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High‐field NMR techniques and molecular modelling in the study of the inclusion complex of the cognition activator suronacrine (HP‐128) with cyclodextrins
Author(s) -
Amato Maria E.,
Pappalardo Giuseppe C.,
Perly Bruno
Publication year - 1993
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.1260310508
Subject(s) - chemistry , intramolecular force , proton nmr , nuclear magnetic resonance spectroscopy , molecular model , hydrogen bond , carbon 13 nmr , stereochemistry , computational chemistry , crystallography , molecule , organic chemistry
The structural features of the inclusion complexes of cyclodextrins (CDs) with the chiral cognition activator drug (±)9‐[(phenylmethyl)amino]‐1,2,3,4‐tetrahydroacridin‐1‐ol maleate (suronacrine maleate, HP‐128) were studied using both high‐resolution 1 H NMR spectroscopy and molecular modelling methods. The partial inclusion of the guest from the secondary hydroxyl side of α‐CD was demonstrated in aqueous solution, in addition to a higher degree of penetration into the cavity of β‐CD from the same side. NMR‐ROESY experiments allowed the unambiguous location of the benzylic ring of the guest inside the β‐CD cavity. The formation of diastereoisomeric pairs was demonstrated by the duplication of the benzylic proton signals. Molecular mechanics calculations were used to complement the NMR analysis. Molecular modelling procedures (MacroModel interactive computer program) allowed the prediction of the most stable structures of the complexes, and showed that specific site interactions, provided by hydrogen bond formation, are capable of differentiating the diastereoisomeric intramolecular inclusion complexes according to available experimental NMR data.