Unique Ligand‐Based Oxidative DNA Cleavage by Zinc(II) Complexes of Hpyramol and Hpyrimol

Abstract

The zinc(II) complexes reported here have been synthesised from the ligand 4‐methyl‐2‐N‐(2‐pyridylmethyl)aminophenol (Hpyramol) with chloride or acetate counterions. All the five complexes have been structurally characterised, and the crystal structures reveal that the ligand Hpyramol gradually undergoes an oxidative dehydrogenation to form the ligand 4‐methyl‐2‐N‐(2‐pyridylmethylene)aminophenol (Hpyrimol), upon coordination to ZnII. All the five complexes cleave the ϕX174 phage DNA oxidatively and the complexes with fully dehydrogenated pyrimol ligands were found to be more efficient than the complexes with non‐dehydrogenated Hpyramol ligands. The DNA cleavage is suggested to be ligand‐based, whereas the pure ligands alone do not cleave DNA. The DNA cleavage is strongly suggested to be oxidative, possibly due to the involvement of a non‐diffusible phenoxyl radical mechanism. The enzymatic religation experiments and DNA cleavage in the presence of different radical scavengers further support the oxidative DNA cleavage by the zinc(II) complexes.

Phosphodiester hydrolysis and specific DNA binding and cleavage promoted by guanidinium-functionalized zinc complexes

“…The results indicate that 1 and 2 are able to cleave plasmid DNA more efficiently than 3 which suggest that a possible synergistic effect may exist between the Zn(II) ion and the functional organic ligand, which, in turn, contributes to the complex's relatively high nucleolytic efficiency [60][61][62].…”

“…It may contribute to the structure of the ligands which could have high binding ability to phosphodiester backbone of nucleic acid, but can not generate radical to accelerate DNA cleavage like those ligands with phenolate groups [57,[59][60][61][62]. Based on the previous research [57,[66][67][68][69], the Zn(II)/H 2 O 2 system can more efficiently cleavage DNA than these Zn(II) complexes without any reductor, due to the peroxide ion coordinated to the zinc(II) ion enhanced its nucleophilicity.…”

Synthesis and characterization of some water soluble Zn(ii) complexes with (E)-N-(pyridin-2-ylmethylene)arylamines that regulate tumour cell death by interacting with DNA

“…[21][22][23] In addition, Zn(II) complexes are often utilized in many fields such as radioprotection, 24 antidiabetic insulinmimemetism, 25,26 antibacterial or antimicrobial agents, [27][28][29] tumour photosensitizers 30 and binder complexes at DNA sites [31][32][33][34] . The development of metal chelators for the attenuation of metalinvolved neurodegeneration in Alzheimer's disease (AD) and other neurodegenerative diseases are matters of current interest.…”

Spectroelectrochemical studies of nuclease-active zinc(II) coordination compounds from the ligands Hpyramol and Hpyrimol

“…The ligands Hpyramol and Hpyrimol and their Zn(II) coordination compounds, Zn 2 (pyramol) 2 (OAc) 2 , Zn 2 (pyramol) 2 Cl 2 , Zn 3 (pyrimol) 2 (OAc) 4 and Zn 2 (pyrimol) 2 Cl 2 , were prepared following our published methods [23,24].…”

“…Recently, some of us have reported about four zinc compounds obtained from the ligands Hpyramol and Hpyrimol, and which have been described crystallographically as well [23,24]. The DNAcleavage properties of these compounds have been shown to be unique, since these zinc coordination compounds interestingly can act as artificial nucleases, capable of performing the oxidative cleavage of DNA.…”