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.
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.
The starting complex [Pt(Me)(DMSO)(pbz)], (1, (pbz = 2-(2pyridyl)benzimidazolate) was prepared by a known method using the 1 reaction of [Pt(Me) 2 (DMSO) 2 ], A, with Hpbz at room temperature. Reaction of 1 with an equivalent of a phosphine ligand gave the neutral mononuclear complexes [Pt(Me)(L)(pbz)], )] ( 2, (L = PPh 3 ) or and 3, (L =PPh 2 Me). Reaction of 1 with 0.5 equivalent of the linear diphosphine 1,1'-bis(diphenylphosphino)acetylene (dppac) gave the binuclear complex [Pt 2 (Me) 2 (μ-dppac)(pbz) 2 ], 4. All Each the complexes were was fully characterized by NMR spectroscopy, X-ray crystallography and mass spectrometry. The photophysical properties of the complexes were investigated in under different conditions and interpretation was, supported by TD-DFT calculations. The low-lying transitions in the absorption and emission spectra were assigned as having LLCT/MLCT (ligand to ligand charge transfer/metal-to-ligand charge transfer) character. We also describe the luminescence properties of [Pt(Me)(PPh 3 ) (ppy)], 7, and [Pt(Me)(PPh 2 Me)(ppy)], 8, (ppy is 2-phenylpyridinate), the (N^C ) analogues of 2 and 3.
The reactivity of new organoplatinum(ii)–pincer complexes in their oxidative addition reactions with MeI is related to the ancillary ligand and the number of cyclometalated rings present in the coordination sphere of the Pt centre.
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