(253g) A Computational Investigation of the Solubility and Hydrophobic Collapse of Heavy N-Alkanes in Water

The aqueous solubility of heavy n-alkanes is so slight that equilibrium concentrations become immeasurably low, leading to significant scatter in experimental solubility data for chains heavier than tetradecane and essentially no reliable data beyond hexadecane. Computer simulations provide a method to determine the long chain solubilities, but due in part to the severe sampling difficulties associated with the Widom insertion of long chains into the solvent, have only been conducted for the lighter chains. We present a heteropolymer generalization of the incremental Widom insertion technique combined with replica exchange molecular dynamics simulations to obviate these sampling problems and provide a reliable determination of n-alkane solubilities up to docosane. Agreement of our results with experimental data for the lighter chains is excellent and the results for the heavier chains are, to our knowledge, the first ever reported. Henry's constant exhibits a maximum as a function of chain length around hexadecane, which is attributable to an increasing proportion of compact conformers that possess more favorable free energies of solvation. The solvated chains show remarkable structural similarity to the ideal gas phase, but with the longer alkanes exhibiting an increased propensity for elongated and compact conformations relative to intermediate states. Solvated and ideal gas phase free energy landscapes for chains shorter than decane are strikingly similar, but inadequate sampling in the solvated systems precludes this analysis for longer chains.