Understanding the Binding and Structures in Model Complexes of Polypeptides and Cofactors.

Area of Science:

• Bioinorganic Chemistry
• Coordination Chemistry
• Chemical Physics

Background:

• Metalloproteins feature diverse structures and chemistries due to competitive binding between metal cofactors and polypeptide functional groups.
• Understanding these interactions is crucial for deciphering metalloprotein function and designing novel metal-based therapeutics.

Purpose of the Study:

• To investigate competitive binding in model [metal-(auxiliary ligand)-(peptide)] complexes.
• To elucidate the structural diversity and fragmentation mechanisms of these complexes using various analytical techniques.

Main Methods:

• Synthesis and characterization of metal complexes with auxiliary ligands (terpy, salen) and peptides (arginine-tyrosine (RY), arginine-tyrosine-glycine (RYG)).
• Tandem mass spectrometry (MS/MS) with and without peptide derivatization/substitution.
• Density functional theory (DFT) calculations.
• Infrared multiple-photon dissociation (IRMPD) spectroscopy.

Main Results:

• Complex dissociation yielded abundant peptide radical cations ([RY]•+ and [RYG]•+) with structures dependent on the metal complex composition.
• DFT calculations provided insights into binding modes and fragmentation mechanisms.
• IRMPD spectroscopy confirmed carboxylate binding for [Cu-(terpy)-RYG]2+, with DFT showing facile conversion to a phenolate-bound structure.

Conclusions:

• The complex chemistry, despite its apparent complexity, can be rationalized using fundamental acid-base chemistry and hard/soft Lewis acid/base (HSLAB) principles.
• Experimental and computational results align, supporting the predictive power of these chemical concepts.
• Energy minimization pathways involving multiple functional groups drive the rich structural diversity observed in these metal-peptide complexes.