Ligand-Mediated C-Br Oxidative Addition to Cycloplatinated(II) Complexes and Benzyl-Me C-C Bond Reductive Elimination from a Cycloplatinated(IV) Complex.

Reaction of the Pt(II) complexes [PtMe2(pbt)], 1a, (pbt = 2-(2-pyridyl)benzothiazole) and [PtMe(C^N)(PPh2Me)] [C^N = deprotonated 2-phenylpyridine (ppy), 1b, or deprotonated benzo[h]quinoline (bhq), 1c] with benzyl bromide, PhCH2Br, is studied. The reaction of 1a with PhCH2Br gave the Pt(IV) product complex [PtBr(CH2Ph)Me2(pbt)]. The major trans isomer is formed in a trans oxidative addition (2a), while the minor cis products (2a' and 2a″) resulted from an isomerization process. A solution of Pt(II) complex 1a in the presence of benzyl bromide in toluene at 70 °C after 7 days gradually gave the dibromo Pt(IV) complex [Pt(Br)2Me2(pbt)], 4a, as determined by NMR spectroscopy and single-crystal XRD. The reaction of complexes 1b and 1c with PhCH2Br gave the Pt(IV) complexes [PtMeBr(CH2Ph)(C^N)(PPh2Me)] (C^N = ppy; 2b; C^N = bhq, 2c), in which the phosphine and benzyl ligands are trans. Multinuclear NMR spectroscopy ruled out other isomers. Attempts to grow crystals of the cycloplatinated(IV) complex 2b yielded a previously reported Pt(II) complex [PtBr(ppy)(PPh2Me)], 3b, presumably from reductive elimination of ethylbenzene. UV-vis spectroscopy was used to study the kinetics of reaction of Pt(II) complexes 1a-1c with benzyl bromide. The data are consistent with a second-order SN2 mechanism and the first order in both the Pt complex and PhCH2Br. The rate of reaction decreases along the series 1a ≫ 1c > 1b. Density functional theory calculations were carried out to support experimental findings and understand the formation of isomers.

Chelating and Bridging Roles of 2-(2-Pyridyl)benzimidazole and Bis(diphenylphosphino)acetylene in Stabilizing a Cyclic Tetranuclear Platinum(II) Complex.

The reaction of complex [Pt(Me)(DMSO)(pbz)], 1, (pbz = 2-(2-pyridyl)benzimidazolate) with [PtMe(Cl)(DMSO)2], B, followed by addition of bis(diphenylphosphino)acetylene (dppac), gave the novel tetranuclear platinum complex [Pt4Me4(µ-dppac)2(pbz)2Cl2], 2, bearing both the pbz and dppac ligands. In this structure, the pbz ligands are both chelating and bridging to stabilize the tetraplatinum framework. The tetranuclear Pt(II) complex was fully characterized by NMR spectroscopy, X-ray crystallography, and mass spectrometry, and its electronic structure was investigated and supported by DFT calculations.

Effects of the number of cyclometalated rings and ancillary ligands on the rate of MeI oxidative addition to platinum(ii)-pincer complexes.

Organoplatinum(ii)-pincer complexes [Pt(C^N^C)(L)] (2a; L = PPh2Me, 2b; L = pyridine (py), 2c; L = 4-picoline (pic)) are synthesized by the reaction of [Pt(C^N^C)(DMSO)], 1, with 1 equiv. of L, where HC^N^CH = 2,6-diphenylpyridine. Complexes 2 have 5d(Pt) →π*(pincer) metal-to-ligand charge-transfer bands in the visible region, which were used to easily follow the kinetics of their reactions with MeI by using UV-vis spectroscopy. An SN2 mechanism is suggested and the proposed intermediates were supported by DFT calculations. Consistent with the proposed mechanism, the rates of the reactions at different temperatures were slower for L = PPh2Me than those for L = N-donor ligands and large negative ΔS‡ values were found for all oxidative addition reactions. The rates are almost 2 times slower for L = PPh2Me as compared to L = 4-picoline because of the steric effects and the electronic effects transmitted through the ligands. To investigate the effect of the number of cyclometalated rings on the rate of MeI oxidative addition, the kinetics of the reaction of [Pt(Ph)(ppy)(py)] (Hppy = 2-phenylpyridine) and [Pt(Ph)2(py)2] (having 1 and zero cyclometalated ring, respectively) with MeI were also studied and a correlation between the number of cyclometalated rings and the rate of the oxidative addition reaction was found.

Anticancer and DNA binding activities of platinum (IV) complexes; importance of leaving group departure rate.

The two six-coordinate Pt(IV) complexes, containing bidentate nitrogen donor/methyl ligands with general formula [Pt(X)2Me2((t)bu2bpy)], where (t)bu2bpy = 4,4'-ditert-butyl-2,2'-bipyridine and X = Cl (C1) or Br (C2), serving as the leaving groups were synthesized for evaluation of their anticancer activities and DNA binding properties. To examine anticancer activities of the synthetic complexes, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ethidium bromide/acridine orange (EB/AO) staining method were performed. The binding properties of these complexes to DNA and purine nucleotides were examined, using different spectroscopic techniques. These complexes demonstrated significant anticancer activities against three cancer cell lines Jurkat, K562, and MCF-7. On the basis of the results of EB/AO staining, C1 and C2 were also capable to induce apoptosis in cancer cells. These complexes comprise halide leaving groups, displaying different departure rates; accordingly, they demonstrated slightly dissimilar anticancer activity and significantly different DNA/purine nucleotide binding properties. The results of DNA interaction studies of these complexes suggest a mixed-binding mode, comprising partial intercalation and groove binding. Overall, the results presented herein indicate that the newly synthesized Pt(IV) complexes are promising class of the potential anticancer agents which can be considered as molecular templates in designing novel platinum anticancer drugs. This study also highlights the importance of leaving group in anticancer activity and DNA binding properties of Pt(IV) complexes.