Labile Pd-sulphur and Pt-sulphur bonds in organometallic palladium and platinum complexes [(COD)M(alkyl)(S-ligand)]n+-A speciation study

Verena Lingen; Anna Lüning; Alexander Krest; Glen B Deacon; Julia Schur; Ingo Ott; Ingo Pantenburg; Gerd Meyer; Axel Klein

doi:10.1016/j.jinorgbio.2016.06.009

Labile Pd-sulphur and Pt-sulphur bonds in organometallic palladium and platinum complexes [(COD)M(alkyl)(S-ligand)]ⁿ⁺-A speciation study

J Inorg Biochem. 2016 Dec:165:119-127. doi: 10.1016/j.jinorgbio.2016.06.009. Epub 2016 Jun 4.

Authors

Verena Lingen¹, Anna Lüning¹, Alexander Krest¹, Glen B Deacon², Julia Schur³, Ingo Ott³, Ingo Pantenburg¹, Gerd Meyer¹, Axel Klein⁴

Affiliations

¹ Department of Chemistry, Institute for Inorganic Chemistry, University of Cologne, Greinstrasse 6, D-50939 Cologne, Germany.
² School of Chemistry, Monash University, PO Box 23, Victoria 3800, Australia.
³ Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, D-38106 Braunschweig, Germany.
⁴ Department of Chemistry, Institute for Inorganic Chemistry, University of Cologne, Greinstrasse 6, D-50939 Cologne, Germany. Electronic address: axel.klein@uni-koeln.de.

PMID: 27338203
DOI: 10.1016/j.jinorgbio.2016.06.009

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.

Keywords: Antiproliferative effects; Crystal structures; Ligand strength; Organopalladium; Organoplatinum; Sulphur ligands.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / chemical synthesis
Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Humans
MCF-7 Cells
Organoplatinum Compounds* / chemical synthesis
Organoplatinum Compounds* / chemistry
Organoplatinum Compounds* / pharmacology
Palladium / chemistry*
Platinum / chemistry*
Sulfur / chemistry*
X-Ray Diffraction

Substances

Antineoplastic Agents
Organoplatinum Compounds
Platinum
Palladium
Sulfur