Exploring anticancer activity and DNA binding of metal (II) salicylaldehyde Schiff base complexes : a convergence of experimental and computational perspectives
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DATA AVAILABILITY STATEMENT : The data that support the findings of this study are available from the corresponding author upon reasonable request.
SUPPLEMENTARY INFORMATION : FIGURE S1. 1H NMR spectrum of HL recorded at room temperature using (500 MHz, DMSO-d6). FIGURE S2. 13C NMR spectrum of HL recorded at room temperature using (125 MHz, DMSO-d6). FIGURE S3. FTIR spectrum of HL obtained in solid state at room temperature using ATR method. FIGURE S4. U-Vis spectrum of HL obtained at room temperature using (DMSO, 10−3M). FIGURE S5. Mass spectrum of HL obtained using high resolution mass spectroscopy (HRMS). FIGURE S6. Scanning Electron Microscope (SEM) Image of HL shows block-like structures surface morphology in different forms and are well arranged, confirming the crystalline nature of the ligand. This was similar to previously reported structures. FIGURE S7. 1H NMR spectrum of C1 recorded at room temperature using (500 MHz, DMSO-d6). FIGURE S8. 13C NMR spectrum of C1 recorded at room temperature using (125 MHz, DMSO-d6). FIGURE S9. FTIR spectrum of C1 obtained in solid state at room temperature using ATR method. FIGURE S10. UV-Vis spectrum of C1 obtained at room temperature using (DMSO, 10−3 M). FIGURE S11. TGA Thermograph of C1 obtained under inert condition (N2). FIGURE S12. Mass spectrum of C1 obtained using high resolution mass spectroscopy (HRMS). FIGURE S13. FTIR spectrum of C2 obtained in solid state at room temperature using ATR method. FIGURE S14. UV-Vis spectrum of C2 obtained at room temperature using (DMSO, 10−3 M). FIGURE S15. TGA Thermogram of C2 obtained under inert condition (N2). FIGURE S16. Mass spectrum of C2 obtained using high resolution mass spectroscopy (HRMS). FIGURE S17. Scanning Electron Microscope (SEM) Image of C2. SEM image of the ligand, HL (Figure S6) shows block-like structures surface morphology in different forms and are well arranged, confirming the crystalline nature of the ligand. But the complex's surface morphology here displayed a fine wide surface area with agglomeration of particles of different sizes and shapes scattered over it, indicating the amorphous nature of the complex. This change in the surface morphology of the ligand compared with the C2 herein confirmed the formation of new material (complex). FIGURE S18. Energy Dispersive X-ray Spectroscopy (EDX) micrograph of C2confirming the presence of Co (II) ion in the complex. In addition, carbon, nitrogen and oxygen atoms from the ligand were also confirmed. The presence of these elements within the compound has further affirmed the formation of the complex (C2). The trace amount of sulfur (0.3%) could be due to impurity arising from coating of the sample. FIGURE S19. FTIR spectrum of C3 obtained in solid state at room temperature using ATR method. FIGURE S20. UV-Vis spectrum of C3 obtained at room temperature using (DMSO, 10−3 M). FIGURE S21. TGA Thermogram of C3obtained under inert condition (N2). FIGURE S22. Mass spectrum of C3 obtained using high resolution mass spectroscopy (HRMS). FIGURE S23. 1H NMR spectrum of C4 recorded at room temperature using (500 MHz, DMSO-d6). FIGURE S24. 