Cleavage Of Supercoiled Plasmid DNA Research Articles

Ternary Schiff base metal (II) complexes with N,N,N′,N′-Tetramethylethylenediamine: Influence of secondary chelates on antimicrobial, scavenging activity, DNA interaction and cytotoxicity

A series of complexes involving bivalent metal ions such as cobalt, nickel, copper, and zinc were synthesized using Schiff bases derived from l-tyrosine and salicylaldehyde. Utilizing both analytical and spectroscopic methods, the compounds underwent analysis. In terms of their potential biological effects, the antioxidant properties of the samples were gauged by their ability to scavenge DPPH radicals. Notably, all the compounds demonstrated enhanced activity in this aspect, with the exception of the ligand. To investigate their impact on DNA, the compounds' capability to cleave DNA was assessed via gel electrophoresis. Remarkably, the compounds effectively induced the cleavage of supercoiled plasmid DNA. Moreover, the interaction between calf thymus DNA and the metal-imine chelates were examined. The Cu(II) complex had a significant interaction, as evidenced by its binding constant of (3.46 ± 0.02 x 105 M−1).

Roles of DNA Target in Cancer Cell-Selective Cytotoxicity by Dicopper Complexes with DNA Target/Ligand Conjugates.

The DNA target/ligand conjugates (HLX, X = Pn and Mn, n = 1-3) were synthesized where various lengths of -CONH(CH2CH2O)nCH2CH2NHCO- linkers with a 9-phenanthrenyl (P) or methyl (M) terminal as DNA targets replace the methyl group of 2,6-di(amide-tether cyclen)-p-cresol ligand (HL). DNA binding, DNA cleavage, cellular uptake, and cytotoxicity of [Cu2(μ-OH)(LX)](ClO4)2 (1X) are examined and compared with those of [Cu2(μ-OH)(L)](ClO4)2 (1) to clarify roles of DNA targets. Upon reaction of 1X with H2O2, μ-1,1-O2H complexes are formed for DNA cleavage. 1P1, 1P2, and 1P3 are 22-, 11-, 3-fold more active for conversion of Form II to III in the cleavage of supercoiled plasmid DNA with H2O2 than 1, where the short P-linker may fix a dicopper moiety within a small number of base pairs to facilitate DNA double-strand breaks (dsb). This enhances the proapoptotic activity of 1P1, 1P2, and 1P3, which are 30-, 12-, and 9.9-fold cytotoxic against HeLa cells than 1. DNA dsb and cytotoxicity are 44% correlated in 1P1-3 but 5% in 1M1-3, suggesting specific DNA binding of P-linkers and nonspecific binding of M-linkers in biological cells. 1P1-3 exert cancer cell-selective cytotoxicity against lung and pancreas cancer and normal cells where the short P-linker enhances the selectivity, but 1M1-3 do not. Intracellular visualization, apoptosis assay, and caspase activity assay clarify mitochondrial apoptosis caused by 1P1-3. The highest cancer cell selectivity of 1P1 may be enabled by the short P-linker promoting dsb of mitochondrial DNA with H2O2 increased by mitochondrial dysfunction in cancer cells.

DNA interaction, cytotoxic and phototoxic properties of new water‐soluble zinc (II) phthalocyanines

In this paper, we have synthesized water‐soluble peripherally tetra and octa‐({6‐[3‐(dimethylamino)phenoxy]hexyl}oxy) groups substituted zinc (II) phthalocyanines (DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ). Also, we have investigated ct‐DNA binding, supercoiled plasmid DNA cleavage properties of DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ by using spectrophotometric and electrophoretic methods. On the other hand, cytotoxic and phototoxic effects of DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ were examined using (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay on human lung adenocarcinoma (A549) cell lines. In UV–Vis absorption studies, hypochromism was observed about 18% for DM‐C6‐ZnQ and 57% for o‐DM‐C6‐ZnQ on addition of increasing concentrations of ct‐DNA. The intrinsic binding constant (Kb) values of DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ were 3.82 (±0.14) × 104 M−1 and 2.34 (±0.05) × 105 M−1, respectively. The supercoiled plasmid DNA cleavage studies showed that DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ had no DNA damage actions in the dark. On the other hand, they caused DNA damage depending on the light dose. In the MTT assay, the compounds had low cytotoxic properties on A549 cell lines, but they showed significant phototoxic actions. These results reveal that the compounds interact with DNA and have phototoxic properties; it has been determined that they have the potential to be photosensitizing agents for photodynamic therapy.

