Synthesis, characterization and assessment of the cytotoxic properties of cis and trans-[Pd(L)2Cl2] complexes involving 6-benzylamino-9-isopropylpurine derivatives

A series of square-planar Pd(II) complexes of the composition cis-[Pd(Ln)2Cl2] {L1 = 2-chloro-6-benzylamino-9-isopropylpurine (1), L2 = 2-chloro-6-[(4-methoxybenzyl)amino]-9-isopropylpurine (2), L3 = 2-chloro-6-[(2-methoxybenzyl)amino]-9-isopropylpurine (3) and 2-[(chloropropyl)amino]-6-benzylamino-9-isopropylpurine (6)} has been synthesized by the reaction of PdCl2 with Ln in a 1:2 molar ratio. In contrast, the same reaction followed by recrystallization of the product from N,N′-dimethylformamide (DMF) leads to trans-[Pd(Ln)2Cl2] · nDMF {L3, n = 0 (4), n = 1(4∗DMF); L4 = 2-chloro-6-[(2,3-dimethoxybenzyl)-amino]-9-isopropylpurine, n = 0 (5), n = 1.5 (5∗DMF). The compounds have been characterized by elemental analyses, conductivity measurements, electrospray mass spectra in the positive ion mode (ES + MS), FTIR, 1H and 13C NMR spectra, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Moreover, the complexes 2 and 6 have been also investigated by 15N NMR spectroscopy. The molecular structures of L5, {(H2+L5)(Cl−)2} · H2O, i.e. the protonated form of L5, trans-[Pd(L3)2Cl2] (4) and trans-[Pd(L4)2Cl2] (5) have been determined by single crystal X-ray analysis. NMR data and X-ray structures revealed that the organic molecules are coordinated to Pd via N7 atom of a purine moiety. All the complexes and the corresponding ligands have been tested in vitro for their cytotoxicity against four human cancer cell lines: breast adenocarcinoma (MCF7), malignant melanoma (G361), chronic myelogenous leukaemia (K562) and osteogenic sarcoma (HOS). Promising in vitro cytotoxic effect has been found for cis-[Pd(L2)2Cl2] (2), having the IC50 values of 12, 10, 25, and 14 μM against MCF7, G361, K562, and HOS, respectively, and for trans-[Pd(L3)2Cl2] · DMF (4) with the IC50 value of 15 μM against G361.