Potentiometric and DFT studies of Cu(II) complexes with glycylglycine and methionine of interest for the brain chemistry

• In the Cu:Met system the sulfur atom moved around the metal coordination sphere.
• DFT results indicated bidentate behavior of GlyGly at physiological pH value.
• In the Cu(H-1GlyGly)Met species the sulfur atom does not belong to the metal coordination sphere.

A large number of copper (II) complexes have been used as mimetic models for metalloproteins and metalloenzymes. Due to the lack of structural information about copper (II) complexes in aqueous solution, the coordination environment of this metal is not well established. In this work, pKa values of the complexes in the Cu:GlyGly, Cu:Met and Cu:GlyGly:Met systems were calculated by potentiometric titration at 25 °C and ionic strength of 0.1 mol L−1. The coordination modes of the ligands were explored for the main hydrolytic species throught RI-PBE/def2-SVP/COSMO level. In the Cu:GlyGly system, DFT results indicated that the NamineNpept coordination of dipeptide is 2.1 kcal mol−1 more stable than the tridentate NamineNpeptOcarboxy coordination moiety. The deprotonation of the peptide nitrogen is 13.7 kcal mol−1 more favorable than the hydrolysis of the water molecule coordinated to the metal. In the Cu:GlyGly:Met system, the sulfur atom does not belong to the copper (II) coordination sphere. Once the copper ion is incorporated into peptides, another ligand as methionine could bind to this system and carry an antioxidant site to different brain regions.

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