1H NMR spectrum of C4 recorded at room temperature using (125 MHz, DMSO-d6). FIGURE S25. FTIR spectrum of C4 obtained in solid state at room temperature using ATR method. FIGURE S26. UV-Vis spectrum of C4 obtained at room temperature using (DMSO, 10−3 M). FIGURE S27. TGA Thermogram of C4 obtained under inert condition (N2). FIGURE S28. Mass spectrum of C4 obtained using high resolution mass spectroscopy (HRMS). FIGURE S29. Packing viewed along b axis showing the non-classical hydrogen bonds which contribute to the formation of a three-dimensional supramolecular network; C1; (a)C3; (b) andC4; (c). FIGURE S30. UV-vis spectra of 50 μM solutions of (a) C2, (b) C3, (c) C1 and (d) C4 (bottom) recorded as a function of time in KH2PO4 buffer (50 mM pH 7.5). C2 was present with a final concentration of 10% (v/v) acetonitrile, while the other three metal complexes were present with 10% (v/v) DMF. All four metal complexes were dissolved in DMF for a control spectrum to be compared. FIGURE S31. (a) Morphology of MCF-7 cells before treatment of any drug. (b) Morphological changes in MCF-7 cells induced by HL (5 μM). (b) Morphological changes in MCF-7 cells induced by complex Dox(5 μM). Captured using Wirsam Olympus inverted light microscope (CKX 41) equipped with Olympus C5060-ADUS digital camera at × 400 magnification. FIGURE S32. The Highest XP docked pose of C2 within the active site of LDH (2V7P) [30]. The docked pose indicates the C2 binds to the NADH binding site and can compete or prevent NADH binding. Therefore, C2 may interfere with the LDH activity assay. FIGURE S33. The experimental and DFT calculated UV–Vis spectra of C1, C3, and C4 as well as 60 excited singlet state transitions. FIGURE S34. The experimental and DFT calculated UV–Vis spectra of C1–C4 as well as 60 excited singlet state transitions. Oscillator strength of the 60 transition states id illustrate with the green lines. FIGURE S35. 3D model of the optimized structures for HL, and C1-C4 calculated atM06-2X/3-21G andM06/3-21G level for HL, and C1-C4, respectively. The colour scheme for different atoms (blue for nitrogen, red for oxygen, grey for carbon, and white for hydrogen). FIGURE S36. (a) The LD spectrum of EB with ctDNA, with an induced LD at 515 nm indicating binding of EB to ctDNA. (b) The best docking pose generated of EB intercalated with double stranded DNA (PDB: 2O1I).[31](c) The LD spectrum of HS with ctDNA, with an induced LD at 347 nm indicating binding of HS to ctDNA. (d) An XRD crystal structure of HS in the minor groove of DNA (PDB: 8BNA).[32] FIGURE S37. GLIDE XP docking analysis of the binding of complex C2 to an oligonucleotide of DNA (PDB 4E1U; 5’-D (CGGAAATTACCG)-3’ bound with a cationic ruthenium complex [Ru (bpy)2(dppz)]2+)[10]. A large target grid was generated for ligand docking at the [Ru (bpy)2(dppz)]2+) site close to the centre of the DNA (with [Ru (bpy)2(dppz)]2+) removed), spanning 40 x 40 x 40 Å3, thereby facilitating a search of alternative binding packets radiating throughout the oligonucleotide. The structure shown displays the best XP ligand pose (complex C2 is displayed in blue) within the AT pocket, with the most favourable docking score. The black box is a close-up view of complex C2 intercalating the AT nucleobase of the 5’-D (CGGAAATTACCG)-3’ oligonucleotide strand. TABLE S1. Crystallographic data. TABLE S2. Full list of 60 TD-DFT-calculated excited singlet states (CAM-B3LYP/DEF2-QZVP/GD3BJ in a DMSO solvent continuum) for C1. State energies are uncorrected. DMSO was chosen as the solvent medium to allow assignment of the UV-vis spectra of C1. TABLE S3. Full list of 60 TD-DFT-calculated excited singlet states (CAM-B3LYP/DEF2-QZVP/GD3BJ in a DMSO solvent continuum) for C2. State energies are uncorrected. DMSO was chosen as the solvent medium to allow assignment of the UV-vis spectra of C2. TABLE 4. Full list of 60 TD-DFT-calculated excited singlet states (CAM-B3LYP/DEF2-QZVP/GD3BJ in a DMSO solvent continuum) for C3. State energies are uncorrected. DMSO was chosen as the solvent medium to allow assignment of the UV-vis spectra of C3. TABLE S5. Full list of 60 TD-DFT-calculated excited singlet states (CAM-B3LYP/DEF2-QZVP/GD3BJ in a DMSO solvent continuum) for C4. State energies are uncorrected. DMSO was chosen as the solvent medium to allow assignment of the UV-vis spectra of C4. TABLE S6. Optimization energies C1 with various DFT methods. TABLE S7. Quantum chemical descriptors.
