Cytotoxicity and Antibacterial Potentials of Mixed Ligand Cu(II) and Zn(II) Complexes: A Combined Experimental and Computational Study

Mamaru Bitew Alem; Tegene Desalegn; Tadewos Damena; Enyew Alemayehu Bayle; Moses O Koobotse; Kennedy J Ngwira; Japheth O Ombito; Matshediso Zachariah; Taye B Demissie

doi:10.1021/acsomega.3c00916

Cytotoxicity and Antibacterial Potentials of Mixed Ligand Cu(II) and Zn(II) Complexes: A Combined Experimental and Computational Study

ACS Omega. 2023 Mar 29;8(14):13421-13434. doi: 10.1021/acsomega.3c00916. eCollection 2023 Apr 11.

Authors

Mamaru Bitew Alem¹, Tegene Desalegn¹, Tadewos Damena², Enyew Alemayehu Bayle^{3

4}, Moses O Koobotse⁵, Kennedy J Ngwira⁶, Japheth O Ombito⁷, Matshediso Zachariah⁵, Taye B Demissie⁷

Affiliations

¹ Department of Applied Chemistry, Adama Science and Technology University, P.O.Box 1888, Adama 251, Ethiopia.
² Department of Chemistry, Wachemo University, P.O.Box 667, Hossana 667, Ethiopia.
³ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, 10607 Taipei, Taiwan.
⁴ Department of Chemistry, Debre Markos University, P.O. Box 269, Debre Markos 269, Ethiopia.
⁵ School of Allied Health Professions, University of Botswana, P/bag UB, 0022 Gaborone, Botswana.
⁶ Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits, 2050 Johannesburg, South Africa.
⁷ Department of Chemistry, University of Botswana, P/bag UB, 0022 Gaborone, Botswana.

Abstract

[Cu(C₁₅H₉O₄)(C₁₂H₈N₂)O₂C₂H₃]·3H₂O (1) and [Zn(C₁₅H₉O₄)(C₁₂H₈N₂)]O₂C₂H₃ (2) have been synthesized and characterized by ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, mass spectrometry, thermogravimetric analysis/differential thermal analysis (TGA/DTA), X-ray diffraction (XRD), scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX), and molar conductance, and supported by density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. Square pyramidal and tetrahedral geometries are proposed for Cu(II) and Zn(II) complexes, respectively, and the XRD patterns showed the polycrystalline nature of the complexes. Furthermore, in vitro cytotoxic activity of the complexes was evaluated against the human breast cancer cell line (MCF-7). A Cu(II) centered complex with an IC₅₀ value of 4.09 μM was more effective than the Zn(II) centered complex and positive control, cisplatin, which displayed IC₅₀ values of 75.78 and 18.62 μM, respectively. In addition, the newly synthesized complexes experienced the innate antioxidant nature of the metal centers for scavenging the DPPH free radical (up to 81% at 400 ppm). The biological significance of the metal complexes was inferred from the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy band gap, which was found to be 2.784 and 3.333 eV, respectively for 1 and 2, compared to the ligands, 1,10-phenathroline (4.755 eV) and chrysin (4.403 eV). Moreover, the molecular docking simulations against estrogen receptor alpha (ERα; PDB: 5GS4) were strongly associated with the in vitro biological activity results (E _B and K _i are -8.35 kcal/mol and 0.76 μM for 1, -7.52 kcal/mol and 3.07 μM for 2, and -6.32 kcal/mol and 23.42 μM for cisplatin). However, more research on in vivo cytotoxicity is suggested to confirm the promising cytotoxicity results.