title: New mixed ligand palladium(II) complexes based on the antiepileptic drug sodium valproate and bioactive nitrogen-donor ligands: synthesis, structural characterization, binding interactions with DNA and BSA, in vitro cytotoxicity studies and DFT calculations.
abstract: The complexes [Pd(valp)2(imidazole)2] (1), [Pd(valp)2(pyrazine)2] (2) (valp is sodium valproate) have been synthesized and characterized using IR, (1)H NMR, (13)C{(1)H} NMR and UV-Vis spectrometry. The interaction of complexes with CT-DNA has been investigated using spectroscopic tools and viscosity measurement. In each case, the association constant (Kb) was deduced from the absorption spectral study and the number of binding sites (n) and the binding constant (K) were calculated from relevant fluorescence quenching data. As a result, a non-covalent interaction between the metal complex and DNA was suggested, which could be assigned to an intercalative binding. In addition, the interaction of 1 and 2 was ventured with bovine serum albumin (BSA) with the help of absorption and fluorescence spectroscopy measurements. Through these techniques, the apparent association constant (Kapp) and the binding constant (K) could be calculated for each complex. Evaluation of cytotoxic activity of the complexes against four different cancer cell lines proved that the complexes exhibited cytotoxic specificity and significant cancer cell inhibitory rate. Moreover, density functional theory (DFT) calculations were employed to provide more evidence about the observed data. The majority of trans isomers were supported not only by energies, but also by the similarity of its calculated IR frequencies, UV adsorptions and NMR chemical shifts to the experimental values.
authors: Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111, Iran.
authors: Leila
authors: L
authors: Tabrizi
authors: Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111, Iran. Electronic address: Chinif@cc.iut.ac.ir.
authors: Hossein
authors: H
authors: Chiniforoshan
authors: Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111, Iran.
authors: Hossein
authors: H
authors: Tavakol
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D009584:Nitrogen; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D011789:Quantum Theory; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D014635:Valproic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014783:Viscosity
chemical_list: D000927:Anticonvulsants; D008024:Ligands; D012710:Serum Albumin, Bovine; D010165:Palladium; D014635:Valproic Acid; D004247:DNA; C427203:calf thymus DNA; D009584:Nitrogen
keywords: Cytotoxicity in vitro; DNA and BSA binding study; Palladium(II) complex; Sodium valproate; Theoretical calculation