Do pi-stacking interactions preserve the solution-state structure un the gas phase? Study of oligorotaxanes by ion mobility mass spectrometry

The development of the so-called soft ionization techniques, namely ESI and MALDI, opened new perspectives for the analysis of large intact molecular ions by mass spectrometry (MS) and set the basis of the native MS field. In this context, the conservation of nonbonded interactions maintaining the physiological conformation of an ion through the ESI process is of major interest. Among these, π-stacking interactions are ubiquitous both within biological (DNA) and synthetic (organic electronic devices) systems. In the present investigation we attempt to probe the conservation of π-stacking interactions on oligorotaxanes, a synthetic π-stacked polymers, after its transfer process to the gas phase. The foundations of native mass spectrometry still constitute a controversial topic. In this context, we here investigate this eventuality using ion mobility on electrosprayed mechanically interlocked molecules (MIMS) called oligorotaxanes. These ones are π-stacked polymers composed of a π electron-donating dumbbell over which a discrete number of π electron-accepting tetracationic cyclophanes are threaded5. The numerous intra-molecular interactions confer to these molecules a highly-stabilized rigid rod-like structure and make them ideal candidates to probe the structural fate of ions following the electrospray process. Both the effects of electrostatic repulsions and of collision-driven internal activation on the ion conformation are considered. The resulting isolated ions were then structurally interrogated by means of ion mobility directly hyphenated with MS (Synapt G2 HDMS, Manchester, UK). Dealing with different polymer lengths and charge states, our results highlight a progressive elongation of the oligorotaxane structure with increasing charge density until it reaches a plateau. Using theoretical models built around a linear assemble of monomeric units with tunable sizes as a reference tool, we show that, at low charge states, the “native” π-stacked rod-like structure of oligoratoxanes is expected to be preserved. However, as the charge density increases, coulombic repulsions occurring between the cyclophanes gradually outweigh the stabilizing π-stacking interactions and force the structure to elongate, eventually resulting in the formation of fully stretched structure. Geometries optimized at a PM6 and DFT level also support these conclusions. Meanwhile, collisional activation experiments highlight potent population shifts towards the formation of slightly elongated conformers. They however remain insufficient to promote the formation of fully extended conformations before the fragmentation occurs, emphasizing the high stability of oligorotaxanes.
Altogether, our results show that the structure of strongly stabilized oligorotaxanes could be preserved from the solution to the gas phase provided that the electrostatic repulsions and the internal heating are kept minimal. Moreover, our results may also constitute a starting point to quantitatively study the strength of π-stacking interactions in the gas phase.