Metal complexes as anticancer agents 2. Iron(III) and copper(II) bio-active complexes with N6-benzylaminopurine derivatives

Iron(III) complexes with 2-(3-hydroxypropylamino)-6-benzylamino-9-isopropylpurine (Bohemin, HL1), in its protonized form, of the composition (H+HL1)2[FeCl5]·2H2O (1), (H+HL1)2[FeCl5]·3H2O (2) have been prepared by two different routes. A new way for synthesis of copper(II) complex with 6-(2-chlorobenzylamino)purine (HL2), [Cu2(μ-Cl)2(μ-HL2)2(HL2)2Cl2]·2H2O (3), together with the preparation of copper(II) complex with 6-(3-chlorobenzylamino)purine (HL3), [Cu2(μ-Cl)2(μ-HL3)2Cl2] (4), is also reported. The characterization have been based on elemental analysis, electronic, infrared, ES+ mass and 57Fe Mössbauer spectra, conductivity data and magnetic susceptibility temperature measurements over the 4.5–300 K for 1–3, and 35–300 K for 4, temperature range, respectively. Molecular structure of an electroneutral form of the HL2 ligand, (HL2·2H2O), and a protonized form of the HL3 ligand, (H+HL3Cl), have been determined by a single-crystal X-ray analysis. A mononuclear trigonal-bipyramidal (for 1 and 2), binuclear octahedral (for 3) and binuclear trigonal-bipyramidal (for 4) structures of the complexes were proposed mainly on the basis of spectral and magnetic properties. An S=3/2–5/2 spin-admixed state in 1 and 2 was found to be related to the presence of [FeCl5]2− (S=3/2) and [FeCl5(H2O)]2− (S=5/2) complex anions in 1 and 2, as found by 57Fe Mössbauer spectroscopy. Cytotoxic activity of the complexes was determined by a calcein AM assay and IC50 values were also estimated. For testing, human malignant melanoma cell line G-361, human osteogenic sarcoma cell line HOS, human chronic myelogenous leukaemia K-562 and human breast adenocarcinoma cell line MCF7 were used. The inhibition of p34cdc2 kinase by the complexes 1 and 2, which is known to be one of the important mechanisms responsible for cytotoxicity of cytokinin-derived compounds, was also studied.