Characterization, phase solubility and molecular modeling of α-cyclodextrin/pyrimethamine inclusion complex

An inclusion complex between the dihydrofolate reductase inhibitor pyrimethamine (PYR) and α-cyclodextrin (α-CD) was prepared and characterized. From the phase-solubility diagram, a linear increase of PYR solubility was verified as a function of α-CD concentration, suggesting the formation of a solu...

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Published in:Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Molecular and biomolecular spectroscopy, 2009-02, Vol.72 (1), p.165-170
Main Authors: Araujo, Marcia Valeria Gaspar de, Macedo, Osmir F.L., Nascimento, Cristiane da Cunha, Conegero, Leila Souza, Barreto, Ledjane Silva, Almeida, Luis Eduardo, Costa, Nivan Bezerra da, Gimenez, Iara F.
Format: Article
Language:English
Subjects:
alpha-Cyclodextrins - chemistry
Inclusion complex
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular modeling
Pyrimethamine
Pyrimethamine - chemistry
Solubility
Thermodynamics
Toxoplasmosis
X-Ray Diffraction
α-CD
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Summary:An inclusion complex between the dihydrofolate reductase inhibitor pyrimethamine (PYR) and α-cyclodextrin (α-CD) was prepared and characterized. From the phase-solubility diagram, a linear increase of PYR solubility was verified as a function of α-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 α-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 1H NMR spectroscopy (ROESY) involves penetration of the p-chlorophenyl ring into the α-CD cavity, in agreement to the orientation optimized by molecular modeling methods.
ISSN:1386-1425
DOI:10.1016/j.saa.2008.09.011