Citation: Xiao-Wen Sun, Wei Zhao, Yougang Yao, Ji Wang, Yifei Liu, Kanglei Liu, Biao Wu. Nucleobase pairing in expanded oligourea macrocycle driven by phosphate coordination[J]. Chinese Chemical Letters, ;2026, 37(11): 112372. doi: 10.1016/j.cclet.2026.112372 shu

Nucleobase pairing in expanded oligourea macrocycle driven by phosphate coordination

Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering of Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China

Received Date: 31 October 2025
Revised Date: 28 December 2025
Accepted Date: 6 January 2026
Available Online: 7 January 2026

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The specific recognition and stable pairing of nucleobases in aqueous solution are challenging due to strong competitive solvation effects. Although synthetic hosts based on cationic scaffolds have successfully stabilized base pairs through synergistic electrostatic and hydrophobic effects, whether hydrogen bonding alone, given its high adaptability and programmability, can drive nucleobase pairing remains an open question. Herein, we present a neutral and expanded oligourea macrocycle, H[14]U, which features a preorganized cavity tailored for nucleotides binding. This host first strongly binds the phosphate groups of mononucleotides through up to fourteen hydrogen bonds. Within its confined microenvironment, the macrocycle facilitates the formation of both homodimers (U·U) and, more importantly, biologically relevant heterodimer (A·U). The 1:2 host-guest complexes were comprehensively characterized by a combination of NMR, ITC, MS, and CD spectroscopy. ITC studies revealed high-affinity binding with remarkable positive cooperativity. This work demonstrates that hydrogen-bonding interactions, without electrostatic assistance, are sufficient to drive nucleotide base pairing, offering a new design strategy for artificial systems targeting nucleobase recognition and assembly.
- Nucleobase pairing,
- Phosphate recognition,
- Oligourea macrocycle,
- Cooperative binding,
- Anion coordination
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