Complexation of Bile Salts by Natural Cyclodextrins

Abstract

The complexation of three trihydroxy sodium bile salts--cholate, glycocholate, and taurocholate--and their three related sodium dihydroxy bile salts--deoxycholate, glycodeoxycholate, and taurodeoxycholate--by f -, g - and n -cyclodextrins ( f -CD, g -CD and n -CD), has been studied by using 1D and 2D-NMR techniques. Trihydroxy bile salts form 1:1 complexes with g -CD and n -CD, while dihydroxy bile salts form 1:2 (bile salt:cyclodextrin) complexes with g -CD and 1:1 complexes with n -CD. ROESY experiments stated that the side chain, ring D, and part of ring C of the steroid body of the bile salts, are included into the cavities of g -CD and n -CD, in 1:1 complexes. The A ring of the steroid body is included into the cavity of the second g -CD in the 1:2 complexes. The only structural difference between related bile salts is the existence or not of a hydroxyl group at C7. The bigger cavity of n -CD allows this region of bile salts to be located inside the cyclodextrin cavity and therefore n -CD does not discriminate between both types of bile salts. However, in trihydroxy bile salts, this region clearly remains outside the g -CD cavity. The absence of the C7 hydroxyl group enlarges the hydrophobic region of the steroid body, allowing a favourable interaction with the hydrophobic cavity of a second g -CD. It is concluded that g -CD molecularly recognises bile salts, distinguishing di- from trihydroxy ones, while n -CD does not. The steroid body of bile salts is too big to enter into the f -CD cavity and only an interaction between their side chain and f -CD is observed.