Photoactivated Cleavage Research Articles

Luminescent bis-tridentate iridium(III) complexes: Overcoming the undesirable reactivity of trans-disposed metallated rings using –N^N^N–-coordinating bis(1,2,4-triazolyl)pyridine ligands

Nine new iridium(III) complexes featuring two tridentate ligands have been synthesised of the form Ir(N^C^N)(–N^N^N–), where N^C^N represents a cyclometallating ligand based on 1,3-di(2-pyridyl)benzene and –N^N^N– is a doubly deprotonated bis(1,2,4-triazolyl)pyridine. Three examples of each ligand have been used, with different substituents in the central aryl ring of the former and para-substituted aryl groups in the 5-positions of the triazole rings of the latter. Two of the complexes have been structurally characterised in the solid-state by X-ray diffraction, confirming the mutually orthogonal arrangement of the two ligands. Unlike related tris-cyclometallated complexes of the type Ir(N^C^N)(C^N^C), which are unstable with respect to photoactivated cleavage of the trans-disposed Ir–C bonds, the new complexes show no evidence of instability. They are phosphorescent in the green region of the spectrum with lifetimes around 200 ns and quantum yields up to 3%, apparently limited by non-radiative decay processes in particular. Although there is some variation in performance with substitution pattern, the only discernible trend is that complexes of the 4-methoxy-substituted N^C^N ligand are the better emitters. Three examples of related complexes of the form Ir(N^C^N)(N^N–)Cl – incorporating a bidentate 1,2,4-triazolylpyridine – have also been prepared. They show no room-temperature emission but the properties at 77 K are similar to those of the bis-tridentate systems.

Induction of Apoptosis in SKOV3 and DNA Binding by Cobalt(III) Polypyridyl Complexes

Three new Co(III) polypyridyl complexes [Co(phen)2CIIP]3+ {CIIP = 2-(5-chloro-3a,H-isoindol-3-yl)-1H-imidazo[4,5-f][1,10]phenantholine} (phen = 1,10 phenanthroline), [Co(bpy)2CIIP]3+ (bpy = 2,2′-bipyridine), and [Co(dmb)2CIIP]3+ (dmb = 4,4′-dimethyl-2,2′-bipyridine) were synthesized and characterized by different spectral methods. The complexes interact with DNA in an intercalation mode as confirmed by spectroscopic titration and viscosity measurements. All three complexes cleaved the pBR322 DNA in photoactivated cleavage studies and exhibited good antimicrobial activity. Anticancer activity of these Co(III) complexes was evaluated on the SKOV3 cell line. Cytotoxicity by MTT assay showed growth inhibition in dose dependent manner. Cell cycle analysis by flow cytometry data showed increase in Sub G1 population. Annexin V FITC/PI staining confirmed that these complexes caused cell death by the induction of apoptosis.

Synthesis, spectral studies, DNA binding, photocleavage, antimicrobial and anticancer activities of isoindol Ru(II) polypyridyl complexes

Three new Ru(II) polypyridyl complexes [Ru(phen)2CIIP]2+ (1) {CIIP = 2-(5-Chloro-3a H-Isoindol-3-yl)-1H-Imidazo[4,5-f][1, 10]phenantholine} (phen = 1, 10 phenanthroline), [Ru(bpy)2CIIP]2+ (2) (bpy = 2, 2′ bipyridine) and [Ru(dmb)2CIIP]2+ (3) (dmb = 4, 4′-dimethyl 2, 2′ bipyridine) were synthesized and characterized by different spectral methods. The DNA-binding behavior of these complexes was investigated by absorption, emission spectroscopic titration and viscosity measurements, indicating that these three complexes bind to CT-DNA in an intercalative mode, but binding affinities of these complexes were different. The DNA-binding constants Kb of complexes 1, 2 and 3 were calculated in the order of 106. All three complexes cleave pBR322 DNA in photoactivated cleavage studies and exhibit good antimicrobial activity. Anticancer activity of these Ru(II) complexes was evaluated in MCF7 cells. Cytotoxicity by MTT assay showed growth inhibition in a dose dependent manner. Cell cycle analysis by flow cytometry data showed an increase in Sub G1 population. Annexin V FITC/PI staining confirms that these complexes cause cell death by the induction of apoptosis.

