Coulombic driven multi-conformational aspects of oligorotaxane switches studied by ion mobility mass spectrometry

Molecular machines, such as Mechanically Interlocked Molecules (MIMs) and foldamers, have recently raised tremendous interest due to their unique properties. Under the influence of an appropriate stimuli (pH, redox potential, light…), such molecules are able to reversibly switch between distinct conformational states. Scientists may capitalize on such exclusive properties to get a better understanding of the biomacromolecular level or to design innovative “smart” materials. At the edge of foldamers and MIMs, oligorotaxanes exhibit a spring-like folded secondary structure with remarkable mechanical and physicochemical properties. In the present study, we use ion mobility coupled with mass spectrometry (IM-MS) to probe the conformational states of differentially charged oligorotaxanes in the gas phase.
Oligorotaxanes are donor-acceptor polymers composed of a π electron-donating dumbbell over which a discrete number of π electron-accepting tetracationic cyclophanes are threaded. The numerous intra-molecular interactions provide them a highly-stabilized rigid rod-like structure in solution. We presently use IM-MS as implemented in the Synapt G2 HDMS (Waters, Manchester, UK) to investigate the structure of the ionized three-ring oligorotaxane. Our purposes are to probe (i) the different populations of stable conformers generated according to the charge state z and (ii) the reversibility of an electron-driven conformational change in the gas phase implemented via an electron transfer process (ETnoD) prior to the mobility separation. Our experimental observations are supported by electronic structure optimizations at the PM6 and DFT levels coupled with Born-Oppenheimer Molecular Dynamic (BOMD) simulations.
Our results highlight a progressive elongation of the oligorotaxane structure with increasing charge numbers until it reaches a plateau. Matching the experimental data with theoretical simulations, we find that the oligorotaxanes adopt an entropically-favored globular shape at low z. As z increases, coulombic repulsions occurring between the cyclophanes gradually outweigh the stabilizing π-stacking interactions and force the structure to elongate. This process occurs in a multistep fashion, each corresponding to a distinct group of conformers, before it eventually results in a fully stretched structure. On the other hand, our results also highlight that a charge reduction driven by the ETnoD process leads to a refolding of the structure so that it adopts a size similar to its electrospray-generated counterpart, therefore attesting of the conformational reversibility of olixorotaxanes in the gas phase.
Altogether, our results show that the oligorotaxanes adopt different conformers associated with increasing levels of extension as a function of the charge state. The transition from one conformer to another is reversible so that the electrostatic balance between the cyclophanes may be used to further tune the structural state adopted by this switch in the gas phase.