Copper−1,10-Phenanthroline Complexes Binding to DNA: Structural Predictions from Molecular Simulations

Abstract

Copper-1,10-phenanthroline (phen) complexes Cu(phen)(2)(), Cu(2-Clip-phen), and Cu(3-Clip-phen) (Clip = a serinol bridge between the phen parts) are typically employed as DNA-cleaving agents and are now becoming increasingly important for building multifunctional drugs with improved cytotoxic properties. For instance, Cu(3-Clip-phen) has been combined with distamycin-like minor-groove binders and cisplatin-derivatives, leading to promising results. Density Functional Theory (DFT) and docking calculations as well as molecular dynamics (MD) simulations were performed to describe the mode of binding to DNA of these complexes. Our data suggest the minor-groove binding to be more probable than (partial) intercalation and major-groove binding. In addition, it was found that a combination of factors including planarity, van der Waals interactions with DNA, and structural complementarities may be the key for the cleavage efficiency of these copper complexes.

Synthesis and crystal structure of new dicopper(II) complexes having asymmetric N,N′-bis(substituted)oxamides with DNA/protein binding ability: In vitro anticancer activity and molecular docking studies

“…The copper parameters, vdW radii of 0.96 Å and vdW well depth of 0.01 kcal/mol, used in the docking calculation were taken from the Ref. [39]. The coordinates of the two complexes were taken from their crystal structures as a CIF file and converted to the PDB format using Mercury software [40].…”

Synthesis, crystal structure and action on Escherichia coli by microcalorimetry of copper complexes with 1,10-phenanthroline and amino acid

“…1,10-phenanthroline (phen) is one of the earliest and most extensively studied N-heterocyclic chelating agents, and was variously researched because of the potential application as nonradioactive nucleic acid probes and DNA cleaving agents [3]. Since Sigman and coworkers discovered that a mixture of phen and CuCl 2 can cleave DNA [4][5][6] the interaction of Cu-phen binding with DNA was widely investigated in recent 30 years [7][8][9][10][11]. In the very recent years ternary Cu-phen-amino acid complexes were designed and synthesized of bioessential amino acid [12][13][14].…”

Synthesis and structure of new dicopper(II) complexes bridged by N-(2-hydroxy-5-methylphenyl)-N′-[3-(dimethylamino)propyl]oxamide with in vitro anticancer activity: A comparative study of reactivities towards DNA/protein by molecular docking and experimental assays

“…Since HS-DNA used in the experimental assays was too large for current computational resources to perform the docking calculation, according to the literature method [25], the structure of the DNA hexamer d(CGATCG) 2 complexed with typical intercalating agent ellipticine (PDB id 1Z3F) obtained from the Protein Data Bank (http://www.rcsb.org/pdb) [26], was employed to establish the docking mode, in which the heteroatoms and ellipticine molecule were removed to expose the intercalation gap, and polar hydrogen atoms as well as Kollman charges were added to the DNA hexamer (receptor molecule). The copper parameters, vdW radii of 0.96 Å and vdW well depth of 0.01 Kcal/mol, used in the docking calculation were taken from the reference [27]. The coordinates of the two complexes were taken from the crystal structures as CIF files and converted to the PDB format using Mercury software [28].…”