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45228-AC4
The Inverted Cucurbit[n]uril Family
The cucurbit[n]uril family (CB[n], n = 5, 6, 7, 8, 10) of macrocycles are composed of n glycoluril rings connected by n pairs of methylene groups. In the past several years, interest in the CB[n] family of macrocycles has grown dramatically because of their extremely high affinity (Ka up to 1012 M-1) and high selectivity (Krel up to 106) binding events toward cationic guests in water. Such high affinity and selectivity along with the environmental responsiveness of these host-guest complexes to suitable stimuli (e.g. pH, photochemical, electrochemical, and chemical) makes them particularly well suited toward the preparation of a variety of molecular machines. To further expand the range of applications to which the CB[n] family may be applied requires the tailor made synthesis of new CB[n]-type receptors which in turn requires a good understanding of the mechanism of CB[n] formation. Toward this goal the Isaacs group has previously investigated the synthesis and isomerization of C- and S-shaped methylene bridged glycoluril dimers and found the operation of an unusual intramolecular diastereoselective isomerization mechanism under anhydrous acidic conditions. In 2005, in collaboration with Prof. Kimoon Kim's group we isolated inverted CB[n] (iCB[n], n = 6, 7) in which the H-atoms on a single glycoluril ring are pointing into the hydrophobic cavity. Such iCB[n] compounds were quickly recognized as being the macrocyclic relatives of the S-shaped compounds studied by us previously. Under this PRF grant we have been further investigating the mechanism of CB[n] formation. For example, we have investigated the transformation of iCB[6] into CB[6] under aqueous and anhydrous acidic conditions. Interestingly, we find that under anhydrous acidic conditions a clean transformation from iCB[6] to CB[6] occurs whereas under aqueous acidic conditions we observe a preference for ring contraction which results in the formation of CB[5] via extrusion of a single glycoluril ring. To establish that the transformation of iCB[6] to CB[6] under anhydrous acidic conditions was an intramolecular process we prepared the 13C labeled isotopomer 13C12-iCB[6] and performed the transformation of a mixture of iCB[6] and 13C12-iCB[6] into CB[6] and 13C12-CB[6]. No cross-over partially labeled products (e.g. 13C<12-iCB[6]) were observed by electrospray mass spectrometry. We propose the intermediacy of an unusual diastereomeric Möboid-CB[6] in this transformation. This study nailed down the fate of one of the final kinetically controlled intermediates in formation of CB[n] and suggests that the use of anhydrous acidic conditions for the preparation of new larger CB[n] compounds and those with multiple inverted substituents.
