title: DNA cleavage activity of Fe(II)N4Py under photo irradiation in the presence of 1,8-naphthalimide and 9-aminoacridine: unexpected effects of reactive oxygen species scavengers.
abstract: The DNA cleavage activity of the iron(II) complex of the ligand N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine (N4Py) was investigated in the presence of the chromophores 1,8-naphthalimide (NI) and 9-aminoacridine (AA) under photo irradiation at 355 and 400.8 nm and compared to the activity of the complex without the chromophores. Whereas in most cases no synergistic effect of the added chromophores on DNA cleavage efficiency was observed, it was found that for Fe(II)N4Py, in combination with NI under irradiation at 355 nm, the DNA cleavage activity was increased. Surprisingly, it was found that the addition of reactive oxygen species (ROS) scavengers gave rise to significantly increased DNA cleavage efficiency, which is a highly counterintuitive observation since ROS are needed to achieve DNA cleavage. A hypothesis is put forward to explain, at least partly, these results. It is proposed that the addition of scavengers inhibits quenching of (3)NI*, thus making photo-induced electron transfer between (3)NI* and Fe(III)N4Py more efficient. This results in reduction of Fe(III)N4Py to Fe(II)N4Py, which can then react with ROS giving rise to DNA cleavage. Hence the role of the scavengers is to maintain a close to optimal concentration of ROS. The present study serves as an illustration of the care that needs to be exercised in interpreting the results of experiments using standard ROS scavengers, since especially in complex systems such as presented here they can give rise to unexpected phenomena. In the presence of 1,8-naphthalimide or 9-aminoacridine, ROS scavengers can increase the DNA cleavage efficiency of Fe(II)N4Py complex under photo irradiation.
authors.affiliation: Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Wesley R
authors.initials: WR
authors.lastname: Browne
authors.forename: Gerard
authors.initials: G
authors.lastname: Roelfes
mesh_terms: D000585:Aminacrine / Q000737:chemistry*; D053837:DNA Cleavage / Q000187:drug effects; D004269:DNA, Bacterial / Q000737:chemistry / Q000187:drug effects; D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects; D005296:Ferrous Compounds / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry*; D015394:Molecular Structure; D053644:Naphthalimides / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000737:chemistry*; D014466:Ultraviolet Rays
chemical_list: D004269:DNA, Bacterial; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D053644:Naphthalimides; D017382:Reactive Oxygen Species; D000585:Aminacrine