ABSTRACT
Coumarins are found in higher plants like Rutaceae and Umbelliferae and essential oils of cinnamon bark, cassia leaf, and lavender oil. Coumarin compounds show different biological properties, viz antimicrobial, antibacterial, antifungal, antioxidant, antitumor, anti-HIV, antihypertension, anticoagulant, anticancer, antiviral, anti-inflammatory, analgesics, antidiabetic, anti-depressive, and other bioactive properties. Coumarin and its derivatives possess anticancer activity against different types of cancers such as prostate, renal, breast, laryngeal, lung, colon, CNS, leukemia, malignant melanoma. In this review, current developments of coumarin-based anticancer agents viz simple coumarin, furanocoumarin, pyranocoumarin, pyrone-substituted coumarin, and their important derivatives have been discussed. The coumarin-triazole, coumarin-chalcone, coumarin-thiosemicarbazone derivatives, and coumarin-metal complexes have been found more potent than coumarin. Hence, further study and structural improvement on coumarin and its derivatives may lead to the design and development of more potent anticancer agents.
Subject(s)
Anti-Infective Agents , Antineoplastic Agents , Neoplasms , Anti-Infective Agents/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Coumarins/chemistry , Coumarins/pharmacology , Humans , Neoplasms/drug therapyABSTRACT
Being a structural and catalytic cofactor in a number of biological pathways, copper accumulates in tumors owing to selective permeability of the cancer cell membranes. Copper(II) ion forms the active centers in a large number of metalloproteins. The coordination of Schiff's base ligands to the metal ion results in the high extent of increase in anticancer activity. The copper(II) complexes can cleave DNA through oxidative and hydrolytic pathways, cell apoptosis via intrinsic reactive oxygen species (ROS) mediated mitochondrial pathway due to excessive production of ROS and hence, are found more active than Ni and Pt complexes. Flexible Cu(I/II) redox behavior helps the copper complexes to form more potent, clinically effective and less toxic copper based antiproliferative drugs of lower IC50 value and higher growth inhibitory activity. Copper(II) complexes of thiosemicarbazones of Isatin, Pyridine, Benzoyl pyridine, Diacetyl/Dimethyl glyoxal, Acetophenone/Acetoacetanalide, Thiazole/Pyrazole, Quinoline, Carboxybenzaldehyde, Cinnamaldehyde/Cuminaldehyde, Citronellal, Chromone, Pyridoxal, 8-Ethyl-2-hydroxytricyclo (7.3.1.02,7) tridecan-13-one, Acyl Diazines, Naphthalene, Proline, 5-Formyluracil, 2-Hydroxy-8-propyltricyclo (7.3.1.02,7) tridecan-13-one, 9-cis-Retinal, Curcumin, Helicin (Salicylaldehyde-ß-D-glucoside), Thiophene carboxaldehyde, Salicylaldehyde, Iminodiacetate, and 3-Formyl-4-hydroxy benzenesulfonic acid have been found to exhibit more anticancer activity toward HCT116, MCF7, A549, U937, HeLa, HepG2, SGC-7901, A2780 cell lines than that of their corresponding thiosemicarbazones and standard topoisomerase-II inhibitors.
Subject(s)
Antineoplastic Agents/therapeutic use , Coordination Complexes/therapeutic use , Neoplasms/drug therapy , Thiosemicarbazones/therapeutic use , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Copper/chemistry , Drug Screening Assays, Antitumor , Humans , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Reactive Oxygen Species/metabolism , Thiosemicarbazones/chemistry , Thiosemicarbazones/pharmacology , Topoisomerase II Inhibitors/chemistry , Topoisomerase II Inhibitors/pharmacology , Topoisomerase II Inhibitors/therapeutic useABSTRACT
Here, we report the delivery of a cell-impermeable [Ru(bpy)2dppz]2+ complex across a cell membrane using a cucurbit[7]uril molecular container. Encapsulation of complex 1 in the cucurbit[7]uril cavity showed an 830-fold enhancement in the luminescence intensity of the non-emissive complex in aqueous solution. This molecular light-switch effect stems from the incorporation of the dppz ligand of 1 inside the CB7 cavity and can be attributed to long range coulombic forces between Ru2+ and the carbonyl portal of CB7 via CHO interactions. This is reflected in the 1H-NMR experiments, and further corroborated by theoretical calculations.
