Abstract

Advances in hyperpolarisation and indirect detection have enabled the development of xenon nuclear magnetic resonance (NMR) biosensors (XBSs) for molecule-selective sensing in down to picomolar concentration. Cryptophanes (Crs) are popular cages for hosting the Xe “spy”. Understanding the microscopic host–guest chemistry has remained a challenge in the XBS field. While early NMR computations of XBSs did not consider the important effects of host dynamics and explicit solvent, here we model the motionally averaged, relativistic NMR chemical shift (CS) of free Xe, Xe in a prototypic CrA cage and Xe in a water-soluble CrA derivative, each in an explicit H₂O solvent, over system configurations generated at three different levels of molecular dynamics (MD) simulations. We confirm the “contact-type” character of the Xe CS, arising from the increased availability of paramagnetic channels, magnetic couplings between occupied and virtual orbitals through the short-ranged orbital hyperfine operator, when neighbouring atoms are in contact with Xe. Remarkably, the Xe CS in the present, highly dynamic and conformationally flexible situations is found to depend linearly on the coordination number of the Xe atom. We interpret the high- and low-CS situations in terms of the magnetic absorption spectrum and choose our preference among the used MD methods based on comparison with the experimental CS. We check the role of spin–orbit coupling by comparing with fully relativistic CS calculations. The study outlines the computational workflow required to realistically model the CS of Xe confined in dynamic cavity structures under experimental conditions, and contributes to microscopic understanding of XBSs.