Synthesis and Self-Assembly Processes of Monofunctionalized Cucurbit[7]uril

We present a building-block approach toward functionalized
CB[7]
derivatives by the condensation of methylene-bridged glycoluril hexamer 1 and glycoluril bis­(cyclic ethers) 2 and 12. The CB[7] derivatives Me2CB­[7] and CyCB[7]
are highly soluble in water (264 mM and 181 mM, respectively). As
a result of the high intrinsic solubility of Me2CB­[7],
it is able to solubilize the insoluble benzimidazole drug albendazole.
The reaction of hexamer 1 with glycoluril derivative 12, which bears a primary alkyl chloride group, gives CB[7]
derivative 18 in 16% isolated yield. Compound 18 reacts with NaN3 to yield azide-substituted CB[7] 19 in 81% yield, which subsequently undergoes click reaction
with propargylammonium chloride (21) to yield CB[7] derivative 20 in 95% yield, which bears a covalently attached triazolyl
ammonium group along its equator. The results of NMR spectroscopy
(1H, variable-temperature, and DOSY) and electrospray mass
spectrometry establish that 20 undergoes self-assembly
to form a cyclic tetrameric assembly (204)
in aqueous solution. CB[7] derivatives bearing reactive functional
groups (e.g., N3, Cl) are now available for incorporation
into more complex functional systems.