Subject(s)
Bridged-Ring Compounds/chemistry , Imidazoles/chemistry , Organometallic Compounds/chemistry , Organometallic Compounds/metabolism , Ruthenium/chemistry , Biological Transport , Cell Membrane/metabolism , Cell Survival , Humans , Luminescent Measurements , MCF-7 Cells , Models, Molecular , Molecular Conformation , Permeability , Water/chemistryABSTRACT
The reaction of aryl imidazo[4,5f] [1,10]phenanthrolines with Cu(NO3)2 lead to the formation of Cu(II) complexes of the type [Cu(L)(NO3)2] where L=PIP, 2-(phenyl) [4,5f] imidazo phenanthroline; HPIP=2-(2-hydroxyphenyl)imidazo [4,5f] phenanthroline and NIP=2-(naphthyl) [4,5f] imidazo phenanthroline. The interaction of these complexes with calf thymus DNA has been studied using viscosity measurements, UV-visible and fluorescence spectroscopy. Chemical nuclease activity of these complexes has also been investigated. All complexes cleave DNA via oxidative pathway involving singlet oxygen. Molecular docking studies revealed that these complexes bind to DNA through minor groove.
Subject(s)
Coordination Complexes/chemistry , Copper/chemistry , DNA/chemistry , Electrochemical Techniques , Imidazoles/chemistry , Molecular Docking Simulation , Phenanthrolines/chemistry , Singlet Oxygen/chemistryABSTRACT
Two new zinc(ii) complexes, [Zn(l-His)(NIP)]+(1) and [Zn(acac)2(NIP)](2) (where NIP is 2-(naphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline, acac = acetyl acetone), have been synthesized and characterized by elemental analysis, UV-vis, fluorescence, IR, 1H NMR and electron spray ionization mass spectroscopies. Gel retardation assay, atomic force microscopy and dynamic light scattering studies show that 1 and 2 can induce the condensation of circular plasmid pBR322 DNA into nanometer size particles under ambient conditions. Treatment of 2 with 5 mM EDTA restored 30% of the supercoiled form of DNA, revealing partial reversibility of DNA condensation. The in vitro transfection experiment demonstrates that the complexes can be used to deliver pCMV-tdTomato-N1 plasmid which expresses red fluorescent protein. The confocal studies show that the fluorescent nature of complexes is advantageous for visualizing the intracellular delivery of metal complexes as well as transfection efficiency using two distinct emission windows.
Subject(s)
Coordination Complexes/chemistry , DNA, Circular/administration & dosage , Fluorescent Dyes/chemistry , Plasmids/administration & dosage , Transfection/methods , Zinc/chemistry , DNA, Circular/genetics , Gene Expression , Gene Transfer Techniques , Humans , Imidazoles/chemistry , Luminescent Proteins/genetics , MCF-7 Cells , Microscopy, Confocal , Naphthalenes/chemistry , Optical Imaging , Phenanthrolines/chemistry , Plasmids/genetics , Red Fluorescent ProteinABSTRACT
A series of Ru(II) arene complexes of mono- and bidentate N-donor ligands with carboxyl or ester groups and chlorido ancillary ligands were synthesised and structurally characterised. The complexes have a distorted tetrahedral piano-stool geometry. The binding interaction was studied with calf thymus DNA (CT-DNA) by absorption titration, viscosity measurement, thermal melting, circular dichroism, ethidium bromide displacement assay and DNA cleavage of plasmid DNA (pBR322), investigated by gel electrophoresis. The dichlorido complexes bind covalently to DNA in the dark, similar to cisplatin, while the monochlorido complexes bind covalently on irradiation, similar to cisplatin analogues. The compounds are selectively cytotoxic against several tumour cell lines and show specific nonlinear correlation between dose and activity. This phenomenon is closely related to their potential to act preferentially as inhibitors of cell division.
Subject(s)
Antineoplastic Agents/pharmacology , Coordination Complexes/pharmacology , Pyridines/pharmacology , Ruthenium/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Coordination Complexes/chemistry , DNA/metabolism , DNA Cleavage , Humans , Ligands , Plasmids , Pyridines/chemistry , Ruthenium/chemistryABSTRACT
An efficient route was developed for synthesis of bicyclic benzimidazole nucleosides from readily available d-glucose. The key reactions were Vörbruggen glycosylation and ring closing metathesis (RCM). Primarily, to understand the mode of DNA binding, we performed a molecular docking study and the binding was found to be in the minor groove region. Based on the proposed binding model, UV-visible and fluorescence spectroscopic techniques using calf thymus DNA (CT-DNA) demonstrated a non-intercalative mode of binding. Antiproliferative activity of nucleosides was tested against MCF-7 and MDA-MB-231 breast cancer cell lines and found to be active at low micromolar concentrations. Compounds and displayed significant antiproliferative activity as compared to and with the reference anticancer drug, doxorubicin. Cell cycle analysis showed that nucleoside induced cell cycle arrest at the S-phase. Confocal microscopy has been performed to validate the induction of cellular apoptosis. Based on these findings, such modified bicyclic benzimidazole nucleosides will make a significant contribution to the development of anticancer drugs.
