Palladium Complexes of N,N'-Bis(2-aminoethyl)oxamide (H2L): Structural (PdIIL, PdII2L2, and PdIVLCl2), Electrochemical, Dynamic 1H NMR, and Cytotoxicity Studies.

Abstract

The monomeric (PdL·2H2O) and dimeric (Pd2L2·7H2O) palladium(II) complexes of N,N'-bis(2-aminoethyl)oxamide (H2L) were isolated, and their structures were established by single-crystal X-ray diffraction. Both compounds display identical cis-(2Namide + 2Namine) coordination environments of the metal ion. The dimer, representing a combination of two PdL species with an open lateral chelate ring, has an "open clamshell"-like structure. The intramolecular metal-metal separation in Pd2L2 (3.215 Å) is slightly shorter than the sum of the van der Waals radii of the palladium(II) atoms. The dimeric complex is relatively stable to dissociation, and its spectral features in aqueous solutions have been compared to those of the monomeric complex. A 1H NMR spectroscopic study revealed the presence of the dynamic conformational exchange process assigned to a turning of the dimeric molecule "inside out" with an activation energy of 65 kJ/mol. Cyclic voltammetry of PdL in perchlorate-, chloride-, and sulfate-containing electrolytes revealed two-electron oxidation of the palladium center. For the dimeric complex similar, though irreversible, oxidation to the palladium(IV) state was observed in NaCl electrolyte. At the same time, in NaClO4 or Na2SO4 solutions oxidation of Pd2L2 occurs in two distinct steps. The first step is quasi-reversible and can be assigned to the formation of species in an intermediate PdIIIPdIII state. Monomeric palladium(IV) complex PdIVLCl2 was generated via chemical oxidation of PdIIL by peroxodisulfate in the presence of chloride ions and structurally characterized. The related MIIL complexes (M = Pd, Ni, Cu) showed low cytotoxicity in human cancer cell lines AGS (gastric adenocarcinoma) and HCT116 (colorectal carcinoma) with IC50 values from 204 to 525 μM, while the proligand H2L was devoid of antiproliferative activity (IC50 > 1000 μM).