Stereochemistry at the Single-Molecule Level: From Monitoring to Regulation

Traditional stereochemistry analysis is crucial for understanding the molecular behavior, but relies on measurements that encompass multiple molecules and obscure individual molecular dynamics. Single-molecule techniques enable real-time tracking of stereochemical transformations. These techniques include electrical methods (such as scanning probe microscopy, single-molecule junction techniques, and nanopore technology) and non-electrical approaches (such as circular dichroism spectroscopy and surface-enhanced Raman spectroscopy). This review highlights recent advances in monitoring and regulation of stereochemical properties at the single-molecule level. Techniques that bridge macroscopic observations with molecular-scale dynamics are emphasized. Key isomerization phenomena (constitutional, configurational, and conformational isomerizations) are explored to demonstrate how light, electric field, and mechanical force regulate molecular states. The use of chiral molecules in optical tweezers, chiral-modified scanning tunneling microscopies, and graphene-based single-molecule junctions to leverage the chirality-induced spin selectivity effect for enantiomer discrimination and manipulation is highlighted. Despite progress in this field, challenges persist in resolving ultrafast isomerization pathways, understanding chiral origin mechanisms, and integrating single-molecule devices. Emerging strategies combining multimodal stimuli, machine learning, and nanofabrication are promising for advancing stereochemical research and applications in molecular electronics and nanotechnology. This work underscores the transformative potential of single-molecule techniques in unveiling fundamental chemical dynamics and designing functional molecular systems.