ACID–BASE PROPERTIES - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 67

biological reactions [115]. Stability of complexes, formed from these interac-
tions, may influence reactions of metal centers and proteins with reactive
species. Potentiometric titration curves suggested 1 : 1 and 1 : 2 binary com-
plexes. Tertiary complexes were in a molar ratio of 1 : 1 : 1 (MAB), in which
ATP was the primary ligand and Asp or Glu was the secondary ligand (e.g.,
M(II)ATP(Asp)). The stability of ternary complexes was of the order of
Cu(II) > Ni(II) > Zn(II). Furthermore, ternary complexes containing Asp
were more stable than those with Glu. The formation of binary and ternary
complexes of Cu(II) and Ni(II) occurred with bicine ( N , N ′-bis(2-hydroxyethyl)
glycine; zwitterionic buffer) and selected amino acids containing mono- and
dicarboxylic acids (Gly, α-Ala, β-Ala, Val, Leu, Asp, Glu, Asn, and Phe) in
aqueous solution because of function of ternary coordination in biological
processes. Several ligands tend to compete for metals in biological fluids. The
studied system may therefore mimic biological reactions (enzyme-metal ion-
buffer interactions) [116].
Metal complexation with GSH (L) has been evaluated due to importance
of metal-GSH interactions in living systems [16, 117, 118]. GSH is a major
metal-binding ligand in cells, and the complexes may serve as carriers to metal-
dependent proteins [17]. For example, GSH reduces first Cu(II) ion to Cu(I)
and then forms a Cu(I)-[GSH] 2 complex, which has been characterized by 1 H-
NMR and electron paramagnetic resonance (EPR) techniques [119]. This
complex may react with O 2 to ultimately form superoxide radicals [119]. The
generation of hydroxyl radicals from the reduction and release of iron from
ferritin by the Cu(I)-[GSH] 2 complex has also been demonstrated [18]. The
interaction of copper with GSSG (L), a primary oxidized product of GSH, has
also been studied due to the importance of Cu(I)/Cu(II)-glutathione system
in operation of enzymes (e.g., glutathione reductase and glutathione peroxi-
dase) and in active transport of amino acids (γ-glutamyl cycle) [117, 120, 121].
In the structure elucidation of complexes, CuLH 2 and CuLH − , the complexes
contain two isomers and one of the copper atoms is bound solely to the car-
bonyl or carboxylate groups in the Cu 2 L and Cu L

3− complexes [121]. Structural
information of the complexes may provide insight into their participation in
the redox cycle of oxygen [18].
The Ni(II) complexes, NiHL, Ni L
2

3 2

2− , NiHL 3− , NiL 4− , and NiH L

5 have been
obtained in the pH range of 6-12 when fourfold GSH in excess was added to
Ni(II) [117]. The structures of the complexes were characterized spectroscopi-
cally. These complexes of Ni(II) were effective in causing damage to DNA in
the presence of H 2 O 2 [31]. A study on the complexation of Zn(II) and Ni(II)
with an important intracellular NO carrier, nitrosoglutathione (GSNO, L′)
[122], showed the formation of the ML′ and ML 2 complexes [123]. Zn(II)
increased the stability of GSNO in the buffered solution at pH 7.4. However,
Ni(II) ion destabilized GSNO, which depended on the concentration of NiL.
This ability of Ni(II) to damage GSNO may ultimately result in loss of cellular
redox signaling [123]. In contrast, stable complexes of GSNO with Zn(II) may
provide some protection to GSNO from the reactive species.

−

− 1 2