Synthesis and Evaluation of In Vitro DNA/Protein Binding Affinity, Antimicrobial, Antioxidant and Antitumor Activity of Mononuclear Ru(II) Mixed Polypyridyl Complexes.

The four novel Ru(II) complexes [Ru(phen)2MAFIP](2+) (1) [MAFIP=2-(5-(methylacetate)furan-2-yl)-1H-imidazo[4,5-f] [1, 10]phenanthroline, phen=1,10-Phenanthroline], [Ru(bpy)2MAFIP](2+) (2) (bpy=2,2'-bipyridine) and [Ru(dmb)2MAFIP](2+) (3) (dmb=4,4'-dimethyl-2,2'-bipyridine) and [Ru(hdpa)2MAFIP](2+) (4) (hdpa=2,2-dipyridylamine) have been synthesized and fully characterized via elemental analysis, NMR spectroscopy, EI-MS and FT-IR spectroscopy. In addition, the DNA-binding behaviors of the complexes 1-4 with calf thymus DNA were investigated by UV-Vis absorption, fluorescence studies and viscosity measurement. The DNA-binding experiments showed that the complexes 1-4 interact with CT-DNA through an intercalative mode. BSA protein binding affinity of synthesized complexes was determined by UV/Vis absorption and fluorescence emission titrations. The binding affinity of ruthenium complexes was supported by molecular docking. The photoactivated cleavage of plasmid pBR322 DNA by ruthenium complexes 1-4 was investigated. All the synthesized compounds were tested for antimicrobial activity by using three Gram-negative (Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa) and three Gram-positive (Micrococcus luteus, Bacillus subtilis and Bacillus megaterium) organisms, these results indicated that complex 3 was more activity compared to other complexes against all tested microbial strains while moderate antimicrobial activity profile was noticed for complex 4. The antioxidant activity experiments show that the complexes exhibit moderate antioxidant activity. The cytotoxicity of synthesized complexes on HeLa cell lines has been examined by MTT assay. The apoptosis assay was carried out with Acridine Orange (AO) staining methods and the results indicate that complexes can induce the apoptosis of HeLa cells. The cell cycle arrest investigated by flow cytometry and these results indicate that complexes 1-4 induce the cell cycle arrest at G0/G1 phase.

Synthesis and Biological Studies of Some Lanthanide Complexes of Schiff Base

Four new solid ternary complexes of lanthanide with Schiff base (isoniazid furalacylhydrazone) and sodium salicylate [Ln(FLSY)(Lin)(NO3)] NO3·H2O (Ln = La, Ce, Nd, Er; FLSY = isoniazid furalacylhydrazone; Lin = sodium salicylate) have been synthesized and characterized by elemental analysis, FT-IR, UV-Vis, 1H NMR, TG-DTA, and XPS. The antibacterial activities test indicate that all the complexes exhibit moderate antibacterial ability against Escherichia coli and Staphylococcus aureus with broad antimicrobial spectrums. The cytotoxic activity of the complexes has been tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method. The complexes can effectively inhibit the proliferation of K562 tumor cells. The authors investigate the interactions of the Er complex with calf-thymus DNA (CT DNA) employing florescence spectroscopic studies, cyclic voltammetric experiment, ultraviolet spectrum studies, and photoactivated cleavage. DNA interaction studies suggest the Er complex can intercalate between DNA base pairs and the complex can photocleave pBR322 DNA in vitro.

