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Two Ru(II) complexes, [Ru(pydppn)(bim)(py)] 2+ [ 2 ; pydppn = 3-(pyrid-2'-yl)-4,5,9,16-tetraaza-dibenzo[ a,c ]naphthacene; bim = 2,2'-bisimidazole; py = pyridine] and [Ru(pydppn)(Me 4 bim)(py)] 2+ [ 3 ; Me 4 bim = 2,2'-bis(4,5-dimethylimidazole)], were synthesized and characterized, and their photophysical properties, DNA binding, and photocleavage were evaluated and compared to [Ru(pydppn)(bpy)(py)] 2+ ( 1 ; bpy = 2,2'-bipyridine). Complexes 2 and 3 exhibit broad 1 MLCT (metal-to-ligand charge transfer) transitions with maxima at ∼470 nm and shoulders at ∼525 and ∼600 nm that extend to ∼800 nm. These bands are red-shifted relative to those of 1 , attributed to the π-donating ability of the bim and Me 4 bim ligands. A strong signal at 550 nm is observed in the transient absorption spectra of 1 - 3 , previously assigned as arising from a pydppn-centered 3 ππ* state, with lifetimes of ∼19 μs for 1 and 2 and ∼270 ns for 3 . A number of methods were used to characterize the mode of binding of 1 - 3 to DNA, including absorption titrations, thermal denaturation, relative viscosity changes, and circular dichroism, all of which point to the intercalation of the pydpppn ligand between the nucleobases. The photocleavage of plasmid pUC19 DNA was observed upon the irradiation of 1 - 3 with visible and red light, attributed to the sensitized generation of 1 O 2 by the complexes. These findings indicate that the bim ligand, together with pydppn, serves to shift the absorption of Ru(II) complexes to the photodynamic therapy window, 600-900 nm, and also extend the excited state lifetimes for the efficient production of cytotoxic singlet oxygen.

The present work reports the spectroscopic and theoretical evaluation of the interaction between calf-thymus DNA (CT-DNA) and free-base meso-tetra-(ruthenated) porphyrin (H 2 RuTPyP) or its corresponding Zn(II) complex (ZnRuTPyP). Spectroscopic measurements (UV-vis, circular dichroism and steady-state fluorescence emission) combined with theoretical molecular docking calculations suggest that Ru(II)-porphyrins interact with the DNA backbone by external mode via electrostatic forces. In addition, gel electrophoresis analysis demonstrate that these porphyrins promote efficient plasmidial DNA photocleavage upon white-light irradiation conditions, indicating H 2 RuTPyP and ZnRuTPyP as potential candidates for photodynamic therapy., Competing Interests: Declaration of Competing Interest We the undersigned declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We declare that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

CRISPR-Cas systems provide versatile tools for programmable genome editing. Here, we developed a caged RNA strategy that allows Cas9 to bind DNA but not cleave until light-induced activation. This approach, referred to as very fast CRISPR (vfCRISPR), creates double-strand breaks (DSBs) at the submicrometer and second scales. Synchronized cleavage improved kinetic analysis of DNA repair, revealing that cells respond to Cas9-induced DSBs within minutes and can retain MRE11 after DNA ligation. Phosphorylation of H2AX after DNA damage propagated more than 100 kilobases per minute, reaching up to 30 megabases. Using single-cell fluorescence imaging, we characterized multiple cycles of 53BP1 repair foci formation and dissolution, with the first cycle taking longer than subsequent cycles and its duration modulated by inhibition of repair. Imaging-guided subcellular Cas9 activation further facilitated genomic manipulation with single-allele resolution. vfCRISPR enables DNA-repair studies at high resolution in space, time, and genomic coordinates., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Aim and Objective: Isoxazole is an active core found in many drugs. The aim of this work was to synthesize bis-isoxazoline compounds and to analyze the effect of linker chain length on biological activities., Material and Methods: A simple, convenient, and efficient method for the conversion of bischalcones to new bis(4,5-dihydroisoxazole) derivatives was developed by using hydroxylamine hydrochloride under basic medium. Synthesized moieties were also evaluated for their antimicrobial potencies and DNA photocleavage assay., Results and Discussion: The synthesized compounds were more active than their chalcone precursors and the long-chain linkers (4e&4f) were more potent in antimicrobial, as well as in DNA photocleavage activity., Conclusion: It was found that many of the tested bischalcones and bis-isoxazolines exhibited moderate to significant antimicrobial activity against various strains. Furthermore, the present study also provides significant information and interesting outcomes regarding cyclization, increasing the length of linker chains, and their effects on the DNA photocleavage and antimicrobial activities., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

We have synthesized symmetrical carbocyanine dyes in which two 4-quinolinium rings are joined by a pentamethine bridge that is meso-substituted with H or Cl. Irradiation of the halogenated dye at 830 nm produces hydroxyl radicals that generate DNA direct strand breaks. This represents the first reported example of DNA photocleavage upon single photon excitation of a chromophore at wavelengths above 800 nm.

For ionising radiation (IR)-induced cellular toxicity, DNA cleavage is thought to be a crucial step. In this paper, the genome-wide DNA sequence preference of gamma radiation-induced cleavage was investigated in purified human DNA. We utilised Illumina short read technology and over 80 million double-strand breaks (DSBs) were analysed in this study. The frequency of occurrence of individual nucleotides at the 50,000 most frequently cleaved sites was calculated and C nucleotides were found to be most prevalent at the cleavage site, followed by G and T, with A being the least prevalent. 5'-C*C and 5'-CC* dinucleotides (where * is the cleavage site) were found to be the present at the highest frequency at the cleavage site; while it was 5'-CC*C for trinucleotides and 5'-GCC*C and 5'-CC*CC for tetranucleotides. The frequency of occurrence of individual nucleotides at the most frequently cleaved sites was determined and the nucleotides in the sequence 5'-GGC*MH (where M is A or C, H is any nucleotide except G) were found to occur most frequently for DNA that was treated with endonuclease IV (to remove blocking 3'-phosphoglycolate termini); and 5'-GSC*MH (where S is G or C) for non-endonuclease IV-treated DNA. It was concluded that GC-rich sequences were preferentially targeted for cleavage by gamma irradiation. This was the first occasion that an extensive examination of the genome-wide DNA sequence preference of IR-induced DSBs has been performed.

