Cyclometalated rollover complexes of the type [PtMe(κ N,C-bipyO-H)(L)] [bipyO-H=cyclometalated 2,2'-bipyridine N-oxide; L=tricyclohexylphosphine (PCy , 2 a), 2-(diphenylphosphino)pyridine (PPh py, 2 b), P(OPh) (2 c)] were synthesized by treating [PtMe(κ N,C-bipyO-H)(SMe )] (1) with various monodentate phosphine and phosphite ligands. These complexes were characterized by NMR spectroscopy, and the structure of 2 a was confirmed by single-crystal X-ray diffraction. Complex 1 was treated with bis(diphenylphosphino)methane (dppm) at a 1:1 ratio to give the corresponding [PtMe(κ N,C-bipyO-H)(κ P-dppm)] (3 b) complex, in which the dppm ligand acts as a monodentate pendant ligand. The biological activities of these complexes were evaluated against a panel of four standard cancer cell lines: lung carcinoma (A549), ovarian carcinoma (OV-90 and SKOV3), and breast carcinoma (MCF-7). Complexes 2 c and especially 3 b indicated effective potent cytotoxic activity regarding the cell lines. Electrophoresis mobility shift assays and molecular-modeling investigations were performed to determine the specific binding mode and the binding orientation of these alkylating agents to DNA. Detection of cellular reactive oxygen species was also determined.

Half-lantern Pt(ii) and Pt(iii) cyclometalated binuclear complexes, bridged with various heterocyclic thiolate ligands, were synthesized and studied by electrochemical and photophysical techniques.

The known cyclometalated platinum(II) complex [Pt(ppy)(DMSO)(Cl)] (A) in which ppy = 2‐phenylpyridinate, was treated with 2‐(diphenylphosphino)pyridine (PPh2py, PN) (1 equiv.) and readily afforded complex [Pt(ppy)(PPh2py‐κ1P)(Cl)] (1). The transphobia effect (T) and single‐crystal X‐ray diffraction crystallography confirmed that the phosphine ligand in 1 is located trans to the nitrogen atom of the cyclometalating fragment (ppy). Compound 1 was treated with various thiolate reagents (1 equiv.) at room temperature, leading to the displacement of the chloride ligand in 1 by thiolate ligands through a salt metathesis reaction. The reaction led to the formation of a series of monomeric complexes with the general formula [Pt(ppy)(PPh2py‐κ1P)(SR)] (2a–2d), where SR = deprotonated form of pyridine‐2‐thiol (HSpy, 2a), pyrimidine‐2‐thiol (HSpyN, 2b), thiophenol (HSPh, 2c), and 2‐thiazoline‐2‐thiol (HSt, 2d). All complexes have been characterized by NMR spectroscopy. The biological activities of the complexes were evaluated against three human cancer cell lines, including A549 (human lung cancer), SKOV3 (human ovarian cancer), and MCF7 (human breast cancer), by means of the MTT assay [MTT = 3‐(4,5‐dimethylthiazol‐yl)‐2,5‐diphenyltetrazolium bromide]. Compounds 2a and 2b presented effective, potent cytotoxic activity regarding the cell lines. Electrophoretic mobility shift assays on plasmid DNA and molecular modeling investigations were also performed to determine the specific binding mode or the binding orientation of the complexes to DNA.

Complex 1 was reacted with different alkyl halides at room temperature. This reaction proceeded via formation of binuclear intermediate complex 3 and through C–S bond reductive coupling to produce alkyl sulfides and corresponding halide complexes 2.