Complexation of bile salts by natural cyclodextrins

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 alpha-, beta- and gamma-cyclodextrins (alpha-CD, beta-CD and gamma-CD), has been studied by using 1D and 2D-NMR techniques. Trihydroxy bile salts form 1:1 complexes with beta-CD and gamma-CD, while dihydroxy bile salts form 1:2 (bile salt:cyclodextrin) complexes with beta-CD and 1:1 complexes with gamma-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 beta-CD and gamma-CD, in 1:1 complexes. The A ring of the steroid body is included into the cavity of the second beta-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 gamma-CD allows this region of bile salts to be located inside the cyclodextrin cavity and therefore gamma-CD does not discriminate between both types of bile salts. However, in trihydroxy bile salts, this region clearly remains outside the beta-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 beta-CD. It is concluded that beta-CD molecularly recognises bile salts, distinguishing di- from trihydroxy ones, while gamma-CD does not. The steroid body of bile salts is too big to enter into the alpha-CD cavity and only an interaction between their side chain and alpha-CD is observed.