Previously, we reported that coralyne and UVA combination sensitized a wide range of human carcinoma cells regardless of their p53 status. The coralyne induced photosensitization of cancer cells may be clinically attractive, as mutation in the p53 gene is prevalent in many types of tumors. Coralyne mediated photosensitization of cancer cells is attributable to its ability to cause extensive DNA single strand breaks (SSB). However, the precise mechanism of coralyne induced DNA photo-damage is not yet known. The present study was aimed to understand the hitherto unknown mechanism of the coralyne-induced DNA photo-cleavage process. To this end, we compared the DNA photo-nicking properties of berberine, jatrorrhizine and coralyne, and deciphered involvement of the photochemical processes in the photo-nuclease action of coralyne using absorption and electron spin resonance spectroscopy, high performance liquid chromatography and mass spectroscopy (MS) techniques in conjunction with relevant in vitro studies with plasmid DNA. In association with UVA, coralyne, but not berberine and jatrorrhizine induced significant nicking of plasmid DNA via an O 2 -independent photo-chemical process. The Job's plot of our spectrophotometric data suggested that one coralyne molecule remains intercalated with two DNA base pairs (i. e., 1:2) and starts forming aggregates beyond this molar ratio. The DNA photo-nicking by the combination of coralyne and UVA (designated as CUVA) was primarily caused by the coralyne aggregates without any significant contribution from the DNA-intercalated coralyne monomer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Peptide nucleic acids (PNA) are one of many synthetic mimics of DNA and RNA that have found applications as biological probes, as nano-scaffold components, and in diagnostics. In an effort to use PNA as constructs for cellular delivery we investigated the possibility of installing a biologically susceptible disulfide bond in the backbone of a PNA oligomer. Here we report the synthesis of a new abasic Fmoc monomer containing a disulfide bond that can be incorporated into a PNA oligomer (DS-PNA) using standard solid phase peptide synthesis. The disulfide bond survives cleavage from the resin and DS-PNA forms duplexes with complementary PNA oligomers. Initial studies aimed at determining if the disulfide bond is cleavable to reducing agents while in a duplex are explored using UV thermal analysis and HPLC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Nitric oxide has been involved in many key biological processes such as vasodilation, platelet aggregation, apoptosis, memory function, and this has drawn attention to the development of exogenous NO donors. Metallonitrosyl complexes are an important class of these compounds. Here, two new ruthenium nitrosyl complexes containing a thiocarbonyl ligand, with the formula cis-[Ru(phen) 2 (L)(NO)](PF 6 ) 3 (phen = phenantroline, L = thiourea or thiobenzamide), were synthesized and characterized by electronic spectroscopy, FTIR, NMR , mass spectrometry and voltammetric techniques. Theoretical calculations using Density Functional Theory (DFT) and Time-dependent Density Functional Theory (TD-DFT) were also used and further supported the characterizations of these complexes. An efficient release of nitric oxide by blue light was validated using a NO/HNO probe: 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, known as cPTIO. Interestingly, the complex containing thiourea cleaved DNA even in the dark, while both complexes showed great DNA photocleavage activity in blue light. This process might work mainly through NO and hydroxyl radical production. Additionally, these complexes showed promising vasodilator activity, whose mechanism of action was investigated using N-Nitro-l-arginine methyl ester hydrochloride (L-NAME) and 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and compared to sodium nitroprusside. Both compounds were indeed NO-mediated heme-dependent activators of soluble guanylate cyclase. Additionally, they did not show any significant cytotoxicity against cancer cell lines U87 and GBM02. Altogether, these results supported both complexes having potential pharmacological applications that deserve further studies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In this work, we examined the DNA sequence preference of gamma-radiation-induced DNA damage in purified DNA sequences after heat treatment. DNA was fluorescently end-labeled and gamma-radiation-induced DNA cleavage was examined using capillary electrophoresis with laser-induced fluorescence detection. Our findings provide evidence that gamma-radiation-induced DNA damage to end-labeled DNA is nonrandom and has a sequence preference. The degree of cleavage was quantified at each nucleotide, and we observed that preferential cleavage occurred at C nucleotides with lesser cleavage at G nucleotides, while being very low at T nucleotides. The differences in percentage cleavage at individual nucleotides ranged up to sixfold. The DNA sequences surrounding the most intense radiation-induced DNA cleavage sites were examined and a consensus sequence 5'-AGGC*C (where C* is the cleavage site) was found. The highest intensity gamma-radiation-induced DNA cleavage sites were found at the dinucleotides, 5'-GG*, 5'-GC*, 5'-C*C and 5'-G*G and at the trinucleotides, 5'-GG*C, 5'-TC*A, 5'-GG*G and 5'-GC*C. These findings have implications for our understanding of ionizing radiation-induced DNA damage.

Copper(ii) complexes [Cu(L 1 /L 2 /L 3 )(A)] (1-3), where H 2 A·HCl is a vitamin B 6 Schiff base, viz. 3-hydroxy-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylpyridin-1-ium chloride, L 1 and L 2 are 2-(2-pyridyl)benzimidazole based borondipyrromethene (BODIPY) ligands and L 3 is 2-(2-pyridyl)benzimidazole, were prepared, characterized and their visible light-induced anti-cancer activity was studied. Complex 3, characterized by X-ray crystallography, exhibits a distorted square-pyramidal geometry for copper (τ = 0.33). Complexes 1 and 2 showed absorption bands at 500 and 535 nm, respectively, in 20% DMSO/Dulbecco's phosphate buffered saline (DPBS) medium. Complex 1 exhibited emission at ∼510 nm (λ exc = 480 nm) (Φ F = 0.1) in 20% DMSO/DPBS, while the non-emissive diiodo-BODIPY complex 2 is an efficient photosensitizer. The green fluorescent complex 1 enabled us to study its cellular uptake and localization. It showed selective uptake in proliferating cancer cells and significant mitochondrial localization (Pearson's coefficient = 0.7). Complex 2 showed excellent photocytotoxicity (400-700 nm, 10 J cm -2 ) in HeLa, MCF-7 and HepG2 cancer cells with IC 50 values within 0.4-0.6 μM, while remaining less toxic in the dark and in non-cancerous HPL1D cells (photocytotoxic index ∼50). Complex 2, remarkable in targeting cancer cells over non-cancerous cells, showed photoinduced generation of singlet oxygen, causing apoptotic cell death, thus satisfying the major requirements of targeted photodynamic therapy.

