. The thermodynamic parameters of solubility are presented. The free energies of transfer of cholesterol from the bile salt environment to the environments of bile salt and hydrophilic additives are positive, while those to the NaC + CTAB as well as NaC + NaS and NaDC + NaS environments are negative. The transfer free energies reveal that at equal concentration aqueous NaDC environment is twice as effective as aqueous NaC environment in the presence of most of the additives. The enthalpy-entropy compensation phenomenon reveals the importance of the environmental order-disorder on solubility.