Zheng-Zheng Li

Synthesis of ruthenium(II) complexes and characterization of their cytotoxicity in vitro, apoptosis, DNA-binding and antioxidant activity

A new ligand DBHIP and its two ruthenium (II) complexes [Ru(bpy)(2)(DBHIP)](ClO(4))(2) (1) and [Ru(phen)(2)(DBHIP)](ClO(4))(2) (2) have been synthesized and characterized. The binding behaviors of the two complexes to calf thymus DNA were investigated by absorption spectra, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants for complexes 1 and 2 have been determined to be 8.87+/-0.27 x 10(4)M(-1) (s=1.83) and 1.32+/-0.31 x 10(5)M(-1) (s=1.84). The results suggest that these complexes interact with DNA through intercalative mode. The cytotoxicity of DBHIP, complexes 1 and 2 has been evaluated by MTT assay. The apoptosis assay was carried out with acridine orange/ethidium bromide (AO/EB) staining methods. The studies on the mechanism of photocleavage demonstrate that superoxide anion radical (O(2)(-)) and singlet oxygen ((1)O(2)) may play an important role.

Cytotoxicity In Vitro, Apoptosis, Cellular Uptake, Cell Cycle Distribution, Mitochondrial Membrane Potential Detection, DNA Binding, and Photocleavage of Ruthenium(ii) Complexes

Four new ruthenium(ii) complexes [Ru(bpy)2(NHPIP)](ClO4)2 (Ru-1), [Ru(phen)2(NHPIP)](ClO4)2 (Ru-2), [Ru(bpy)2(AHPIP)](ClO4)2 (Ru-3), and [Ru(phen)2(AHPIP)](ClO4)2 (Ru-4) (bpy = 2,2′-bipyridine; phen = 1,10-phenanthroline; NHPIP = 2-(3-nitro-4-hydroxylphenyl)imidazo[4,5-f][1,10]phenanthroline; AHPIP = 2-(3-amino-4-hydroxylphenyl)imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized by elemental analysis, electrospray mass spectrometry, and 1H NMR spectroscopy. The cytotoxicity in vitro of these complexes against BEL-7402, HeLa, MG-63, and MCF-7 cells was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. Ru-4 shows the highest cytotoxic activity towards the selected cell lines among the four complexes. The morphological apoptosis was assayed by an acridine orange/ethidium bromide staining method, and the percentages of necrotic and apoptotic cells were determined by flow cytometry. The cellular uptake and the cell cycle arrest in BEL-7402 cell was investigated. The results showed these complexes inhibit the proliferation of BEL-7402 cells at G0/G1 phase arrest. The detection of mitochondrial membrane potentials using the fluorescence probe JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide) exhibited that the mitochondrial membrane potentials decrease. Upon irradiation, these complexes can effectively cleave pBR322 DNA.

Ruthenium(II) complexes: synthesis, cytotoxicity in vitro, apoptosis, DNA-binding, photocleavage, and antioxidant activity studies

Two new ruthenium(II) complexes, [Ru(dmp)2(APIP)](ClO4)2 (1) (APIP = 2-(2-aminophenylimidazo[4,5-f][1,10]phenanthroline), dmp = 2,9-dimethyl-1,10-phenanthroline) and [Ru(dmp)2(HAPIP)](ClO4)2 (2) (HAPIP = 2-(2-hydroxyl-5-aminophenyl)imidazo[4,5-f][1,10]phenanthroline), were synthesized and characterized. The DNA-binding properties of these complexes were investigated by absorption titration, viscosity measurements, and photoactivated cleavage. The DNA-binding constants for 1 and 2 have been determined to be 2.3 (± 0.3) × 104 (mol L−1)−1 and 3.3 (± 0.4) × 104 (mol L−1)−1. The results indicate that 1 and 2 interact with DNA through intercalative mode. The cytotoxicities of 1 and 2 were assessed against BEL-7402, HepG-2 and MCF-7 cell lines using standard MTT assay. The apoptosis induced by these complexes was studied with the acridine orange/ethidium bromide staining method. The antioxidant activity on hydroxyl radical was also investigated.

Cytotoxicity, Apoptosis, Cellular Uptake, Cell Cycle Arrest, Photocleavage, and Antioxidant Activity of 1, 10-Phenanthroline Ruthenium(II) Complexes

Two new ruthenium(II) complexes, [Ru(phen)2(DNPIP)](ClO4)2 (1) and [Ru(phen)2(DAPIP)](ClO4)2 (2), were synthesized and characterized. The DNA-binding properties of these complexes were investigated using UV/vis absorption titration, viscosity measurements, thermal denaturation, and photoactivated cleavage. The DNA binding constants for complexes 1 and 2 are 2.63 ± 0.25×10(5) M(-1) (s=2.45) and 1.51±0.18×10(5) M(-1) (s=1.34). The results indicated that these complexes interacted with DNA through the intercalative mode. The cytotoxicity in vitro of complexes 1 and 2 were assessed against BEL-7402, HepG-2, and MCF-7 cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was studied with the acridine orange/ethidium bromide staining method. The antiproliferative mechanism was explored with flow cytometry. Cellular uptake studies showed that complexes 1 and 2 can enter into the cytoplasm and accumulate in the nuclei. Cell cycle arrest and antioxidant activity were also investigated.

Synthesis, characterization, cellular uptake, apoptosis, cytotoxicity, dna-binding, and antioxidant activity studies of ruthenium(II) complexes.