In this study, novel peripherally tetra 3-morpholinophenol substituted zinc(II) phthalocyanine (4) and its water soluble form quaternized zinc(II) phthalocyanine (ZnQ) were synthesized for the first time. These novel compounds were characterized by a combination of different spectroscopic techniques such as FT-IR, 1 H NMR, 13 C NMR, UV-vis and mass. The DNA binding of ZnQ was investigated using UV-vis absorption titration, competitive ethidium bromide, thermal denaturation and viscosity experiments that the ZnQ bound to CT-DNA via intercalation mode. ZnQ indicated photocleavage activity on supercoiled pBR322 plasmid DNA via formation of singlet oxygen under irradiation at 700nm. Besides, the topoisomerase I inhibitory effect experiments showed that ZnQ inhibited topoisomerase I enzyme in a concentration-dependent manner. The bovine serum albumin (BSA) binding experiments indicated that ZnQ bound to proteins through a static quenching mechanism. All of these results claim that ZnQ has potential agent for photodynamic therapy owing to its nucleic acid interactions and photobiological or photochemical properties., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Two new series of binary metal complexes [M(L 1 ) 2 ] and [M(L 2 ) 2 ] where, M=Cu(II), Ni(II) & Co(II) and L 1 =4-((3,4-dimethylisoxazol-5-ylimino)methyl)benzene-1,3-diol; L 2 =2-((3,4-dimethylisoxazol-5-ylimino)methyl)-5-methoxyphenol were synthesized and characterized by elemental analysis, 1 H NMR, 13 C NMR, FT-IR, ESI mass, UV-Visible, magnetic moment, ESR, SEM and powder XRD studies. Based on these results, a square planar geometry is assigned for all the metal complexes where the Schiff base acts as uninegatively charged bidentate chelating agent via the hydroxyl oxygen and azomethine nitrogen atoms. DNA binding studies of all the complexes with calf thymus DNA have been comprehensively investigated using electronic absorption spectroscopy, fluorescence quenching and viscosity studies. The oxidative and photo cleavage affinity of metal complexes towards supercoiled pBR322 DNA has been ascertained by agarose gel electrophoresis assay. From the results, it is observed that all the metal complexes bind effectively to CT-DNA via an intercalative mode of binding and also cleave pBR322 DNA in a promising manner. Further the Cu(II) complexes have shown better binding and cleavage properties towards DNA. The antimicrobial activities of the Schiff bases and their metal complexes were studied on bacterial and fungal strains and the results denoted that the complexes are more potent than their Schiff base ligands., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In order to explore the biological potential, some synthesized triazolylnucleosides were evaluated for their antibacterial, tyrosinase and DNA photocleavage activities. Triazolylnucleosides (5-12) were screened against Staphylococcus aureus (ATCC 6538), gram-positive and Escherichia coli (ATCC 10536), gram-negative bacterial strains. Among the series, compound 9 exhibited a significant level of antibacterial activity against both strains at higher concentration in reference to the standard drug, Levofloxacin. Tyrosinase activity and inhibition of these compounds were also studied, and it has been found that compounds 8 and 11 displayed more than 50% inhibitory activity. In addition, six compounds (7-12) were evaluated for their DNA photocleavage activity. The compounds 8 and 12 exhibited excellent DNA photocleavage activity at a concentration of 10 μg and may be used as template for antitumor drugs in the future.

The light sensitive compound riboflavin-5'-phosphate (or flavin mononucleotide, FMN) generates reactive oxygen species (ROS) upon photo-irradiation. FMN is required by all flavoproteins because it is a cofactor of biological blue-light receptors. The photochemical effects of FMN after irradiation by blue or violet light on the inactivation of Staphylococcus aureus strains, including a methicillin-resistant strain (MRSA), were investigated in this study. Upon blue- or violet-light photo-treatment, FMN was shown to inactivate S. aureus due to the generated ROS. Effective bacterial inactivation can be achieved by FMN photolysis without an exogenous electron provider. Inactivation rates of 94.9 and 95.2% in S. aureus and MRSA, respectively, can be reached by blue light irradiation (2.0mW/cm 2 ) with 120μM FMN for 120min. A lower FMN concentration and a shorter time are required to reach similar effects by violet light irradiation. Inactivation rates of 96.3 and 97.0% in S. aureus and MRSA, respectively, can be reached by violet light irradiation (1.0mW/cm 2 ) with 30μM FMN for 30min. The sensitivity of the inherent photosensitizers is lower under blue-light irradiation. A long exposure photolytic treatment of FMN by blue light is required to inactivate S. aureus. Violet light was found to be more efficient in S. aureus inactivation at the same radiant intensity. FMN photolysis with blue or violet light irradiation enhanced the inactivation rates of S. aureus and MRSA. FMN photochemical treatment could be a supplemental technique in hygienic decontamination processes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A novel supramolecular assembly was constructed by the noncovalent complexation of hexa-cata-hexabenzocoronene modified permethyl-β-cyclodextrins with tetrasodium tetraphenylporphyrintetrasulfonate in water, exhibiting highly efficient excited energy transfer behaviors and a promising DNA photocleavage ability.

Sensory photoreceptors have enabled non-invasive and spatiotemporal control of numerous biological processes. Photoreceptor engineering has expanded the repertoire beyond natural receptors, but to date no generally applicable strategy exists towards constructing light-regulated protein actuators of arbitrary function. We hence explored whether the homodimeric Rhodobacter sphaeroides light-oxygen-voltage (LOV) domain (RsLOV) that dissociates upon blue-light exposure can confer light sensitivity onto effector proteins, via a mechanism of light-induced functional site release. We chose the RNA-guided programmable DNA endonuclease Cas9 as proof-of-principle effector, and constructed a comprehensive library of RsLOV inserted throughout the Cas9 protein. Screening with a high-throughput assay based on transcriptional repression in Escherichia coli yielded paRC9, a moderately light-activatable variant. As domain insertion can lead to protein destabilization, we also screened the library for temperature-sensitive variants and isolated tsRC9, a variant with robust activity at 29°C but negligible activity at 37°C. Biochemical assays confirmed temperature-dependent DNA cleavage and binding for tsRC9, but indicated that the light sensitivity of paRC9 is specific to the cellular setting. Using tsRC9, the first temperature-sensitive Cas9 variant, we demonstrate temperature-dependent transcriptional control over ectopic and endogenous genetic loci. Taken together, RsLOV can confer light sensitivity onto an unrelated effector; unexpectedly, the same LOV domain can also impart strong temperature sensitivity., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

This article describes the synthesis and characterization of three new Ru(II) polypyridyl complexes including [Ru(phen) 2 (dpphz)] 2+ (1), [Ru(bpy) 2 (dpphz)] 2+ (2) and [Ru(dmb) 2 (dpphz)] 2+ (3) where dpphz = dipyrido[3,2-a:2',3'-c] phenazine-11-hydrazide, phen =1,10-phenanthroline, bpy = 2,2'-bipyridine and dmb = 4,4'-dimethyl2,2'-bipyridine. The binding behaviors of these complexes to calf thymus DNA (CT-DNA) were explored by spectroscopic titrations, viscosity measurements. Results suggest that these complexes can bind to CT-DNA through intercalation. However, their binding strength differs from each other; this may be attributed to difference in the ancillary ligand. The cytotoxicity of 1-3 was evaluated by MTT assay; results indicated that all complexes have significant dose dependent cytotoxicity with HeLa tumor cell line. All complexes exhibited efficient photocleavage of pBR322 DNA upon irradiation. The DNA binding ability of 1-3 was also studied by docking the complexes into B-DNA using docking program.

