Abstract
Confinement within nanoscale spaces can dramatically alter the ensemble of conformations flexible species explore. For example, chaperone complexes take advantage of confinement to fold misfolded proteins, while viral capsids transport genomic materials in tight packings. Here we examine the free energy landscapes of n-alkanes confined within supramolecular dimeric complexes of deep-cavity cavitand octa-acid, which have been experimentally demonstrated to force these chains with increasing length to adopt extended, helical, hairpin, and spinning top conformational motifs, using molecular simulations. Alkanes up to n-docosane in both vacuum and water predominantly exhibit a free energy minimum for elongated conformations with a majority of trans dihedrals. Within harmonically sealed cavitand dimers, however, the free energy landscapes as a function of the end-to-end distance between their terminal methyl units exhibit minima that evolve with the length of the alkane. Distinct free energy basins are observed between the helical and hairpin motifs and between the hairpin and chicane motifs whose relative stability changes with the number of carbons in the bound guest. These changes are reminiscent of two state-like protein folding, although the observed alkane conformations confined are more insensitive to temperature perturbation than proteins are. While the chicane motif within the harmonically sealed dimers has not been observed experimentally, this conformation relaxes to the observed spinning top motif once the harmonic restraints are released for the complexes in aqueous solution, indicating that these motifs are related to one another. We do not observe distinct minima between the confined extended and helical motifs, suggesting these conformers are part of a larger linear motif family whose population of gauche dihedral angles grows in proportion to the number of carbons in the chain to ultimately form a helix that fits the alkane within the complex.
Highlights
The spontaneous organization of molecular host and guest species in solution into well-defined supramolecular assemblies offers an attractive route toward building synthetic complexes that potentially possess biomimetic functions
The nonpolar pockets of OA readily bind to hydrophobic guest species in water to form 1:1, 2:1, and 2:2 supramolecular complexes depending on the guest’s size and shape.[11−13] Guests confined within these supramolecular complexes can adopt conformations rarely observed in bulk solution, which in turn can enable the cavitand to mimic an enzymatic pocket.[14,15]
While molecular simulation of free alkanes up to C22 in vacuum and aqueous solution do not exhibit conformational transitions, when these guests are confined within dimeric supramolecular complexes composed of cavitand hosts, a succession of conformational motifs from extended, to helical, to hairpin, to chicane/spinning top are observed
Summary
The spontaneous organization of molecular host and guest species in solution into well-defined supramolecular assemblies offers an attractive route toward building synthetic complexes that potentially possess biomimetic functions. Free energies associated with growing the alkanes within OA dimers by addition of −CH2− groups found breaks in the incremental free energy change at the chain lengths at which the dominant motif changed. While this suggested that the conformational motifs observed were associated with transitions between distinct basins in the underlying free energy landscape, we could not directly address the thermodynamic differences between conformers. We release the harmonic restraint between the cavitands to unseal the dimer complexes in aqueous solution This allows the dimer capsule some latitude to “breathe” and reveal the equilibrium guest conformation that would be experimentally observable
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