Comparative Study of Antioxidant and Pro-Oxidant Properties of Homoleptic and Heteroleptic Copper Complexes with Amino Acids, Dipeptides and 1,10-Phenanthroline: The Quest for Antitumor Compounds
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis
2.2. Crystal Structure of Cu–AlaLeu
2.3. Structural Characterization in Solution
2.4. Assessment of Oxidative Damage to 2-Deoxi-d-ribose (Using TBARS Method)
2.5. Determination of SOD-like Activity
2.6. Structural and Electronic Determinants of the Redox Behavior
2.6.1. Antioxidant Activity
2.6.2. Pro-Oxidant Activity
3. Materials and Methods
3.1. Reagents
3.2. Synthesis of Complexes
3.2.1. Homoleptic Copper Complexes with Amino Acids
3.2.2. Homoleptic Copper Complexes with Dipeptides
3.2.3. Heteroleptic Copper Complexes with Peptides and 1,10 Phenantroline
3.3. Characterization
3.4. Oxidative Damage to 2-Deoxi-d-ribose (TBARS Method)
3.5. Determination of SOD-like Activity
3.6. DFT Calculations
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Bond | Distance (Å) | Bond | Distance (Å) | Bond | Distance (Å) |
---|---|---|---|---|---|
Cu1–N11 | 2.014(9) | Cu2–N21 | 2.040(10) | Cu3–N31 | 2.011(10) |
Cu1–N12 | 1.903(10) | Cu2–N22 | 1.891(10) | Cu3–N32 | 1.897(9) |
Cu1–O1 | 1.956(8) | Cu2–O2 | 1.954(8) | Cu3–O3 | 1.923(8) |
Cu1–O12 | 1.996(7) | Cu2–O22 | 2.005(8) | Cu3–O32 | 2.008(8) |
Cu1–O1W | 2.499(9) | Cu2–O2W | 2.547(11) | Cu3–O3W | 2.407(9) |
Type | Complex | IC50 (μM) |
---|---|---|
Cu–AA | Cu–Val | 30.3 [44] |
Cu–Ala | 32.3 [44] | |
Cu–Ile | 33.1 [44] | |
Cu–Gly | 34.0 [44] | |
Cu–Ser | 37.2 [44] | |
Cu–dip | Cu–AlaPhe | 5.0 [36] |
Cu–AlaLeu | 22 [45] | |
Cu–PheAla | 45 | |
Cu–GlyVal | 56 | |
Cu–ValGly | 57 | |
Cu–AlaGly | 124 [45] | |
Cu–dip–phen | Cu–AlaGly–phen | 10 |
Cu–PheAla–phen | 2.5 | |
Cu–PheVal–phen | 3.7 | |
[Cu(H2O)6]2+ | 30 [46] | |
Cu–SOD * | 0.04 |
Complex | Global Descriptors | Condensed Descriptors (Cu Atom) | Cu Contribution (%) | ||
---|---|---|---|---|---|
Dipole Moment (D) | Hirshfeld Atomic Charge | Electrophilicity | Local Softness a | β LUMO | |
Cu–AlaPhe | 19.8 | 1.15 | 1.74 | 5.27 | 68.8 |
Cu–AlaGly–phen | 26.1 | 1.31 | 1.05 | 3.24 | 0.37 |
Cu–Ala | 0.46 | 0.98 | 1.37 | 3.79 | 1.87 |
Cu–PheAla | 19.1 | 1.17 | 1.80 | 5.39 | 0.54 |
Cu–AlaGly | 20.2 | 1.00 | 1.35 | 3.96 | 0.85 |
Complex | Global Descriptors | Condensed Descriptors (Cu Atom) | |
---|---|---|---|
Hardness η (eV) | Electrophilicity | Local Softness a | |
Cu–Ala | 3.65 | 1.37 | 3.79 |
Cu–AlaGly | 3.53 | 1.35 | 3.96 |
Cu–AlaGly–phen | 3.37 | 1.05 | 3.24 |
Cu–AlaPhe | 3.50 | 1.74 | 5.27 |
Cu–PheAla | 3.48 | 1.80 | 5.39 |
Empirical Formula | C28 H53 Cu3 F6 N6 O16 P |
---|---|
Formula weight | 1065.35 |
Temperature | 120(2) K |
Wavelength | 0.71073 Å |
Crystal system | Orthorhombic |
Space group | P212121 |
Unit cell dimensions | a = 10.420(1) Å |
b = 16.295(1) Å | |
c = 28.236(1) Å | |
Volume | 4794.3(6) Å3 |
Z | 4 |
Density (calculated) | 1.476 Mg/m3 |
Absorption coefficient | 1.439 mm−1 |
F(000) | 2188 |
Crystal size | 0.22 × 0.21 × 0.18 mm3 |
Theta range for data collection | 2.32 to 25.00°. |
Index ranges | −12 ≤ h ≤ 12, −19 ≤ k ≤ 19, −33 ≤ l ≤ 33 |
Reflections collected | 8081 |
Independent reflections | 8081 (R(int) = 0.0560) |
Completeness to theta = 25.00° | 99.2% |
Absorption correction | Semi-empirical from equivalents |
Max. and min. transmission | 0.7817 and 0.7425 |
Refinement method | Full-matrix least-squares on F2 |
Data/restraints/parameters | 8081/2/541 |
Goodness-of-fit on F2 | 1.044 |
Final R indices (I > 2σ (I)) | R1 = 0.0546, wR2 = 0.1330 |
R indices (all data) | R1 = 0.0663, wR2 = 0.1409 |
Absolute structure parameter | 0.018(16) |
Largest diff. peak and hole | 1.224 and −0.560 e.Å−3 |
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Veiga, N.; Alvarez, N.; Castellano, E.E.; Ellena, J.; Facchin, G.; Torre, M.H. Comparative Study of Antioxidant and Pro-Oxidant Properties of Homoleptic and Heteroleptic Copper Complexes with Amino Acids, Dipeptides and 1,10-Phenanthroline: The Quest for Antitumor Compounds. Molecules 2021, 26, 6520. https://doi.org/10.3390/molecules26216520
Veiga N, Alvarez N, Castellano EE, Ellena J, Facchin G, Torre MH. Comparative Study of Antioxidant and Pro-Oxidant Properties of Homoleptic and Heteroleptic Copper Complexes with Amino Acids, Dipeptides and 1,10-Phenanthroline: The Quest for Antitumor Compounds. Molecules. 2021; 26(21):6520. https://doi.org/10.3390/molecules26216520
Chicago/Turabian StyleVeiga, Nicolás, Natalia Alvarez, Eduardo E. Castellano, Javier Ellena, Gianella Facchin, and María H. Torre. 2021. "Comparative Study of Antioxidant and Pro-Oxidant Properties of Homoleptic and Heteroleptic Copper Complexes with Amino Acids, Dipeptides and 1,10-Phenanthroline: The Quest for Antitumor Compounds" Molecules 26, no. 21: 6520. https://doi.org/10.3390/molecules26216520