Dysprosium(III)-diethylenetriaminepentaacetate complexes of aminocyclodextrins as chiral NMR shift reagents

Abstract

A metal chelating ligand is bonded to alpha-, beta-, and gamma-cyclodextrin by the reaction of diethylenetraminepentaacetic dianhydride with the corresponding 6-mono- and 2-mono(amine)cyclodextrin. Adding Dy(III) to the cyclodextrin derivatives causes shifts in the (1)H-NMR spectra of substrates such as propranolol, tryptophan, aspartame, carbinoxamine, pheniramine, doxylamine, and 1-anilino-8-naphthalenesulfonate. The Dy(III)-induced shifts enhance the enantiomeric resolution in the NMR spectra of several substrates. Enhancements in enantiomeric resolution using cyclodextrin derivatives with the amine tether are compared to previously described compounds in which the chelating ligand is attached through an ethylenediamine tether. In general, the Dy(III) complex of the 6-beta-derivative with the amine tether is a more effective chiral resolving agent than the complex with the ethylenediamine tether. The opposite trend is observed with the 2-beta-derivatives. The presence of the chelating ligand in the 2-beta-derivative hinders certain substrates from entering the cavity. For cationic substrates, evidence suggests that a cooperative association involving inclusion in the cavity and association with the Dy(III) unit occurs. Enhancements in enantiomeric resolution in the spectrum of tryptophan are greater for the secondary alpha- and gamma-derivatives than the beta-derivative.