Copper-peptide complex structure and reactivity when found in conserved His-X(aa)-His sequences

Area of Science:

• Bioinorganic Chemistry
• Coordination Chemistry
• Protein Chemistry

Background:

• Oxygen-activating copper proteins often feature His-X(aa)-His chelating motifs.
• Imidazole rings in these proteins can exist in tautomeric forms (δN vs. εN), influencing copper ion interactions.

Purpose of the Study:

• To investigate how δN vs. εN tautomeric preferences of histidine residues affect copper ion coordination, redox properties, and reactivity.
• To synthesize and characterize copper(I) complexes with δ-HGH and ε-HGH tripeptides.

Main Methods:

• X-ray absorption spectroscopy
• Density functional theory calculations
• Solution conductivity measurements
• Synthesis and characterization of copper(I) complexes

Main Results:

• δ-HGH formed a Cu(I) dimer complex [{Cu(I)(δ-HGH)}2](2+), while ε-HGH formed a monomeric complex [Cu(I)(ε-HGH)](+).
• The monomeric complex [Cu(I)(ε-HGH)](+) showed reactivity, forming a CO adduct similar to copper monooxygenase PHM.
• This complex also reacted with O2 and H2O2 to form novel O2-adducts or Cu(II)-OOH complexes.

Conclusions:

• Histidine tautomeric preferences critically influence copper coordination geometry and reactivity in bioinorganic systems.
• The ε-HGH-Cu(I) complex serves as a functional model for copper monooxygenases, highlighting the importance of specific coordination environments.
• This study provides insights into the mechanisms of copper-dependent oxygen activation and oxidation reactions.