title: Labile Pd-sulphur and Pt-sulphur bonds in organometallic palladium and platinum complexes [(COD)M(alkyl)(S-ligand)]n+-A speciation study.
abstract: Reaction of various sulphur ligands L (SEt-, SPh-, SC6F4H-4-, SEt2, StBu2, SnBu2, DMSO, DPSO) with the precursors [(COD)M(R)Cl] (COD=1,5-cyclooctadiene, M=Pd or Pt; R=methyl (Me) or benzyl (Bn); DMSO=dimethyl sulfoxide; DPSO=diphenyl sulfoxide) allowed isolation and characterisation of mononuclear neutral (n=0) or cationic (n=1) complexes [(COD)Pt(R)(L)]n+. Reaction of l-cysteine (HCys) with [(COD)Pt(Me)Cl] under similar conditions gave the binuclear cationic complex in [{(COD)Pt(Me)}2(μ-Cys)]Cl. Detailed NMR spectroscopy and single crystal X-ray diffraction in the case of [(COD)Pt(Me)(SEt2)][SbF6] and [(COD)Pt(Me)(DMSO)][SbF6] reveal markedly labilised Pt-S bonds as a consequence of the highly covalent Pt-C bonds of the R coligands in these organometallic species. Cationic charge (n=1) seems to lower the Pt-S bond strength further. Consequently, most of these complexes are not stable long-term in aqueous DMF (N,N-dimethylformamide) solutions. This made the evaluation of their antiproliferative properties towards HT-29 colon carcinoma and MCF-7 breast adenocarcinoma cell lines impossible. Only the two complexes [(COD)Pt(R)(SC6F4H-4)] with R=Me or SC6F4H-4 coligands could be tested with the R=Me complex showing promising activity (in the range of cisplatin), while the R=SC6F4H-4 derivative is largely inactive, as were the phosphane complexes [(dppe)Pt(SC6F4H-4)2] (dppe=1,2-bis(diphenylphosphino)ethane), cis-[(PPh3)2Pt(SC6F4H-4)2] and cis-[(PPh3)2PtCl2] which were tested for comparison. In turn, our findings might pave the way to new Pt anti-cancer drugs with largely reduced unwanted depletion of incorporated drugs and reduced side-effects from binding to S-containing biomolecules.
authors.affiliation: Department of Chemistry, Institute for Inorganic Chemistry, University of Cologne, Greinstrasse 6, D-50939 Cologne, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Lingen
authors.affiliation: Department of Chemistry, Institute for Inorganic Chemistry, University of Cologne, Greinstrasse 6, D-50939 Cologne, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Lüning
authors.affiliation: Department of Chemistry, Institute for Inorganic Chemistry, University of Cologne, Greinstrasse 6, D-50939 Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Krest
authors.affiliation: School of Chemistry, Monash University, PO Box 23, Victoria 3800, Australia.
authors.forename: Glen B
authors.initials: GB
authors.lastname: Deacon
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, D-38106 Braunschweig, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Schur
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, D-38106 Braunschweig, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Ott
authors.affiliation: Department of Chemistry, Institute for Inorganic Chemistry, University of Cologne, Greinstrasse 6, D-50939 Cologne, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Pantenburg
authors.affiliation: Department of Chemistry, Institute for Inorganic Chemistry, University of Cologne, Greinstrasse 6, D-50939 Cologne, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Meyer
authors.affiliation: Department of Chemistry, Institute for Inorganic Chemistry, University of Cologne, Greinstrasse 6, D-50939 Cologne, Germany. Electronic address: axel.klein@uni-koeln.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Klein
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010165:Palladium / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D013455:Sulfur / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010984:Platinum; D010165:Palladium; D013455:Sulfur
keywords: Antiproliferative effects; Crystal structures; Ligand strength; Organopalladium; Organoplatinum; Sulphur ligands