Synthesis, Characterization, and DNA-Binding Properties of (l,2-Diaminoethane)platinum(II) Complexes Linked to the DNA Intercalator Acridine Orange by Trimethylene and Hexamethylene Chains

We report the syntheses of intercalator-linked platinum complexes, [Pt{AO(CH₂)_nen}Cl₂]Cl, where (CH₂)_n is a polymethylene chain having n = 6 (9) or n = 3 (20) linking the DNA intercalator acridine orange (AO) to the Pt-binding ligand ethylenediamine (en). Single-crystal X-ray diffraction studies of the oxalate (ox) derivative of 9, [Pt{AO(CH₂)₆en}(ox)](NO₃).7H₂O (10), and of the ligand precursors, [AO(CH₂)₆OH]I (5) and [AO(CH₂)₃OH]I (15), revealed the molecular structures and crystal packing of these compounds. In 10, infinite “head-to-tail” stacking of the acridine orange rings occurs while the (Pt(en)(ox)} groups stack in a pairwise fashion. In compounds 5 and 15, there are head-to-tail stacked acridine orange dimers with only weak interactions between the dimers. Visible absorption spectroscopy has been used to compare the effects of different chain lengths and substituents on the stacking interactions of these modified acridine orange compounds in solution. The tendency of molecules to aggregate in acidic aqueous solution follows the order [Pt{AO(CH₂)₃en}Cl₂]⁺ » [Pt{AO(CH₂)₆en}Cl₂]⁺ > AO » [AO(CH₂)₆(en)]⁺ > [AO(CH₂)₃(en)]⁺. The interaction of compounds 9 and 20 with DNA has also been studied by absorption spectroscopy. These results, together with the previously reported covalent binding to, and superhelical unwinding of, DNA by 9, support a model in which the platinum moiety binds covalently to DNA while the AO moiety is intercalated one or two base pairs away.