Study of the physicochemical properties in aqueous medium and molecular modeling of tagitinin C/cyclodextrin complexes.
The inclusion complexes of tagitinin C with beta-, 2,6-di-O-methyl-beta- and gamma-cyclodextrin (CyD) was investigated in aqueous medium. The stoichiometric ratios and stability constants (K(f)) which describe the extent of formation of the complexes have been determined by UV spectroscopy and direct current tast polarography (DC(tast)), respectively. For each complex, a 1:1 molar ratio was formed in solution and the trend of stability constants was K(f) (2,6-di-O-methyl-beta-CyD)>K(f) (gamma-CyD)>K(f) (beta-CyD). The effect of molecular encapsulation on the photochemical conversion of tagitinin C was evaluated. No significant protection efficacy was noticed with beta- and gamma-CyD for the complexed drug with the respect to the free one. On the other hand, the photochemical conversion rate was slowed in presence of 2,6-di-O-methyl-beta-CyD. Data from (1)H NMR and ROESY experiments provided a clear evidence of formation of inclusion complexes. The lactone, the ester and the unsaturated ketone parts of tagitinin C inserted into the wide rim of the CyDs torus. These experimental results were confirmed by the molecular modeling using semiempirical Austin Model 1 (AM1) method.
Ziémons
E
E
Laboratory of Analytical Chemistry, Bioanalytical Chemistry Research Unit, Department of Pharmacy, University of Liège, Liège, Belgium. eziemons@ulg.ac.be
Dive
G
G
Debrus
B
B
Barillaro
V
V
Frederich
M
M
Lejeune
R
R
Angenot
L
L
Delattre
L
L
Thunus
L
L
Hubert
Ph
P
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003505:Cyclodextrins / Q000737:chemistry*; D004339:Drug Compounding; D004563:Electrochemistry; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010777:Photochemistry; D011048:Polarography; D012717:Sesquiterpenes / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D014867:Water
D003505:Cyclodextrins; D007202:Indicators and Reagents; D012717:Sesquiterpenes; D014867:Water; C012565:tagitinin