Characterization, phase solubility and molecular modeling of alpha-cyclodextrin/pyrimethamine inclusion complex.
An inclusion complex between the dihydrofolate reductase inhibitor pyrimethamine (PYR) and alpha-cyclodextrin (alpha-CD) was prepared and characterized. From the phase-solubility diagram, a linear increase of PYR solubility was verified as a function of alpha-CD concentration, suggesting the formation of a soluble complex. A 1:1 host-guest stoichiometry can be proposed according to the Job's plot, obtained from the difference of PYR fluorescence intensity in the presence and absence of alpha-CD. Differential scanning calorimetry (DSC) measurements provided additional evidences of complexation such as the absence of the endothermic peak assigned to the melting of the drug. The inclusion mode characterized by two-dimensional (1)H NMR spectroscopy (ROESY) involves penetration of the p-chlorophenyl ring into the alpha-CD cavity, in agreement to the orientation optimized by molecular modeling methods.
de Araujo
Marcia Valeria Gaspar
MV
Departamento de Química, Universidade Federal de Sergipe, Av. Marechal Rondon s/n, Campus Universitário Prof. José Aloísio de Campos, CEP 491000-000, São Cristóvão, SE, Brazil.
Macedo
Osmir F L
OF
Nascimento
Cristiane da Cunha
Cda C
Conegero
Leila Souza
LS
Barreto
Ledjane Silva
LS
Almeida
Luis Eduardo
LE
da Costa
Nivan Bezerra
NB
Gimenez
Iara F
IF
D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011739:Pyrimethamine / Q000737:chemistry*; D012995:Solubility; D013816:Thermodynamics; D014961:X-Ray Diffraction; D047391:alpha-Cyclodextrins / Q000737:chemistry*
D047391:alpha-Cyclodextrins; C032613:alpha-cyclodextrin; D011739:Pyrimethamine