Subject(s)
Antineoplastic Agents/pharmacology , Benzimidazoles/pharmacology , DNA, Neoplasm/drug effects , Nucleosides/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Benzimidazoles/chemical synthesis , Benzimidazoles/chemistry , Binding Sites/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Conformation , Molecular Docking Simulation , Nucleosides/chemical synthesis , Nucleosides/chemistry , Structure-Activity RelationshipABSTRACT
Mixed-ligand Cu(ii) complexes of the type [Cu(doxycycline)(L)(H2O)2](NO3)2, where doxycycline = [4-(dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide] and L = 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3) and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 4) have been synthesised and characterised by structural, analytical, and spectral methods. The single-crystal X-ray structures of 1 and 2 exhibited two different geometries, distorted square-pyramidal and octahedral respectively as well as different coordination modes of doxycycline. Complexes 2-4 exhibit prominent plasmid DNA cleavage at significantly low concentrations probably by an oxidative mechanism. Matrix Metalloproteinase (MMP-2) inhibition studies revealed that all complexes inhibit MMP-2 similar to doxycycline which is a well-known MMP inhibitor with 3 being the most potent. IC50 values of doxycycline and 1-4 against MCF-7 (human breast cancer) and HeLa cell lines were almost equal in which 3 showed the highest efficiency (IC50 = 0.46 ± 0.05 µM), being consistent with its increased MMP inhibition potency. The antimalarial activities of these complexes against the chloroquine-sensitive Plasmodium falciparum NF54 and chloroquine-resistant Plasmodium falciparum Dd2 strains reveal that complex 3 exhibited a higher activity than artesunate drug against the chloroquine-resistant Dd2 strain.
Subject(s)
Antimalarials/chemistry , Antineoplastic Agents/chemistry , Coordination Complexes/chemistry , Copper/chemistry , Doxycycline/chemistry , Matrix Metalloproteinase Inhibitors/chemistry , Pyridines/chemistry , Antimalarials/chemical synthesis , Antimalarials/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Coordination Complexes/chemical synthesis , Coordination Complexes/pharmacology , Crystallography, X-Ray , DNA Cleavage/drug effects , HeLa Cells , Humans , Ligands , Matrix Metalloproteinase Inhibitors/chemical synthesis , Matrix Metalloproteinase Inhibitors/pharmacology , Molecular Structure , Parasitic Sensitivity Tests , Plasmodium falciparum/drug effectsABSTRACT
The thiosemicarbazone derivative of anthracene (ATSC, anthracene thiosemicarbazone 1) and its copper(II) complex (CuATSC, 2) were synthesized and characterized by spectroscopic, electrochemical, and crystallographic techniques. Interaction of 1 and 2 with calf thymus (CT) DNA was explored using absorption and emission spectral methods, and viscosity measurements reveal a partial-intercalation binding mode. Their protein binding ability was monitored by the quenching of tryptophan emission using bovine serum albumin (BSA) as a model protein. Furthermore, their cellular uptake, in vitro cytotoxicity testing on the HeLa cell line, and flow cytometric analysis were carried out to ascertain the mode of cell death. Cell cycle analysis indicated that 1 and 2 cause cell cycle arrest in sub-G1 phase.
Subject(s)
Antineoplastic Agents/pharmacology , Copper/chemistry , Fluorescence , Organometallic Compounds/pharmacology , Thiosemicarbazones/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Cycle/drug effects , Cell Death/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Ligands , Molecular Structure , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , Structure-Activity RelationshipABSTRACT
The thiosemicarbazide derivative of anthracene, ATSC, has been synthesized and characterized by elemental analysis, IR, UV-visible, (1)H NMR, fluorescence, and mass spectroscopy experiments. The interaction of hydrated electron (e(-)aq) with ATSC proceeds via radical anion formation followed by intramolecular transfer that cleaves the thiosemicarbazide side chain on the anthracene moiety. HPLC and ESI-MS experiments suggested that the anthrylmethyl radical combines with different ATSC fragments during the reaction. ATSC, its one-electron reduction products, and dimers were analyzed combining experiments with density functional theory.
