Intercalative interaction of asymmetric copper(II) complex with DNA: Experimental, molecular docking, molecular dynamics and TDDFT studies

Abstract

The intercalative interactions of small molecules with DNA are important in a variety of biological processes including mutagenesis, carcinogenesis, and chemotherapy. A comprehensive research protocol including experiments and calculations was employed to investigate the intercalative interaction between metallointercalator copper(II) complex and DNA. The intercalative binding mode has been validated by UV spectra, fluorescence spectra, CD spectra and viscosity measurements. The classical molecular dynamics simulation was carried out to investigate the intercalative interaction between asymmetric copper(II) complex and DNA. An analytical method was proposed to simulate the dynamically changing absorption spectra of intercalator/DNA system. According to the established model, the changing process of the electronic absorption spectra for intercalator/DNA system can be predicted accurately. A rational explanation for the change law of absorption spectra has been proposed. Moreover, the analyses of the frontier orbital reveal that the red shift of the absorption spectra is due to the increase of π orbital energy caused by the coupling of the π orbital of the intercalated ligand with the π orbital of DNA. This cause of red shift of spectra is completely different from the previous inference. All these insights are of crucial importance for correctly analyzing the absorption spectra of intercalative interaction, as well as for explaining the macroscopic phenomena observed in experiments at the molecular level.

Studying non-covalent drug–DNA interactions

“…Intercalation occurs when the small molecules intercalate within the nucleic acid base pairs [2,3]. Many small molecules of biological importance are known to interact with DNA through non-covalent interactions [4][5][6]. These small molecules are known to interact with DNA by a specific binding mode.…”

Intercalation processes of copper complexes in DNA

“…Further computational studies modeling the drug-DNA interactions have suggested the atomic mechanism by which complexes can interact with either the grooves of the DNA or via intercalation between base pairs, and these studies have suggested information about the thermodynamic and energetic properties ( 2 , 40 ). Several groups have applied molecular dynamics (MD), quantum mechanics (QM) and hybrid methodologies (QM/MM) to models of copper complexes binding with DNA ( 41 – 45 ). The complex Cu[1,10-phenthroline] 2+ with multiple functional groups and a serinol link between the ligands have been studied by Magistrato and co-workers using MD and QM and the simulations and energetic analyses suggest that these complexes bind to the DNA in the minor groove with a partial intercalation between base pairs ( 43 ) with related calculations using QM methodologies yielding similar results ( 42 ).…”

Theoretical study on binding models of copper nucleases containing pyridyl groups to DNA

“…Molecular dynamics (MD) calculations provide powerful tools for studying the structural, interaction potentials and dynamic characterization of biological macromolecules involving nuclear acid [27]. For example, binding properties of the reversible diamidines with DNA by using MD simulations were investigated that influence of the central heterocycle is greater than that of tail part for reversible amidines binding affinity to DNA [28].…”