Dinuclear platinum(II) complexes of imidazophenanthroline-based bridging ligands as potential anticancer agents: synthesis, characterization, and in vitro cytotoxicity studies.

The synthesis and characterization of the dinucleating ligands 1,2-bis(2-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenoxy)ethane (L1) and 1,2-bis(2-(1H-imidazo[4,5-f][1, 10]phenanthrolin-2-yl)phenoxy)hexane (L2) and their dinuclear complexes [Pt2(L1)Cl4] (1) and [Pt2(L2)Cl4] (2) and the in vitro cytotoxicity of the complexes against HeLa, HepG2, and MCF-7 cell lines are reported. Ligand L1 crystallizes in the orthorhombic system with the space group Pbca. The complexes 1 and 2 undergo aquation following first-order kinetics. The MTT and trypan blue assays indicate higher cytotoxicity of the complexes towards the HepG2 and MCF-7 cell lines compared to cisplatin. The AO/EB assay and flow cytometry by Annexin V alexa fluor®488/PI double staining assay demonstrate distinct morphological changes of apoptosis in a dose dependent manner. The cell cycle analysis shows a marked decrease in the DNA content in the G0/G1 phase with an increase in the G2/M phase on increasing the concentration of the complexes. The potential of the complexes as anticancer agents is demonstrated by their antiproliferative activity on the cell lines. The complexes interact with the major groove of DNA through H-bonding between the imidazole N-H protons and the nucleotide residues DC`21/N4 (cytosine) for complex 1 and DT`7/O2 (thymine) and DT`19/O2 (thymine) for complex 2, with the binding energy of - 1.98 and - 4.45 kcal/mol, respectively. Dinuclear Pt(II) complexes of imidazophenanthroline-based dinucleating ligands exhibit antiproliferative activity against HeLa, HepG2, and MCF-7 cell lines.

Platinum(II) complexes of imidazophenanthroline-based polypyridine ligands as potential anticancer agents: synthesis, characterization, in vitro cytotoxicity studies and a comparative ab initio, and DFT studies with cisplatin, carboplatin, and oxaliplatin.

The synthesis of the platinum(II) complexes, [Pt(AIP)(bpy)](PF6)2 (1) and [Pt(PIP)(phen)](PF6)2 (2), of anthracene- and pyrene-conjugated imidazophenanthroline ligands and their in vitro cytotoxicity toward the fibroblast cells and the HeLa cell lines are reported. MTT assay demonstrates their cytotoxicity against the HeLa cell lines with the IC50 values of 1.35 and 1.56 µM, respectively, and the cytotoxicity profiles indicate that the HeLa cell lines show more activity than the fibroblast cells. Trypan blue assay highlights significant damage on the HeLa cell lines with a pronounced reduction on their clonogenicity. AO/EB staining shows marked morphologic signs of apoptosis in a dose-dependent manner and the LDH and DNA laddering assays also lend support to the cytotoxicity of the complexes. The molecular docking study reveals that the complexes interact with DNA through hydrogen bonding. The TD-DFT energy-optimized structures of the complexes show that the platinum(II) center has a slightly distorted square-planar geometry. The TD-DFT modelled LUMOs receive major contributions from the platinum d-orbitals, while the HOMOs are delocalized largely on the anthracenyl- and pyrenyl ligands, resulting in the LMCT transition at 352 nm. The structural, bonding, electronic, and optical properties of the complexes 1 and 2 reported in the present work and that of [Pt(AIP)(phen)](PF6)2 (3) and [Pt(PIP)(bpy)](PF6)2 (4), reported by us recently, and the approved drugs cisplatin, carboplatin, and oxaliplatin are described in the light of the optimized geometries, ΔEHOMO-LUMO, polarizability (α), hyperpolarizability (ß), Mulliken negativities, and dipole moments computed from the ab initio and DFT computational studies. The synthesis of Pt(II) complexes of anthracene- and pyrene-appended imidazophenanthroline ligands and their in vitro cytotoxicity against fibroblast cells and HeLa cell lines are reported. The DFT computational study of the complexes and cisplatin, carboplatin, and oxaliplatin are described in search of the ligand design features for the development of new Pt-drugs.

Synthesis, relaxivity, and in vitro fluorescence imaging studies of a novel d-f heterometallic trinuclear complex as a potential bimodal imaging probe for MRI and optical imaging.

A new trinuclear heterometallic Ru(II)-Gd complex of 4-aminopyridine appended DO3A (DO3A = 1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) with 2,2'-bipyridine as ancillary ligands is synthesized and its relaxometry and in vitro fluorescence imaging studies are reported. The complex [Ru(bpy)2{Gd(DOTA-AMpy)(H2O)}2]Cl2 (7) exhibits a "per Gd" longitudinal relaxivity (r1p) of 5.80 and 14.30 mM(-1) s(-1) in aqueous solution and in the presence of HSA, respectively (20 MHz, pH = 7.4, PBS, 37 °C). The complex 7 exhibits an intense (1)MLCT absorption band at 480 nm and luminesces at 595 nm with a luminescence quantum yield of 3.2%. The fluorescence microscopy imaging study of HeLa cells incubated with 7 and stained with ethidium bromide and acridine orange confirms that the cells are viable throughout the imaging experiments and its cytotoxicity against HeLa cells, studied by the MTT assay, demonstrates its use for bioimaging studies. HeLa cell lines treated with the complex 7 and stained with Hoechst-33342 showed marked morphological signs of apoptosis in a dose-dependent manner by inducing changes in cell cycle arrest at the G2/M phase. Furthermore, apoptosis of HeLa cells, studied by the DNA ladder assay, indicates apoptotic cell death lending support for the antitumor activity of 7. A molecular docking study reveals that the complex 7 intercalates into the major groove of the DNA stabilized by hydrogen bonding and it binds with HSA by electrostatic- and hydrogen bonding interactions. The relaxometry, luminescence and fluorescence imaging studies indicate that the Ru(II)-Gd complex 7 has a good cell membrane permeability and could be considered as a potential bimodal imaging probe.