Synthesis, characterization and in vitro cytotoxicity of the first palladium(II) oxalato complexes involving adenine-based ligands

The first [Pd(L-n)(2)(ox)] xH(2)O oxalato(ox) complexes involving 2-chloro-N6-(benzyl)-9-isopropyladenine (L-1: complex 1), 2-chloro-N6-(4-methoxybenzyl)-9-isopropyladenine (L-2; 2), 2-chloro-N6-(2,3-dimethoxybenzyl)-9-isopropyladenine (L-3; 3), 2-chloro-N6-(2,4-dimethoxybenzyl)-9-isopropyladenine (L-4; 4), and 2-chloro-N6-(4-methylbenzyl)-9-isopropyladenine (L-5; 5) have been synthesized by the reactions of potassium bis(oxalato)palladate(II) dihydrate, [K2Pd(ox)(2)]center dot 2H(2)O, with the mentioned organic compounds (H(2)ox = oxalic acid; x = 0 for 1-3 and 5 or 2 for 4). Elemental analyses (C, H, N), FTIR, Raman and NMR (H-1, C-13, N-15) spectroscopies, conductivity measurements and thermal studies (thermogravimetric and differential thermal analyses, TG/DTA) have been used to characterize the prepared complexes. The molecular structures of [Pd(L-2)(2)(ox)] (2) and [Pd(L-5)(2)(ox)]center dot L-5 center dot Me2CO (5 center dot L-5 center dot Me2CO) have been determined by a single crystal X-ray analysis. The geometry of these complexes is slightly distorted square-planar with two appropriate L-n (n = 2 or 5) molecules mutually arranged in the head-to-head (2) or head-to-tail (5) orientation. The L-n ligands are coordinated to the central Pd(II) ion via the N7 atoms. The same conclusions regarding the binding properties of L-1-L-5 ligands can be made based on multinuclear NMR spectra. In vitro cytotoxicity of the complexes 1-5 has been evaluated against human chronic myelogenous leukaemia (K562) and human breast adenocarcinoma (MCF7) cancer cell lines. Significant cytotoxicity has been determined for the complexes 3 (IC50 = 6.2 mu M) and 5 (IC50 m 6.8 mu M) on the MCF7 cell line, which is even better than that found for the well-known and widely-used platinum-bearing antineoplastic drugs, i.e. oxaliplatin and cisplatin. (C) 2009 Elsevier Inc. All rights reserved.