New phosphorus ylide palladacyclic: Synthesis, characterization, X-Ray crystal structure, biomolecular interaction studies, molecular docking and in vitro cytotoxicity evaluations

Abstract

The ylide-phosphonium salt [PPh3CH2C(O)CH2Cl]+Cl− was reacted with Pd(OAc)2 to give the chloro-bridged dinuclear complex [Pd{C(H)PPh3C(O)CH2Cl}(μ-Cl)(OAc)]2, which experienced bridge cleavage reactions with triphenylphosphine (PPh3) and pyridine (Py), and to prepare the new orthometallated complexes [Pd{(C,C)C6H4PPh2C(H)C(O)CH2Cl}L]Cl, [L = PPh3 (1) and Py (2)]. The complexes were identified and characterized using various techniques. X-ray crystallography was used to determine the crystal structure of 1, which revealed the presence of an orthometallated C6H4-PPh2 unit. CT-DNA binding interaction of the synthesis compounds was tested by fluorescence spectroscopy, UV–Vis absorption spectroscopy, and the viscometric titration method. The analysis of the obtained data indicated that the Pd complexes could bind to DNA via groove binding by the partial intercalation mode. The emission titration of bovine serum albumin (BSA) with two Pd complexes showed a static process for the fluorescence quenching mechanism of BSA. In addition, the results of competitive binding by Eosin-Y, Ibuprofen and Digoxin site markers revealed that the complexes were bound to the site I of BSA. The donor (BSA) - acceptor (Pd complexes) distance was calculated using fluorescence resonance energy transfer (FRET). Notably, molecular docking studies were used for the determination of DNA and BSA-Pd (II) complexes binding. Finally, the two complexes exhibited significant in vitro cytotoxicity against human leukemic T cell (Jurkat) and chronic myelogenous leukemia (K562) cancer cell lines using MTT([3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] colorimetric. In cell cycle analysis conducted on Jurkat and K562 cells treated with ligand and Pd complexes, a decrease in DNA cell content and shift in the main population of cells toward the subG1 phase were observed.