Benzocaine Complexation with p‐Sulfonic Acid Calix[n]arene: Experimental (¹H‐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.

Host-Guest Complexation of Oxaliplatin and Para-Sulfonatocalix[n]Arenes for Potential Use in Cancer Therapy

“…The stability constants of the complexes were detected using methods detailed previously [31,70,71] to be 5.07 × 10 4 M −1 and 6.3 × 10 4 M −1 which correspond to complexation free energy of −6.39 and −6.52 kcal/mol, for oxaliplatin/p-SC4, and oxaliplatin/p-SC6, respectively. These values are within the range of the stability constants (0.01 × 10 3 -1.7 × 10 5 ) M −1 previously reported for host-guest complexes, many of which are proposed for drug delivery, and many of them showed improved bioavailability, stability, and enhanced therapeutic effects [31,[72][73][74][75][76][77][78][79][80][81][82][83].…”

para‐Sulfonatocalix[n]arenes Inhibit Amyloid β‐Peptide Fibrillation and Reduce Amyloid Cytotoxicity

“…This might be due to the fact that in the larger SC[n]A (i.e.,S C[8]A), the cone is more flexible, which made it easier for the hydrogen bonding and electrostatic interactions to occur. [29] Because all of the binding sites on Ab 42 are limited, the number of bindings ites decreased as the calixarene size increased ( Table 1).…”

Biomedical Applications of Calixarenes: State of the Art and Perspectives

“…Noncovalent encapsulation of drugs into CA cavities has been widely used to improve drug properties (e.g.s olubility and stability) and/or realize drug delivery. [102] Menon et al reported the complexation of 1 and 2 with carvedilol (CDL), apoorly water-soluble drug, revealing that this complexation greatly increased CDL solubility and demonstrating al inear relationship between CDL solubility in water and CA concentration. [103] Amphiphilic CAsc an self-assemble as nanoparticles and act as drug nanocarriers.R aston et al reported that vesicles formed by amphiphilic phosphonomethyl C4A (47 in Scheme 6) effectively bind carboplatin and increase its anticancer efficacy.…”