Non-covalent interactions constitute a fundamental basis for sustaining life activities and enabling biological functions. Traditional research has predominantly focused on gas-phase systems or common biological groups within known protein structures, while interactions involving non-canonical groups in nature have often been overlooked, creating potential blind spots in the current understanding.

In a study published in Communications Chemistry, Prof. HUANG Yougui and Prof. WANG Wei from the Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, in collaboration with ZHANG Lu’s group, Unveiled the alkyne-π interaction using metal-organic cage compounds.

The researchers selected two structurally highly similar yet subtly distinct metal‑organic cages (Red-1 and Orange-1) as model systems to investigate potential interactions between alkyne groups and aromatic rings. By eliminating interference from other intermolecular forces and integrating experimental observations with theoretical calculations, the researchers unequivocally confirmed the existence of "alkyne–π interactions" and revealed their decisive influence on the spectroscopic properties of the compounds.

The alkyne group represents a typical example within this research blind spot. As a relatively rare functional group in fundamental biological molecules, the alkyne moiety even resides within the "Raman‑silent window" of cells and has thus long received insufficient attention in supramolecular chemistry studies. Although structural clues have hinted at its potential involvement in π‑system interactions, conclusive experimental evidence has been lacking. This stands in contrast to the practical significance of alkynes in biomedical fields—where they serve as essential structural units for Raman probes and numerous pharmaceutical agents, playing indispensable roles in related applications.

The researchers provided the first definitive experimental confirmation that "alkyne–π interactions" constitute a genuine, functionally significant type of intermolecular force. The discovery not only theoretically expands the understanding of non-covalent interactions and fills a gap in knowledge regarding supramolecular roles of non-canonical groups, but also methodologically demonstrates how exquisitely designed comparative models can be used to isolate and validate weak interactions.

This study offers a novel perspective for understanding the behavior of alkyne-containing drugs and probes in biological systems, opening new pathways for the rational design of alkyne‑based functional materials from a molecular interaction standpoint.

Systematic confirmation of the existence of alkyne-π interactions through structure-to-spectrum studies(Image by Prof. WANG's group)

Contact:

Prof. WANG Wei

Fujian Institute of Research on the Structure of Matter

Chinese Academy of Sciences

Email:Wei Wang@fjirsm.ac.cn