Novel benzothiazole Schiff bases L 1 [1-((4,6-difluorobenzo[d]thiazol-2-ylimino)methyl) naphthalen-2-ol], L 2 [3-((4,6-difluorobenzo[d]thiazol-2-ylimino) methyl)benzene-1,2-diol], L 3 [2-((4,6-difluorobenzo[d]thiazol-2-ylimino)methyl)-5-methoxyphenol], L 4 [2-((4,6-difluorobenzo[d]thiazol-2-ylimino)methyl)-4-chlorophenol] and their binary Cu(II) complexes were synthesized. The structures of all the compounds have been discussed on the basis of elemental analysis, FT-IR, NMR, UV-Visible, ESI-Mass, TGA, ESR, SEM, powder XRD and magnetic moments. Based on the analytical and spectral data a square planar geometry has been assigned to all complexes in which the Schiff bases act as monobasic bidentate ligands, coordinating through the azomethine nitrogen and phenolic oxygen atom. DNA binding ability of these complexes was studied on CT-DNA by using UV-Vis absorption, fluorescence and viscometry. DNA cleavage ability of the complexes was examined on pBR322 DNA by using gel electrophoresis method. All the DNA binding studies reveal that they are good intercalators. The bioefficacy of the ligands and their complexes was examined against the growth of bacteria and fungi in vitro to evaluate their antimicrobial potential. The screening data revealed that the complexes showed more antimicrobial activity than the corresponding free ligands.

In this study, [2-(2-morpholin-4-ylethoxy)ethoxy] group substituted zinc(ii), manganese(iii) and copper(ii) phthalocyanines 2-4 and their water soluble derivatives 2a, 3a and 4a were synthesized and the interactions of compounds 2a, 3a and 4a with CT-DNA and supercoiled pBR322 plasmid DNA were investigated. The results of binding experiments showed that these compounds were able to interact with CT-DNA via intercalative mode with a strong binding affinity in the order 3a > 2a > 4a. DNA-photocleavage activities of compounds 2a, 3a and 4a were determined. These compounds cleaved supercoiled pBR322 plasmid DNA efficiently under irradiation at 650 nm for 2a and 4a, and at 750 nm for 3a. These compounds displayed remarkable inhibitory activities against topoisomerase I enzyme in a dose-dependent manner. All of these results suggest that these phthalocyanines might be suitable anticancer agents due to their strong binding affinities, significant cleavage activities and effective topoisomerase I inhibition.

Functional cooperativity among transcription factors on regulatory genetic elements is pivotal for milestone decision-making in various cellular processes including mammalian development. However, their molecular interaction during the cooperative binding cannot be precisely understood due to lack of efficient tools for the analyses of protein-DNA interaction in the transcription complex. Here, we demonstrate that photoinduced excess electron transfer assay can be used for analysing cooperativity of proteins in transcription complex using cooperative binding of Pax6 to Sox2 on the regulatory DNA element (DC5 enhancer) as an example. In this assay, (Br)U-labelled DC5 was introduced for the efficient detection of transferred electrons from Sox2 and Pax6 to the DNA, and guanine base in the complementary strand was replaced with hypoxanthine (I) to block intra-strand electron transfer at the Sox2-binding site. By examining DNA cleavage occurred as a result of the electron transfer process, from tryptophan residues of Sox2 and Pax6 to DNA after irradiation at 280 nm, we not only confirmed their binding to DNA but also observed their increased occupancy on DC5 with respect to that of Sox2 and Pax6 alone as a result of their cooperative interaction., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The DNA-binding, photocleavage, and antitumor activity of three free base pyridyl corroles 1, 2, and 3 have been investigated. The binding affinity toward CT-DNA decreases with increasing number of pentafluorophenyl, whereas the photocleavage activity toward pBR322 DNA becomes more efficient. Singlet oxygen was demonstrated as active species responsible for DNA cleavage. These corroles exhibited high cytotoxicity against three tested cancer cells (Hela, HapG2, and A549) and the cytotoxicity could be further enhanced under irradiation. Intracellular reactive oxygen species level was also monitored using HeLa Cells upon the combined treatment of corroles and light. These corroles could be absorbed by HeLa cells at low concentration. They can induce the decrease of mitochondrial membrane potential and apoptosis of tumor cells under irradiation.

New copper(II)-based complex (1) was synthesized and characterized by analytical, spectroscopic and single crystal X-ray diffraction. The in vitro binding studies of complex 1 with CT DNA and HSA have been investigated by employing biophysical techniques to examine the binding propensity of 1 towards DNA and HSA. The results showed that 1 avidly binds to CT DNA via electrostatic mode along with the hydrogen bonding interaction of NH2 and CN groups of Schiff base ligand with the base pairs of DNA helix, leads to partial unwinding and destabilization of the DNA double helix. Moreover, the CD spectral studies revealed that complex 1 binds through groove binding interaction that stabilizes the right-handed B-form of DNA. Complex 1 showed an impressive photoinduced nuclease activity generating single-strand breaks in comparison with the DNA cleavage activity in presence of visible light. The mechanistic investigation revealed the efficiency of 1 to cleave DNA strands by involving the generation of reactive oxygen species. Furthermore, the time dependent DNA cleavage activity showed that there was gradual increase in the amount of NC DNA on increasing the photoexposure time. However, the interaction of 1 and HSA showed that the change of intrinsic fluorescence intensity of HSA was induced by the microenvironment of Trp residue., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We report DNA cleavage by ruthenium(II) arene anticancer complex [(η(6)-p-terp)Ru(II)(en)Cl](+) (p-terp=para-terphenyl, en=1,2-diaminoethane, complex 1) after its photoactivation by UVA and visible light, and the toxic effects of photoactivated 1 in cancer cells. It was shown in our previous work (T. Bugarcic et al., J. Med. Chem. 51 (2008) 5310-5319) that this complex exhibits promising toxic effects in several human tumor cell lines and concomitantly its DNA binding mode involves combined intercalative and monofunctional (coordination) binding modes. We demonstrate in the present work that when photoactivated by UVA or visible light, 1 efficiently photocleaves DNA, also in hypoxic media. Studies of the mechanism underlying DNA cleavage by photoactivated 1 reveal that the photocleavage reaction does not involve generation of reactive oxygen species (ROS), although contribution of singlet oxygen ((1)O2) to the DNA photocleavage process cannot be entirely excluded. Notably, the mechanism of DNA photocleavage by 1 appears to involve a direct modification of mainly those guanine residues to which 1 is coordinatively bound. As some tumors are oxygen-deficient and cytotoxic effects of photoactivated ruthenium compounds containing {Ru(η(6)-arene)}(2+) do not require the presence of oxygen, this class of ruthenium complexes may be considered potential candidate agents for improved photodynamic anticancer chemotherapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In this work, we demonstrate for the first time that [Ru(bpy)2(R-OQN)](+) complexes (bpy = 2,2'-bipyridine, R-OQN = 5-chloro-8-oxyquinolate or 5-bromo-8-oxyquinolate) are able to generate hydroxyl radicals and cleave DNA effectively upon visible light irradiation. The potent electron-donating ability of the R-OQN-based non-innocent ligands gives the complexes a high reducing capability, favoring the generation of superoxide anion radicals from which hydroxyl radicals may be generated. More interestingly, halogen substitution plays an important role. When the 5-Cl- or 5-Br-8-oxyquinolate ligand is replaced by 8-oxyquinolate or 5-CH3-8-oxyquinolate, the corresponding complexes lose their hydroxyl radical-generation and DNA photocleavage abilities. These findings open new applications for the non-innocent ligand-based Ru(II) complexes in the fields of biology and medicine, such as in photodynamic therapy (PDT).