Two new ruthenium(II) polypyridyl complexes [Ru(dmb)2(HECIP)](ClO4)2 (1) (HECIP = N-ethyl-4-[(1,10)-phenanthroline(5,6-f)imidazol-2-yl]carbazole, dmb = 4,4’-dimethyl-2,2’-bipyridine) and [Ru(dmp)2(HECIP)](ClO4)2 (2) (dmp = 2,9-dimethyl-1,10-phenanthroline) have been synthesized and characterized. The DNA-binding behaviors of the two complexes were investigated by absorption spectra, viscosity measurements, and photoactivated cleavage. The DNA-binding constants for complexes 1 and 2 were determined to be 8.03 (± 0.12) × 104 M−1 (s = 1.62) and 2.97 (± 0.15) × 104 M−1 (s = 1.82), respectively. The results suggest that these complexes interact with DNA through intercalative mode. The photocleavage of pBR322 DNA by Ru(II) complexes was investigated. The cytotoxicity of complexes 1 and 2 has been evaluated by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)] method. Complex 1 shows higher anticancer potency than 2 against the four tumor cell lines. Apoptosis and cellular uptake were investigated. The antioxidant activities of the ligand and these complexes were also performed.

Cytotoxicity, apoptosis, interaction with DNA, cellular uptake, and cell cycle arrest of ruthenium(II) polypyridyl complexes containing 4,4′-dimethyl-2,2′-bipyridine as ancillary ligand

Two new ruthenium(II) polypyridyl complexes, [Ru(dmb)2(DNPIP)](ClO4)2 (1) (DNPIP = 2-(2,4-dinitrophenyl)imidazo[4,5-f][1,10]phenanthroline, dmb = 4,4′-dimethyl-2,2′-bipyridine) and [Ru(dmb)2(DAPIP)](ClO4)2 (2) (DAPIP = 2-(2,4-diaminophenyl)imidazo[4,5f][1,10]phenanthroline), were synthesized and characterized. The DNA-binding behaviors of these complexes have been studied by UV-Vis absorption titration, viscosity measurements, and photocleavage. The DNA-binding constants are 7.39 (±0.16) × 104 (s = 2.68) and 2.73 (±0.16) × 104 (mol L−1)−1 (s = 0.64) for 1 and 2, respectively. Their evaluation as cytotoxic agents on different cancer cell lines was investigated with IC50 values of 59.5, 51.3, and 70.3 µmol L−1 for 1, >100, 87.9, and 77.9 µmol L−1 for 2 against BEL-7402, HepG-2, and MCF-7 cells, respectively. Complex 1 is more active than 2 against selected cancer cell lines. The apoptosis induced by these complexes was studied. Cellular uptake showed that these complexes could enter into the cytoplasm and accumulate in the nuclei. The cell cycle arrest and antioxidant activity against hydroxyl radicals were also investigated.

Synthesis, DNA-binding, photocleavage, cytotoxicity, and apoptosis studies of ruthenium(II) complexes containing 3,6-dimethyldipyrido[3,2-a:2′,3′-c]phenazine

Two new ruthenium(II) polypyridyl complexes, [Ru(bpy)2(DMDPPZ)](ClO4)2 (1) (bpy = 2,2′-bipyridine, DMDPPZ = 3,6-dimethyldipyrido[3,2-a:2′,3′-c]phenazine) and [Ru(dmb)2(DMDPPZ)](ClO4)2 (2) (dmb = 4,4′-dimethyl-2,2′-bipyridine), have been synthesized and their DNA-binding, photoinduced DNA cleavage, and cell cytotoxicity are studied. The complexes show good binding to calf thymus DNA in the order: 1 > 2. Both complexes exhibit efficient DNA cleavage upon irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. The cytotoxic activity of 1 and 2 was tested by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method. These complexes effectively inhibit the proliferation of tumor cells. The antioxidant activity against hydroxyl radical (•OH) was also explored.

Bis(2,9-dimethyl-1,10-phenanthroline-κ2N,N′)(10,11,12,13-tetra­hydro­dipyrido[3,2-a:2′,3′-c]phenazine-κ2N4,N5)ruthenium(II) bis­(perchlorate) dihydrate

The title compound, [Ru(C14H12N2)2(C18H14N4)](ClO4)2·2H2O, consists of an RuII complex cation, two perchlorate anions and two uncoordinated water molecules. The RuII ion is chelated by a 10,11,12,13-tetrahydrodipyrido[3,2-a:2′,3′-c]phenazine ligand and two 2,9-dimethyl-1,10-phenanthroline ligands in a distorted octahedral geometry. The two uncoordinated water molecules are disordered over five positions, with an occupancy factor of about 0.4 for each site. A supramolecular structure is formed by weak π–π interactions between neighbouring molecules, with centroid–centroid distances of 3.618 (2) and 3.749 (2) Å.

Bis[bis-(4,4'-dimethyl-2,2'-bipyridine)(10,11,12,13-tetra-hydro-dipyrido[3,2-a:2',3'-c]phenazine)ruthenium(II)] tetra-kis(perchlorate) acetonitrile disolvate monohydrate.

The asymmetric unit of the title compound, [Ru(C12H12N2)2(C18H14N4)]2(ClO4)4·2CH3CN·H2O, contains two RuII complex cations, four perchlorate counter-anions, two uncoordinated acetonitrile molecules and one water molecule. The RuII ions are chelated by one 10,11,12,13-tetrahydrodipyrido[3,2-a:2′,3′-c]phenazine (dpqc) and two 4,4′-dimethyl-2,2′-bipyridine (dmb) ligands in a distorted octahedral geometry. The uncoordinated water molecule is disordered over three positions, with occupancy factors of 0.398 (9), 0.312 (8) and 0.290 (8). A supramolecular structure is formed by weak π–π interactions between neighbouring molecules, with face-to-face distances of 3.51 (1) Å [centroid–centroid distance 3.81 (1) Å].