Molecular recognition in the gas phase: benzocaine–phenol as a model of anaesthetic–receptor interaction

Abstract

The benzocaine–phenol complex is proposed as a model system of the interaction between the local anaesthetic benzocaine and the tyrosine residue. The complex has been generated by supersonic expansion of benzocaine and phenol in helium and probed by 1- and 2-color mass-resolved laser spectroscopies. The electronic excitation spectrum of the 1 : 1 complex spans some ∼700 cm⁻¹ and includes well resolved bands from at least two isomers, as demonstrated using UV–UV hole burning spectroscopy. The combination of ion dip infrared spectroscopy (IDIRS) and ab initio calculations shows that both isomers are stabilized by an OH⋯N hydrogen bond between the phenol hydroxyl group and the benzocaine amino moiety, differing only in the conformation adopted by the benzocaine monomer (trans and gauche). The application of the fragmentation threshold method to benzocaine–phenol suggests the existence of chemical reactions in the electronic excited state of the complex and/or in the ion. Such hypothesis is also supported by the calculated potential energy curves along the hydrogen bond coordinate.