A series of four novel neodymium(iii) complexes of the formulation [Nd(R-tpy)(O-O)(NO3)2] (), where R-tpy is 4'-phenyl-2,2':6',2''-terpyridine (Ph-tpy; , ) and 4'-ferrocenyl-2,2':6',2''-terpyridine (Fc-tpy; , ); O-O is the conjugate base of acetylacetone (Hacac; , ) or curcumin (Hcurc; , ), are synthesized and characterized. The single crystal structure of shows that the complex is a discrete mononuclear species with the Nd(iii) centre in a nine coordinate environment provided by a set of O6N3 donor atoms. Complexes and having the simple acac ligand are prepared as control compounds. Complex , possessing an appended ferrocenyl (Fc) and the curcumin moiety, is remarkably photocytotoxic to HeLa and MCF-7 cancer cells in visible light giving respective IC50 values of 0.7 μM and 2.1 μM while being significantly less toxic to MCF-10A normal cells (IC50 = 34 μM) and in the dark (IC50 > 50 μM). The phenyl appended complex , lacking a ferrocenyl moiety, is significantly less toxic to both the cell lines when compared with . Complexes and , lacking the photoactive curcumin moiety, do not show any apparent toxicity both in light and in the dark. The cell death is apoptotic in nature and is mediated by the light-induced formation of reactive oxygen species (ROS). Fluorescence imaging experiment with HeLa cells reveals mitochondrial accumulation of complex within 4 h of incubation. The complexes bind to calf thymus (ct) DNA with moderate affinity giving Kb values in the range of 10(4)-10(5) M(-1). The curcumin complexes and cleave plasmid supercoiled DNA to its nicked circular form in visible light via(1)O2 and ˙OH pathways. The presence of the ferrocenyl moiety is likely to be responsible for the enhanced cellular uptake and photocytotoxicity of complex . Thus, the mitochondria targeting complex , being remarkably cytotoxic in light but non-toxic in the dark and to normal cells, is a potential candidate for photochemotherapeutic applications.

Several stable O-alkyl and aryl sulfonyl conjugated p-nitro-Ph and o-, m-, p-pyridine N'-hydroxy imidamides, were subjected to UV irradiation at 312 nm with supercoiled circular plasmid DNA pBluescript KS II. The generated amidinyl and sulfonyloxyl radicals led to effective DNA photo-cleavage. Both alkyl and aryl sulfonyl derivatives were active and the order p-pyridine > p-nitro-Ph > o-pyridine > m-pyridine was schematized for the N'-hydroxy imidamides moiety. Calf thymus-DNA affinity studies which comprised UV interactions, viscosity experiments and competitive studies with ethidium bromide showed good to excellent affinity of the compounds. These properties revealed sulfonyl amidoximes as novel effective DNA-photo-cleavers and may serve in the discovery of new leads for "on demand" biotechnological and medical applications.

This study aimed to investigate the degradation of three transgenic Bacillus thuringiensis (Bt) genes (Cry1Ab, Cry1Ac, and Cry1Ab/Ac) and the corresponding encoded Bt proteins in KMD1, KF6, and TT51-1 rice powder, respectively, following autoclaving, cooking, baking, or microwaving. Exogenous Bt genes were more stable than the endogenous sucrose phosphate synthase (SPS) gene, and short DNA fragments were detected more frequently than long DNA fragments in both the Bt and SPS genes. Autoclaving, cooking (boiling in water, 30 min), and baking (200 °C, 30 min) induced the most severe Bt protein degradation effects, and Cry1Ab protein was more stable than Cry1Ac and Cry1Ab/Ac protein, which was further confirmed by baking samples at 180 °C for different periods of time. Microwaving induced mild degradation of the Bt and SPS genes, and Bt proteins, whereas baking (180 °C, 15 min), cooking and autoclaving led to further degradation, and baking (200 °C, 30 min) induced the most severe degradation. The findings of the study indicated that degradation of the Bt genes and proteins somewhat correlated with the treatment intensity. Polymerase chain reaction, enzyme-linked immunosorbent assay, and lateral flow tests were used to detect the corresponding transgenic components. Strategies for detecting transgenic ingredients in highly processed foods are discussed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Two water-soluble polysaccharide-porphyrin-fullerene supramolecular conjugates were constructed from the non-covalent incorporation of triphenyl Zn-porphyrin-modified β-cyclodextrins, adamantyl-modified hyaluronate and C60. Significantly, these supramolecular conjugates, which exist as cross-linked or discrete nanoparticles with a diameter of 50-200 nm, can completely cleave closed supercoiled DNA to nicked DNA under light irradiation.

In this study, the influence of the terminal phosphorothioate (PT) internucleotide bond in ds-DNA on the oxidation process was taken into consideration. The interaction of UV with the targeted oligonucleotide leads to an electron ejection and radical cation "hole" migration through the ds-DNA until it is trapped irreversibly in a suitable place. Phosphorothiate internucleotide bonds were detected in the bacterial genome; however, their role is still unclear. In this study a PAGE analysis of irradiated ds-DNA showed that the degradation rea ction was slowed down by the presence PT next to the anthraquinone moiety. Further, theoretical study shows that [RP] AQ-PS-dG can adopt a slightly lower ionisation potential energy and triplet excited state with a subsequent slightly higher adiabatic electron affinity value in comparison with [SP] AQ-PS-dG and AQ-PO-dG. Moreover, the energy gap between HOMO and LUMO, indicated the radical stabilisation properties of [RP] AQ-PS-dG, which can hinder the charge transfer through ds-DNA.

