The mechanism of complexation between risperidone (RISP) and (−)-epigallocatechin gallate (EGCg) was clarified by 1H-NMR and molecular modeling studies. RISP and EGCg formed an insoluble complex with a 1 : 1 stoichiometry in aqueous solution. In the 1H-NMR spectra of RISP in DMSO-d6, the chemical shifts of protons neighboring the N atom on the piperizine ring clearly moved downfield upon formation of the complex. In the molecular modeling study, the 1H-chemical shifts for nine optimized structures of the complex were calculated to compare them with those of the experimental results. Only one conformer with the second minimum energy for the complex supported the downfield shifts of RISP protons. It was found from the structure of the complex that the two hydrogen bonds between hydroxyl groups of the galloyl ring in EGCg and N atoms in RISP, one of which was on the piperizine ring, were formed to stabilize the complex.