ABSTRACT
Cu3G is a Cu(II) complex of a photoactive tetradentate ligand that is cleaved upon UV irradiation to release Cu. Here we show that the cytotoxicity of Cu3G increases in response to brief UV stimulation to result in extensive cytoplasmic vacuolization that is indicative of nonapoptotic cell death.
Subject(s)
Copper/chemistry , Ultraviolet Rays , Cell Death/drug effects , Cell Death/radiation effects , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Coordination Complexes/toxicity , Crystallography, X-Ray , HL-60 Cells , HeLa Cells , Humans , Hydrogen Peroxide/metabolism , Ligands , MCF-7 Cells , Molecular ConformationABSTRACT
Complexes of the type [Ru(bxbg)(2) (N-N)](2+), where N-N denotes 2,2'-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), dipyrido[3,2-d:2',3-f] quinoxaline (dpq) (3), and dipyrido[3,2-a:2',3'-c]phenazine (dppz) (4), incorporating bis(o-xylene)bipyridine-glycoluril (bxbg) as an ancillary "molecular clip" ligand, have been synthesized and characterized. These ruthenium(II) complexes of bis(o-xylene)bipyridine-glycoluril self-associate in water through specific molecular recognition processes to form polycationic arrays. These arrays containing electrostatic binders as well as intercalator ligands at micromolar doses rapidly condense free DNA into globular nanoparticles of various sizes. The DNA condensation induced by these complexes has been investigated by electrophoretic mobility assay, dynamic light scattering, and transmission electron microscopy. The cellular uptake of complex-DNA condensates and the low cytotoxicity of these complexes satisfy the requirements of a gene vector.
Subject(s)
2,2'-Dipyridyl/chemistry , Alkynes/chemistry , DNA/chemistry , Imidazoles/chemistry , Phenanthrolines/chemistry , Ruthenium Compounds/chemistry , Ruthenium/chemistry , Crystallography, X-Ray , DNA Cleavage , Genetic Therapy , Ligands , Molecular Structure , Spectrophotometry, Ultraviolet , TemperatureABSTRACT
Two novel water soluble ruthenium(II) complexes [Ru(bpy)(2)(bqbg)](2+) and [Ru(phen)(2)(bqbg)](2+) have been structurally characterized and their DNA condensation activity, cytotoxicity, and cellular uptake studies of DNA condensates as potential non-viral DNA carriers were evaluated.
Subject(s)
DNA/metabolism , Drug Carriers/chemistry , Organometallic Compounds/chemistry , Ruthenium/chemistry , Biological Transport , HeLa Cells , Humans , Intracellular Space/metabolismABSTRACT
Complexes of the type [Co(pic)(2)(NN)], where pic = picolinate, NN = dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) (4) and 4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f][1,10]-phenanthroline-6,13-dione (bipyridyl-glycoluril) (bpg) (6) have been synthesized and characterized by elemental analysis, IR, UV-vis, NMR and ESI-MS spectroscopy and thermogravimetic analysis (TGA). Their physicochemical properties are compared with previously synthesized complexes, where NN = (H(2)O)(2) (1), 2,2'-bipyridine (bpy) (2), 1,10-phenanthroline (phen) (3) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) (5). The crystal structures of the complexes 4-6 were solved by single-crystal X-ray diffraction. The complexes 4 and 5 crystallize from a mixture of chloroform and methanol in monoclinic and orthorhombic crystal systems, respectively, whereas complex 6 crystallizes from dimethyl sulfoxide (DMSO) in a tetragonal crystal system. The coordination sphere consists of two oxygen atoms and two nitrogen atoms from the two picolinates and two nitrogen atoms from the dpq, dppz or bpg ligand, respectively. Co(ii)/Co(iii) oxidation potentials have been determined by cyclic voltammetry. The DNA binding of complexes 1-5 has been investigated using thermal melting, fluorescence quenching and viscosity measurements, which indicate the partial intercalation of complex 5 with an apparent binding constant (k(app)) of 8.3 × 10(5) M(-1). DNA cleavage studies of complexes 1-5 have been investigated using gel electrophoresis in the presence of H(2)O(2) as an oxidizing agent and also by photoirradiation at 365 nm. The mechanistic investigations suggest that singlet oxygen ((1)O(2)) is the major species involved in the DNA cleavage by these complexes. The structures of complexes 2-6 were optimized with density functional theory (DFT) method (B3LYP/6-31G(d,p)). The low vertical ionization potential values indicate photoredox pathways for the DNA cleavage activity by complexes 4 and 5, which is corroborated by DNA cleavage experiments.
