Differentiating geometrical isomers of retinoids and controlling their photo-isomerization by complexation with cyclodextrins Original Research Article

Inclusion complexes between retinoids (retinal, retinol, retinyl acetate and retinoic acid) and β-cyclodextrins (β-CD, native and chemically modified) are described, finding a similar behaviour for the set of modified β-CDs under study. Proof of the inclusion is given by the changes in the chemical shift detected for the H3 and H5 protons of β-CD and hydroxypropyl-β-cyclodextrin (HPβ-CD) by 1H-NMR as well as by the changes in the coupling constants. UV–VIS spectrophotometry allows the determination of stoichiometry and association constants of the complexes. The stoichiometries are 1:2 of retinoid:CD, although these complexes may co-exist with the correponding 1:1 species. The association constants are very high as expected for hydrophobic molecules. Values for log Ka are in the ranges of 2.8–5.9 depending on the type of cyclodextrin and also the nature of the guest molecule. Due to the extreme photolability of this class of polyenes the handling of their samples normally requires numerous precautions. In homogeneous solutions as well as in micellar solutions, all-trans-retinoids are very easily photo-isomerized. In contrast to this behaviour, it is observed that the photo-isomerization of all-trans-retinoids is considerably hampered following their encapsulation in the CD cavities.