Inclusion complexes of pyrimethamine in 2-hydroxypropyl-beta-cyclodextrin: characterization, phase solubility and molecular modelling.
The inclusion complexation of pyrimethamine in 2-hydroxypropyl-beta-cyclodextrin has been investigated by 2D (1)H NMR, FTIR and UV/visible spectroscopy and also by molecular modelling methods (AM1, PM3, MM3). From the phase-solubility diagram a linear increase was observed in pyrimethamine aqueous solubility in the presence of 2-hydroxypropyl-beta-cyclodextrin, evidencing the formation of a soluble inclusion complex. According to the continuous variation method (Job's plot) applied to fluorescence measurements, a 1:1 stoichiometry has been proposed for the complex. Concerning the structure of the complex, a Cl-in orientation of pyrimethamine in the 2-hydroxypropyl-beta-cyclodextrin cavity has been proposed from the theoretical calculations, being confirmed by two-dimensional (1)H NMR spectroscopy (ROESY). The thermal behaviour has also been studied, providing complementary evidences of complex formation.
de Araújo
Márcia Valéria Gaspar
MV
Departamento de Química, Universidade Federal de Sergipe (UFS), Av Marechal Rondon s/n, Campus Universitário Prof. José Aloísio de Campos, CEP 491000-000, São Cristóvão, SE, Brazil.
Vieira
Elze Kelly Barbosa
EK
Lázaro
Gilderman Silva
GS
de Souza Conegero
Leila
L
Ferreira
Odair Pastor
OP
Almeida
Lui S Eduardo
LS
Barreto
Ledjane Silva
LS
da Costa
Nivan Bezerra
NB
Gimenez
Iara F
IF
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002152:Calorimetry, Differential Scanning; D008958:Models, Molecular; D015394:Molecular Structure; D011739:Pyrimethamine / Q000737:chemistry*; D012995:Solubility; D013053:Spectrophotometry; D013818:Thermogravimetry; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011739:Pyrimethamine