(662e) Succession of Alkane Conformational Motifs Bound within Hydrophobic Nano-Capsule Assemblies

As an approach to computationally predict the preferred conformation of molecules confined within nano-spaces, we report here on a strategy that accurately reproduces the binding motif of n-alkanes within dimeric octa-acid capsular complexes. Previously, NMR analysis of these complexes revealed a succession of guest packing motifs from extended, to helical, to hairpin, to spinning top structures with increasing chain length. Here, we report a molecular simulation study of alkane conformational preferences within these host-guest assemblies to uncover the factors stabilizing distinct conformers. The simulated alkane conformers follow the trends inferred from ¹H-NMR experiments, while guest proton chemical shifts evaluated from Gauge Invariant Atomic Orbital calculations provide further evidence our simulations capture guest packing within these assemblies. Analysis of chain length and dihedral distributions indicates that packing under confinement to minimize non-polar guest and host interior contact with water largely drives the transitions. Mean intramolecular distance maps and transfer free energy differences suggest the transition between the extended and helical motifs is a continuous process accompanied by increases in the guest gauche population to allow accommodation within the complex, while breaks observed between the helical/hairpin and hairpin/spinning top motifs are indicative of true transitions. Our results represent the first bridging of empirical and simulation data for flexible guests encapsulated within confined nano-spaces, and constitute an effective strategy by which guest packing motifs within artificial or natural compartments can be rationalized and/or predicted a priori.