News Release

Fundamental discoveries for future nanotools: Chemists distinguish multiple weak forces

Peer-Reviewed Publication

University of Tokyo

Nanocube Paper Craft

image: Fold your own nanocube! Although the nanocubes used in the research project build themselves, you can fold your own using this model. Each yellow X represents locations where researchers at the University of Tokyo used different atoms with different levels of polarizability. view more 

Credit: Image by Shuichi Hiraoka, CC-BY-ND

The process of building a tiny cube has revealed some of the fundamental mysteries of how molecules bind together in natural environments. Researchers hope to apply this knowledge to future projects designing complex structures that can mimic life.

When two molecules surrounded by water move towards each other, part of their initial attraction is sometimes due to the chemical force to repel water -- the hydrophobic effect.

Once the molecules are near each other, but not yet formally bound, a much weaker force becomes important -- the dispersion force.

"Our dream is to control the dispersion force and provide a simple design principle to use the dispersion force to build complex self-assembling structures," said Professor Shuichi Hiraoka, leader of the laboratory where the research was performed in the University of Tokyo Department of Basic Science.

Dispersion forces are one type of van der Waals forces, some of the weakest chemical interactions known in nature. Although weak, van der Waals forces are important; they help geckos walk up walls and were previously identified in 2018 by the same research group as locking together the gear- or snowflake-shaped molecules of the self-assembling nanocubes.

Measuring the dispersion force under natural conditions, such as when molecules are in solution with water, has been impossible. The force is so weak it cannot be identified separately from the other forces at play.

However, in new experiments, the research team used their self-assembling nanocubes as tools to amplify differences in the dispersion force.

The molecules that make up the sides of the cubes were modified to contain atoms selected for their polarizability, meaning their responsiveness to the surrounding electric field. Each fully assembled nanocube contained 18 of those polarizable atoms.

The combined effect of 18 atoms was enough to create measurable differences in the dispersion force depending on which polarizable atom was attached.

The dispersion force is calculated mathematically after using a technique called isothermal titration calorimetry to measure the amount of heat released when molecules bind together.

More polarizable atoms created stronger dispersion forces and made the nanocubes more stable. Depending on the estimated value of the hydrophobic effect, the dispersion force contributes 0.6 to 2.2 times greater attractive force and stability to the cube than the hydrophobic effect.

Researchers plan to use this knowledge about more polarizable atoms creating stronger dispersion forces to design future artificial molecular structures with more complex shapes and increased functions.

"For example, we could design molecules with larger binding surface areas and place polar atoms along the edges to enhance overall stability through the attraction of dispersion forces," said Hiraoka.

Solving a mystery in drug design

Hiraoka states that the measurements for nanocubes built with normal hydrogen compared to deuterium, the "heavy" isotope of hydrogen, should be relevant to drug design theory. Research by other groups had led to conflicting reports among chemists on whether swapping hydrogen with the twice-as-heavy and larger deuterium would create stronger dispersion force.

As a general rule, larger atoms are more polarizable and researchers had new data indicating increased polarizability led to stronger dispersion forces. However, in some cases the smaller hydrogen actually makes a stronger dispersion force than heavy deuterium, but other reports showed the opposite or negligibly small difference between the two atoms.

"In our experiments, the entropy-enthalpy difference is completely balanced. The free energy released by nanocubes with hydrogen or deuterium is essentially identical, so there may be no difference between them," said Hiraoka.

An essential difference between previous research and these experiments is that the UTokyo team used a more lifelike condition of being in solution with water and amplified the effect using the nanocube design.


Research Paper

Yi-Yang Zhan, Qi-Chun Jiang, Kentaro Ishii, Takuya Koide, Osamu Kobayashi, Tatsuo Kojima, Satoshi Takahashi, Masanori Tachikawa, Susumu Uchiyama, and Shuichi Hiraoka. 12 December 2019.

Polarizability and isotope effects on dispersion interactions in water. Communications Chemistry. DOI: 10.1038/s42004-019-0242-0

Related Links

Graduate School of Arts and Sciences:

Department of Basic Science (Japanese):

Hiraoka Group laboratory website (Japanese):

Research contact

Professor Shuichi Hiraoka
Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan
Tel: +81-(0)3-5465-7659

Press Contacts

Ms. Caitlin Devor
Division for Strategic Public Relations, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654, JAPAN
Tel: +81-(0)3-5841-0876

Public Relations Office

Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan
Tel: +81-3-5454-4920

About the University of Tokyo

The University of Tokyo is Japan's leading university and one of the world's top research universities. The vast research output of some 6,000 researchers is published in the world's top journals across the arts and sciences. Our vibrant student body of around 15,000 undergraduate and 15,000 graduate students includes over 4,000 international students. Find out more at or follow us on Twitter at @UTokyo_News_en.


Japan Society for the Promotion of Science, the Mitsubishi Foundation, Sekisui Integrated Research, the Joint Research by Exploratory Research Center on Life and Living Systems.


JSPS KAKENHI Grant Numbers 25102001, 25102005, and 16H00780

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