A dinuclear ruthenium(II) complex [(bpy)2Ru(L(1))Ru(bpy)2]Cl4 {bpy=2,2'-bipyridine, L(1)=1,6-bis(3-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)-9H-carbazol-9-yl)hexane} was synthesised and characterized. The calf thymus DNA (ct-DNA) binding properties of the complex were investigated by means of UV-Visible absorption and emission spectrophotometric titrations, ethidium bromide competitive binding, steady-state emission quenching with ferrocyanide, DNA viscosity measurements, and DNA thermal denaturation. The results indicated that the complex avidly binds to ct-DNA most probably through a threading bis-intercalative mode. The complex was also evidenced to act as an efficient DNA photocleaver, and an effective luminescent stain for cytoplasmic of HeLa cells with low cytotoxicity., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A new ligand mhcip (mhcip=2-(4-methyl-7-hydroxyl-8-coumarinyl)imidazo[4,5-f]-[1,10]phenanthroline) and its ruthenium complexes, [Ru(L)2mhcip](2+) (L=bpy (2,2'-bipyridine), phen (1,10-phenanthroline)), have been synthesized and characterized. The introduction of coumarin ring may play an important role in the strong fluorescence of the complexes. Intercalative binding mode between both complexes and CT-DNA was determined by UV-visible spectroscopy, fluorescence spectroscopy and viscosity measurements. The two complexes show efficient DNA photocleavage under irradiation at 365 nm. The cycling of light switch off and on has been achieved for both complexes through the introduction of Cu(2+) and EDTA in the absence or presence of DNA., (Copyright © 2015. Published by Elsevier B.V.)

Two new Ru(II) complexes, [Ru(Htip)3]Cl2 (1) and [Ru(Htip)2(dppz)]Cl2 (2), were synthesised and were characterised. The ground- and excited-state acid-base properties of 1 and 2 were studied and demonstrated that 1 acted as a pH-induced "on-off-on" luminescence switch. The binding behaviours of 1 and 2 to calf thymus DNA were studied with absorption and emission spectroscopy, DNA viscosities and density functional theory calculations. 2 was found to act as a DNA molecular light switch and as an efficient photocleaver of pUC 18 DNA. The cytotoxicities of the complexes were evaluated with the MTT method and it was found that 1 displayed apparent anticancer activity against MCF-7 cell, whereas 2 exhibited more potent and wider-spectrum antitumor activities against all cancer cell lines tested., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The aim of our study was to investigate DNA-binding and cytotoxic activity of the four new Ru(II) polypyridyl complexes [Ru(dmb)₂(HMHPIP)](ClO₄)₂ (1), [Ru(bpy)₂(HMHPIP)](ClO₄)₂ (2), [Ru(phen)₂(HMHPIP)](ClO₄)₂ (3) and [Ru(dmp)₂(HMHPIP)](ClO₄)₂ (4). The complexes interact with DNA through intercalative mode and show relatively high cytotoxic activity against A549 cells, no cytotoxicity toward MG-63 cells. Complexes 1-4 can enhance the levels of ROS in A549 cells and induce the decrease of the mitochondrial membrane potential. These complexes inhibit the cell growth in A549 cells at G0/G1 or S phase. Complex 3 activated caspase 7, and down-regulated the expression of the anti-apoptotic protein Bcl-2. Complexes 1-4 induce apoptosis in A549 cells through ROS-mediated mitochondrial dysfunction pathway., (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)

Oxovanadium(IV) complexes, viz. [VO(Fc-tpy)(Curc)](ClO4) (1), [VO(Fc-tpy)(bDHC)](ClO4) (2), [VO(Fc-tpy)(bDMC)](ClO4) (3) and [VO(Ph-tpy)(Curc)](ClO4) (4), of 4'-ferrocenyl-2,2':6',2″-terpyridine (Fc-tpy) and 4'-phenyl-2,2':6',2″-terpyridine (Ph-tpy) and monoanionic curcumin (Curc), bis-dehydroxycurcmin (bDHC) and bis-demethoxycurcumin (bDMC) were prepared, characterized and their photo-induced DNA cleavage activity and photocytotoxicity in visible light studied. The ferrocenyl complexes 1-3 showed an intense metal-to-ligand charge transfer band near 585 nm in DMF and displayed Fc(+)/Fc and V(IV)/V(III) redox couples near 0.65 V and -1.05 V vs. SCE in DMF-0.1 M TBAP. The complexes as avid binders to calf thymus DNA showed significant photocleavage of plasmid DNA in red light of 647 nm forming OH radicals. The complexes showed photocytotoxicity in HeLa and Hep G2 cancer cells in visible light of 400-700 nm with low dark toxicity. ICP-MS and fluorescence microscopic studies exhibited significant cellular uptake of the complexes within 4 h of treatment with complexes. The treatment with complex 1 resulted in the formation of reactive oxygen species inside the HeLa cells which was evidenced from the DCFDA assay., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The synthesis and photophysical studies of two cationic Tröger's base (TB)-derived bis-naphthalimides 1 and 2 and the TB derivative 6, characterized by X-ray crystallography, are presented. The enantiomers of 1 and 2 are separated by cation-exchange chromatography on Sephadex C25 using sodium (-)-dibenzoyl-l-tartarate as the chiral mobile phase. The binding of enantiomers with salmon testes (st)-DNA and synthetic polynucleotides are studied by a variety of spectroscopic methods including UV/vis absorbance, circular dichroism, linear dichroism, and ethidium bromide displacement assays, which demonstrated binding of these compounds to the DNA grooves with very high affinity (K ∼ 10(6) M(-1)) and preferential binding of (-)-enantiomer. In all cases, binding to DNA resulted in a significant stabilization of the double-helical structure of DNA against thermal denaturation. Compound (±)-2 and its enantiomers possessed significantly higher binding affinity for double-stranded DNA compared to 1, possibly due to the presence of the methyl group, which allows favorable hydrophobic and van der Waals interactions with DNA. The TB derivatives exhibited marked preference for AT rich sequences, where the binding affinities follow the order (-)-enantiomer > (±) > (+)-enantiomer. The compounds exhibited significant photocleavage of plasmid DNA upon visible light irradiation and are rapidly internalized into malignant cell lines.

