Novel cis-[(NHC)1(NHC)2(L)Cl]platinum(ii) complexes - synthesis, structures, and anticancer activities.
A general synthesis of novel platinum(ii) complexes bearing two different, cis-oriented, N-heterocyclic carbene (NHC) ligands is presented. Easily accessible cis-[PtII(NHC)(DMSO)] precursor complexes were converted to either cis-[PtII(NHC)2Cl2] complexes such as 5a and 5b, or to novel mixed cis-[PtII(NHC)1(NHC)2Cl2] complexes such as 5c-h by successive introduction of the individual carbene ligands. The 'symmetric' complexes 5a and 5b were also converted to cationic cis-[PtII(NHC)2(PPh3)Cl]+Cl-complexes 8a and 8b. The structures of the ten new complexes, comprising benzylated and alkylated imidazol-2-ylidene ligands, were analysed by1H,13C and195Pt NMR spectroscopy and also by X-ray diffraction for 5a, 5d, 5h, and 8a. The neutral complexes 5 were cytotoxic against a panel of seven human cancer cell lines with IC50values in the low micromolar range, while the cationic complexes 8 reached even nanomolar IC50values. Complex 5h carrying the substitution pattern of the natural antitumoral agent Combretastatin A-4 showed a conspicuous specificity for cancer cell lines sensitive to this drug. In electrophoretic mobility shift assays, the cis-biscarbene complexes 5b and 8b led to an unwinding or aggregation of plasmid DNA, while the trans-biscarbene complex 1b showed no such effect.
Organic Chemistry Laboratory, University Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany. Rainer.Schobert@uni-bayreuth.de.
Tobias
T
Rehm
Matthias
M
Rothemund
Julienne K
JK
Muenzner
Awal
A
Noor
Rhett
R
Kempe
Rainer
R
Schobert
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D015394:Molecular Structure; D010984:Platinum / Q000737:chemistry*
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D006571:Heterocyclic Compounds; D008024:Ligands; C030011:carbene; D010984:Platinum; D008697:Methane