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

Sciortino, Giuseppe; Lubinu, Giuseppe; Maréchal, Jean‐Didier; Garribba, Eugenio

doi:10.3390/magnetochemistry4040055

Cited by 37 publications

(50 citation statements)

References 105 publications

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“…[69] The experimental g iso values are underestimated for both Cu (l-Asn) 2 and Cu(l-His)(l-Asn), by 0.034 and 0.028 on average by our B3LYP calculations (Table 6), respectively. A similar underestimation of g values was also obtained for some other copper (II) complexes by Sciortino et al [70] In accord with the known fact that the presence of ligands in the axial positions causes an increase of g z and a decrease of A z , [70] our DFT/B3LYP results gave a ca. 40 MHz lower j A Cu iso j , a bit larger g iso value, and slightly lower A N iso values for the conformers with intramolecular axial Cu-donor bond (CN = 5) than for the conformers with CN = 4, independently on the cisor trans-configuration for all of the studied complexes (Tables 6 and S96).…”

Section: Dft/b3lyp Prediction Of G-factor and Hfcc A Valuessupporting

confidence: 89%

“…The experimental g iso values are underestimated for both Cu( l ‐Asn) 2 and Cu( l ‐His)( l ‐Asn), by 0.034 and 0.028 on average by our B3LYP calculations (Table ), respectively. A similar underestimation of g values was also obtained for some other copper(II) complexes by Sciortino et al …”

Section: Resultsmentioning

confidence: 99%

“…In accord with the known fact that the presence of ligands in the axial positions causes an increase of g z and a decrease of A z , our DFT/B3LYP results gave a ca. 40 MHz lower | A Cu iso |, a bit larger g iso value, and slightly lower A N iso values for the conformers with intramolecular axial Cu‐donor bond (CN=5) than for the conformers with CN=4, independently on the cis ‐ or trans ‐configuration for all of the studied complexes (Tables and S96).…”

Section: Resultsmentioning

confidence: 99%

“…The [Cu(H 2 O) 6 ] 2+ structure was taken without further optimization from the literature . Since B3LYP and PBE0 were reported to give good magnetic properties for several copper(II) complexes with the lowest mean absolute percent deviation of less than 3.5 % for g z (PBE0), and 9.5 % for A z (B3LYP), we tested these two DFT functionals with different basis sets for copper [including def2‐TZVP, Wachters’ basis for Cu with and without f‐functions, and Pople's 6‐311G(d,p) basis set]. For the [Cu(H 2 O) 6 ] 2+ complex, PBE0 performed better, but for Cu(Gly) 2 , the B3LYP functional with the Wachters′ Cu basis set showed better agreement with experimental EPR parameters .…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Conformational Analyses of Physiological Binary and Ternary Copper(II) Complexes with l‐Asparagine and l‐Histidine; Study of Tridentate Binding of Copper(II) in Aqueous Solution

et al. 2019

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This study explores the structural properties and energy landscapes of the physiologically important bis( l ‐asparaginato)copper(II) [Cu( l ‐Asn) 2 ] and ( l ‐histidinato)( l ‐asparaginato)copper(II) [Cu( l ‐His)( l ‐Asn)]. The conformational analyses in the gas phase and implicitly modeled water medium, and magnetic parameters of electron paramagnetic resonance spectra were attained using density functional theory calculations. The apical Cu II coordination and hydrogen bonding were analyzed. Predicted lower‐energy structures enabled the confirmation and, for apical bonding, also the refinement of structural proposals from literature. Available experimental results were indecisive regarding the amido‐group binding in the Cu II equatorial plane in solutions, but the examination of the relative stability of Cu( l ‐Asn) 2 conformers in 30 binding modes confirms the glycine‐like mode as the most stable one. Previously reported experimental results for Cu( l ‐His)( l ‐Asn) were interpreted for l ‐His to have a tridentate histamine‐like mode. However, the aqueous conformers with l ‐His in the glycinato mode are also predicted to have low energies, which does not contradict the tridentate l ‐His binding. The predicted magnetic parameters of conformers with an apical oxygen atom (intramolecular or from a water molecule) can reproduce the experimental data. An extent of conformational flexibility and abundance of l ‐His‐containing ternary copper(II) amino acid complexes under physiological conditions may be related.

