Glutathione complex formation with mercury(II) in aqueous solution at physiological pH

Area of Science:

• Coordination Chemistry
• Biochemistry
• Spectroscopy

Background:

• Mercury(II) is a toxic heavy metal with significant biological implications.
• Glutathione (GSH) is a crucial endogenous antioxidant involved in metal detoxification.
• Understanding mercury-glutathione complexation is vital for toxicology and environmental science.

Purpose of the Study:

• To elucidate the structural characteristics and coordination modes of mercury(II)-glutathione complexes in aqueous solutions.
• To determine the stoichiometry and stability of mercury(II)-glutathione complexes under varying conditions.
• To provide accurate speciation data for mercury(II) in the presence of glutathione at physiological conditions.

Main Methods:

• Hg L(III)-edge extended X-ray absorption fine structure (EXAFS) spectroscopy to determine bond distances and coordination numbers.
• (199)Hg Nuclear Magnetic Resonance (NMR) spectroscopy for chemical shift analysis and speciation.
• Electrospray ionization mass spectrometry (ESI-MS) to identify complex species.

Main Results:

• The dominant complex at low glutathione excess is [Hg(AH)(2)](2-) with linear S-Hg-S coordination (Hg-S: 2.325 ± 0.01 Å).
• At high glutathione excess, the [Hg(AH)(3)](4-) complex with trigonal HgS(3) coordination (Hg-S: 2.42 ± 0.02 Å) becomes prevalent.
• Speciation analysis at physiological conditions (pH 7.4) indicates a high abundance (95%) of the HgS(2) species [Hg(AH)(2)](2-).

Conclusions:

• The study provides detailed structural insights into mercury(II)-glutathione complexation, favoring discrete monomeric species.
• Results contradict previous proposals of dimeric mercury(II)-GSH complexes.
• Accurate speciation data are crucial for understanding mercury's biological fate and toxicity.