de Sousa Frederico B, Denadai Angelo M Leite, Lula Ivana S, Lopes Juliana F, Dos Santos Hélio F, De Almeida Wagner B, Sinisterra Rubén D
Laboratório de Encapsulamento Molecular e Biomateriais (LEMB), Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
Int J Pharm. 2008 Apr 2;353(1-2):160-9. doi: 10.1016/j.ijpharm.2007.11.050. Epub 2007 Dec 3.
In this work the complex formed between beta-cyclodextrin (betaCD) and fluoxetine (FLU) was investigated by experimental and computational methods. From Horizontal Attenuated Total Reflectance (HATR) was possible to verify a strong modification in the vibrational modes of betaCD and FLU, indicating interactions between them. The Nuclear Magnetic Resonance (NMR) experiments confirm these interactions through the change in chemical shifts in (1)H spectra, reduction in longitudinal relaxation times values, and the Nuclear Ouverhauser Effect confirm the inclusion of aromatic rings of FLU into the betaCD. The structures of the proposed inclusion compounds were optimized at PM3 semiempirical level of theory. In addition, single point calculations at the Density Functional Theory (DFT) level, using the Becke, Lee, Yang, and Parr functional and 6-31G(d,p) basis set, were used to determine the interaction energy for these structures. The DFT calculations identified the aromatic ring, which contains the CF(3) group as the most stable into the betaCD by an amount of, 11.7 kcal mol(-1), in the gas phase. Polarized continuum model, at the DFT level mentioned, was used to investigate the solvent effect, and the results corroborated the gas phase analysis. A high equilibrium constant (K approximately 6921+/-316) and the stoichiometry, 1:1, were obtained by Isothermal Titration Calorimetry (ITC) experiments.
在这项工作中，通过实验和计算方法研究了β-环糊精（βCD）与氟西汀（FLU）形成的复合物。通过水平衰减全反射（HATR）可以验证βCD和FLU振动模式的强烈变化，表明它们之间存在相互作用。核磁共振（NMR）实验通过¹H谱化学位移的变化、纵向弛豫时间值的降低以及核Overhauser效应证实了这些相互作用，证实了FLU的芳香环被纳入βCD中。在PM3半经验理论水平上对所提出的包合物结构进行了优化。此外，使用Becke、Lee、Yang和Parr泛函以及6-31G(d,p)基组在密度泛函理论（DFT）水平上进行单点计算，以确定这些结构的相互作用能。DFT计算确定，在气相中，含有CF(3)基团的芳香环以11.7 kcal mol⁻¹的量最稳定地存在于βCD中。在上述DFT水平上使用极化连续介质模型研究溶剂效应，结果证实了气相分析。通过等温滴定量热法（ITC）实验获得了高平衡常数（K约为6921±316）和化学计量比1:1。
