ABSTRACT
Linear diaryliodonium salts are widely used as arylating reagents for C-C and C-X bond formation. Meanwhile, synthetic applications of cyclic iodoniums are relatively rare although they offer the opportunity to set up reaction cascades. We demonstrate an atom and step economical three-component reaction involving cyclic diphenyleneiodoniums, alkynes, and boronic acids, resulting in the construction of methylidenefluorenes in a single operation. Our route enables facile access to both symmetrical and unsymmetrical methylidenefluorene derivatives, compounds that have attracted interest due to their optical properties.
Subject(s)
Boronic Acids/chemistry , Copper/chemistry , Fluorenes/chemical synthesis , Onium Compounds/chemistry , Palladium/chemistry , Catalysis , Fluorenes/chemistry , Molecular StructureABSTRACT
Many ruthenium(II) complexes show high antitumor activities, and the in vitro antitumor activities are usually related to DNA binding. We designed and synthesized two Ru(II) polypyridyl complexes, [Ru(dmp)2(fpp)]2+ (dmp=2,9-dimethyl-1,10-phenanthroline; fpp=2-[3,4-(difluoromethylenedioxy)phenyl]imidazo[4,5-f] [1,10]phenanthroline and [Ru(phen)(2)(fpp)]2+ (phen=1,10-phenanthroline). The DNA-binding properties of these complexes have been investigated by spectroscopic titration, DNA melting experiments, viscosity measurements, and photoactivated cleavage. The mechanism studies of photocleavage revealed that singlet oxygen (1O2) and superoxide anion radical (O2(.-)) may play an important role in the photocleavage. The cytotoxicity of complexes 1 and 2 have been evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) method; complex 2 shows slightly higher anticancer potency than 1 does against all the cell lines screened.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , DNA/metabolism , Neoplasms/drug therapy , Ruthenium Compounds/chemistry , Ruthenium Compounds/pharmacology , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Cell Survival/drug effects , Humans , Models, Molecular , Molecular Structure , Nucleic Acid Denaturation/drug effects , Phenanthrolines/chemical synthesis , Phenanthrolines/chemistry , Phenanthrolines/pharmacology , Photochemical Processes/drug effects , Ruthenium Compounds/chemical synthesis , Viscosity/drug effectsABSTRACT
A new ligand DBHIP and its two ruthenium(II) complexes [Ru(dmb)(2)(DBHIP)](ClO(4))(2) (1) and [Ru(dmp)(2)(DBHIP)](ClO(4))(2) (2) have been synthesized and characterized. The cytotoxicity of DBHIP and complexes 1 and 2 has been assessed by MTT assay. The apoptosis studies were carried out with acridine orange/ethidium bromide (AO/EB) staining methods. The binding behaviors of these complexes to calf thymus DNA (CT-DNA) were studied by absorption titration, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants of complexes 1 and 2 were determined to be 8.64 +/- 0.16 x 10(4) (s = 1.34) and 2.79 +/- 0.21 x 10(4) (s = 2.17) M(-1). The results suggest that these complexes interact with DNA through intercalative mode. 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 in the DNA cleavage. The experiments on antioxidant activity show that these compounds also exhibit good antioxidant activity against hydroxyl radical (OH*).
Subject(s)
Antioxidants , Apoptosis/drug effects , DNA/drug effects , DNA/metabolism , Phenanthrolines/chemistry , Ruthenium Compounds , Animals , Antioxidants/chemical synthesis , Antioxidants/chemistry , Antioxidants/pharmacology , Cattle , Cell Line , DNA/chemistry , DNA Cleavage/drug effects , Ligands , Molecular Structure , Nucleic Acid Denaturation , Ruthenium Compounds/chemical synthesis , Ruthenium Compounds/chemistry , Ruthenium Compounds/pharmacology , ViscosityABSTRACT
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.
