A Universal Mg–Zn–S Catalytic Framework for RNA Duplex Stabilization and Phosphodiester Activation

Magnesium, zinc, and sulfur are cosmochemically abundant elements that play central roles in biological catalysis and planetary geochemistry. Here, density functional theory (DFT) and molecular dynamics (MD) simulations are used to test whether mixed Mg²⁺–Zn²⁺–S environments can stabilize an RNA duplex while lowering phosphodiester activation barriers relative to Mg²⁺ alone. DFT calculations on model phosphodiester cleavage pathways show that the inclusion of Zn²⁺ and a thiophilic sulfur ligand reduces activation barriers from approximately 31 kcal mol^{-1} for Mg²⁺-only systems to below 20 kcal mol^{-1} in Mg²⁺–Zn²⁺–S triads. All-atom MD simulations of a 12-mer RNA duplex in explicit solvent reveal that mixed-metal systems maintain lower backbone root-mean-square deviations (RMSD) and higher hydrogen-bond persistence than Mg²⁺ alone, consistent with enhanced structural stability. Coordination analysis indicates tighter Zn–phosphate interactions and a distinct S-bridged P···P distance distribution, supporting a cooperative Mg–Zn–S catalytic motif. A simple power-law relation between relative catalytic efficiency and planetary (Zn + S)/Mg ratio reproduces the qualitative trend expected from cosmochemical abundance variations. Together, these results support a physically plausible Mg–Zn–S catalytic framework in which mixed metal–chalcogen environments simultaneously stabilize RNA structure and promote phosphodiester activation, providing a mechanistic bridge between planetary composition and information-bearing polymers. [1–3]