Brownian motion, the rotation of molecules, and vibrations within molecules are typical forms of thermal motion. Fast chemical equilibria, such as the inversion at the ammonia nitrogen atom, the interconversion of conformers in alkanes, or highly dynamic association/dissociation processes in weakly bound noncovalent complexes are also thermally induced. In the context of noncovalent complexes, it is fascinating to examine whether an intracomplex migration of a guest molecule between different binding sites of a multitopic host is possible and how a motion like this could be monitored. Herein, the first five generations (G1–G5) of polyamino propylene amine (POPAM) dendrimers serve as prototypical multitopic hosts. We address the question, whether crown ethers can directly move from binding site to binding site on the dendrimers periphery without intermediate dissociation/reassociation (Figure 1). Furthermore, if this molecular “spacewalk” is indeed possible, it raises the question as to by what mechanism it proceeds. In solution, the detection of such an intracomplex binding-site hopping is challenging if not impossible, because it is always superimposed by dissociation/reassociation equilibria. Therefore, it is necessary to isolate the complexes from each other and from the corresponding free building blocks to suppress any intercomplex guest-exchange reactions. The high vacuum inside a mass spectrometer is ideally suited to achieve the isolation of the complexes as the complexes there are like-charged and thus efficiently separated from each other by charge repulsion. Also, reactions with neutral crown ether molecules can be excluded. Fragmentation of the crown ether/dendrimer complexes would be the only source for the appearance of neutral crown ethers in the gas phase. Therefore, their partial pressure is much too low to result in an efficient reattachment during the short time they spend inside the instrument before being pumped away. However, this approach comes with the difficulty that any intramolecular process does not change the complex ion s molecular mass and thus remains undetectable by a simple determination of the mass-to-charge ratio (m/z). Therefore, a gas-phase reaction is required that probes the guest s motion. Such a reaction must a) proceed energetically below the complex dissociation energy, b) cause a mass shift, and c) be directly linked to the guest movement. To realize this idea, we chose POPAM dendrimers as the multitopic scaffold. These dendrimers have highly branched onion-layer-type structures (Figure 1). From each generation (Gn) to the next, the number of peripheral amino groups doubles from four in theG1 dendrimer to 64 inG5. Their gasphase chemistry has been studied in detail. In the absence of a solvating agent, protonation is likely to occur at interior tertiary amines rather than the peripheral primary NH2 groups. To examine the host–guest chemistry of dendritic molecules in the gas phase is generally a challenging and byand-large unexplored field of research. Only a few examples exist to date. In our study, [18]crown-6 serves as the guest, it binds to primary ammonium ions in solution, and in the gas phase. Dendritic crown ether/ammonium complexes are Figure 1. Chemical structure of [18]crown-6 and a fourth generation (G4) POPAM dendrimer. Starting with a 1,4-diaminobutane core, the nth shell of branches is divergently grown on the (n 1)th generation dendrimer by two Michael additions of acrylnitrile to each branch and subsequent hydrogenolytic reduction of the nitrile groups. The red arrows symbolize the main question of the present study: Can crown ethers move freely along the periphery of POPAM dendrimers without intermediate dissociation of the complex? As this process proceeds in the high vacuum inside a mass spectrometer, we refer to it as a molecular “spacewalk”.