Synthesis and antiproliferative activity of a series of new platinum and palladium diphosphane complexes

Synthesis and antiproliferative activity of a series of new platinum and palladium diphosphane complexes†

Carleen Cullinane,

^a Glen B. Deacon,

*^b Penny R. Drago,^b Anja P. Erven,^b Peter C. Junk,

^c Jenny Luu,^b Gerd Meyer,^d Simon Schmitz,^d Ingo Ott,

^e Julia Schur,^e Lorraine K. Webster^a and Axel Klein

*^d

Author affiliations

* Corresponding authors

^a Peter MacCallum Cancer Center, 305 Grattan Street, Melbourne Vic 3000, Australia and Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Melbourne Vic 3052, Australia

^b School of Chemistry, Monash University Clayton, Vic, 3800, Australia
E-mail: glen.deacon@monash.edu

^c College of Science and Engineering, James Cook University, Townsville, QLD, Australia

^d University of Cologne, Department of Chemistry, Institute for Inorganic Chemistry, Greinstrasse 6, 50939 Cologne, Germany
E-mail: axel.klein@uni-koeln.de

^e Institute of Medicinal and Pharmaceutical Chemistry, Technische Universitaet Braunschweig, Beethovenstrasse 55, D-38106 Braunschweig, Germany

Abstract

New organometallic complexes [M(dppe)(R)₂] {where M = Pt or Pd, dppe = 1,2-bis(diphenylphosphano)ethane, and R = C₆F₄H-x (x = 6,5,4), C₆F₃H₂-3,5, C₆F₃H₂-5,6, C₆F₃H₂-3,6, C₆F₄(OMe)-4, and C₆F₄(cyclo-C₅H₁₀N)-4, the numbers x refer to the positions of the protons in the polyfluoroaryl ligands} were synthesised either through transmetalation from the dichlorido complexes [M(dppe)Cl₂] or through ligand exchange using [M(diene)Cl₂] precursor complexes with diene = 1,5-cyclooctadiene (cod) or 1,5-hexadiene (hex). Alternatively, [M(dppX)Cl(R)] complexes with dppX = dppm (1,1-bis(diphenylphosphano)methane), dppe, dppp (1,3-bis(diphenylphosphano)propane), and dppb (1,4-bis(diphenylphosphano)butane) were prepared in decarboxylation reactions from thallium(I) carboxylates Tl(O₂CR). The different preparative methods were compared in terms of yield and purity. Structural and spectroscopic data are reported for the new dppX- and diene-M(R)₂ complexes. Antiproliferative activity was investigated for these new complexes against the HT-29 (colon carcinoma) and MCF-7 (breast adenocarcinoma) cell lines, and the active compounds of this first series together with organometallic dppX or hex Pt^II or Pd^II complexes were then included in cell tests using L1210 (leukaemia cells) and the cisplatin-resistant L1210/DDP cell line. Remarkably, promising antiproliferative results were found for a few Pt^II and Pd^II complexes, while structurally closely related compounds were essentially nontoxic.