Supramolecular nanocomplexes in Traditional Chinese Medicine decoctions: Challenges and methodologies for structural characterization.

Traditional Chinese Medicine (TCM) decoctions represent intricate chemical systems comprising numerous supramolecular nanocomplexes that self-assemble through intermolecular forces, including hydrogen bonding and hydrophobic interactions. These self-assembled nanocomplexes significantly influence the in vivo disposition of active pharmaceutical ingredients. Therefore, a comprehensive analysis of their fine structure and assembly mechanisms is essential for elucidating the scientific principles underlying TCM decoctions. This review synthesizes existing research on the structural characterization of supramolecular complexes within TCM decoctions and their corresponding structure-activity relationships. It highlights that current structural analysis strategies predominantly rely on a combination of "passive observation" and "model assumptions," which hinders the acquisition of direct experimental evidence regarding intermolecular interactions. This limitation constitutes a significant bottleneck in advancing our understanding of precise molecular arrangements, dynamic assembly mechanisms, and the in vivo fate of these molecular assemblies. In pursuit of this objective, this article endeavors to delineate potential strategies for structural analysis of supramolecular nanocomplexes.