Complexation of Al(III) with reduced glutathione in acidic aqueous solutions

The complexation of reduced glutathione (GSH) in its free and Al(III)-bound species in acidic aqueous solutions was characterized by means of multi-analytical techniques: pH-potentiometry, multinuclear (1H, 13C and 27Al) and two-dimensional nuclear Overhauser enhancement NMR spectroscopy (1H, 1H-NOESY), electrospray mass spectroscopy (ESI-MS), and ab initio electronic structure calculations. The following results were found. In the 25 °C 0.1 M KCl and 37 °C 0.15 M NaCl ionic medium systems, Al3+ coordinates with the important biomolecule GSH through carboxylate groups to form various mononuclear 1:1 (AlHL, AlH2L and AlH−1L), 1:2 (AlL2) complexes, and dinuclear (Al2H5L2) species, where H4L+ denotes totally protonated GSH. Besides the monodentate complexes through carboxylate groups, the amino groups and the peptide bond imino and carbonyl groups may also be involved in binding with Al3+ in the bidentate and tridentate complexes. The present data reinforce that the glycine carboxylate group of GSH has a higher microscopic complex formation constant than γ-glutamyl carboxylate. Compared with simple amino acids, the tripeptide GSH displays a greater affinity for the Al3+ ion and thus may interfere with aluminum’s biological role more significantly.