Cellular uptake, cytotoxicity, apoptosis, DNA-binding, photocleavage and molecular docking studies of ruthenium(II) polypyridyl complexes

Three new mononuclear [Ru (phen)2 ptip]2+ (1), [Ru (bpy)2 ptip]2+ (2) and [Ru (dmb)2 ptip]2+ (3) [ptip=(2-(5-phenylthiophen-2-yl)-1H-imidazo[4, 5-f][1,10 phenanthroline, phen=1, 10 phenanthroline, bpy=2, 2′ bipyridine, dmb=4, 4′-dimethyl 2, 2′ bipyridine] complexes were synthesized and characterised by elemental analysis, IR, NMR and Mass spectra. The DNA-binding behaviours were investigated by electronic absorption titration, luminescence spectra, viscosity measurements and photo-activated cleavage. The DNA-binding constants Kb of complexes 1, 2 and 3 were determined to be 7.0 (±0.06)×105, 3.87 (±0.04)×105, 2.79 (±0.07)×105 respectively. The results showed that these complexes interact with CT-DNA by intercalative mode. Cell viability experiments indicated that the Ru(II) complex showed significant dose-dependent cytotoxicity to HeLa tumour cell lines. Further flow cytometry experiments showed that the cytotoxic Ru(II) complex induced apoptosis of HeLa tumour cell lines. Our data demonstrated that the Ru(II) polypyridyl complex binds to DNA and thereby induces apoptosis in tumor cells, suggesting that anti-tumor activity of the Ru(II) complex could be related to its interaction with DNA. The molecular dynamic simulations and docking methods were used to predict the DNA binding affinity of ruthenium complexes and with good visualisation images supporting with experimental results.

Synthesis, Characterization, DNA Binding Studies, Photocleavage, Cytotoxicity and Docking Studies of Ruthenium(II) Light Switch Complexes

A new ligand 3-(1H-imidazo[4,5-f][1,10]phenanthrolin-2yl)phenylboronic acid and its (IPPBA) three ruthenium(II) complexes [Ru(phen)2(IPPBA)](ClO4)2 (1), [Ru(bpy)2(IPPBA)](ClO4)2 (2) and [Ru(dmb)2(IPPBA)](ClO4)2 (3) have been synthesized and characterized by elemental analysis, UV/VIS, IR, (1)H-NMR,(13)C-NMR and mass spectra. The binding behaviors of the three complexes to calf thymus DNA were investigated by absorption spectra, emission spectroscopy, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants for complexes 1, 2 and 3 have been determined to be 7.9 × 10(5) M(-1), 6.7 × 10(5) M(-1) and 2.9 × 10(5) M(-1). The results suggest that these complexes bound to double-stranded DNA in an intercalation mode. Upon irradiation at 365 nm, three ruthenium complexes were found to promote the cleavage of plasmid pBR322 DNA from super coiled form І to nicked form ІІ. Further in the presence of Co(2+), the emission of DNA-Ru(ΙΙ) complexes can be quenched. And when EDTA was added, the emission was recovered. The experimental results show that all three complexes exhibited the "on-off-on" properties of molecular "light switch". The highest Cytotoxicity potential of the complex1 was observed on the Human alveolar adenocarcinoma (A549) cell line. Good agreement was generally found between the spectroscopic techniques and molecular docked model which provides further evidence of groove binding.

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.

DNA-binding and photocleavage, cytotoxicity, apoptosis and antioxidant activity studies of ruthenium(II) complexes

Two ruthenium(II) polypyridyl complexes, namely [Ru(phen)2(DMDPPZ)](ClO4)21 (phen = 1,10-phenanthroline, DMDPPZ = 3,6-dimethyldipyrido[3,2-a:2′,3′-c]phenazine) and [Ru(dmp)2(DMDPPZ)](ClO4)22 (dmp = 2,9-dimethyl-1,10-phenanthroline), have been synthesized and characterized. The DNA-binding properties of the complexes were investigated by spectrophotometric methods, viscosity measurements, and photoactivated cleavage studies. The DNA-binding constants for complexes 1 and 2 have been determined as 8.78 (±0.94) × 105 M−1 (s = 3.02) and 1.26 (±0.35) × 105 M−1 (s = 1.69), respectively. The results suggest that these complexes bind to calf thymus DNA through intercalation. When irradiated at 365 nm, the complexes promote the photocleavage of pBR322 DNA, and complex 1 cleaves DNA more effectively than complex 2 under comparable experimental conditions. The cytotoxicities of complexes 1 and 2 have been evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) method. Complex 2 shows higher anticancer potency than complex 1 against four tumor cell lines. The apoptosis-inducing activity was assessed by acridine orange/ethidium bromide staining assay, and the antioxidant activities of these complexes against hydroxyl radical were also explored.

