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 129Xe 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. Comparative study of the complexes of two cryptophane diastereomers with xenon via accelerated methods of ab-initio molecular dynamics reveals totally distinctive behavior for the escape of xenon from the cages, thereby explaining their difference in detectability through hyperpolarized 129Xe NMR.image