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Benzocaine Complexation with p ‐Sulfonic Acid Calix[ n ]arene: Experimental ( 1 H‐NMR) and Theoretical Approaches
Author(s) -
Arantes Lucas M.,
Varejão Eduardo V. V.,
PelizzaroRocha Karin J.,
Cereda Cíntia M. S.,
Paula Eneida,
Lourenço Maicon P.,
Duarte Hélio A.,
Fernandes Sergio A.
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12267
Subject(s) - benzocaine , chemistry , solubility , cyclodextrin , proton nmr , chemical shift , computational chemistry , stereochemistry , organic chemistry , immunology , biology
The aim of this work was to study the interaction between the local anesthetic benzocaine and p‐ sulfonic acid calix[ n ]arenes using NMR and theoretical calculations and to assess the effects of complexation on cytotoxicity of benzocaine. The architectures of the complexes were proposed according to 1 H NMR data (Job plot, binding constants, and ROESY ) indicating details on the insertion of benzocaine in the cavity of the calix[ n ]arenes. The proposed inclusion compounds were optimized using the PM 3 semiempirical method, and the electronic plus nuclear repulsion energy contributions were performed at the DFT level using the PBE exchange/correlation functional and the 6‐311G(d) basis set. The remarkable agreement between experimental and theoretical approaches adds support to their use in the structural characterization of the inclusion complexes. In vitro cytotoxic tests showed that complexation intensifies the intrinsic toxicity of benzocaine, possibly by increasing the water solubility of the anesthetic and favoring its partitioning inside of biomembranes.