Synthesis of two acridine conjugates of the bis(phenanthroline) ligand "Clip-Phen" and evaluation of the nuclease activity of the corresponding copper complexes

The synthesis of three novel derivatives [N-acetyl-Clip-Phen (1), Clip-Phen -hexylaminoacridine (4) and Clip-Phenhexylchloromethoxyaminoacridine (5)] o f the bis(phenanthroline) ligand "Clip-Phen", are described. Complexation o f these ligands with copper(II) afforded the 1:1 complexes as hexafluoropho sphate salts. The relaxation of phi X 174 DNA was used as a DNA cleavage as say, with the following results. [Cu(1)](2+) was found to show a diminished activity relative to the parent complex [Cu(Clip-Phen)](2+). However, the acridine-containing complexes [Cu(4)H](3+) and [Cu(5)H](3+) exhibited signi ficantly enhanced cleavage efficiencies, which has been attributed to incre ased affinity of the complexes for DNA. UV/Vis-spectral data of the complex es in the presence of calf-thymus DNA was consistent with an intercalative mode of binding.