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.

Figure 1

Effect of concentration of γ-CD on the EPR spectra of CT02-VT. Gray and black lines denote experimental and simulated spectra, respectively.

Figure 2

Experimental (gray) and simulated (black) EPR spectra of CT02-VT in the presence of M-β-CD (100 mM) and H-β-CD (100 mM).

Figure 3

Experimental (gray) and simulated (black) EPR spectra of free CT02-AT (A) and its complex with M-β-CD (B) and free CT02-GT (C) and its complex with M-β-CD (D).

Figure 4

(A) Plot of the concentrations of trityl monoradicals as a function of time which were generated by the reaction of CT02-GT (50 µM) with 500 µM (square), 800 µM (circle) and 1000 µM (triangle) of ascorbic acid in the presence (unfilled) or absence (filled) of M-β-CD (50 mM) in phosphate buffer (50 mM, pH 7.4). (B) Plot of k[Asc] as a function of the concentrations of ascorbate (Asc). Values of k[Asc] were obtained according to the data shown in Fig. 4A. Linear regression of kinetic data to yield the second-order rate constants for reduction of CT02-GT by ascorbate in the presence (circle) or absence (square ) of M-β-CD. Data were shown in Table 2.

Chart 1

Molecular structure of TN biradicals studied in this paper