One-pot synthesis of a new 2-substituted 1,2,3-triazole 1-oxide derivative from dipyridyl ketone and isonitrosoacetophenone hydrazone: Nickel(II) complex, DNA binding and cleavage properties

• Published in: Bioorganic chemistry 2017-04, Vol.71, p.325-334
• Main Authors: Gup, Ramazan, Erer, Oktay, Dilek, Nefise
• Format: Article
• Language: English
• Subjects: 1,2,3-Triazole 1-oxide; Animals; Cattle; Combinatorial Chemistry Techniques - methods; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Crystallography, X-Ray; DNA - metabolism; DNA binding; DNA cleavage; DNA Cleavage - drug effects; Hydrazones - chemistry; Models, Molecular; Nickel - chemistry; Nickel - pharmacology; Nickel(II) complex; Oxime; Phenylglyoxal - analogs & derivatives; Phenylglyoxal - chemistry; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - pharmacology
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2017.03.003

[Display omitted] •A new 1,2,3-triazole 1-oxide was synthesized through a simple one-pot method.•X-ray crystal structure of the 1,2,3-triazole 1-oxide compound was reported.•It was as a chelator for biorelevant NiII ion.•DNA binding and cleavage activities the 1,2,3-triazole 1-oxide and its Ni (II) complex were studied. An efficient and simple one-pot synthesis of a new 1,2,3-triazole-1-oxide via reaction between isonitrosoacetophenone hydrazone and dipyridyl ketone in the EtOH/AcOH at room temperature has been developed smoothly in high yield. The reaction proceeds via metal salt free, in-situ formation of asymmetric azine followed by cyclization to provide 1,2,3-triazole 1-oxide compound. It has been structurally characterized. The 1:1 ratio reaction of the 1,2,3-triazole 1-oxide ligand with nickel(II) chloride gives the mononuclear complex [Ni(L)(DMF)Cl2], hexa-coordinated within an octahedral geometry. Characterization of the 1,2,3-triazole compound and its Ni(II) complex with FTIR, 1H and 13C NMR, UV–vis and elemental analysis also confirms the proposed structures of the compounds. The interactions of the compounds with Calf thymus DNA (CT-DNA) have been investigated by UV–visible spectra and viscosity measurements. The results suggested that both ligand and Ni(II) complex bind to DNA in electrostatic interaction and/or groove binding, also with a slight partial intercalation in the case of ligand. DNA cleavage experiments have been also investigated by agarose gel electrophoresis in the presence and absence of an oxidative agent (H2O2). Both 1,2,3-triazole 1-oxide ligand and its nickel(II) complex show nuclease activity in the presence of hydrogen peroxide. DNA binding and cleavage affinities of the 1,2,3-triazole 1-oxide ligand is stronger than that of the Ni(II) complex.