SUPPLEMENTARY INFORMATION : FIGURE S1. 1H NMR spectrum of HL recorded at room temperature using (500 MHz, DMSO-d6). FIGURE S2. 13C NMR spectrum of HL recorded at room temperature using (125 MHz, DMSO-d6). FIGURE S3. FTIR spectrum of HL obtained in solid state at room temperature using ATR method. FIGURE S4. U-Vis spectrum of HL obtained at room temperature using (DMSO, 10−3M). FIGURE S5. Mass spectrum of HL obtained using high resolution mass spectroscopy (HRMS). FIGURE S6. Scanning Electron Microscope (SEM) Image of HL shows block-like structures surface morphology in different forms and are well arranged, confirming the crystalline nature of the ligand. This was similar to previously reported structures. FIGURE S7. 1H NMR spectrum of C1 recorded at room temperature using (500 MHz, DMSO-d6). FIGURE S8. 13C NMR spectrum of C1 recorded at room temperature using (125 MHz, DMSO-d6). FIGURE S9. FTIR spectrum of C1 obtained in solid state at room temperature using ATR method. FIGURE S10. UV-Vis spectrum of C1 obtained at room temperature using (DMSO, 10−3 M). FIGURE S11. TGA Thermograph of C1 obtained under inert condition (N2). FIGURE S12. Mass spectrum of C1 obtained using high resolution mass spectroscopy (HRMS). FIGURE S13. FTIR spectrum of C2 obtained in solid state at room temperature using ATR method. FIGURE S14. UV-Vis spectrum of C2 obtained at room temperature using (DMSO, 10−3 M). FIGURE S15. TGA Thermogram of C2 obtained under inert condition (N2). FIGURE S16. Mass spectrum of C2 obtained using high resolution mass spectroscopy (HRMS). FIGURE S17. Scanning Electron Microscope (SEM) Image of C2. SEM image of the ligand, HL (Figure S6) shows block-like structures surface morphology in different forms and are well arranged, confirming the crystalline nature of the ligand. But the complex's surface morphology here displayed a fine wide surface area with agglomeration of particles of different sizes and shapes scattered over it, indicating the amorphous nature of the complex. This change in the surface morphology of the ligand compared with the C2 herein confirmed the formation of new material (complex). FIGURE S18. Energy Dispersive X-ray Spectroscopy (EDX) micrograph of C2confirming the presence of Co (II) ion in the complex. In addition, carbon, nitrogen and oxygen atoms from the ligand were also confirmed. The presence of these elements within the compound has further affirmed the formation of the complex (C2). The trace amount of sulfur (0.3%) could be due to impurity arising from coating of the sample. FIGURE S19. FTIR spectrum of C3 obtained in solid state at room temperature using ATR method. FIGURE S20. UV-Vis spectrum of C3 obtained at room temperature using (DMSO, 10−3 M). FIGURE S21. TGA Thermogram of C3obtained under inert condition (N2). FIGURE S22. Mass spectrum of C3 obtained using high resolution mass spectroscopy (HRMS). FIGURE S23. 1H NMR spectrum of C4 recorded at room temperature using (500 MHz, DMSO-d6). FIGURE S24. 1H NMR spectrum of C4 recorded at room temperature using (125 MHz, DMSO-d6). FIGURE S25. FTIR spectrum of C4 obtained in solid state at room temperature using ATR method. FIGURE S26. UV-Vis spectrum of C4 obtained at room temperature using (DMSO, 10−3 M). FIGURE S27. TGA Thermogram of C4 obtained under inert condition (N2). FIGURE S28. Mass spectrum of C4 obtained using high resolution mass spectroscopy (HRMS). FIGURE S29. Packing viewed along b axis showing the non-classical hydrogen bonds which contribute to the formation of a three-dimensional supramolecular network; C1; (a)C3; (b) andC4; (c). FIGURE S30. UV-vis spectra of 50 μM solutions of (a) C2, (b) C3, (c) C1 and (d) C4 (bottom) recorded as a function of time in KH2PO4 buffer (50 mM pH 7.5). C2 was present with a final concentration of 10% (v/v) acetonitrile, while the other three metal complexes were present with 10% (v/v) DMF. All four metal complexes were dissolved in DMF for a