Subject(s)
Cobalt/chemistry , Coordination Complexes/chemistry , DNA/chemistry , Picolinic Acids/chemistry , 2,2'-Dipyridyl/chemistry , Coordination Complexes/chemical synthesis , Crystallography, X-Ray , DNA Cleavage , Intercalating Agents/chemistry , Molecular Conformation , Phenanthrolines/chemistry , PhotolysisABSTRACT
Two mononuclear fluorophore-labeled copper(II) complexes [Cu(nip)(acac)](+)(2) and [Cu(nip)2](2+) (3), where fluorophore is 2-(naphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (nip) (1) and acac is acetylacetone, have been synthesized and characterized by various techniques. The ligand 1 and complex 2 are structurally characterized by single-crystal X-ray diffraction. The coordination geometries around the copper are square planar in solid as well as solution state as evidenced by electron paramagnetic resonance (EPR) spectroscopy. The density functional calculations carried out on 1-3 have shown that electron-rich regions in the highest occupied orbital are localized on the naphthalene and partly on the phenanthroline moiety. Both complexes 2 and 3 in dimethyl sulfoxide (DMSO) exhibit near square planar structure around the metal ion in their ground state. Time-dependent density functional theory (TD-DFT) calculations reveal that Cu(II) ion in complex 2 shows tetrahedral coordination around the metal while 3 retains its square planar geometry in the lowest excited state. The interaction of complexes with calf-thymus DNA (CT DNA) has been explored by using absorption, emission, thermal denaturation, and viscosity studies, and the intercalating mode of DNA binding has been proposed. The complexes cleave DNA oxidatively without any exogenous additives. The protein binding ability has been monitored by quenching of tryptophan emission in the presence of complexes using bovine serum albumin (BSA) as model protein. The compounds showed dynamic quenching behavior. Further, the anticancer activity of the complexes on MCF-7 (human breast cancer), HeLa (human cervical cancer), HL-60 (human promyelocytic leukemia), and MCF-12A (normal epithelial) cell lines has been studied. It has been observed that 3 exhibits higher cytotoxicity than 2, and the cells undergo apoptotic cell death.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Copper/chemistry , DNA Cleavage/drug effects , DNA/drug effects , DNA/metabolism , Antineoplastic Agents/metabolism , Binding, Competitive/drug effects , Cell Death/drug effects , Computational Biology , Copper/metabolism , DNA/chemistry , Drug Screening Assays, Antitumor , HL-60 Cells , HeLa Cells , Humans , Indicators and Reagents , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Protein Binding , Ribonucleases/chemistry , Serum Albumin, Bovine/chemistry , Spectrometry, Fluorescence , Spectrophotometry, Ultraviolet , Tetrazolium Salts , ThiazolesABSTRACT
Four vanadium(III) complexes of the general formula [V(maltol)(2)(N-N)]ClO(4), where N-N is 2,2'-bipyridine (bpy) (1); 1,10-phenanthroline (phen) (2); dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) (3), and dipyrido[3,2-a:2',3'-c]phenazine (dppz) (4), have been synthesized and characterized by IR, UV-visible, NMR spectroscopies, and electrospray ionization mass spectra (ESI-MS). The complexes exhibit the typical (1)H NMR spectra for paramagnetic V(III) species. The structures of complexes 1, 2, and 3 were characterized by single crystal X-ray diffraction. All complexes are monomeric and cationic containing V(III) species ligated to one neutral polypyridyl ligand and two monoanionic bidentate maltolate ligands with a distorted octahedral geometry. The complexes show an irreversible redox peak around +0.80 V versus Ag/AgCl corresponding to one-electron oxidation of V(III) to V(IV). The time-resolved UV-visible spectral changes for the complexes during the electrolysis in acetonitrile solution at +1.0 V are consistent with one-electron oxidation of the complexes to yield the stable V(IV) species. All complexes cleave plasmid pBR322 DNA without the addition of any external agents. In vitro insulin mimetic activity against insulin responsive RIN 5f cells indicates that complex 1 has similar activity to insulin while the others have moderate insulin mimetic activity.
