title: First solid-state NMR spectroscopy evaluation of complexes of benznidazole with cyclodextrin derivatives.
abstract: Complexation of benznidazole (BZL), a drug of choice for the treatment of Chagas'neglected disease, with cyclodextrin (CD) derivatives was analyzed by solid-state NMR. (13)C cross polarization/magic angle spinning spectra were recorded from BZL and from BZL:β-CD, BZL:methyl β-CD and BZL:hydroxypropyl β-CD complexes, which were obtained by the solvent evaporation technique. No significant evidence was obtained on BZL inclusion complexes involving either β-CD or hydroxypropyl β-CD. Conversely, BZL:methyl β-CD displayed BZL resonances characteristic of an amorphous drug and data analysis confirmed the presence of stable BZL:methyl β-CD inclusion complexes, with benzene encapsulated into the host cavity. Further evidences on complex structure and dynamics were obtained from proton and carbon spin-lattice relaxation times in the rotating frame. These data are consistent with a common guest-host spin reservoir. The BZL interaction with methyl β-CD provided a route to stabilize amorphous BZL. Physical mixtures with identical BZL and CD compositions were also studied for comparison.
authors.affiliation: IQUIR-CONICET, Suipacha 531, 2000 Rosario, Argentina.
authors.forename: Josefina
authors.initials: J
authors.lastname: Priotti
authors.affiliation: CQE, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: M João G
authors.initials: MJ
authors.lastname: Ferreira
authors.affiliation: IQUIR-CONICET, Suipacha 531, 2000 Rosario, Argentina; Área Técnica Farmacéutica, Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Lamas
authors.affiliation: IQUIR-CONICET, Suipacha 531, 2000 Rosario, Argentina; Área Técnica Farmacéutica, Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
authors.forename: Darío
authors.initials: D
authors.lastname: Leonardi
authors.affiliation: IQUIR-CONICET, Suipacha 531, 2000 Rosario, Argentina; Área Técnica Farmacéutica, Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
authors.forename: Claudio J
authors.initials: CJ
authors.lastname: Salomon
authors.affiliation: CQE, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal. Electronic address: teresa.nunes@tecnico.ulisboa.pt.
authors.forename: Teresa G
authors.initials: TG
authors.lastname: Nunes
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002244:Carbon / Q000737:chemistry; D066241:Carbon-13 Magnetic Resonance Spectroscopy / Q000379:methods*; D003505:Cyclodextrins / Q000737:chemistry*; D009593:Nitroimidazoles / Q000737:chemistry*; D011522:Protons; D013997:Time Factors; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D003505:Cyclodextrins; D009593:Nitroimidazoles; D011522:Protons; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002244:Carbon; C009999:benzonidazole
keywords: Benznidazole; Chagas’ disease; Inclusion complex; Solid-state NMR; β-Cyclodextrins