Developing a cyclic molecule that captures phosphate in harmony with water molecules

Tsukuba, Japan—Cyclic molecules are used in a wide range of applications, including molecular sensing, because they can incorporate specific molecules of interest into their inner cavities. Particularly, the ability to precisely recognize and capture specific molecules in water is critical for drug development and environmental analysis. Cyclic molecules typically employ hydrogen bonding to capture molecules, whereby neighboring molecules are attracted to each other via functional groups bearing hydrogen atoms. However, water molecules present competition for the hydrogen bonding sites, making it challenging to develop cyclic molecules that can recognize target molecules for hydrogen bonding in aqueous systems.

In this project, the researchers developed a new cyclic molecule that achieves precise molecular recognition through hydrogen bonding in harmony with water molecules. Specifically, a novel cyclodextrin (cyclic oligosaccharide) was synthesized with numerous amide groups (-CONH-) that act as hydrogen bonding units. This molecule shows excellent selectivity for target molecules in water, whereby it traps phosphate, but not sulfate or carboxylate species. The detailed mechanism by which this cyclic molecule selectively traps phosphate species through multi-point hydrogen bonding in harmony with water molecules was elucidated using nuclear magnetic resonance (NMR) spectroscopy, isothermal titration thermometry (ITC), and molecular dynamic (MD) simulations.

The findings of this study provide guidelines to design new cyclic molecules, while elucidating the interaction between water molecules and other substances. Therefore, it is significant for the development of materials that function in an aqueous environment.

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This research was supported by JSPS KAKENHI (Grant Numbers JP19H05714, JP19H05718, JP19H05719, JP20H05202, JP22H04519 (Aquatic Functional Materials), JP21H01946, and JP22K05124), JST ACT-X (Grant Number JPMJAX23D3) and CREST (Grant Number JPMJCR23O1), the Kurita Water and Environment Foundation (Grant Numbers 23H033 and 24H021), and the Asahi Glass Foundation. Y. I. was also supported by the Kitasato University Research Grant for Young Researchers. The MD simulations were implemented using the supercomputers of the Research Center for Computational Science in Okazaki (22-IMS-C043 and 23-IMS-C038), Grand Chariot at Hokkaido University, and OCTOPUS at Osaka University, partially through the HPCI System Research Project (hp230083 and hp230132).

_{Original Paper}

Title of original paper:
Amide Cyclodextrin That Recognises Monophosphate Anions in Harmony with Water Molecules

Journal:
Chemical Science

DOI:
10.1039/D4SC04529G

_{Correspondence}

Assistant Professor NAKAMURA, Takashi
Institute of Pure and Applied Sciences, University of Tsukuba

Assistant Professor NAKAHATA, Masaki
Graduate School of Science, Osaka University

Professor WATANABE, Go
School of Frontier Engineering, Kitasato University

_{Related Link}

Institute of Pure and Applied Sciences