Modulating the oxidation of cucurbit[n]urils.

The functionalisation of cucurbit[n]uril macrocycles carried out through an oxidative approach in water using ammonium persulfate was studied. Through complexation with a doubly-charged bisimidazolium guest we were able to detect, distinguish and quantify the presence of each CB[n]-(OH) (where 1 ≤ x ≤ 2n) derivative for the first time. The impact of oxidation on each CB[n] (n = 6-8) was studied individually, as well as in the presence of other competing CB[n] species. We were able to understand the reactivity of the parent CB[n] alongside its hydroxylated derivatives, CB[n]-(OH), and show that the oxidation of CB[n] through a free-radical approach cannot result in stoichiometric hydroxylation despite previous literature reports by Bardelang, Ouari and co-workers, J. Am. Chem. Soc., 2015, 137, 10238. Furthermore, an in-depth study on hydroxylation of CB[7] was conducted. Through DFT calculations we were able to show that the second hydroxy substituent is preferentially located on the same glycoluril unit. Moreover, through optimisation of the reaction conditions we were able to access a protocol for controlled oxidation to yield a chemically monofunctional CB[7] derivative.