Structural changes in DNA by binding mitochondrion-targeted monofunctional platinum(II) complexes using molecular dynamics simulation study

Triphenylphosphonium (Ph₃P⁺, TPP) is a highly effective mitochondrial targeting group, an example of using which on mitochondrion-targeted monofunctional platinum(II) agent as anticancer drug was OPT, with the -CH₂Ph₃P⁺ group at ortho position of the pyriplatin pyridine ring. To study how carrier ligands might affect the efficacy of OPT, we constructed two platinum(II) agents with bulky bidentate ligands based on OPT. DNA structural changes caused by these three platinum(II) agents using molecular dynamics simulations were analysed. Data regarding DNA conformational changes including helical parameter, base stacking, average structure, and principal component analyses has been obtained. We found that TPP-based monofunctional platinum(II) complexes with bulky carrier ligands may induce more significant DNA conformational changes. These results are beneficial for developing highly efficient mitochondrion-targeted platinum anticancer drugs with carrier ligands of different steric hindrance.