Coordination mode and oxidation susceptibility of nickel(II) complexes with 2'-deoxyguanosine 5'-monophosphate and l-histidine

The formation of binary and ternary complexes of Ni(II) with two biologically relevant molecules, 2'-deoxyguanosine 5'-monophosphate (dGMP) and l-histidine (histidine or His) was characterized by potentiometry and UV-visible spectroscopy. For dGMP, the mononuclear complexes with stoichiometries NiH(2)L(+), NiHL and NiL(-) were found. In the mixed system the ternary complexes NiH(2)LA, NiHLA(-) and NiLA(2-) were detected. In binary systems, the Ni(II) ion coordinates to dGMP through the N-7 atom of its purine ring and indirectly through a water molecule bonded to the phosphate group, while in ternary complexes Ni(II) is bonded to all three histidine donors and directly to the phosphate group of dGMP. Both binary and ternary complexes are susceptible to oxidation by H(2)O(2), with the increased formation of 8-oxo-dGMP in the ternary system. The toxicological relevance of these findings stems from possible disturbance by the major biological Ni(II)-His complex of the nucleotide pools homeostasis through the formation of ternary species and oxidation promotion, as well as from 8-oxo-dGMP capacity to inhibit enzymatic elimination of promutagenic oxidized nucleotides from such pools.