Fine-tuning alkyl chain length in copper(II) complexes: effects on DNA binding and catalytic cleavage

Area of Science:

• Coordination Chemistry
• Bioinorganic Chemistry
• Chemical Biology

Background:

• Metal complexes are recognized for their DNA cleavage capabilities.
• Copper complexes, in particular, can induce DNA cleavage via oxidative mechanisms, often involving the Haber-Weiss cycle.

Purpose of the Study:

• To synthesize and characterize two novel copper(II) complexes with long-chain ligands.
• To evaluate and compare the DNA binding and cleavage activities of these new complexes against a reference compound.
• To investigate the influence of ligand alkyl chain length on DNA targeting and cleavage efficiency.

Main Methods:

• Synthesis and physicochemical characterization (elemental analysis, EPR, spectroscopy, electrochemistry) of copper(II) complexes.
• Density Functional Theory (DFT) modeling to determine the electronic structure and coordination environment.
• Spectrophotometric monitoring of DNA interaction and binding constant determination (Kb).
• Molecular docking studies using CCDC GOLD® suite to support DNA interaction analysis.

Main Results:

• Two new copper(II) complexes (2 and 3) were synthesized and characterized, alongside a reference complex (1).
• DFT calculations indicated a pseudo-octahedral geometry with trans ligands for all complexes.
• Complexes 2 and 3 exhibited DNA binding with binding constants (Kb) of 1.92 × 10⁴ L mol⁻¹ and 1.15 × 10⁴ L mol⁻¹, respectively.
• All complexes demonstrated DNA cleavage activity, with complex 2 showing the highest observed rate (kobs = 0.88 ± 0.09 h⁻¹).

Conclusions:

• The synthesized copper(II) complexes effectively bind to and cleave DNA.
• The length of the alkyl chain in the ligands plays a significant role in modulating DNA-targeting efficacy.
• These findings contribute to the development of novel copper-based agents for catalytic nucleic acid cleavage.