A new pH-metric methodology for the determination of thermodynamic inclusion constants of guest/cyclodextrin complexes.
A new methodology of pH-metric data treatment was developed to extract the stoichiometry and the thermodynamic association constants of guest-cyclodextrin inclusion complexes in dilute aqueous solution when the guest is a participant in an acid-base equilibrium. pH-metric titration curves in the presence of cyclodextrin (CD) were treated by a curve-fitting technique according to a nonlinear least-squares regression. Equations corresponding to the different kinds of acid-base pairs (AH/A-, BH+/B) and stoichiometries (1:1 and 1:2) were established. The methodology was validated by studying the 5-phenylbarbituric acid complexation with beta-CD and the 4-cyanobenzoic acid complexation with alpha-CD. Then it was applied to chlorpromazine. Both the acid form (constant K1 = 3260) and the base form (constant G1 = 13,100) gave complexes with beta-CD according to 1:1 stoichiometry.
Boudeville
P
P
Département de Physicochimie et Biocinétique des Pharmacosystèmes 2, Rennes, France.
Burgot
J L
JL
D001462:Barbital / Q000031:analogs & derivatives / Q000737:chemistry; D001565:Benzoates / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002746:Chlorpromazine / Q000737:chemistry; D003505:Cyclodextrins / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D012995:Solubility; D013816:Thermodynamics
D001565:Benzoates; D003505:Cyclodextrins; C056941:5-phenylbarbituric acid; C097383:4-cyanobenzoic acid; D001462:Barbital; D002746:Chlorpromazine