Bio-soft matter derived from traditional Chinese medicine:Characterizations of hierarchical structure,assembly mechanism,and beyond

Structural and functional explorations on bio-soft matter such as micelles,vesicles,nanoparticles,aggregates or polymers derived from traditional Chinese medicine(TCM)has emerged as a new topic in the field of TCM.The discovery of such cross-scaled bio-soft matter may provide a unique perspective for unraveling the new effective material basis of TCM as well as developing innovative medicine and biomaterials.Despite the rapid rise of TCM-derived bio-soft matter,their hierarchical structure and assembly mechanism must be unambiguously probed for a further in-depth understanding of their pharmacological activity.In this review,the current emerged TCM-derived bio-soft matter assembled from either small molecules or macromolecules is introduced,and particularly the unambiguous elucidation of their hierarchical structure and assembly mechanism with combined electron microscopic and spectroscopic techniques is depicted.The pros and cons of each technique are also discussed.The future challenges and perspective of TCM-derived bio-soft matter are outlined,particularly the requirement for their precise in situ structural determination is highlighted.

CuBr-promoted domino Biginelli reaction for the diastereoselective synthesis of bridged polyheterocycles:Mechanism studies and in vitro anti-tumor activities

The low-cost CuBr-promoted domino Biginelli reaction among readily available ketones,salicylaldehyde derivatives and 3-amino-1,2,4-triazole was studied under solvothermal conditions,giving the novel bridged polyheterocycles bearing two or three stereocenters depending on the starting ketones.This multicomponent reaction proceeded with high diastereoselectivity(dr>20:1)based on a combined~1 H NMR,crystallographic and supercritical fluid chromatographic(SFC)analysis of the product.Time-dependent high-resolution mass spectrometry(HRMS)was performed to track the reaction process,and several key intermediates were identified,leading to the drawing of a plausible reaction mechanism.Density functional theory(DFT)calculation was supplemented,and two reaction pathways were differentiated.Moreover,in vitro antitumor activity was evaluated using HeLa and HepG2 cell lines,and two of these polyheterocycles demonstrated promising activities against HepG2 cells with EC50 down to 10μmol/L.Additionally,ESI-MS/MS studies on all the polyheterocycles suggest a common fragmentation pathway(loss of one molecule of amino-triazole)they shared,providing the first-hand fragmentation rules for future rapid structural identification of them.The multicomponent domino reaction presented here may offer prospects for future design of more efficient strategies to access medicinally important bridged polyheterocycles.