Supramolecular host–guest interaction of trityl-nitroxide biradicals with cyclodextrins: modulation of spin–spin interaction and redox sensitivity

Abstract

Supramolecular host–guest interactions of trityl-nitroxide (TN) biradicals CT02-VT, CT02-AT and CT02-GT with methyl-β-cyclodextrin (M-β-CD), hydroxypropyl-β-cyclodextrin (H-β-CD) and γ-cyclodextrin (γ-CD) were investigated by EPR spectroscopy. In the presence of cyclodextrins (i.e., γ-CD, M-β-CD and H-β-CD), host–guest complexes of CT02-VT are formed where the nitroxide and linker parts possibly interact with the cyclodextrins’ cavities. Complexation with cyclodextrins leads to suppression of the intramolecular through-space spin–spin exchange coupling in CT02-VT, thus allowing the determination of the through-bond spin–spin exchange coupling which was calculated to be 1.6 G using EPR simulations. Different types of cyclodextrins have different binding affinities with CT02-VT in the order of γ-CD (95 M⁻¹) > M-β-CD (70 M⁻¹) > H-β-CD (32 M⁻¹). In addition, the effect of the linkers in TN biradicals on the host–guest interactions was also investigated. Among the three TN biradicals studied, CT02-VT has the highest association constant with one designated cyclodextrin derivative. On the other hand, the complexes of CT02-GT (∼22 G) and CT02-AT (7.7–9.0 G) with cyclodextrins have much higher through-bond spin–spin exchange couplings than those of CT02-VT (1.6 G) due to the shorter linkers than those of CT02-VT. Furthermore, the stability of TN biradicals towards ascorbate was significantly enhanced after the complexation with CDs, with an almost 2-fold attenuation of the second-order rate constants for all the biradicals. Therefore, the supramolecular host–guest interactions with cyclodextrins will be an alternative method to modulate the magnitude of the spin–spin interactions and redox sensitivity of TN biradicals, and the resulting complexes are promising as highly efficient DNP polarizing agents as well as EPR redox probes.