Interaction of substituted cobalt(III) cage complexes with DNA

Polycyclic aromatic moieties covalently bound to the inert cationic cobalt(III)-sar cage complex (sar = sarcophagine = 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) intercalate with negatively supercoiled plasmid DNA, as shown by both spectrophotometric and gel electrophoresis studies. Although anthracene itself is not a good intercalating agent, the association constant of the complex between anthracene tied to the cobalt(III)-sar cage and DNA is ≈2 × 10⁶ dm³ mol^-1 and the average binding-site size on supercoiled plasmid DNA is ≈2.4 base pairs. The hydrophilic complex cation (a) sobilizes the anthracene moiety in water and (b) enhances DNA binding by its electrostatic interaction with the anionic phosphodiester backbone of DNA. While irradiation of the intercalated complexes at 254 nm led to single-strand cleavage of DNA, irradiation at higher wavelength, 302 and 365 nm, was much less effective. Neither molecular oxygen nor excited singlet or triplet states of anthracene appear to be involved in the cleavage process, and it is likely that the N-radical cation arising from ligand to metal charge or electron transfer in the phosphodiester-complex ion pair gives rise to oxidation of the deoxyribose moieties. Fission of the resulting deoxyribose diphosphate radical cation follows, leading to DNA single-strand cleavage. It also appears that the most easily reduced complex moieties are the most effective cleavage agents. Excited singlet and triplet states of anthracene arising from irradiation at 365 nm are efficiently quenched by DNA and the allowedness of the short-axis in-plane aromatic transitions is also sharply diminished. This in itself is unusual.