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Section: Dft/b3lyp Prediction Of G-factor and Hfcc A Valuessupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Conformational Analyses of Physiological Binary and Ternary Copper(II) Complexes with l‐Asparagine and l‐Histidine; Study of Tridentate Binding of Copper(II) in Aqueous Solution

et al. 2019

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“…Thus, if one is restricted by choice or practical necessity to use DFT instead of rigorous wave function based methods for predicting EPR parameters in transition metal systems, the choice of functional is typically dictated by experience accumulated in previously published studies of related systems or by performing an initial benchmarking study. Among the EPR parameters that react most sensitively to the choice of computational methodology are hyperfine coupling constants [7][8][9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

First-Principles Calculation of Transition Metal Hyperfine Coupling Constants with the Strongly Constrained and Appropriately Normed (SCAN) Density Functional and its Hybrid Variants

Pantazis

2019

Magnetochemistry

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Density functional theory (DFT) is used extensively for the first-principles calculation of hyperfine coupling constants in both main-group and transition metal systems. As with many other properties, the performance of DFT for hyperfine coupling constants is of variable quality, particularly for transition metal complexes, because it strongly depends on the nature of the chemical system and the type of approximation to the exchange-correlation functional. Recently, a meta-generalized-gradient approximation (mGGA) functional was proposed that obeys all known exact constraints for such a method, known as the Strongly Constrained and Appropriately Normed (SCAN) functional. In view of its theoretically superior formulation a benchmark set of complexes is used to assess the performance of SCAN for the challenging case of transition metal hyperfine coupling constants. In addition, two global hybrid versions of the functional, SCANh and SCAN0, are described and tested. The values computed with the new functionals are compared with experiment and with those of other DFT approximations. Although the original SCAN and the SCAN-based hybrids may offer improved hyperfine coupling constants for specific systems, no uniform improvement is observed. On the contrary, there are specific cases where the new functionals fail badly due to a flawed description of the underlying electronic structure. Therefore, despite these methodological advances, systematically accurate and system-independent prediction of transition metal hyperfine coupling constants with DFT remains an unmet challenge.

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Incorporation of β‐Alanine in Cu(II) ATCUN Peptide Complexes Increases ROS Levels, DNA Cleavage and Antiproliferative Activity**

Heinrich

Bossad-Ahmad

Riisom

et al. 2021

Chemistry A European J

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Redox‐active Cu(II) complexes are able to form reactive oxygen species (ROS) in the presence of oxygen and reducing agents. Recently, Faller et al. reported that ROS generation by Cu(II) ATCUN complexes is not as high as assumed for decades. High complex stability results in silencing of the Cu(II)/Cu(I) redox cycle and therefore leads to low ROS generation. In this work, we demonstrate that an exchange of the α‐amino acid Gly with the β‐amino acid β‐Ala at position 2 (Gly2→β‐Ala2) of the ATCUN motif reinstates ROS production (•OH and H2O2). Potentiometry, cyclic voltammetry, EPR spectroscopy and DFT simulations were utilized to explain the increased ROS generation of these β‐Ala2‐containing ATCUN complexes. We also observed enhanced oxidative cleavage activity towards plasmid DNA for β‐Ala2 compared to the Gly2 complexes. Modifications with positively charged Lys residues increased the DNA affinity through electrostatic interactions as determined by UV/VIS, fluorescence, and CD spectroscopy, and consequently led to a further increase in nuclease activity. A similar trend was observed regarding the cytotoxic activity of the complexes against several human cancer cell lines where β‐Ala2 peptide complexes had lower IC50 values compared to Gly2. The higher cytotoxicity could be attributed to an increased cellular uptake as determined by ICP‐MS measurements.

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

Cited by 37 publications

References 105 publications

Conformational Analyses of Physiological Binary and Ternary Copper(II) Complexes with l‐Asparagine and l‐Histidine; Study of Tridentate Binding of Copper(II) in Aqueous Solution

Conformational Analyses of Physiological Binary and Ternary Copper(II) Complexes with l‐Asparagine and l‐Histidine; Study of Tridentate Binding of Copper(II) in Aqueous Solution

First-Principles Calculation of Transition Metal Hyperfine Coupling Constants with the Strongly Constrained and Appropriately Normed (SCAN) Density Functional and its Hybrid Variants

Incorporation of β‐Alanine in Cu(II) ATCUN Peptide Complexes Increases ROS Levels, DNA Cleavage and Antiproliferative Activity**

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