Theoretical insights into the Activation of Carboplatin and its Interaction with DNA Bases on Magnesia: Synergistic Drug Delivery and Magnesium Supplementation

Abstract

This study employs first-principles calculations and molecular dynamics simulations to reveal atomic-scale mechanisms governing carboplatin interactions with magnesia (MgO) films. We demonstrate MgO functions as a synergistic drug delivery platform through three key actions: High-affinity adsorption (-2.24 eV binding energy) via dual N-H···Os hydrogen bonding and carbonyl oxygen coordination to Mg2+ sites; Enhanced hydrolysis activation (-0.84 eV reaction energy) that cleaves the dicarboxylate ligand to form bioactive [Pt(NH3)2(H2O)2]2+; Efficient DNA targeting with strong guanine N(7) binding (-2.03 eV). Electronic structure analysis (charge transfer, ELF, DOS/pCOHP) confirms MgO maintains electronic integrity while polarizing carboplatin to weaken Pt-O bonds. Molecular dynamics further reveals stable Mg2+-carboxylate coordination (radial distribution peak at 2.23 Å), indicating MgO's dual-action capability as both drug carrier and magnesium supplement. These atomic-level insights establish a theoretical framework for developing lower-toxicity platinum nanotherapeutics using inorganic oxide carriers.