Correlations between complexation modes and redox activities of Ni(II)-GSH complexes

Area of Science:

• Biochemistry
• Coordination Chemistry
• Toxicology

Background:

• Glutathione (GSH) is a crucial cellular antioxidant and chelator.
• Nickel(II) (Ni(II)) is a transition metal with known toxicity.
• Understanding Ni(II)-GSH interactions is vital for assessing nickel toxicity mechanisms.

Purpose of the Study:

• To characterize the Ni(II) complexes formed with GSH under varying conditions.
• To investigate the impact of Ni(II) complexation on GSH stability and reactivity.
• To evaluate the role of Ni(II)-GSH interactions in DNA damage and cellular Ni(II) distribution.

Main Methods:

• Potentiometric titrations to determine complex formation and stability constants.
• UV-vis and CD spectroscopies to analyze complex structures and electronic properties.
• Magnetic susceptibility measurements to probe spin states and coordination geometries.
• Numerical simulations for intracellular Ni(II) distribution modeling.

Main Results:

• Multiple Ni(II)-GSH complexes were identified, with varying coordination modes (octahedral and square-planar).
• Ni(II) complexation accelerates GSH air oxidation in alkaline solutions.
• Ni(II) ions facilitate H(2)O(2)-induced DNA damage, particularly via octahedral complexes.
• Simulations suggest histidine and ATP are preferred intracellular Ni(II) ligands over GSH.

Conclusions:

• Ni(II) forms diverse complexes with GSH, affecting its redox state and DNA interaction.
• The direct impact of GSH on Ni(II) toxicity appears limited in vivo.
• Cellular Ni(II) levels are likely regulated by other ligands like histidine and ATP.