Pd(II) and Pt(II) Complexes of 2-Phenyl- and 2-Benzyl-imidazoline: Synthesis, Structural Characterization, DNA Modification andin vitro Antileukaemic Activity

Abstract

In this paper we describe the synthesis and chemical characterization of three new Pd(II)–imidazoline complexes: [PdCl2 (C6H5–CH2–C3H5N2)2] (2), [PdCl(SEt2) (C6H4‐C3H5N2)] (5) and [Pd(C6H4‐C3H5N2) (μ‐Br)]2 (6). We have also analyzed the DNA modifications and in vitro antileukaemic activity of these compounds and of their previously reported analogs [Pd Cl2 (C6H5–C3H5N2)2] (1), [Pd (C6H4–C3H5N2) (μ‐OAc)]2 (3), [Pd (C6H4–C3H5N2) (μ‐Cl)]2 (4) and [Pt(C6H4–C3H5N2)(μ‐Cl] (7). All these compounds modify the DNA secondary structure since they alter the melting temperature (Tm) of the DNA. Circular dichroism spectra indicated, moreover, that compounds 3, 5 and 6 induced higher modification on the double helix than compounds 1, 2 and 4. While compounds 1, 2 and 5 seem to induce slight changes in the electrophoretic mobility of the open and covalently closed circular forms of pUC8 DNA at high ri (input molar ratio of Pd or Pt to nucleotides), compounds 3, 6 and 7 do not modify at any ri the tertiary structure of the plasmid DNA. Antileukaemic tests suggest that compounds 1, 4 and 7 exhibit important cytotoxic activity since their IC50 values against HL‐60 human leukaemic cells were below 10 μg ml−1. © 1997 John Wiley & Sons, Ltd.