Advanced 19F-NMR studies shed new light on encapsulation of isosteric guests in the hexameric capsules of resorcin[4]arenes and pyrogallol[4]arenes

The hexameric capsules of resorcin[4]arenes and pyrogallol[4]arenes are fascinating, catalytically active, and highly accessible structures having large cavities. Despite the apparent similarity between these two types of hexamers, the hexameric capsules of C11-resorcin[4]arenes (1) are much more efficient nanoreactors than the C11-pyrogallol[4]arene (2) capsules. In this study, we investigated the encapsulation of two bulky and structurally related isosteric guests namely adamantane-1-carboxylic acid (3) and 3,5,7-tri-fluoro adamantane-1-carboxylic acid (4) into these hexamers in a competitive (chloroform) and a non-competitive (benzene) solvent. Through the application of NMR spectroscopy, diffusion NMR, and 19F guest exchange saturation transfer (GEST) applied for the first time on such hexameric capsules, we show that the two apparently similar hexamers behave differently towards these two isosteric guests. We found that in C6D6 the hexamers of 1 preferentially encapsulate the non-fluorinated guest 3 over guest 4, while the hexamers of 2 preferentially encapsulate the fluorinated isosteric guest 4. For the hexameric capsule of 2 encapsulating guest 4, 19F-NMR shows that the disruption of the hexameric capsule by methanol is a more complex process than one would have anticipated revealing, for the first time, three populations of 4 having different exchange rates. The combination of 1H/19F diffusion and 19F-GEST NMR provides new insights into these important and catalytically active capsular systems demonstrating the advantages of using this combination of NMR methods to explore such supramolecular systems in solution.