Studies of curcumin and curcuminoids. XXXVI. The stoichiometry and complexation constants of cyclodextrin complexes as determined by the phase-solubility method and UV-Vis titration

Cyclodextrin (CD) complex stoichiometry and complexation constant with two symmetric curcuminoids and two unsymmetric curcuminoid-like compounds were investigated and compared by two independent methods, the phase-solubility method and ultraviolet-visible absorption spectroscopy (UV-Vis) titration. Two different methods were applied in an effort to increase the apparent intrinsic solubility of the compounds and make the investigation of stoichiometry and complexation constants possible. The intrinsic solubility could be determined for all four compounds in aqueous 10% (v/v) ethanolic solutions. Higher order complexation or solubilization through complex aggregation was observed for the symmetric molecules, while 1:1 complexation was observed for the unsymmetric molecules in the phase-solubility diagram. The UV-Vis investigation showed 1:1 complexation for all compounds, with some indication of higher order complexation for the symmetric molecules. Thus the stoichiometry found with the two methods correlated well for the unsymmetric, but not for the symmetric compounds where the phase-solubility investigations clearly indicated higher order complexation and possible aggregation of complexes. There was also a difference between the 1:1 complexation constants found with the two methods, especially for the compounds with low intrinsic solubility (i.e. the symmetric curcuminoids). However, they agree in the ranking of complexes according to the strength of the association. The 1:2 complexation constant observed with the phase-solubility method was more than 100 times the complexation constant found with the UV-Vis method, which explains why solubility is poorly predicted from the UV-Vis data. This discrepancy may be explained by solubilization by aggregation of complexes or some phenomena other than inclusion complexation.