Inclusion complexes between α-Cyclodextrins and Xenon: Molecular Dynamics Simulations and Experimental study

Xenon (Xe) is an inert noble gas that is receiving increasing attention in medical research due to its anesthetic properties, its ability to regulate metabolic processes, and its broad organoprotective effects [1]. Due to its low molecular weight and small size, xenon can be encapsulated in α-cyclodextrins (α-CDs), which possess the smallest internal cavity (0.47 – 0.53 nm) among CDs [2,3]. In this study, we present theoretical study based on molecular mechanics (MM) and molecular dynamics (MD) simulations at the atomistic level of the intermolecular interactions between α-CD and xenon. Inclusion complexes at different stoichiometries are studied, involving both encapsulation in the small cavity of the α-CD and favourable intermolecular interactions with the external surface of α-CD. In particular, by increasing the xenon concentration [4], there is a tendency for this noble gas to form aggregates of three or more atoms near the secondary and primary edges of the α-CD and on the external surface of the α-CD (see Figure 1). Following the computational investigation, experimental work was conducted to synthesize and characterize the α-CD/Xe inclusion complex using a liquid-phase encapsulation method. The complex was prepared at three different pressures: 2, 4, and 8 bar at a constant temperature of 25 ± 1 °C. Thermogravimetric analysis (TGA) revealed a weight loss between 100 and 180 °C at 4 and 8 bar, consistent with encapsulated xenon release (Figure 2). The effective encapsulation of xenon was unambiguously confirmed by solid-phase microextraction coupled with gas chromatography–mass spectrometry (SPME-GC-MS), which detected the characteristic m/z signals of xenon and allowed monitoring of its release over time upon contact with aqueous solution.