Theoretical insights into the activation of carboplatin and its interaction with DNA bases on magnesia: synergistic drug delivery and magnesium supplementation

Abstract

We employed first-principles calculations and molecular dynamics simulations to reveal atomic-scale mechanisms governing carboplatin interactions with magnesia (MgO) films. We demonstrated MgO functions as a synergistic drug delivery platform through three key actions: (i) high-affinity adsorption (binding energy of −2.24 eV) via dual N–H⋯O_s hydrogen bonding and carbonyl oxygen coordination to Mg²⁺ sites; (ii) enhanced hydrolysis activation (reaction energy of −0.84 eV) that cleaved the dicarboxylate ligand to form bioactive [Pt(NH₃)₂(H₂O)₂]²⁺; (iii) efficient DNA targeting with strong guanine N(7) binding (−2.03 eV). Electronic structure analysis (charge transfer, ELF, DOS/pCOHP) confirmed that MgO maintained electronic integrity while polarizing carboplatin to weaken Pt–O bonds. Molecular dynamics further revealed stable Mg²⁺–carboxylate coordination (radial distribution peak at 2.23 Å), indicating the dual-action capability of MgO as a drug carrier and magnesium supplement. These atomic-level insights establish a theoretical framework for developing lower-toxicity platinum nanotherapeutics using inorganic oxide carriers.