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.

Cellular uptake, cytotoxicity, apoptosis, antioxidant activity and DNA binding of polypyridyl ruthenium(II) complexes

Ruthenium(II) polypyridyl complexes [Ru(phen) 2(APIP)](ClO 4) 2 1 and [Ru(phen) 2(HAPIP)](ClO 4) 2 2 have been synthesized and characterized. The DNA-binding behaviors were investigated by electronic absorption titration, luminescence spectra, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants K b for complexes 1 and 2 were determined to be 3.38 (±0.42) × 10 5 M −1 ( s = 1.48) and 3.93 (±0.60) × 10 5 M −1 ( s = 3.14), respectively. The studies on the photocleavage demonstrated that the effects of cleavage are concentration-dependent. The results showed that complexes 1 and 2 interact with CT-DNA by intercalative mode. The cytotoxicity of complexes 1 and 2 has been evaluated by MTT method. The apoptosis assay was carried out with acridine orange/ethidium bromide (AO/EB) staining methods. The cellular uptake showed that complexes can enter into the cytoplasm and accumulate in the nuclei. The antioxidant activity studies suggested that the ligands and complexes may be potential drugs to eliminate the radical.

Synthesis, DNA-binding, DNA-photocleavage and antioxidant activity of ruthenium(II) complex containing triazine ring ligand: [Ru(dmb) 2(pdta)](ClO 4) 2

A new Ru(II) complex [Ru(dmb) 2(pdta)](ClO 4) 2 ( 1) (dmb = 4,4′-dimethyl-2,2′-bipyridine, pdta = 3-(pyridine-2-yl)-as-triazino [5,6-f]-acenaphthylene) was synthesized and characterized by elemental analysis (EA), ES–MS, 1H NMR, UV–Vis and CV. The DNA-binding properties of complex 1 were investigated by absorption titration, thermal denaturation, viscosity measurement and photoactivated cleavage. The DNA-binding constant was determined to be 2.37 ± 0.14 × 10 5 M −1 ( s = 1.90 ± 0.04) by electronic absorption titration, indicating that complex 1 interacts with DNA through intercalative mode. The redox peak potentials of this complex in CV were rationally assigned with the frontier molecular orbital stereographs resulting from the density functional theory (DFT) calculation. The photoactivated cleavage and cleavage mechanism of plasmid pBR322 DNA in the presence of complex 1 and various inhibitors were studied. The experiment for detecting the formation of singlet oxygen photo-sensitized by complex 1 was carried out, and the antioxidant activity of the Ru-complex and the ligand pdta against hydroxyl radical was also investigated.

Synthesis, Structure, DNA‐Binding Properties, and Cytotoxicity of Ruthenium(II) Polypyridyl Complexes

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.

2-(3,5-Dibromo-4-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthrolinoruthenium(II) complexes: synthesis, characterization, cytotoxicity, apoptosis, DNA-binding and antioxidant activity

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*).

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 × 10 4 M −1 ( s = 1.83) and 1.32 ± 0.31 × 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 ( 1O 2) may play an important role.

