Investigation of tetracaine complexation with beta-cyclodextrins and p-sulphonic acid calix[6]arenes by nOe and PGSE NMR |
| |
Authors: | Sergio Antonio Fernandes Luiz Fernando Cabeça Anita Jocelyne Marsaioli Eneida de Paula |
| |
Institution: | 1. Departamento de Química, Universidade Federal de Vi?osa, Vi?osa, Brazil 2. Departamento de Química Organica, Instituto de Química – Universidade Estadual de Campinas, Campinas, SP, Brazil 3. Departamento de Bioquímica, Instituto de Biologia – Universidade Estadual de Campinas (UNICAMP), Campus Univers. Zaferino Vaz, Caixa Postal 6109, CEP 13083-970, Campinas, SP, Brazil
|
| |
Abstract: | Cyclodextrins (CD) and calixarenes are complexing agents that have been successfully used as pharmaceutical drug carriers,
to improve the bioavailability of medicines. The aim of this work was to investigate the complexation of the local anesthetic
tetracaine 1 with β-cyclodextrin 2, as well as with p-sulphonic acid calix6]arene 3. 1H NMR experiments were carried out in D2O, i.e., with the charged tetracaine species 1. HR-DOSY 1H NMR allowed determination of the fraction of complexed population (%p
bound = 55% and 70%) and the apparent association constants (K
a = 1358 and 3889 M−1), respectively, for 1/2 and 1/3. These results confirm that a strong association takes place between 1 and 2, while the 1/3 complex is even more stable, due to the negatively charged sulphonic groups of 3. Studies conducted at pH 10 revealed that the association of the uncharged form of 1 with 3 is considerably weaker, while that with 2 increased significantly (K
a
= 6597 M−1), protecting the anesthetic against alkaline hydrolysis. 1H-ROESY 1D NMR experiments allowed determination of the host-guest relative positions, revealing that the proposed topologies
for the 1/2 and 1/3 complexes were quite different. The complexation of 1 with either 2 or 3 is being investigated in view of its potential use in new therapeutic formulations, designed to increase the bioavailability
and/or to decrease the systemic toxicity of tetracaine, in anesthesia procedures. |
| |
Keywords: | Tetracaine Cyclodextrin Calixarene Nuclear magnetic resonance |
本文献已被 SpringerLink 等数据库收录! |
|