Subject(s)
Biomimetic Materials/chemical synthesis , Biomimetic Materials/metabolism , DNA/metabolism , Insulin/metabolism , Organometallic Compounds/chemical synthesis , Organometallic Compounds/metabolism , Vanadium/chemistry , 2,2'-Dipyridyl/chemistry , Animals , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Cell Line, Tumor , Crystallography, X-Ray , Electrochemistry , Humans , Ligands , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Rats , Spectrum AnalysisABSTRACT
Neutral dinuclear Cu(II) complexes of Schiff base ligands derived from D-glucose have been synthesized and structurally characterized. These complexes were evaluated for their interaction with DNA, and DNA cleavage was observed even in the presence of radical inhibitors.
Subject(s)
Carbohydrates/chemistry , Copper/chemistry , DNA/metabolism , Organometallic Compounds/chemistry , Organometallic Compounds/metabolism , Schiff Bases/chemistry , Crystallography, X-Ray , Glycosylation , Ligands , Organometallic Compounds/chemical synthesisABSTRACT
Nine complexes of the type [Ru(N-N)(2)(BPG)]Cl(2) 1-4, [Ru(N-N)(BPG)(2)]Cl(2) 5-8, and [Ru(BPG)(3)]Cl(2) 9 where N-N is 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), dipyrido[3,2-a:2',3'-c]phenazine (dppz), which incorporates bipyridine-glycoluril (BPG-4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f][1,10]phenanthroline-6,13-dione) as the ancillary ligand, have been synthesized and characterized. These complexes with the peripheral polypyridyl ligands have the ability to form conjugates with DNA. The DNA binding (absorption spectroscopy, steady-state and time-resolved emission measurements, steady-state emission quenching measurements) and cleavage (under dark and irradiated conditions) by these complexes has been studied to investigate the influence of the ancillary ligand. The binding ability of these complexes to DNA is dependent on the planarity of the intercalative polypyridyl ligand, which is further affected by the ancillary bipyridine-glycoluril ligand. The complexes 3, 4, 7, and 8 bind to CT-DNA with binding constants on the order of 10(4) M(-1). Time-resolved emission measurements on the DNA-bound complexes 1, 3, 5-7, and 9 show monoexponential decay of the excited states, whereas complexes 2, 4, and 8 show biexponential decay with short- and long-lived components. Interaction of complexes 2-9 with plasmid pBR322 DNA studied by gel electrophoresis experiments reveals that all complexes cleave DNA efficiently at micromolar concentrations under dark and anaerobic conditions probably by a hydrolytic mechanism. Complexes 3, 4, 7, 8, and [Ru(bpy)(2)(dppz)](2+) show extensive DNA cleavage in the presence of light with a shift in mobility of form I of DNA probably due to the high molecular weight of DNA-complex conjugates. However, the extent of the cleavage is augmented on irradiation in the case of complexes 3, 4, 7, and 8, which include the planar dpq and dppz ligands, suggesting a combination of hydrolytic and oxidative mechanism for the DNA scission. Molecular mechanics calculations of these systems corroborate the DNA binding and cleavage mechanisms.
Subject(s)
2,2'-Dipyridyl/chemistry , Alkynes/chemistry , DNA/metabolism , Imidazoles/chemistry , Ruthenium Compounds/chemistry , 2,2'-Dipyridyl/chemical synthesis , 2,2'-Dipyridyl/metabolism , Alkynes/chemical synthesis , Alkynes/metabolism , Animals , Binding Sites , Cattle , DNA/chemistry , DNA Cleavage , Imidazoles/chemical synthesis , Imidazoles/metabolism , Models, Molecular , Photochemistry , Ruthenium Compounds/chemical synthesis , Ruthenium Compounds/metabolism , Spectrophotometry, Ultraviolet , Temperature , ViscosityABSTRACT
The isolation and characterization of an unusual spiroanthracene, from the reaction of bisdichlororuthenium(II)bipyridine dihydrate with 3-(9-anthrylmethyl)pentane-2,4-dione (AMPD), is reported. This metal-promoted formation of spiroanthracene has been obtained for the first time during the synthesis of metal complexes.
Subject(s)
Anthracenes/chemical synthesis , Metals/chemistry , Spiro Compounds/chemical synthesis , Anthracenes/chemistry , Crystallography, X-Ray , Methylation , Models, Molecular , Molecular Structure , Spectrum Analysis , Spiro Compounds/chemistryABSTRACT
The complex [Ru(bpy)2(BPG)]Cl2 (1) containing hydrogen-bond donor (N-H atoms) and acceptor (O atoms) groups mediates hydrolytic cleavage of plasmid pBR322 DNA in an enzyme-like manner. The kinetic aspects of DNA cleavage under pseudo- and true-Michaelis-Menten conditions are detailed.
