Cisplatin-based platinum compounds are important clinical chemotherapeutic agents that participate in most tumor chemotherapy regimens. Through density-functional theory calculations, the formation and stability of the inorganic oxide carrier, the mechanisms of the hydrolysis reaction of the activated platinum compound, and its binding mechanism with DNA bases can be studied. The higher the oxidation state of Pt (II to IV), the more electrons transfer from the magnesia-gold composite material to the platinum compound. After adsorption on the composite carrier, 5d←2p coordination bonds of Pt-N are strengthened. For flat and oblique adsorption modes of cisplatin, there is no significant difference in the density of states of the gold and magnesium oxide film, indicating the maintenance of the heterojunction structural framework. However, there are significant changes in the electronic states of cisplatin itself with different adsorption configurations. In the flat configuration, the band gap width of cisplatin is larger than that of the oblique configuration. The Cl-Pt bond range in the Pt(III) compound shows a clear charge reduction on the magnesia film, indicating the Cl-Pt bond is an active site with the potential for decomposition and hydrolysis. The substitution of chloride ions by water can lead to hydrolysis products, enhancing the polarization of the composite and showing strong charge separation. The hydrolysis of the free platinum compound is endothermic by 0.309 eV, exceeding the small activation energy barrier of 0.399 eV, indicating that hydrolysis of this platinum compound is easily achievable. ADME (absorption, distribution, metabolism, and excretion) prediction parameters indicate that hydrolysis products have good ESOL (Estimated SOLubility) solubility and high gastrointestinal absorption, consistent with Lipinski's rule. During the coordination reaction process, there are significant changes in the distribution of frontier molecular orbitals, with the HOMO (highest occupied molecular orbital) of the initial state primarily located on the purine base, providing the possibility for electron transfer to the empty orbitals of the platinum compound in the LUMO (lowest unoccupied molecular orbital). The HOMO and HOMO-1 of the transition state and product are mainly distributed on the platinum compound, indicating clear electron transfer and orbital rearrangement. The activation energy barrier for the purine coordination reaction with the hydrolysis products is reduced to 0.61 eV, and the dipole moment gradually decreases to 6.77 Debye during the reaction, indicating a reduction in the system's charge separation and polarization. This contribution is anticipated to provide a new theoretical clue for developing inorganic oxide carriers of platinum compounds.
Keywords: density-functional theory; gold–magnesia interface; guanine; hydrolysis; platinum compound.