Volume 90 Issue 46 | p. 7 | News of The Week
Issue Date: November 12, 2012

Molecular Building Blocks Self-Assemble Into Trefoil Knot

Organic Chemistry: Hydrophobic effect drives spontaneous formation of three-loop knot
Department: Science & Technology
News Channels: Materials SCENE
Keywords: molecular knots, self-assembly
This molecular knot’s building block (shown) forms reversible disulfide bonds and eventually adopts a trefoil knot formation in equilibrium.
A mechanism for trefoil knot self assembly with an overlay box showing the structure of the molecular building block.
This molecular knot’s building block (shown) forms reversible disulfide bonds and eventually adopts a trefoil knot formation in equilibrium.

Serendipity, along with the hydrophobic effect and a relatively simple chemical building block, has led to the creation of the world’s first molecular knot that forms in water with stereochemical purity.

A team of U.K.-based researchers led by Jeremy Sanders of the University of Cambridge and G. Dan Pantoş of the University of Bath reports the new trefoil knot—the simplest of all knots, with three topological crossings (Science, DOI: 10.1126/science.1227032).

Molecular knots and other higher molecular topologies could form the basis of new pharmaceuticals and materials, comments University of Zurich chemist Jay S. Siegel, who was not involved in the work. He says he believes that knot topologies “will lead to new catalytic, bioactive, and nanotech materials rich in function.”

When chemists build a molecular knot, they typically have to anchor the molecular strand, Siegel notes in an associated commentary, to keep the “relative orientation of the entwined strands in place until the knot is tied off” (Science, DOI: 10.1126/science.1230319). Researchers often rely on metal complexation or functional group coordination as anchoring mechanisms while tying the knot, he adds.

A three-dimensional model of the new knot.
Credit: Science
Trefoil knot
A three-dimensional model of the new knot.
Credit: Science

Sanders and Pantoş instead use building blocks that assemble into knots spontaneously without anchoring. Each building block consists of three hydrophobic naphthalene diimide moieties linked by two β-aminoalanine units. The molecule is capped at each end by a cysteine.

In the presence of salty water, the building blocks spontaneously link when their thiols form disulfide bonds with thiols on other building blocks. Meanwhile, the hydrophobic naphthalene diimides try to sequester themselves from the polar solvent, much like hydrophobic amino acids in a protein do.

When the solution reaches equilibrium, three building blocks form a macrocycle that adopts a trefoil knot topology, Sanders explains.

“We actually did not set out to build a knot,” Sanders says. “We set out to explore the dynamic, combinatorial chemistry of this building block. But the first time I saw the NMR and HPLC [data] I thought, ‘This is astonishing. It’s a knot.’ Further work confirmed it.”

The knot is “remarkable and surprising,” comments David Leigh of the University of Edinburgh, in Scotland. “One wouldn’t normally expect the most stable form of a closed loop to be a tight knot. Generally, a simple unentangled macrocycle would be energetically more favorable,” he continues. “But for this molecule, the hydrophobic effect provides a strong driving force” that leads to the more topologically complex fold, Leigh adds.

Northwestern University chemist J. Fraser Stoddart says the new research illustrates some of “the finest aspects of synthetic and physical organic chemistry and is one of these rare instances where stereochemistry is being expressed at its most elegant.”

Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society
Steven Wheeler (Mon Nov 12 10:36:29 EST 2012)
The DOI in the link to the original article is incorrect. The correct link is:

Sarah Everts (Mon Nov 12 17:18:13 EST 2012)
Thanks for catching that, Steven.

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