Scientists Reveal How “Molecular Boxes” Self-Assemble, Stretch to Fit Contents

Think back to your high-school biology class, where you learned about DNA. Deoxyribonucleic acid is the building block of life. It is present in each of our cells and determines countless physical traits. But this incredibly complex molecule is impressive for another reason: single strands can spontaneously connect with each other to form the familiar double helix structure.

DNA isn’t the only biological example of a self-assembling molecule, either: proteins and enzymes, the molecular machines that keep us alive, fold themselves into complicated structures to carry out their duties. Numerous research projects over the years have sought to artificially mimic these interactions found so commonly in nature—with mixed results. However, recent work out of the University of Tokyo has shed new light on the forces that allow molecular self-assembly and points to new synthetic applications.

Dr. Shuichi Hiraoka’s lab is dedicated to studying molecular self-assembly and the forces that drive it. The lab’s most recent publication, a paper in Nature Communications details one fascinating process they found involving a snowflake-shaped molecule known as hexaphenylbenzene.

A representation of the snowflake-shaped hexaphenylbenzene. Its molecular formula is C42H30, indicating that it is composed of 42 carbon atoms and 30 hydrogen.
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When dry, this molecule just looks like any other white powder you might find in a laboratory. But when exposed to water, the molecules spring into action: each joins up with five others to form a cube with one molecule to each side. The entire process is so quick that the research team hasn’t managed to observe it directly, but they do have a neat animation:

Shuichi Hiraoka. (CC BY-ND-SA)

Although the cubes are stable up to temperatures of nearly 270°F, it turns out that the forces holding them together are few and weak. The most important of these, the Hiraoka team found, is the van der Waals force, which arises from the polarizability of molecules. Some molecules, like water, are naturally polar: they have a negative end where there tends to be more electrons, and a positive end where there tends to be fewer. This lets one water molecule attract another like a pair of magnets, forming a bond that contributes to water’s surface tension.

But even a normally nonpolar molecule, like hexaphenylbenzene, can become temporarily polarized. Since the electrons that orbit the nuclei aren’t fixed to a specific location but instead shift around randomly, they can sometimes end up disproportionately on one side or another. This brief fluctuation is enough to induce a similar effect in the molecule’s neighbors, temporarily polarizing them as well—and creating an attraction between them.

Other forces at play include the hydrophobic effect, or the molecules’ aversion to water, which pushes the hexaphenylbenzene together and away from the water molecules. There is also a weak cation-π interaction, an interaction between the covalent bonds that hold the molecule together and the positively-charged ions in the extremities of the molecule.

Now, these cubes are tiny, just 2 nanometers to a side—that’s one four-thousandth the size of a human red blood cell. (Coincidentally, it’s also roughly the width of a DNA helix diameter.) However, that didn’t stop the researchers from stuffing additional molecules inside, like a box. In fact, they found that the weak bonds holding the sides together actually allowed the “box” to expand or shrink to suit the contents. When a negatively-charged molecule was placed inside, the box shrank around it to create a volume of just 74 cubic angstroms, the volume of a cube just 0.4 nanometers in width! When larger molecules were placed inside, the box expanded to up to more than seven times that size. This finding was particularly exciting to the team, since many biological receptors also change based on the size and electrostatic properties of the molecules that bind to them.

Even though there’s a lot left to uncover about this particular process—exactly how the molecules link together in the first place, for example—this research is an exciting advancement in understanding how the compounds that make up biological systems form. “I want to understand self-assembly systems, which are essential for life. Building artificial self-assembling cubes helps us understand how biological systems function,” Hiraoka said in a press release. The fact that his team has identified the forces that allow for such self-assembly is a good indication that he’s getting close.

Eleanor Hook

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