Isomer-Dependent Escape Rate of Xenon from a Water-Soluble Cryptophane Cage Studied by Ab Initio Molecular Dynamics

The escape of xenon from the anti and syn diastereomers of hexacarboxylic-cryptophane-222 in water has been studied by ab initio molecular dynamics simulations. The structures of both complexes, when the xenon atom is trapped inside their cages, have been compared and show no major differences. The free-energy profiles corresponding to the escape reaction have been calculated with the Blue Moon ensemble method using the distance between Xe and the center of mass of the cage as the reaction coordinate. The resulting free-energy barriers are very different; the escape rate is much faster in the case of the syn diastereomer, in agreement with experimental data obtained in hyperpolarized ¹²⁹ Xe NMR. Our simulations reveal the mechanistic details for each diastereomer and provide an explanation for the different in-out xenon rates based on the solvation structure around the cages.