Subject(s)
Apoptosis/drug effects , DNA/metabolism , Free Radical Scavengers/metabolism , Free Radical Scavengers/pharmacology , Organometallic Compounds/metabolism , Organometallic Compounds/pharmacology , Ruthenium/chemistry , Absorption , Animals , Cattle , Cell Line, Tumor , DNA/chemistry , Electrons , Free Radical Scavengers/chemical synthesis , Free Radical Scavengers/chemistry , Humans , Hydroxyl Radical/chemistry , Inhibitory Concentration 50 , Luminescent Measurements , Nucleic Acid Denaturation , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , Phenanthrolines/chemistry , Photochemical Processes , Plasmids/genetics , Transition Temperature , ViscosityABSTRACT
Two new ligands maip (1) (maip = 2-(3-aminophenyl)imizado[4,5-f][1,10]phenanthroline), paip (2) (paip = 2-(4-aminophenyl)imidazo[4,5-f][1,10]phenanthroline), and their ruthenium (II) complexes [Ru(phen)(2)(maip)](ClO(4))(2) (3) and [Ru(phen)(2)(paip)](ClO(4))(2) (4) (phen = 1,10-phenanthroline) have been synthesized and characterized. The cytotoxicity of these compounds was evaluated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The apoptosis assay was carried out with acridine orange/ethidium bromide staining methods. The DNA-binding behaviors of complexes 3 and 4 were investigated by viscosity measurements, thermal denaturation, photocleavage, and spectroscopic methods. The results show that the two complexes intercalate into the base pairs of DNA. In the presence of a complex, apoptosis of BEL-7402 cells was observed. Experiments show that these compounds exhibit antioxidant activity against hydroxyl radicals.
Subject(s)
DNA/metabolism , Intercalating Agents/toxicity , Ruthenium/toxicity , Animals , Apoptosis/drug effects , Cell Line, Tumor , Humans , Intercalating Agents/chemistry , Intercalating Agents/metabolism , Phenanthrolines/chemical synthesis , Phenanthrolines/chemistry , Phenanthrolines/toxicity , Ruthenium/chemistry , Ruthenium/metabolism , ViscosityABSTRACT
The title compound, [Ru(C(14)H(12)N(2))(2)(C(18)H(14)N(4))](ClO(4))(2)·2H(2)O, consists of an Ru(II) complex cation, two perchlorate anions and two uncoordinated water mol-ecules. The Ru(II) ion is chelated by a 10,11,12,13-tetra-hydro-dipyrido[3,2-a:2',3'-c]phenazine ligand and two 2,9-dimethyl-1,10-phenanthroline ligands in a distorted octa-hedral geometry. The two uncoord-inated water mol-ecules are disordered over five positions, with an occupancy factor of about 0.4 for each site. A supra-molecular structure is formed by weak π-π inter-actions between neighbouring mol-ecules, with centroid-centroid distances of 3.618â (2) and 3.749â (2)â Å.
ABSTRACT
Two new ligands maip (1a), paip (1b) with their ruthenium (II) complexes [Ru(bpy)(2)(maip)](ClO(4))(2) (2a) and [Ru(bpy)(2)(paip)](ClO(4))(2) (2b) have been synthesized and characterized. The results show that complexes 2a and 2b interact with DNA through intercalative mode. The cytotoxicity of these compounds has been evaluated by MTT assay. The experiments on antioxidant activity show that these compounds exhibit good antioxidant activity against hydroxyl radical (OH).
Subject(s)
DNA/metabolism , Free Radical Scavengers/chemical synthesis , Free Radical Scavengers/metabolism , Organometallic Compounds/chemical synthesis , Organometallic Compounds/metabolism , Photochemical Processes , Pyridines/chemistry , Ruthenium/chemistry , Absorption , Animals , Cattle , Cell Line, Tumor , Cell Survival/drug effects , DNA/chemistry , Electrons , Free Radical Scavengers/pharmacology , Free Radical Scavengers/toxicity , Humans , Hydroxyl Radical/chemistry , Nucleic Acid Denaturation , Organometallic Compounds/pharmacology , Organometallic Compounds/toxicity , Rats , Spectrum Analysis , Transition Temperature , ViscosityABSTRACT
Two new ligands, 3-(pyrazin-2-yl)-as-triazino[5,6-f]-5-methoxylisatin (dtmi), 3-(pyrazin-2-yl)-as-triazino[5,6-f]-5-nitroisatin (dtni) and their ruthenium(II) complexes [Ru(phen)2(dtmi)](ClO4)2 (1) and [Ru(phen)2(dtni)](ClO4)2 (2) have been prepared and characterized by elemental analysis, FAB-MS, ES-MS and 1H NMR. The DNA-binding behaviors of complexes have been studied by spectroscopic titration, viscosity measurements, thermal denaturation and circular dichromism (CD). The results indicate that the complexes 1 and 2 interact with calf thymus DNA (CT-DNA) by intercalative mode. The DNA-binding affinity of the complexes 2 is larger than that complex 1 does.
