Physicochemical characterization of sildenafil: Ionization, lipophilicity behavior, and ionic-partition diagram sturdied by two-phase titration and electrochemistry
V. Gobry et al., Physicochemical characterization of sildenafil: Ionization, lipophilicity behavior, and ionic-partition diagram sturdied by two-phase titration and electrochemistry, HELV CHIM A, 83(7), 2000, pp. 1465-1474
Sildenafil (Viagra(TM)) was examined for its ionization and lipophilicity b
y two-phase titration and electrochemistry at the interface between two imm
iscible electrolyte solutions (ITIES) in the 12-dichloroethane/H2O system.
The dissociation constants (basic pK(a) = 6.78, acidic pK(a) = 9.12) and pa
rtition coefficients of the various species, together with the effects of e
lectrical potential, were used to construct an ionic partition diagram (pH-
potential representation). This allowed to interpret the transfer mechanism
s of sildenafil at liquid/liquid interfaces, suggesting in particular that
an intramolecular H-bond influences the lipophilicity of the neutral and ca
tionic species. Conformational calculations confirmed this hypothesis.