Guest Inclusion in Cucurbiturils Studied by ESR and DFT: The Case of Nitroxide Radicals and Spin Adducts of DMPO and MNP

We present an ESR and DFT study of the interaction of cucurbiturils CB6], CB7], and CB8] with di-tert-butyl nitroxide ((CH(3))(3)C)(2)NO (DTBN) and with spin adducts of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 2-methyl-2-nitrosopropane (MNP). The primary goal was to understand the structural parameters that determine the inclusion mechanism in the CBs using DTBN, a nitroxide with great sensitivity to the local environment. In addition, we focused on the interactions with CBs of the spin adducts DMPO/OH and MNP/CH(2)COOH generated in aqueous CH(3)COOH. A range of interactions between DTBN and CBs was identified for pH 3.2, 7, and 10. No complexation of DTBN with CB6] was deduced in this pH range. The interaction between DTBN and CB7] is evident at all pH values: "in" and "out" nitroxides, with (14)N hyperfine splitting, a(N), values of 15.5 and 17.1 G, respectively, were detected by ESR. Interaction of DTBN with CB8] was also detected for all pH values, and the only species had a(N) = 16.4 G, a result that can be rationalized by an "in" nitroxide in a less hydrophobic environment compared to CB7]. Computational studies indicated that the DTBN complex with CB7] is thermodynamically favored compared to that in CB8]; the orientations of the NO group are parallel to the CB7] plane and perpendicular to the CB8] plane (pointing toward the annulus). Addition of sodium ions led to the ESR detection of a three-component complex between CB7], DTBN, and the cations; the ternary complex was not detected for CB8]. The DMPO/OH spin adduct was stabilized in the presence of CB7], but the effect on a(N) was negligible, indicating that the N-O group is located outside the CB cavity. Computational studies indicated more favorable energetics of complexation for DMPO/OH in CB7] compared to DTBN. An increase of a(N) was detected in the presence of CB7] for the MNP/CH(2)COOH adduct generated in CH(3)COOH, a result that was assigned to the generation of the three-component radical between the spin adduct, sodium cations, and CB7].