control spectrum to be compared. FIGURE S31. (a) Morphology of MCF-7 cells before treatment of any drug. (b) Morphological changes in MCF-7 cells induced by HL (5 μM). (b) Morphological changes in MCF-7 cells induced by complex Dox(5 μM). Captured using Wirsam Olympus inverted light microscope (CKX 41) equipped with Olympus C5060-ADUS digital camera at × 400 magnification. FIGURE S32. The Highest XP docked pose of C2 within the active site of LDH (2V7P) [30]. The docked pose indicates the C2 binds to the NADH binding site and can compete or prevent NADH binding. Therefore, C2 may interfere with the LDH activity assay. FIGURE S33. The experimental and DFT calculated UV–Vis spectra of C1, C3, and C4 as well as 60 excited singlet state transitions. FIGURE S34. The experimental and DFT calculated UV–Vis spectra of C1–C4 as well as 60 excited singlet state transitions. Oscillator strength of the 60 transition states id illustrate with the green lines. FIGURE S35. 3D model of the optimized structures for HL, and C1-C4 calculated atM06-2X/3-21G andM06/3-21G level for HL, and C1-C4, respectively. The colour scheme for different atoms (blue for nitrogen, red for oxygen, grey for carbon, and white for hydrogen). FIGURE S36. (a) The LD spectrum of EB with ctDNA, with an induced LD at 515 nm indicating binding of EB to ctDNA. (b) The best docking pose generated of EB intercalated with double stranded DNA (PDB: 2O1I).[31](c) The LD spectrum of HS with ctDNA, with an induced LD at 347 nm indicating binding of HS to ctDNA. (d) An XRD crystal structure of HS in the minor groove of DNA (PDB: 8BNA).[32] FIGURE S37. GLIDE XP docking analysis of the binding of complex C2 to an oligonucleotide of DNA (PDB 4E1U; 5’-D (CGGAAATTACCG)-3’ bound with a cationic ruthenium complex [Ru (bpy)2(dppz)]2+)[10]. A large target grid was generated for ligand docking at the [Ru (bpy)2(dppz)]2+) site close to the centre of the DNA (with [Ru (bpy)2(dppz)]2+) removed), spanning 40 x 40 x 40 Å3, thereby facilitating a search of alternative binding packets radiating throughout the oligonucleotide. The structure shown displays the best XP ligand pose (complex C2 is displayed in blue) within the AT pocket, with the most favourable docking score. The black box is a close-up view of complex C2 intercalating the AT nucleobase of the 5’-D (CGGAAATTACCG)-3’ oligonucleotide strand. TABLE S1. Crystallographic data. TABLE S2. Full list of 60 TD-DFT-calculated excited singlet states (CAM-B3LYP/DEF2-QZVP/GD3BJ in a DMSO solvent continuum) for C1. State energies are uncorrected. DMSO was chosen as the solvent medium to allow assignment of the UV-vis spectra of C1. TABLE S3. Full list of 60 TD-DFT-calculated excited singlet states (CAM-B3LYP/DEF2-QZVP/GD3BJ in a DMSO solvent continuum) for C2. State energies are uncorrected. DMSO was chosen as the solvent medium to allow assignment of the UV-vis spectra of C2. TABLE 4. Full list of 60 TD-DFT-calculated excited singlet states (CAM-B3LYP/DEF2-QZVP/GD3BJ in a DMSO solvent continuum) for C3. State energies are uncorrected. DMSO was chosen as the solvent medium to allow assignment of the UV-vis spectra of C3. TABLE S5. Full list of 60 TD-DFT-calculated excited singlet states (CAM-B3LYP/DEF2-QZVP/GD3BJ in a DMSO solvent continuum) for C4. State energies are uncorrected. DMSO was chosen as the solvent medium to allow assignment of the UV-vis spectra of C4. TABLE S6. Optimization energies C1 with various DFT methods. TABLE S7. Quantum chemical descriptors.
Keywords
Cancer, Metal complexes, Metallodrugs, Schiff base
Sustainable Development Goals
SDG-03: Good health and well-being
Citation
Waziri, I., Sookai, S., Yusuf, T.L. et al. 2025, 'Exploring anticancer activity and DNA binding of metal (II) salicylaldehyde Schiff base complexes: a convergence of experimental and computational perspectives', Applied Organometallic Chemistry, vol. 39, no. 5, art. e70162, pp. 1-14, doi : 10.1002/aoc.70162.