Pyrazolone incorporating N-acetylcysteine (NAC) mixed-ligand complexes are described as promising anti-inflammatory, anticonvulsant, SODs mimetic and cytotoxic compounds possibly due to its antioxidant profile. In this study, we have evaluated the pharmacologic activity, antioxidant and toxicological profiles of compounds (1-6). Among them, compounds 1 and 4 were haemobiocompatible than the others. Both complexes 1 and 4 display efficient photo-nuclease activity upon irradiation with UV-A light of 365 nm and red light of 647 nm as compared with others. Mechanistic studies reveal that the DNA cleavage oxidative pathway involves H2O2 and singlet oxygen as the reactive oxygen species. Interestingly, both compounds 1 and 4, show non-toxic effects in vitro to human normal lymphocyte cells, revealing that they are selective in killing only the cancer cells as expected for a better drug. In addition, considering the safety profile, these compounds are promising as preventive and/or therapeutic agents against oxidative damage., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Theoretical studies on the DNA-photocleavage mechanism and efficiency of some Ru(II) polypyridyl complexes as novel reagents have been carried out using the density functional theory (DFT) method. Stable DNA-docking models of Ru(II) polypyridyl complexes were obtained using the docking and DFT methods. The excited-state reduction potentials, electron-transfer (ET) activation energies, and intramolecular reorganization energies were theoretically calculated, and the corresponding frontier molecular orbitals of complexes were also presented. Based on these properties of excited states, the essential component of two different DNA-photocleavage mechanisms, i.e., the photoinduced oxidation-reduction mechanism and the singlet oxygen photosensitization mechanism, has been revealed, and the DNA-photocleavage efficiencies were reasonably explained, and hereby a complex with excellent DNA-photocleavage ability was also designed. This work offers valuable theoretical insight into the property of excited-states and the DNA-photocleavage mechanism of Ru(II) polypyridyl complexes as novel reagents.

In continuation of our efforts to find new biologically active agents, regioselective synthesis of a series of 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-arylethanones 4a-k has been achieved under facile, extremely mild and greener reaction conditions with excellent yields. Moreover, one pot multicomponent reaction has also been reinvestigated under previously reported solvent conditions to prepare 4a-b and found that the reaction generates significant amount of side products. The chemical structures of 4a-k were established on the basis of a combined use of IR, NMR ((1)H, (13)C) spectroscopy, mass spectrometry and elemental analysis. All the compounds were evaluated for their antibacterial, DNA photocleavage and anticancer activities. Among all, 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-(naphth-2-yl)ethanone 4j displayed good inhibitory profile against Escherichia coli and Staphylococcus aureus which was about 50% and 25% of the Ampicillin (standard drug), respectively. The compounds, 4a and 4f showed relatively moderate inhibition against Psuedomonas aeruginosa and E. coli. In DNA photocleavage study, compounds 4c and 4d were found to be highly active and completely degraded both forms of DNA (SC and OC), even at a very low concentration of 1 μg (4c) under irradiation of UV light. However, 4h and 4f resulted in complete DNA degradation at 30 μg concentration. Moreover, 4h showed fluorescence at 15 μg concentration and increased the intensity of both bands of DNA (SC and OC) as compared to control. On the other hand, to valorize the biological potential, the compounds were screened for their cytotoxic activity on colon (HCT116 and HT29), prostate (DU145), ovarian (SKOV3) and lung (A549) cancer cell lines. The compound 4j was found to be cytotoxic to all the cancer cell lines, except SKOV3, with more selectivity towards the colon cancer cell lines (HCT116, HT29) and A549 lung cancer cell line. On A549 lung cancer cell line, 4j and 4k exhibited similar potency as carboplatin in inhibiting cell viability., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Here we report a systematic and comparative study to define a correlation between the structure and function of a series of simple, biologically active small inorganic Schiff base copper complexes for the occurrence of charge transfer phenomenon in calf thymus DNA (CT-DNA) using transient absorption spectroscopy corroborated with magnetic field effect. Four copper(II) Schiff base complexes with differently substituted heterocyclic ligands with antioxidant activity have been used. The binding constants of the order of ∼ 10(4) support the moderate binding affinity of the complexes towards CT-DNA. The methyl-substituted pyrrole complex shows maximum binding affinity (Kb: 8.33 × 10(4)) compared to others. The occurrence of photoinduced electron transfer (PET) from CT-DNA to pyrrole containing complexes has been confirmed by identifying the corresponding transient radical ions whereas the extent of PET with pyridine substituted complexes is too small to be observed. The increase of the yield of radical ions in presence of magnetic field depicts that the initial spin correlation in geminate radical ion pair is triplet. The difference between experimental and calculated B½ values, the measure of hyperfine interactions (HFI) present in the system, arises due to hole hopping through intrastrand and interstrand DNA bases. The unsubstituted pyrrole complexes cleave DNA much more than the methyl-substituted one. Therefore, the probability of intrastrand superexchange increases with methyl-substituted complexes, that reduces the rate of hole hopping and hence the B½ value., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A nanoconjugate was composed of metal oxide nanoparticles decorated with peptides and fluorescent dye and tested for DNA cleavage following UV light activation. The peptide design was based on a DNA binding domain, the so called KH domain of the hnRNPK protein. This "KH peptide" enabled cellular uptake of nanoconjugates and their entry into cell nuclei. The control nanoconjugate carried no peptide; it consisted only of the metal oxide nanoparticle prepared as Fe3O4@TiO2 nanocomposite and the fluorescent dye alizarin red S. These components of either construct are responsible for nanoconjugate activation by UV light and the resultant production of reactive oxygen species (ROS). Production of ROS at different subcellular locations causes damage to different components of cells: only nanoconjugates inside cell nuclei can be expected to cause DNA cleavage. Degradation of cellular DNA with KH peptide decorated nanoconjugates exceeded the DNA damage obtained from control, no-peptide nanoconjugate counterparts. Moreover, caspase activation and cell death were more extensive in the same cells.

Naproxen is an important non-steroidal anti-inflammatory drug with many pharmacological and biological properties. In this study, we have attempted to ascertain the mode of action and the mechanism of binding of naproxen to DNA. We have also demonstrated that, upon irradiation with white light, naproxen generates reactive oxygen species, causing DNA cleavage. Generation of reactive oxygen species from photo-irradiated naproxen as determined spectrophotometrically was found to lead to nicking of plasmid DNA as analyzed by agarose gel electrophoresis. Without photo-irradiation, naproxen binds to DNA and forms drug-DNA complexes as revealed by spectroscopic techniques. Several experiments such as determination of the effect of urea, iodide-induced quenching and a competitive binding assay with ethidium bromide showed that naproxen binds to DNA primarily in an intercalative manner. These observations were further supported by CD analysis, viscosity measurements and molecular docking. Using DNA as a template, fluorescence resonance energy transfer between naproxen and ethidium bromide was also observed, further strengthening the evidence for intercalative binding of naproxen with DNA., (© 2013 FEBS.)

