Study of Association of 12-Monoketocholic Acid by H-1 NMR Relaxation Method

12-Monoketocholic acid (12-MKC) shows a promotive effect in the transport of some drugs (lidocaine, morphine, quinine, gliclazide, etc.). In the mechanism of pharmacological action of 12-MKC an important role plays its aggregation (self-association), as well as formation of mixed micelles. These phenomena were studied by the H-1 NMR spin-lattice relaxation method using solutions of sodium salt of 12-MKC in D2O and in D2O solution saturated with 1-octanol. The function describing the dependence of the spin-lattice relaxation time (T-1) on the concentration of Na-12-MKC (c(BA)) in D2O has one inflexion point (at the concentration of 48 mM), whereas the same function for the saturated solution of 1-octanol has two inflexion points (one at the concentration of 45 mM and the other at 87 mM). These differences in the curves T-1 = f(c(BA)), as well as the shift of the solubilization curve of lecithin in the presence of 1-octanol towards higher concentrations of Na-12-MKC, indicate that sodium salt of this keto-bile acid forms mixed micelles with 1-ocatnol, so that the application of the micellar solution of Na-12-MKC in the presence of 1-octanol decreases membrane toxicity (membrane lysis) of this bile acid. The curves T-1 = f(c(BA)) for methyl esters of 12-MKC and cholic acid in the CDCl3 solution have one inflexion point at the concentration above 5 mM, indicating formation of the micelles of Small's type, whereas methyl ester of 3,7,12-triketocholic acid forms a gel-like structure.