Palladium(II) complexes with tris(2-carboxyethyl)phosphine, structure, reactions and cytostatic activity

• P(C2H4COOH)3, reductant of S–S bond, forms mono- and polynuclear Pd(II) complexes.
• TCEP complexes of Pd(II) react with H2O giving compounds with TCEP-κO,κP ligands.
• X-ray structure of PdCl2(TCEP)2, Pd2Cl4(TCEP)2 and [PdCl{P(C2H4COOH)2C2H4COO}]n
• DFT optimization shows that Pd2Cl4(TCEP)2 in the gas phase has butterfly structure.
• PdCl2(TCEP)2, Pd2Cl4(TCEP)2 complexes are active antitumor agents in vitro.

Water soluble and air stable P(RCOOH)3 (R = C2H4) (TCEP) is an efficient reducing agent used in biochemistry to break S–S bond in peptides, proteins and other compounds containing S–S bonds. The similarity between the coordination chemistry of Pd(II) and Pt(II) led to the investigations of antitumor activity of palladium(II) compounds however the Pd(II) complexes with TCEP were not investigated. New palladium(II) complexes with (TCEP): trans-[PdCl2(TCEP)2] (1) and trans-[Pd2(μ-Cl)2Cl2(TCEP)2] (2) were fully characterized by 1H, 13C, 31P NMR, IR and ESI-MS spectroscopic techniques. Complexes are stable in non-aqueous DMSO and DMF. In aqueous solutions Cl ligands are substituted by COO groups of phosphines. Complex 2, after crystallization from water gives polymeric compound with bridging phosphine ligand [PdCl{P(RCOO-κO-μ-O′)(RCOOH)2-κP}] (3). Structures of trans-[PdCl2{P(RCOOD)3}2] (1a), trans-[Pd2(μ-Cl)2PdCl2{P(RCOOD)3}2] (2a), and [PdCl{P(RCOO-κO-μ-O′)(RCOOD)2-κP}]n (3a) have been determined by X-ray crystallography. NMR and ESI-MS spectra reveal that [PdP2(RCOO-κO)2(RCOO)n(RCOOH)4 − n]n– complexes are formed in aqueous solution of 1. Geometry optimization in the gas phase at the B3LYP/3-21G** level indicated that complex 2 with butterfly structure is more stable than that with coplanar coordination. In aqueous solution of 2, the main products [Pd2{P(RCOO-κO-μ-O′)(RCOO-κO)(RCOOH)}2] and [Pd{P(RCOO-κO)2(RCOOH)}(H2O)] exist in equilibrium which depends on temperature: content of mononuclear compound increases as the temperature is raised. Complexes 1 and 2 are active agents against melanoma and breast cancer cells.

Structures and reactivity of Pd(II) complexes with P(C2H4COOH)3 (TCEP), reductant of S–S bonds and promoter of reaction of cisplatin with Zn finger protein and Cu(I) transporters, were investigated. TCEP in nonaqueous solvent is coordinated via P atom but in water through P and O atoms. Complexes are active antitumor agents in vitro.Figure optionsDownload as PowerPoint slide