Synthesis of Two Acridine Conjugates of the Bis(phenanthroline) Ligand “Clip-Phen” and Evaluation of the Nuclease Activity of the Corresponding Copper Complexes

Abstract

The synthesis of three novel derivatives [N-acetyl-Clip-Phen (1), Clip-Phen-hexylaminoacridine (4) and Clip-Phen-hexylchloromethoxyaminoacridine (5)] of the bis(phenanthroline) ligand “Clip-Phen”, are described. Complexation of these ligands with copper(II) afforded the 1:1 complexes as hexafluorophosphate salts. The relaxation of ϕX 174 DNA was used as a DNA cleavage assay, 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 significantly enhanced cleavage efficiencies, which has been attributed to increased affinity of the complexes for DNA. UV/Vis-spectral data of the complexes in the presence of calf-thymus DNA was consistent with an intercalative mode of binding.