Synthesis of bis[palladium(II)] and bis[platinum(II)] complexes containing chiral, linear quadridentate ligands with a P₂N₂ donor set

A number of bis[palladium(II)] and bis[platinum(II)] complexes of the type [(MCl₂)₂(μ-quadridentate)] [where M = Pd(II) or Pt(II)] and [(PtClMe)₂(μ-quadridentate)] have been prepared containing the linear quadridentate NPPN ligands 1,3-bis[(2-aminophenyl)phenylphosphino]propane, 1; 1,4-bis[(2-aminophenyl)phenylphosphino]butane, 2; 1,5-bis[(2-aminophenyl)phenylphosphino]pentane, 3 [Pd(II) only]; 1,6-bis[(2-aminophenyl)phenylphosphino]hexane, 4; and 1,3-bis[(2-aminoethyl)phenylphosphino]propane, 5; and the related PNNP ligands 1,3-bis[(2-diphenylphosphinophenyl)amino]propane, 6; and 1,2-bis[(2-diphenylphosphinophenyl)amino]ethane, 7 [Pt(II) only]. Separation of the racemic and meso diastereomers of the linear quadridentate NPPN ligands and the resolution of (R_p*,R_p*)-1 have been achieved via separation by fractional crystallisation of a pair of bis[palladium(II)] complexes containing the respective ligand and orthometallated N,N-dimethylbenzylamine or (S)-dimethyl(1-phenylethyl)amine, respectively. The structure of the bis[palladium(II)] complex containing (R_p,R_p)-1 has been confirmed by X-ray analysis and shown to have the configuration (S_p,S_p,S,S). Subsequent reaction of stereoisomerically pure [{Pd(2-C₆H₄CH₂-NMe₂)} ₂(μ-L)](PF₆)₂ with HCl gave the corresponding complexes [(PdCl₂)₂(μ-L)] [where L = (R_p*,R_p*)-1-5, (R_p,R_p)- or (S_p,S_p)-1, (R_p*,S_p*)-1, -2 or -5]. The analogous complex [(PdCl₂)₂(μ-6)] has been prepared in a similar manner. Bis[platinum(II)] complexes of the type [(PtClMe)₂(μ-L)] [where L = (R_p*,R_p*)-1, -2 or -4; (R_p,R_p)-, (S_p,S_p)- or (R_p*,S_p*)-1; 6 or 7] have been prepared by reaction of L with [PtCl(Me)(cod)] (cod = cyclocta-1,5-diene). Further treatment with HCl gave the analogous complexes [(PtCl₂)₂(μ-L)] [where L = (R_p*,R_p*)-1, -2, -4 or -5; (R_p*,S_p*)-1 or -5; or 6]. The dinuclear compounds and, in particular, the bis[platinum(II)] complexes, are seen as potential anticancer agents. Preliminary in vitro biological studies have shown them to be active against the murine P388 leukaemia cell-line with cytotoxicities of certain of these complexes being comparable to that of cisplatin.