title: Characterization, phase solubility and molecular modeling of alpha-cyclodextrin/pyrimethamine inclusion complex.
abstract: 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.
authors.affiliation: 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.
authors.forename: Marcia Valeria Gaspar
authors.initials: MV
authors.lastname: de Araujo
authors.forename: Osmir F L
authors.initials: OF
authors.lastname: Macedo
authors.forename: Cristiane da Cunha
authors.initials: Cda C
authors.lastname: Nascimento
authors.forename: Leila Souza
authors.initials: LS
authors.lastname: Conegero
authors.forename: Ledjane Silva
authors.initials: LS
authors.lastname: Barreto
authors.forename: Luis Eduardo
authors.initials: LE
authors.lastname: Almeida
authors.forename: Nivan Bezerra
authors.initials: NB
authors.lastname: da Costa
authors.forename: Iara F
authors.initials: IF
authors.lastname: Gimenez
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011739:Pyrimethamine / Q000737:chemistry*; D012995:Solubility; D013816:Thermodynamics; D014961:X-Ray Diffraction; D047391:alpha-Cyclodextrins / Q000737:chemistry*
chemical_list: D047391:alpha-Cyclodextrins; C032613:alpha-cyclodextrin; D011739:Pyrimethamine