Binding profile of a mixed-ligand silver(I) complex with DNA and Topoisomerase I.

A new mixed-ligand Ag(I) complex, [Ag(daf)(phen)]NO3 (daf = 4,5-diazafluoren-9-one and dian = N-(4,5-diazafluoren-9-ylidene)aniline), was synthesized. The elemental analysis, FTIR, 1HNMR, UV-Vis spectroscopy, cyclic voltammetry, and DFT (Density Functional Theory) geometry optimization method were applied in order to predict the Ag(I) complex structure which concluded to a distorted tetrahedral N4 coordination around the Ag(I) center. A detailed in silico analysis of the bioaffinity of the complex to DNA and human DNA-Topoisomerase I was conducted using molecular docking simulations and ONIOM (Our own N-layered Integrated molecular Orbital and molecular Mechanics) techniques. In this overall scenario, the results suggest the dominance of π-π stacking interactions of the heteroaromatic ligands in the intercalating pocket of DNA and the active site of the enzyme and the rational correlation between being a good intercalator and a potent Topoisomerase I inhibitor. In vitro DNA-binding experiments by spectrophotometric, spectrofluorometric, Voltammetric, and viscometric techniques at physiological pH also confirmed the computational results. The complex inhibited MCF-7 cell growth in a dose-dependent manner while being nontoxic on HUVEC normal cells.

A novel Cu(II)-based DNA-intercalating agent: Structural and biological insights using biophysical and in silico techniques.

A new mixed-ligand Cu(II) complex formulated as [Cu(dipic)(amp)(H2O)].H2O (dipic: pyridine-2,6-dicarboxylic acid, amp: 2-amino-4-methylpyridine), was synthesized and structurally characterized by FTIR spectroscopy, CHN analysis, and the single-crystal X-ray crystallographic method. The complex crystallizes in an orthorhombic space group Pna21, and the coordination environment around the metal center was found to be a pentacoordinate CuN2O2OW distorted square-pyramidal geometry. In order to systematically explore a detailed in vitro and in silico study of the DNA binding of the title complex, various biophysical (UV-Vis absorption spectroscopy, fluorescence, competitive binding with ethidium bromide) and theoretical (DFT, molecular docking simulation, and QM/MM) methods were applied which revealed that the complex could intercalate with the insertion of the amp ligand between the DNA base pairs. The experimental thermodynamic parameters of the interaction revealed the spontaneity of the process and the domination of the hydrophobic interactions in the association and stabilization of the DNA-Cu(II) complex adduct, which was in line with the docking and QM/MM data. In vitro cytotoxic potential of the complex against the human breast adenocarcinoma (MCF-7) cells was examined using MTT assay, which indicated that cancerous cells showed inhibition in presence of the complex.

Binding interaction of a heteroleptic silver(I) complex with DNA: A joint experimental and computational study.

A new heteroleptic Ag(I) complex formulated as [Ag(daf)(phen)]NO3, where daf and phen stand for 4,5-diazafluoren-9-one and 1,10-phenanthroline, respectively, has been prepared and structurally characterized by elemental analysis, spectroscopic methods (IR, 1HNMR, and UV-Vis) and cyclic voltammetry. The geometry optimization around Ag(I) at the level of DFT has demonstrated that the Ag(I) center has been nested in a tetrahedral N4 coordination geometry which found to be in close agreement with the experimentally proposed structure. The bond lengths, angles, and the HOMO/LUMO energies have been calculated to substantiate the geometry of the complex. The DNA binding property of the Ag(I) complex has been explored in detail both theoretically (DFT and molecular docking) and experimentally (UV-Vis absorption spectroscopy, circular dichroism spectroscopy, luminescence quenching, competitive binding with ethidium bromide, cyclic voltammetry, and gel electrophoresis), indicating the good affinity of the Ag(I) complex for the intercalation (Kb (binding constant) = 3.45 × 105 M-1). Providing a fuller picture of Ag(I) complex-DNA interaction, the energy-minimized structure of the complex has been docked to the DNA with a d(AGACGTCT)2 sequence and the results are in close agreement with experimental achievements and make a deeper insight into the relationship between the structure and biological activity of the complex.