Sodium–Potassium Competition Controls Xenon Uptake in Cucurbiturils

Abstract

The remarkable specificity of 129Xe magnetic resonance has motivated efforts to expand its application to medical diagnostics and to develop Xe-cage guest–host complexes compatible with in vivo conditions. Cucurbit[n]urils (CB[n]) are among the most promising host molecules for direct biocompatible Xe encapsulation. Building on earlier observations that alkali cations influence the binding of Xe to CB[n], this study provides a comprehensive experimental and computational analysis of how the ratio of Na+ to K+ in the solution governs Xe uptake by CB[6] and CB[5]. Using one- and two-dimensional 129Xe NMR together with quantum-mechanical modeling, we elucidate the molecular mechanism by which alkali cations modulate cage Xe uptake. Our calculations reveal that Na+ can adopt a near-central position inside CB[6], directly competing with Xe for the hydrophobic core, thereby suppressing encapsulation. In contrast, K+ remains confined to peripheral portal sites, leaving the central cavity accessible, and enabling Xe to displace the cation and stabilize inside the cage. Elevated temperatures and cage–cage competition further amplify these effects. By combining experimental and theoretical results, we thus provide the first detailed mechanistic explanation of Na+/K+ competition in Xe-CB[n] systems, and establish clear design principles to optimize Xe hosts for future in vivo applications.