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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Distributed under a Creative Commons Attribution -NonCommercial -NoDerivatives| 4.0 International License Tris-chelated complexes of nickel(II) with bipyridine derivatives: DNA binding and cleavage, BSA binding, molecular docking, and cytotoxicity

The focus of this work is introduction of GelRed (GR) as a stable, sensitive and environmentally safe fluorescent DNA dye instead of the highly toxic ethidium bromide (EB). Competitive DNA-binding studies between metal complexes, [Cu(phen-dion)(phen)Cl]Cl (1), [Cu(phen-dione)(bpy)Cl]Cl (2), [Cu(dppt)2(H2O)]PF6 (3), [Ni(dppt)2Cl2] (4), [Zn(dppt)2Cl2] (5), and K3[Fe(CN)6] (6) (where phen-dione is 1,10-phenanthroline-5,6-dione, phen is 1,10- phenanthroline, bpy is 2,2'-bipyridine, and dppt is 5,6-diphenyl-3-(2-pyridyl)-1,2,4-triazine), and GelRed have been investigated under physiological conditions by fluorescence spectroscopy. This simple method can reveal the binding affinity and mode of metal complexes with DNA. The method is based on the decrease of fluorescence derived from the displacement of GelRed from DNA by metal complexes. The % fluorescence decrease is directly related to the extent of DNA binding. Results indicate the DNA binding affinities of complexes follow the order 3 > 4 > 1 > 2 > 5 > 6. The significant quenching of the emission band of the GR-DNA with the addition of complexes 1, 3, and 4 suggests that complexes compete for DNA-binding sites with GR and displace GR from the GR-DNA, which is usually characteristic of the intercalative interaction of compounds with DNA. A small quenching of the emission band of the GR-DNA with the addition of the complex 2 was observed that show the complex weaker competes for DNA-binding sites with GR than complexes 1, 3, and 4. Results show complexes 5 and 6 cannot compete for DNA-binding sites with GR and their interaction with DNA is external binding (groove or electrostatic bindig).

Despite the extensive and rapid discovery of modern drugs for treatment of cancer, microbial infections, and viral illnesses; these diseases are still among major global health concerns. To take inspiration from natural nucleases and also the therapeutic potential of metallopeptide antibiotics such as the bleomycin family, artificial metallonucleases with the ability of promoting DNA/RNA cleavage and eventually affecting cellular biological processes can be introduced as a new class of therapeutic candidates. Metal complexes can be considered as one of the main categories of artificial metalloscissors, which can prompt nucleic acid strand scission. Accordingly, biologists, inorganic chemists, and medicinal inorganic chemists worldwide have been designing, synthesizing and evaluating the biological properties of metal complexes as artificial metalloscissors. In this review, we try to highlight the recent studies conducted on the nuclease-like metalloscissors and their potential therapeutic applications. Under the light of the concurrent Covid-19 pandemic, the human need for new therapeutics was highlighted much more than ever before. The nuclease-like metalloscissors with the potential of RNA cleavage of invading viral pathogens hence deserve prime attention.