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 b y both spectrophotometric and gel electrophoresis studies. Although anthrac ene itself is not a good intercalating agent, the association constant of t he complex between anthracene tied to the cobalt(III)-sar cage and DNA is a pproximate to 2 x 10(6) dm(3) mol(-1) and the average binding-site size on supercoiled plasmid DNA is approximate to 2.4 base pairs. The hydrophilic c omplex cation (a) solubilizes the anthracene moiety in water and (b) enhanc es DNA binding by its electrostatic interaction with the anionic phosphodie ster backbone of DNA. While irradiation of the intercalated complexes at 25 4 nm led to single-strand cleavage of DNA, irradiation at higher wavelength , 302 and 365 nm, was much less effective. Neither molecular oxygen nor exc ited singlet or triplet states of anthracene appear to be involved in the c leavage process, and it is likely that the N-radical cation arising from li gand to metal charge or electron transfer in the phosphodiester-complex ion pair gives rise to oxidation of the deoxyribose moieties. Fission of the r esulting deoxyribose diphosphate radical cation follows, leading to DNA sin gle-strand cleavage. It also appears that the most easily reduced complex m oieties are the most effective cleavage agents. Excited singlet and triplet states of anthracene arising from irradiation at 365 nm are efficiently qu enched by DNA and the allowedness of the short-axis in-plane aromatic trans itions is also sharply diminished. This in itself is unusual.