Heteroleptic complexes of cocaine/TMEDA with some f block metals: Synthesis, DFT studies, spectral, thermal, cytotoxicity and antimetastatic properties

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Molecular and biomolecular spectroscopy, 2020-03, Vol.229, p.117938, Article 117938
• Main Authors: Zaki, Nadia G., Mahmoud, Walaa H., El Kerdawy, Ahmed M., Abdallah, Abanoub Mosaad, Mohamed, Gehad G.
• Format: Article
• Language: English
• Subjects: Antimetastatic effect; Apoptosis; Cell oxidative stress; Cocaine; Heteroleptic complexes; p21 and p27 tumor suppressor proteins; TD-DFT; TMEDA
• ISSN: 1386-1425
• DOI: 10.1016/j.saa.2019.117938

A series of new three heteroleptic complexes of the general formula [Ln(Cn)(TMEDA)Cl(OH2)]·2Cl·xH2O, (where Ln = La(III), Er(III) and Yb(III), Cn = cocaine and TMEDA = N,N,N′,N′-tetramethylethylenediamine) were synthesized, structurally characterized by elemental analysis, spectroscopic methods, molar conductivity and mass spectrometry. Thermal properties of the synthesized complexes and their kinetic thermodynamic parameters were studied. Theoretical calculations including geometry optimization, electronic structure and electronic and thermal energies were carried out using DFT and TD-DFT calculations at B3LYP/LANL2DZ level of theory and the different quantum chemical parameters were calculated. The in vitro antiproliferative activity of the newly synthesized complexes was assessed by MTT assay on MCF-7 and HepG-2 cancer cell lines. Yb(III) complex showed promising cytotoxic activity comparable to that of cisplatin on both cell lines with minimum effect on human normal cells. Further molecular mechanistic investigations showed that Yb(III) complex is an apoptotic inducer as it raises the caspase-3 and caspase-9 cellular level in the MCF-7 cell line. Furthermore, it showed an elevating effect on the level of the tumor suppressor nuclear proteins P21 and P27 concentrations in MCF-7 cells. Moreover, Yb(III) complex hindered the cellular scavenger system of the reactive oxygen species through reducing the glutathione peroxidase (GPx) cellular level imperiling MCF-7 cells by unmanageable oxidative stress. In addition to its cytotoxic effect, Yb(III) complex showed antimetastatic properties as it decreased the cellular levels of matrix metalloproteinases MMP-3 and MMP-9. These results showed that the Yb(III) complex is a promising cytotoxic metal-based agent that exerts its action through various molecular mechanisms with minimum effects on normal cells and with additional antimetastatic properties. Yb(III) heteroleptic complex of Cn and TMEDA, as a representative example, was synthesized as a potent antiproliferative agent against human HepG-2 and MCF-7 cancer cells and structurally characterized by different spectral and analytical techniques such as elemental analysis, spectroscopic methods, molar conductivity, thermal analysis and DFT studies. Its antiproliferative activity was assessed by studying its cytotoxicity, antimetastatic effect, induction of apoptosis, and its influence on the expression of p21 and p27 tumor suppressor proteins and the glutathione