Jun 292010
 
ResearchBlogging.orgWe all know that linear polymers of amino acids (proteins) adopt complex three-dimensional structures when they are dissolved in water. The process of forming these structures is called folding, and it is understood to occur because proteins are amphiphilic. Some parts of a protein chain like to interact with water (hydrophilic), while others are oily and want to get out of water (hydrophobic). Folding of the chain sticks all the oily parts together on the inside of the structure while the parts of the chain that have favorable interactions with water remain on the outside. An upcoming paper from the Journal of Physical Chemistry B suggests that sufficiently long alkanes might undergo a similar transition, even though they don’t have any chemical groups that like to interact with water.

Researchers from Purdue University performed a variety of simulations of linear alkanes, which are saturated hydrocarbon chains typically designated by the number of carbons they contain (C8 has 8 carbons). Because increasing the length of the chain just involves inserting an identical unit, one might expect that after a certain point the properties of these molecules would scale linearly with chain length. Previous experiments and simulations, however, indicated that the free energy of hydration did not match this predicted linear trend. Instead, the free energy of hydration (ΔG) remained flat or even decreased as chain length increased. This is because the linear extrapolation only holds for a chain that adopts a linear (all-trans) configuration. As chain length increases, however, the numerous additional degrees of freedom allow a chain to adopt a more compact conformation that decreases the penalty incurred by interacting with water.

Given this understanding, the authors asked whether a sufficiently long alkane might be hydrophilic. They established theoretical bounds for this question by examining two extreme possibilities. In the first, the alkane was assumed to be linear, and of course the ΔG never crossed zero. In the second, the alkane was assumed to collapse into a sphere; in this case the free energy becomes favorable after less than a dozen carbons. Presumably the reality lies somewhere in between. To get a more realistic view of the situation, they also simulated the behavior of alkane chains of various sizes, and found that the potential energy released by dissolving an alkane in water was correlated with the solvent-accessible surface area (SASA). From their findings they predicted that an alkane that was long enough would eventually cross over into hydrophilicity.

This is pretty interesting, but there are some significant weaknesses. The work here is purely theoretical and uses a molecular dynamics forcefield with an imperfect model of water behavior. The predictions of this simulation have been validated on real-world chemical samples, but only up to a comparatively modest chain length of C16. Because the surprising prediction lies very far from the zone of simulations that have been experimentally confirmed, one could argue that this is all just an extended discussion of a failure of the model. As they are aware of this shortcoming, the authors performed a number of simulations on collapsed (globular) C100 alkanes in order to determine the energy of the interaction between the chain and water, as well as the SASA. They found that, within error, the simulated values also indicated a negative ΔG of hydration.

As the authors note, this result doesn’t necessarily mean that you could dissolve a whole bunch of C100 in water. The ΔG calculated here is for transfer from the gas phase into water, and C100 is unlikely to be highly volatile, given that all the higher paraffins are solids. In addition, these are simulations of a single hydrocarbon chain in water, and so they don’t tell us about the energetics of lipid-lipid interactions. Oils segregate out of water because the oil-oil interaction is more favorable than the oil-water interaction. If this holds true for C100, even if dissolving in water is itself favorable, the alkane will still form oil droplets more readily than it will dissolve.

Using their models, the authors predict that the surface tension of an oil droplet will be negative at chain lengths greater than C50, thus tending to release oil into solution, but I’m a bit worried about this prediction. First, the molecular surface tensions are very far off from the macroscopic tensions, indicating that this calculation misses a great deal about the interaction. In addition, they perform a linear extrapolation from the approximately linear tail of what appears to be an exponential curve. It’s not clear why this extrapolation was used or what conclusions can be drawn from it; the molecular surface tension could just as easily be asymptotic with respect to the zero point.

Experimental verification of this prediction is unlikely to appear any time soon, if at all. Synthesizing very long alkanes is not trivial, especially in the quantities and purities required to put these simulations to the test. Ultimately the value of a paper like this is not in any practical application, but rather in the fact that it reminds us of the strength of the forces that guide the formation of higher-order chemical structures. Even in the absence of any group that has an intrinsically favorable interaction with water, the energy released by self-binding of hydrophobic groups may give rise to a “folded” structure for very long alkanes.

Underwood, R., Tomlinson-Phillips, J., & Ben-Amotz, D. (2010). Are Long-Chain Alkanes Hydrophilic? The Journal of Physical Chemistry B DOI: 10.1021/jp912089q

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