On Press:
An Al(i)pha(tic) Helix?

By Jason Socrates Bardi

The alpha helix is a common enough structural motif in nature, but how about the aliphatic helix? Can aliphatic hydrocarbons be made to fold into helices in solution?

Conventional wisdom holds that purely hydrophobic compounds like alkanes and other aliphatic hydrocarbons do not make good candidates for helical folding, which help partially hydrophobic structures such as proteins exist in an aqueous environment.

In fact, the opposite is true—alkanes, which are chains of carbon atoms connected by single bonds and decorated with hydrogen atoms, tend to extend to their full length.

Alkanes constitute a class of compounds that, at room temperature, include: colorless gasses, like the stove-burner methane (CH4); clear liquids, like the organic solvent hexane (C6H14), which is used to extract essential oils from plant seeds; and waxy solid compounds with longer carbon chains, like paraffins, which contain more than 16 carbon atoms in their chains. These diverse chemicals are all completely insoluble in water and could share the designation, least likely to twist into a helix.

But a stunning exception was described in the journal Science last month in a report by Laurent Trembleau, who is a former research associate at The Scripps Research Institute (TSRI), and TSRI Professor Julius Rebek, Jr., who is director of the Skaggs Institute for Chemical Biology.

In their paper, Trembleau and Rebek describe using nuclear magnetic resonance to observe the helical folding of the alkyl end of the common detergent sodium dodecyl sulphate (SDS). Trembleau and Rebek observed how this alkane-like end of the SDS molecule folded into a helix in order to achieve a better fit into a synthetic receptor called a "cavitand." The cavitand is a chemical that naturally forms a cavity-shape into which other molecules can bind.

Interestingly enough, four carboxylates on the cavitand make a water-soluble surface on the outside and eight benzene rings make a hydrophobic surface on the inside. Into this hydrophobic cavity, Trembleau and Rebek found, the alkyl chains of the SDS, coiled into helices.

The helix forms because the coiled alkyl chain makes favorable interactions with the benzene rings and because the coiled alkane chain fills the space of the cavity more efficiently. Also favoring the coiling is the fact that the hexane molecules shed water on their surface as they coil—a situation Rebek says is analogous to wringing dry a wet towel by twisting it.

To read the article, "Helical Conformation of Alkanes in a Hydrophobic Cavitand" by Laurent Trembleau and Julius Rebek, Jr., please see the August 29, 2003 issue of the journal Science (301, 1219-1220) or go to: http://www.sciencemag.org/cgi/content/abstract/301/5637/1219.




A side view of a partially coiled SDS molecule inside a synthetic receptor. One wall of the receptor has been removed for viewing. Click to play a short movie showing a rotational view