Determination of the stability constants and oxidation susceptibility of nickel(II) complexes with 2'-deoxyguanosine 5'-triphosphate and L-histidine.
The formation of binary Ni(II) complexes with 2'-deoxyguanosine 5'-triphosphate (dGTP, L) as well as ternary complexes thereof with L-histidine (His, A) was studied with the use of potentiometry and electronic absorption spectroscopy. In the binary and ternary systems, the complexes with stoichiometries NiH2L-, NiHL2-, NiL3- and NiH2LA2-, NiHLA3-, NiLA4- respectively, were detected. The ternary complexes are very stable at pH 7.4 and thus may constitute biologically relevant Ni(II) carriers in the cell. In the presence of hydrogen peroxide, the binary and ternary systems both generate hydroxyl radical-like species and undergo dGTP degradation with the formation of the 8-oxo-dGTP intermediate. The latter, along with dGTP complexation and degradation, may lead to mutagenesis and carcinogenesis due to base-mispairing properties of 8-oxoguanine and the disturbance in the physiological balance among the four canonical triphosphodeoxynucleotide substrates for DNA synthesis.
Kaczmarek
Piotr
P
Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland.
Jezowska-Bojczuk
Małgorzata
M
Bal
Wojciech
W
Kasprzak
Kazimierz S
KS
D020029:Base Pairing / Q000235:genetics; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity; D002413:Cations, Divalent; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D003848:Deoxyguanine Nucleotides / Q000737:chemistry* / Q000378:metabolism; D004355:Drug Stability; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D006639:Histidine / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D016296:Mutagenesis; D009532:Nickel / Q000737:chemistry*; D009711:Nucleotides / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D011199:Potentiometry; D013053:Spectrophotometry; D013997:Time Factors
D002273:Carcinogens; D002413:Cations, Divalent; D003848:Deoxyguanine Nucleotides; D009711:Nucleotides; D006639:Histidine; C024829:8-hydroxyguanine; D006147:Guanine; D009532:Nickel; C029603:deoxyguanosine triphosphate; D004247:DNA