Alternative role of cisplatin in DNA damage-theoretical studies on the influence of excess electrons on the cisplatin-DNA complex

Reliable DFT calculations were used to gain insights into the effects of excess electrons on the cisplatin-DNA complex in a water solution. One electron injection is enough to break the two Pt-N7 bonds, which is driven by the rare symmetrical in-plane bending vibration. The dissociated [Pt(NH₃)₂]⁺ group from the cisplatin-DNA complex could combine with H₂O in the surroundings to form a reactive species, which can abstract the most solvent accessible H4′ of the sugar with a barrier of ca. 17.5 kcal mol^-1. Upon influence of the multiple electrons addition, the H4′-abstraction reaction by the stable radical anion is feasible with a lower barrier and is exothermic. Thereby, they have high efficiency for DNA damage. The synergic effect between the metal and the ligand is highlighted due to failure of the isolated [Pt(NH₃)₂]⁺ and [Pt(NH₃)₂]^- to abstract H4′ of sugar because the overlap between the SOMO (on Pt) and the C4′H4′ anti-bonding orbital is zero. In the present studies, an alternate role of cisplatin in DNA damage was discovered, which strongly confirmed that the cisplatin-DNA complex is more vulnerable to attack from low-energy electrons.