Investigation of tetracaine complexation with beta-cyclodextrins and p-sulphonic acid calix[6]arenes by nOe and PGSE NMR

  • Sergio Antonio Fernandes
  • Luiz Fernando Cabeça
  • Anita Jocelyne Marsaioli
  • Eneida de Paula
Orginal Article


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 calix[6]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.


Tetracaine Cyclodextrin Calixarene Nuclear magnetic resonance 



The authors are indebted to FAPESP (Proc. 2005/00602-4) and CT-PETRO/CNPq (Proc. 360762/2005-0) for financial support and fellowships. The authors also thank Prof. Carol Collins for English text revision.


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Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • Sergio Antonio Fernandes
    • 1
  • Luiz Fernando Cabeça
    • 2
  • Anita Jocelyne Marsaioli
    • 2
  • Eneida de Paula
    • 3
  1. 1.Departamento de QuímicaUniversidade Federal de ViçosaViçosaBrazil
  2. 2.Departamento de Química OrgânicaInstituto de Química – Universidade Estadual de CampinasCampinasBrazil
  3. 3.Departamento de BioquímicaInstituto de Biologia – Universidade Estadual de Campinas (UNICAMP)CampinasBrazil

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