DFT Protocol for EPR Prediction of Paramagnetic Cu(II) Complexes and Application to Protein Binding Sites

• Published in: Magnetochemistry
• Main Authors: Giuseppe Sciortino, Giuseppe Lubinu, Jean-Didier Maréchal, Eugenio Garribba
• Format: Article in Journal/Newspaper
• Language: English
• Published: MDPI AG 2018
• Subjects: copper; EPR spectroscopy; DFT methods; human serum albumin; prion protein; Chemistry; QD1-999; Orca
• Online Access: https://doi.org/10.3390/magnetochemistry4040055; https://doaj.org/article/9c377f64774441e1aeabc95899156658

With the aim to provide a general protocol to interpret electron paramagnetic resonance (EPR) spectra of paramagnetic copper(II) coordination compounds, density functional theory (DFT) calculations of spin Hamiltonian parameters g and A for fourteen Cu(II) complexes with different charges, donor sets, and geometry were carried out using ORCA software. The performance of eleven functionals was tested, and on the basis of the mean absolute percent deviation (MAPD) and standard deviation (SD), the ranking of the functionals for A z is: B3LYP > B3PW91 ~ B3P86 > PBE0 > CAM-B3LYP > TPSSh > BH and HLYP > B2PLYP > MPW1PW91 > ω-B97x-D >> M06; and for g z is: PBE0 > BH and HLYP > B2PLYP > ω-B97x-D > B3PW91~B3LYP~B3P86 > CAM-B3LYP > TPSSh~MPW1PW91 >> M06. With B3LYP the MAPD with respect to <math display="inline"> <semantics> <mrow> <msubsup> <mi>A</mi> <mi>z</mi> <mrow> <mi>exp</mi> <mi>t</mi> <mi>l</mi> </mrow> </msubsup> </mrow> </semantics> </math> is 8.6% with a SD of 4.2%, while with PBE0 the MAPD with respect to <math display="inline"> <semantics> <mrow> <msubsup> <mi>g</mi> <mi>z</mi> <mrow> <mi>exp</mi> <mi>t</mi> <mi>l</mi> </mrow> </msubsup> </mrow> </semantics> </math> is 2.9% with a SD of 1.1%. The results of the validation confirm the fundamental role of the second order spin-orbit contribution to A z . The computational procedure was applied to predict the values of g z and A z of the adducts formed by Cu(II) with albumin and two fragments of prion protein, 106⁻126 and 180⁻193.