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

Abstract

Metal complexes are well known for their DNA cleavage activity. Copper is a metal that stands out for this purpose because it is able to perform cleavage through oxidative mechanisms using the Haber–Weiss cycle. We report two unprecedented copper(II) complexes ( 2 and 3 ) with long-chain ligands and compare the results with those of a previously reported complex ( 1 ), which we use as a reference in our studies. They were all properly characterized using a set of physicochemical methods, including elemental analysis, electron paramagnetic resonance, spectroscopic and electrochemical analysis. Density functional theory (DFT) modeling revealed a pseudo-octahedral environment where the ligands are trans to each other. The interaction of 1 , 2 , and 3 with salmon sperm DNA was monitored spectrophotometrically, and the binding constants (K b ) were 4.24 × 10 4 L mol −1 , 1.92 × 10 4 L mol −1 , and 1.15 × 10 4 L mol −1 , respectively. The interactions were supported by docking studies conducted with the CCDC GOLD® docking suite. Finally, all complexes exhibited DNA binding and cleavage properties, but 2 stood out as the most active one ( 2 , k obs = 0.88 ± 0.09 h −1 > 1 , k obs = 0.54 ± 0.06 h −1 > 3 , k obs = 0.50 ± 0.03 h −1 ). These results support the idea that fine-tuning the length of the alkyl chain can enhance DNA-targeting activity and contribute to the development of efficient strategies for catalytic cleavage of nucleic acids.

Bibliographic Information