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

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.