Evolution of the Free Energy Landscapes of n-Alkane Guests Bound within Supramolecular Complexes

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.

The Effects of Lengths of Flavin Surfactant N-10-Alkyl Side Chains on Promoting Dispersion of a High-Purity and Diameter-Selective Single-Walled Nanotube

“…FC12 shows higher molar solubility (2.32 mM) than others (1.51, 1.99, and 1.93 mM for FC8, FC16 and FC20). The lower solubilities for FC16 and FC20 appear to originate from the aforementioned 'hairpin' folding of n-alkyl chain greater than n-dodecyl [69,70].…”

Host Dynamics under General-Purpose Force Fields

“…Chemical modifications are sometimes introduced to adjust the entrance size [ 70 , 71 , 72 ]. In molecular simulations of OA derivatives, general-purpose force fields such as GAFF derivatives have been widely applied [ 73 , 74 , 75 ]. Unfortunately, to our best knowledge, no validation benchmark has ever been considered up to now.…”

Hiking down the Free Energy Landscape Using Sequential Solvent and Thermal Processing for Versatile Ordering of Block Copolymer Films

“…We note that nature addresses this problem in the context of the ordering of proteins into their functional globular state through the confinement of the proteins inside chaperone complexes that modulate accessible protein conformations and limit the accessible free energy landscape; recent work has been aimed at synthetically emulating this process. 28 Recently, it was found that films of small molecules can be formed in exceptionally low potential energy states through chemical vapor deposition. 29,30 While it is normally quite difficult to volatilize polymers, we can simulate vapor-state deposition by simply dissolving the polymer in a solvent and treating this solution phase deposition as an analogue of chemical vaporization that is appropriate for polymer materials.…”

“…In view of the qualitative analogy of frustrated mesoscale ordering processes in BCP materials and glass-formation in molecular liquids, it is useful to draw upon a methodology developed in the field of glass-forming materials to “chaperone” the system into a target functional state in a way that is both economical and which does not require a great deal of time and effort. We note that nature addresses this problem in the context of the ordering of proteins into their functional globular state through the confinement of the proteins inside chaperone complexes that modulate accessible protein conformations and limit the accessible free energy landscape; recent work has been aimed at synthetically emulating this process …”