The local anaesthetic Tetracain has previously been found to block, induce or potentiate Ca2+ release from
the sarcoplasmic reticulum of skeletal muscle. Cyclodextrins (CD) are complexing agents that have been
successfully used as pharmaceutical drug carriers, to improve the bioavailability of medicines. The aim of this work
is to investigate the inclusion process of the local anesthetic Tetracain with the beta-cyclodextrin at the Hartree–Focklevel
of theory calculations with a 6-31G (d) basis set, and to evaluate stabilization upon the formation of the inclusion
compounds for 1:1 association. The inclusion process pathways are described and the most stable structures
of the different complexes are sought through a global potential energy scan. The data suggest that the most
stable structure for the 1:1 stoichiometry between the Tetracain and the β-CD is obtained when the inclusion
complex formed by Tetracain from the tertiary amine group, entering into the cavity of β-CD from its narrow side
(i.e. the primary 6-CH2OH hydroxyl group). Structure–activity relationship is discussed in terms of different
molecular descriptors and experimental Raman spectroscopy measurements at different mole fraction for
the inclusion complexes analyzed and compared with our theoretical constructed Raman spectra.