A novel 3-(4-methoxybenzylamino) propanoic acid substituted water-soluble zinc phthalocyanine (CNPcZn) was synthesized. The interaction between CNPcZn with calf thymus DNA (CT DNA) was studied using spectroscopic methods. The studies indicated that CNPcZn has strong affinity to CT DNA, and furthermore, CNZnPc showed excellent photodamaging activity to CT DNA. Above results indicated that such CNPcZn has great potential to be used as an effective photosensitizer in the field of photodynamic therapy., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A pair of single-molecule photo-responsive DNA nanoscissors for DNA cleavage based on the regulation of substrate binding affinity was designed and fabricated. Compared with other DNA nanomachines, our DNA nanoscissors have the advantages of a clean switching mechanism, as well as robust and highly reversible operation.

As a continuing investigation of our previous studies about the influence of the different rare earth metal ions on the bioactivity, a family of heavy rare earth metal complexes, [RE(acac)3(dpq)] (RE=Tb (1), Dy (2), Ho (3), Er (4), Tm (5), Yb (6), Lu (7)) and [RE(acac)3(dppz)]·CH3OH (RE=Tb (8), Dy (9), Ho (10), Er (11), Tm (12), Yb (13), Lu (14) viz. acetylacetonate (acac), dipyrido[3,2-d:20,30-f]quinoxaline (dpq), dipyrido[3,2-a:20,30-c] phenazine (dppz)), has been synthesized and their biological activities were also investigated. On the irradiation with UV-A light of 365nm or ambient light, all complexes exhibit efficient DNA cleavage activity via the mechanistic pathway involving the formation of singlet oxygen and hydroxyl radical as the reactive species. In addition, the in vitro cytotoxicity of these complexes on HeLa cells has been examined by MTT assay, which indicate that these compounds have the potential to act as effective anticancer drugs. The results of the above biological experiments also reveal that the choice of different rare earth metal ions has little influence on the DNA binding, DNA cleavage and cytotoxicity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Four new ruthenium(II) polypyridyl complexes-[Ru(phen)2(7-F-dppz)](2+) (7-F-dppz is 7-fluorodipyrido[3,2-a:2',3'-c]phenazine, phen is 1,10-phenanthroline), [Ru(bpy)2(7-F-dppz)](2+)(2) (bpy is 2,2'-bipyridine), [Ru(dmb)2(7-F-dppz)](2+) (dmb is 4,4'-dimethyl-2,2'-bipyridine), and [Ru(hdpa)2(7-F-dppz)](2+) (hdpa is 2,2'-dipyridylamine)-have been synthesized and characterized. Their DNA binding behavior has been explored by various spectroscopic titrations and viscosity measurements, which indicated that all the complexes bind to calf thymus DNA by means of intercalation with different binding strengths. The light switching properties of these complexes have been evaluated, and their antimicrobial activities have been investigated. Photoinduced DNA cleavage studies have been performed. All the complexes exhibited efficient photocleavage of pBR322 DNA on irradiation. The cytotoxicity of these complexes has been evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay with various tumor cell lines. Cellular uptake was studied by flow cytometry and confocal microscopy. Flow cytometry experiments showed that these complexes induced apoptosis of HeLa cell lines.

X-ray photoelectron spectroscopy (XPS) is harnessed as an in situ efficient characterization technique for monitoring chemical bond transformation in DNA and cisplatin-DNA complexes under synergic X-ray irradiation. By analyzing the variation of relative peak area of core elements of DNA as a function of irradiation time, we find that the most vulnerable scission sites in DNA are those containing phosphate and glycosidic bonds. Compared to DNA, the effective rate constants of the corresponding phosphodiester and glycosidic bond cleavages for cisplatin-DNA complexes are 1.8 and 1.9 folds larger. These damages and their enhancements are similar to those induced by low energy electrons (LEE). Consistently, the magnitude of the secondary electron distribution produced by the X-rays on the cisplatin-DNA complexes is considerably increased compared to that of pristine DNA. The data suggest that DNA radiosensization by cisplatin results not only from the sensitization of DNA to the action of LEE, but also from an increase the production of LEE at the site of binding of the cisplatin. The results provide new insights into the mechanisms of cisplatin-induced sensitization of DNA under X-ray irradiation, which could be helpful in the design of new cisplatin-based antitumor drugs.

A family of Phterpy complexes, [Mn(Phterpy)2][N(CN)2]2·0.5H2O (1), [Fe(Phterpy)2](NO3)2 (2), [Ni(Phterpy)2](NO3)2 (3), [Ni(Phterpy)2]Cl2·10H2O (4), [Cd(Phterpy)2](NO3)2·2H2O (5) and [Zn(Phterpy)Cl2] (6) (Phterpy=4'-phenyl-2,2':6',2″-terpyridine), have been synthesized and structurally characterized, and their DNA binding and photo-induced DNA cleavage activities have been investigated. These complexes display binding propensity to the CT-DNA giving a relative order: 1>4>3, 5, 2, 6. Under dark or ambient lighting conditions, all complexes show no efficient DNA cleavage activity to pBR322 DNA. While on irradiation with UV-A light of 365nm, complexes of 1, 3 and 4 exhibit significant cleavage activities. In the presence of H2O2 as a revulsant or an activator, the cleavage ability of complex 2 is obviously enhanced. Complexes 5 and 6 do not exhibit any apparent chemical nuclease activities under irradiation conditions or with the addition of H2O2. The DNA photo-induced cleavage activities are consistent with the number of single-electron in the central metal ion of complexes and singlet oxygen and hydroxyl radical are found as the reactive oxygen species., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Copper(II) complexes [Cu(Fc-aa)(cur)] (1-3) of curcumin (Hcur) and N-ferrocenylmethyl-L-amino acids (Fc-aa), viz., ferrocenylmethyl-L-tyrosine (Fc-TyrH), ferrocenylmethyl-L-tryptophan (Fc-TrpH) and ferrocenylmethyl-L-methionine (Fc-MetH), were prepared and characterized. The DNA photocleavage activity, photocytotoxicity and cellular localization in HeLa and MCF-7 cancer cells of these complexes were studied. Acetylacetonate (acac) complexes [Cu(Fc-aa)(acac)] (4-6) were prepared and used as controls. The chemical nuclease inactive complexes showed efficient pUC19 DNA cleavage activity in visible light. Complexes 1-3 showed high photocytotoxicity with low dark toxicity thus giving remarkable photodynamic effect. FACScan analysis showed apoptosis of the cancer cells. Fluorescence microscopic studies revealed primarily cytosolic localization of the complexes., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)