Mechanically Interlocked Molecules: A Supramolecular Computational Picture of Rotaxane‐Based Switches, Shuttles, and Tristable Devices in Solution

This contribution highlights a coherent series of recent computational studies devoted to the theoretical characterization of mechanically interlocked molecules (MIMs)-specifically [2]rotaxane molecular shuttles and switches-in organic solvents. Combining density functional theory (DFT) and all-atoms molecular dynamics (MD) with the quantum theory of atoms in molecules (QTAIM) and the independent gradient model based on Hirshfeld partition (IGMH), a first-principles picture of the noncovalent and covalent interactions, repertoire that governs macrocycle translocation, metal-induced locking, and stimuli-responsive switching, has emerged. Distinct rotaxane platforms in different exercise conditions suggest that theoretical investigations can quantitatively reproduce and rationalize conformational shaping and spectroscopic observables, thereby providing a design roadmap for next-generation soft molecular machines of increasing complexity and functionalities. In this respect, the simulation scenario is further enriched by a self-consistent graphical visualization of both covalent and noncovalent interactions combining new computational strategies like the interaction region indicator (IRI) and the local electron energy density H(r) (GLED) descriptors over supramolecular assemblies of hundreds of atoms at the DFT cost.