A DFT study on the metal ion selectivity of deferiprone complexes

Area of Science:

• Computational Chemistry
• Materials Science
• Biomedical Engineering

Background:

• Deferiprone (DFP) is a clinically used chelating agent for metal ion overload.
• Understanding metal-DFP interactions is crucial for optimizing chelation therapy.
• Computational methods offer insights into binding affinities and interaction types.

Purpose of the Study:

• To systematically investigate the interactions between various metal ions and deferiprone using DFT.
• To determine the thermodynamic parameters and binding energies of metal-DFP complexes.
• To analyze the nature of metal-oxygen bonds in these complexes.

Main Methods:

• Density Functional Theory (DFT) calculations at the M05-2X/6-31G(d) level.
• Thermodynamic parameter determination in aqueous solution.
• Natural Bond Orbital (NBO) and Quantum Theory of Atoms in Molecules (QTAIM) analyses.

Main Results:

• Binding energy trend: Al³⁺ > Fe³⁺ > Cu²⁺ > Ni²⁺ > Co²⁺ > Zn²⁺, with Al³⁺ exhibiting the highest interaction energy.
• NBO analysis indicated stronger donor-acceptor interactions in the Al-DFP complex.
• QTAIM analysis revealed non-covalent M-O bonds in Al-DFP, contrasting with electrostatic/partially covalent bonds in other complexes.

Conclusions:

• Aluminum (Al³⁺) forms the most stable complex with deferiprone, suggesting enhanced therapeutic potential.
• The bonding in Al-DFP complexes is predominantly non-covalent, differing from other metal complexes.
• DFT calculations provide valuable predictive insights into metal-DFP chelation efficacy.