Development, evaluation and effect of anionic co-ligand on the biological activity of benzothiazole derived copper(II) complexes

Research on development of novel metal based anti-cancer agents continues with its popularity among bioinorganic community. Benzothiazole, an important heterocyclic pharmacophore, was chosen as a valuable and useful scaffold for the synthesis of novel copper(II) complexes. Three new copper(II) complexes obtained from the synthesis of newly synthesized benzothiazole based N-(benzo[d]thiazol-2-ylmethyl)-N-methyl-2-(pyridin-2-yl)ethan-1-amine (btzpy) ligand with CuCl2 [Cu(btzpy)Cl2] (1), Cu(NCS)2 [Cu(btzpy)(NCS)2] (2), and Cu(NO3)2 [Cu(btzpy)(NO3)(H2O)]NO3 (3) were isolated and characterized by physical and spectroscopic measurements, including single-crystal X-ray structures. The interaction of complexes 1 and 3 with calf thymus (CT)-DNA was investigated using ethidium bromide fluorescence quenching assay and weak intercalation with KSV values of 9.8 × 102 M−1 and 8.2 × 102 M−1, respectively was observed. All three complexes have shown DNA cleavage of supercoiled plasmid DNA forming single nicked and double nicked forms in the presence of external reducing agents like 3-mercaptopropionic acid (3-MPA) and ascorbic acid. The water-soluble complexes 1 and 3 also show prominent hydrolytic DNA cleavage. From the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay, it was observed that complex 2 also exhibits good antioxidant properties. The cytotoxicity of complexes 1–3 was tested against the lung cancer cell line (A549) and complex 2 with -NCS moiety shows maximum activity in the micromolar range. A rationale for the observed activity is proposed in light of the other properties of these molecules.

Control of DNA structure and function by phytochemicals/DNA interaction: Resveratrol/piceatannol induces Cu2+-independent, cleavage of supercoiled plasmid DNA

Topoisomerases are enzymes that catalyze DNA unwinding and scissions to resolve topological entanglements possibly arising during DNA replication/transcription. Chemicals which disrupt or inhibit topoisomerase-mediated DNA unwinding can induce breaks that subsequently lead to programmed cell death. Herein we perform experiments guided by the following considerations. First, topoisomerase 1 initiates DNA cleavage utilizing the hydroxyl group of tyrosine 723 on its catalytic site as a nucleophile to attack the electrophilic phosphate on the DNA sugar-phosphate backbone. Secondly, the grape polyphenol resveratrol displays both topoisomerase inhibitory and Cu2+-dependent DNA-cutting activities, which contribute to its DNA replication/transcription inhibitory/anti-tumorigenic effects. Lastly, resveratrol contains a tyrosine-like phenolic ring; thus, upon binding to DNA whether resveratrol could act as a tyrosine mimetic to unwind and cut DNA via its hydroxyl groups warrants investigation. Polyphenol-DNA interactions (PDIs) were investigated using UV–visible spectral analysis; additionally, PDI mediated DNA changes were further analyzed by agarose gel electrophoresis using 3 supercoiled plasmid DNAs (pBR322, pSJ3, pHOT-1) as substrates. Resveratrol mediates time- and temperature-dependent, Cu2+-independent, non-enzymatic cleavage of supercoiled plasmid DNA into open, circular DNA products. Varying degree of unwinding of supercoiled DNA nucleolytic activity was also observed with other polyphenols including, piceatannol, quercetin, myricetin and EGCG. Interestingly, we found that piceatannol mediated Cu2+-independent DNA-cleavage activity was abolished by EDTA. The PDI-mediated nucleolytic cleavage of supercoiled DNA reported herein shows that polyphenolic phytochemicals display genome-active, nuclear effects by directly targeting the DNA topology which in turn could impact macromolecular processes associated with faithful replication and transmission of genetic information.

The Effect of DNA Topology on Observed Rates of R-Loop Formation and DNA Strand Cleavage by CRISPR Cas12a.

Here we explored the mechanism of R-loop formation and DNA cleavage by type V CRISPR Cas12a (formerly known as Cpf1). We first used a single-molecule magnetic tweezers (MT) assay to show that R-loop formation by Lachnospiraceae bacterium ND2006 Cas12a is significantly enhanced by negative DNA supercoiling, as observed previously with Streptococcus thermophilus DGCC7710 CRISPR3 Cas9. Consistent with the MT data, the apparent rate of cleavage of supercoiled plasmid DNA was observed to be >50-fold faster than the apparent rates for linear DNA or nicked circular DNA because of topology-dependent differences in R-loop formation kinetics. Taking the differences into account, the cleavage data for all substrates can be fitted with the same apparent rate constants for the two strand-cleavage steps, with the first event >15-fold faster than the second. By independently following the ensemble cleavage of the non-target strand (NTS) and target strand (TS), we could show that the faster rate is due to NTS cleavage, the slower rate due to TS cleavage, as expected from previous studies.

