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

Introduction Artificial Molecular Machines (AMMs), 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 interface between 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. Method 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 use IM-MS as implemented in the Synapt G2 HDMS (Waters, Manchester, UK) to investigate the structure of the ionized oligorotaxanes. 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 or thermal-driven conformational change in the gas phase implemented via an electron transfer or collisional activation process 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 Dynamics simulations. Preliminary data Our results highlight a progressive elongation of the oligorotaxane structure with increasing charge numbers until it reaches a maximum extension state. 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 helical-shaped conformers, before it eventually results in a fully stretched structure. On the other hand, our results also highlight that a charge reduction driven by a non-dissociative electron transfer process leads to a refolding of the structure so that it adopts a size similar to its electrospray-generated counterpart when the appropriate number of electrons is added. This observation may be imparted to the gradual decrease of the Coulomb repulsions between the cyclophanes mediated through increasing numbers of transferred electrons. These results suggests that 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 artificial molecular switch. The second stimulus relied on collisional activation whose inelastic component provides a way to build up energy into the accessible vibrational degrees of freedom. The conformational landscapes of such-activated oligorotaxanes ions were found unchanged in term of collision cross section position but the repartition of population was altered with a promotion of the most elongated conformer, provided the absence of selective fragmentation. Altogether, these results highlight the feasibility of handling the elongation state of oligorotaxanes in the gas phase through appropriate inputs and underline its conformational reversibility properties. Novel aspect Stimuli-induced reversible conformational rearrangements of innovative AMMs studied by IM-MS and molecular dynamics in the gas phase