Supramolecular encapsulation of benzocaine and its metabolite para-aminobenzoic acid by cucurbit[7]uril

Abstract

An ester-type local anesthetic agent, benzocaine (BZC), and its metabolite, para-aminobenzoic acid (PABA), both form 1 : 1 host-guest complexes with cucurbit[7]uril (CB[7]) in aqueous solution and has been observed by 1H NMR, UV-visible spectroscopic titrations (including Job's plot), electrospray ionization (ESI) mass spectrometry, and density functional theory (DFT) molecular modeling. The host-guest binding affinities are (2.2 ± 0.2) × 104 M-1 and (1.5 ± 0.2) × 104 M-1 for the protonated BZC and PABA, respectively, in acidic solutions. The binding constants decrease by ∼100-fold to approximately 300 and 200 M-1 for BZC and PABA, respectively, upon deprotonation of these guest molecules in PBS buffered solution (pH = 7.4). However, the encapsulation of these guest molecules by CB[7] only resulted in very moderate pKa shifts. This supramolecular encapsulation of BZC and PABA could potentially find applications in drug formulation for the purpose of enhancing bio-absorption as well as reducing methemoglobinemia and allergic reactions caused by the derivation of PABA during the metabolism of BZC. Show more