Efficient copper-based DNA cleavers from carboxylate benzimidazole ligands

Area of Science:

• Coordination Chemistry
• Bioinorganic Chemistry
• Materials Science

Background:

• Copper(II) coordination compounds are explored for their potential biological applications.
• Benzimidazole derivatives are known ligands in coordination chemistry.
• Understanding metal-ligand interactions is crucial for developing new therapeutic agents.

Purpose of the Study:

• To synthesize and characterize novel copper(II) coordination compounds.
• To investigate the DNA-binding modes and nuclease activity of these compounds.
• To elucidate the mechanism of DNA cleavage.

Main Methods:

• Synthesis and full characterization of four copper(II) complexes using elemental analyses, spectroscopy (UV-Vis, FT-IR, Mass Spectrometry), and X-ray crystallography.
• DNA interaction studies employing absorption titration, fluorescence spectroscopy, and circular dichroism.
• Nuclease activity assays using gel electrophoresis.

Main Results:

• Four copper(II) complexes with 2-benzimidazole propionic acid (Hbzpr) and 4-(benzimidazol-2-yl)-3-thiobutanoic acid (Hbztb) were successfully synthesized and structurally characterized.
• Trinuclear complexes bind DNA non-intercalatively, while mononuclear complexes show concentration-dependent groove binding or intercalation.
• All complexes demonstrated nuclease activity, cleaving supercoiled plasmid DNA; compound 4 induced double-strand cleavage.

Conclusions:

• The synthesized copper(II) compounds exhibit diverse DNA binding interactions and potent nuclease activity.
• DNA cleavage is mediated by an oxidative pathway, likely involving Fenton-type reactions and hydroxyl radical generation.
• These findings highlight the potential of these copper(II) complexes as DNA-cleaving agents.