title: Benzocaine complexation with p-sulfonic acid calix[n]arene: experimental ((1) H-NMR) and theoretical approaches.
abstract: 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 PM3 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.
authors.affiliation: Grupo de Química Supramolecular e Biomimética (GQSB), Departamento de Química, Universidade Federal de Viçosa (UFV), Viçosa, Brazil, 36570-000.
authors.forename: Lucas M
authors.initials: LM
authors.lastname: Arantes
authors.forename: Eduardo V V
authors.initials: EV
authors.lastname: Varejão
authors.forename: Karin J
authors.initials: KJ
authors.lastname: Pelizzaro-Rocha
authors.forename: Cíntia M S
authors.initials: CM
authors.lastname: Cereda
authors.forename: Eneida
authors.initials: E
authors.lastname: de Paula
authors.forename: Maicon P
authors.initials: MP
authors.lastname: Lourenço
authors.forename: Hélio A
authors.initials: HA
authors.lastname: Duarte
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Fernandes
mesh_terms: D000818:Animals; D001566:Benzocaine / Q000737:chemistry*; D047250:Calixarenes / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008962:Models, Theoretical; D008968:Molecular Conformation; D013451:Sulfonic Acids / Q000737:chemistry
chemical_list: D013451:Sulfonic Acids; D047250:Calixarenes; D001566:Benzocaine
keywords: NMR; benzocaine; calix[n]arenes; density functional theory; inclusion compounds; semiempirical methods; supramolecular chemistry