With support from the Chemical Structure and Dynamics (CSD) program in the Division of Chemistry, Professor Thanh D. Do at the University of Tennessee, Knoxville is combining sophisticated gas-phase and condensed-phase experimental approaches with density functional theory calculations to investigate the complexation of cyclic depsipeptides with transition metals and lanthanides, resulting in sandwich-like structures that govern metal selectivity and transport. Cyclic depsipeptides are naturally derived macrocycles featuring N-methylated amides, ester-amide linkages, and ion-binding motifs that enable selective interactions with biological targets. Yet, the structures and reactivities of their metal complexes remain poorly understood, despite their relevance to biological activity. Professor Do and his students will investigate how metal size and coordination geometry influence the formation of these complexes, enabling unusual reactivities such as C–H activation. To achieve this, they will employ ion mobility spectrometry–mass spectrometry (IMS-MS), synchrotron-based X-ray spectroscopy (APS, Chicago), and the Free-Electron Lasers for Infrared experiments (FELIX, Netherlands). Their discoveries could advance the fundamental understanding of metal–ligand recognition and reactivity, enabling the design of new macrocyclic scaffolds for metal separation and catalysis. The project supports broader impacts through interdisciplinary training, outreach to high school students, and in