Competitive Coordination and Structural Evolution of Phenylalanine-Mg²⁺ Complexes in Microaqueous Environments:...

This study elucidates the coordination evolution and competitive-cooperative interaction between phenylalanine and Mg²⁺ in microaqueous environments using DFT calculations, AIMD, and WT-metadynamics simulations. Results reveal a hydration-driven shift in the coordination mode from tridentate chelation (carboxyl O, amino N, phenyl π-system) to monodentate carboxyl binding, accompanied by a geometric evolution from a four-coordinate sawhorse to a stable six-coordinate octahedron via a trigonal bipyramidal intermediate. Topology, NBO, and EDA-NOCV analyses demonstrate water's dual role as a competitive ligand and structural regulator, inducing a zwitterionic transition that anomalously enhances the Mg²⁺-carboxyl interaction at moderate hydration (n = 3-4). Notably, AdNDP analysis confirms the preservation of phenyl ring aromaticity. WT-metadynamics simulations validate the thermodynamic stability of the octahedral structure in aqueous solution, providing critical insight into Mg²⁺-amino acid recognition.