The molecular interactions of water-soluble crown resorcinarenes with choline were analyzed. To this end, four sulfonated resorcinarenes were synthesized and characterized by ATR-IR, 1H-NMR, and 13C-NMR spectroscopy. The molecular interaction studies with choline were carried out through FT-IR spectroscopy, 1H-NMR titrations, and conductimetric titrations, with which it was possible to determine that the complexes formed 1:1 stoichiometries with the host, in addition to showing good interaction in the electronic cavity of the macrocycle, demonstrating great potential for host–guest systems for choline detection in aqueous media. Finally, the incidence of the structural aspects of sulfonated resorcinarenes were analyzed.