Synthesis and DNA interaction studies of ruthenium(II) complexes with isatino[1, 2-b]-1,4,8,9-tetraazatriphenylene as an intercalative ligand

The binding of the ruthenium(II) complexes [Ru(bpy)2(ITAP)](ClO4)2 (bpy = 2,2’-bipyridine) and [Ru(phen)2(ITAP)](ClO4)2 (phen = 1,10-phenanthroline, ITAP = isatino[1,2-b]-1,4,8,9-tetraazatriphenylene) to calf thymus DNA (CT-DNA) have been investigated with UV–visible and emission spectroscopy, viscosity measurements, thermal denaturation, and photoactivated cleavage. The experimental results indicate that the two complexes bind to CT-DNA through an intercalative mode. The two Ru(II) complexes in the presence of plasmid pBR322 DNA have been found to give rise to nicking of DNA upon irradiation.

Synthesis, DNA‐Binding and Photocleavage Studies of the Ruthenium(II) Complexes [Ru(phen)2(ppd)]2+ and [Ru(phen)(ppd)2]2+ (ppd=Pteridino[6,7‐f] [1,10]phenanthroline‐11,13(10H,12H)‐dione, phen=1,10‐Phenanthroline)

AbstractTwo new complexes, [Ru(phen)2(ppd)]2+ (1) and [Ru(phen)(ppd)2]2+ (2) (ppd=pteridino[6,7‐f] [1,10]phenanthroline‐11,13(10H,12H)‐dione, phen=1,10‐phenanthroline) were synthesized and characterized by ES‐MS, 1H‐NMR spectroscopy, and elemental analysis. The intercalative DNA‐binding properties of 1 and 2 were investigated by absorption‐spectroscopy titration, luminescence‐spectroscopy studies, thermal denaturation, and viscosity measurements. The theoretical aspects were further discussed by comparative studies of 1 and 2 by means of DFT calculations and molecular‐orbital theory. Photoactivated cleavage of pBR322 DNA by the two complexes were also studied, and 2 was found to be a much better photocleavage reagent than 1. The mechanism studies revealed that singlet oxygen and the excited‐states redox potentials of the complex may play an important role in the DNA photocleavage.

DNA-binding and photoactivated cleavage of enantiomeric ruthenium(II) complexes

A set of enantiomeric RuII complexes Δ- and Λ-[Ru(bpy)2TAPTP](PF6)2(bpy=2,2’-bipyridine, TAPTP=4,5,9,18-tetraazaphenanthreno[9,10-b]triphenylene) have been synthesized and characterized. Binding of both enantiomers to calf thymus DNA has been studied by spectroscopic methods, viscosity, and equilibrium dialysis. The experimental results indicated that both enantiomers bind to DNA by intercalation. Upon irradiation at 302 nm, both enantiomers were found to promote the cleavage of plasmid pBR 322 DNA from supercoiled form I to a nicked form II, and obvious enantioselectively was observed on DNA cleavage, the Λ- enantiomer exhibiting higher cleaving efficiency. The mechanisms for DNA cleavage by the two enantiomers are also proposed.

Metal complex–DNA interactions: from transcription inhibition to photoactivated cleavage

Metal ions and complexes, because of their cationic character, three-dimensional structural profiles, and propensity for performing hydrolysis, redox, or photoreactions, have a natural aptitude for interacting with DNA. Indeed, the need for cellular regulation of DNA led to the evolution of metallonucleases to catalyze and repair DNA strand breaks. Moreover, inorganic constructs such as cisplatin and bimetallic rhodium acetate exert antitumor activity by inner-sphere coordination to DNA. Because binding and cleavage of DNA is at the heart of cellular transcription and translation, it is an obvious target for therapeutic intervention and the development of diagnostic structural probes. To this end, new metal complexes have been designed that utilize or create open coordination positions for DNA binding and hydrolysis, generate reactive oxygen-containing species or other radicals for DNA oxidation, or perform direct redox reactions with DNA. The recent emerging themes are the development of bifunctional architectures containing multiple metal-binding or reactive sites, specialized ligand implementation, or incorporation of site-specific targeting substructures. This review describes their employment in novel reaction strategies that do not require bimolecular cofactors and as site-specific probes or cleavage agents.