The characteristic alkaloid component of the leaves of the catnip shrub (Catha edulis)
is cathinone, and its synthetic analogs form a major group of recreational drugs.
Cathinone derivatives are chiral compounds. In the literature, several chiral methods
using cyclodextrins (CDs) have been achieved so far for diverse sets of analogs; however,
a comprehensive investigation of the stability of their CD complexes has not been
performed yet. To characterize the enantioselective complex formation, a systematic
experimental design was developed in which a total number of 40 neutral, positively,
and negatively charged CD derivatives were screened by affinity capillary electrophoresis
and compared according to their cavity size, substituent type, and location. The functional
groups responsible for the favorable interactions were identified in the case of para-substituted
cathinone analog mephedrone, flephedrone, and 4-methylethcathinone (4-MEC) and in
the case of 3,4-methylendioxy derivative butylone and methylenedioxypyrovalerone (MDPV).
The succinylated-β-CD and subetadex exhibited the highest complex stabilities among
the studied drugs. The complex stoichiometry was determined using the Job’s plot method,
and the complex structures were further studied using ROESY NMR measurements. The
results of our enantioselective complex formation study can facilitate chiral method
development and may lead to evaluate potential CD-based antidotes for cathinone analogs.
