Unique ligand-based oxidative DNA cleavage by zinc(II) complexes of hpyramol and hpyrimol.
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 Zn(II). All the five complexes cleave the phiX174 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.
Maheswari
Palanisamy Uma
PU
Gorlaeus Laboratories, Leiden University, 2300 RA Leiden, The Netherlands.
Barends
Sharief
S
Ozalp-Yaman
Seniz
S
de Hoog
Paul
P
Casellas
Hélène
H
Teat
Simon J
SJ
Massera
Chiara
C
Lutz
Martin
M
Spek
Anthony L
AL
van Wezel
Gilles P
GP
Gamez
Patrick
P
Reedijk
Jan
J
D000085:Acetates / Q000737:chemistry; D000627:Aminophenols / Q000737:chemistry*; D010584:Bacteriophage phi X 174 / Q000737:chemistry / Q000378:metabolism; D002413:Cations, Divalent; D002712:Chlorides / Q000737:chemistry; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D053837:DNA Cleavage; D004563:Electrochemistry; D016166:Free Radical Scavengers / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D008024:Ligands; D008956:Models, Chemical; D009942:Organometallic Compounds / Q000138:chemical synthesis*; D016877:Oxidants / Q000737:chemistry*; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
D000085:Acetates; D000627:Aminophenols; D002413:Cations, Divalent; D002712:Chlorides; D016166:Free Radical Scavengers; D008024:Ligands; D009942:Organometallic Compounds; D016877:Oxidants; D010636:Phenols; C042329:phenoxy radical; D006859:Hydrogen; D004247:DNA; D015032:Zinc