Tris-chelated complexes of nickel(II) with bipyridine derivatives: DNA binding and cleavage, BSA binding, molecular docking, and cytotoxicity

Two nickel(II) complexes with substituted bipyridine ligand of the type [Ni(NN)3](ClO4)2, where NN is 4,4′-dimethyl-2,2′-bipyridine (dimethylbpy) (1) and 4,4′-dimethoxy-2,2′-bipyridine (dimethoxybpy) (2), have been synthesized, characterized, and their interaction with DNA and bovine serum albumin (BSA) studied by different physical methods. X-ray crystal structure of 1 shows a six-coordinate complex in a distorted octahedral geometry. DNA-binding studies of 1 and 2 reveal that both complexes sit in DNA groove and then interact with neighboring nucleotides differently; 2 undergoes a partial intercalation. This is supported by molecular-docking studies, where hydrophobic interactions are apparent between 1 and DNA as compared to hydrogen bonding, hydrophobic, and π–π interactions between 2 and DNA minor groove. Moreover, the two complexes exhibit oxidative cleavage of supercoiled plasmid DNA in the presence of hydrogen peroxide as an activator in the order of 1 > 2. In terms of interaction with BSA, the results of spectroscopic methods and molecular docking show that 1 binds with BSA only via hydrophobic contacts while 2 interacts through hydrophobic and hydrogen bonding. It has been extensively demonstrated that the nature of the methyl- and methoxy-groups in ligands is a strong determinant of the bioactivity of nickel(II) complexes. This may justify the above differences in biomolecular interactions. In addition, the in vitro cytotoxicity of the complexes on human carcinoma cells lines (MCF-7, HT-29, and U-87) has been examined by MTT assay. According to our observations, 1 and 2 display cytotoxicity activity against selected cell lines.Communicated by Ramaswamy H. Sarma

Microwave-assisted synthesis of mixed ligands organotin(IV) complexes of 1,10-phenanthroline and l-proline: Physicochemical characterization, DFT calculations, chemotherapeutic potential validation by in vitro DNA binding and nuclease activity

Diorganotin(IV) and triphenyltin(IV) derivatives of L-proline (HPro) having general formula R2Sn(Pro)2 (R=n-Bu (1), Ph (2)) and Ph3Sn(Pro) (3), respectively, and the mixed ligands di-/triorganotin(IV) derivatives of L-proline and 1,10-phenanthroline (phen) with general formula [R2Sn(Pro)(Phen)Cl] and [R3Sn(Pro)(Phen)] (where R=Me (4 and 7), n-Bu (5 and 8), Ph (6 and 9)), respectively, have been synthesized by microwave-assisted method and characterized by elemental analysis, IR, NMR (1H, 13C and 119Sn) and DART-mass spectral studies. The results suggest bicapped tetrahedron or a skew trapezoidal-bipyramid geometry for R2Sn(Pro)2, a distorted tetrahedral geometry for Ph3Sn(Pro) and a distorted octahedral geometry for [R2Sn(Pro)(Phen)Cl] and [Ph3Sn(Pro)(Phen)] around the Sn atom, and the same has been validated by density functional theory calculations (DFT). In vitro DNA binding studies of 1–9 have been investigated by UV–Vis, fluorescence and circular dichroism titrations, viscosity and DNA melting experiments. The observed hypochromic shift in UV–Vis and fluorescence studies evidenced a partial intercalative mode of binding of complexes to CT-DNA. The binding affinity and quenching ability have been quantified in terms of intrinsic binding constant (Kb) and Stern-Volmer quenching constant (Ksv). The determined values suggest that di- and triorganotin(IV) derivatives of L-proline possess lesser affinity to bind with CT-DNA in comparison to the mixed ligands di-/triorganotin(IV) derivatives of L-proline and 1,10-phenanthroline. The partial intercalative mode of binding of these complexes with CT DNA has also been supported by a change in the viscosity and melting point of DNA as well as a change in the intensity of positive and negative bands in circular dichroism spectra. The cleavage studies by agarose gel electrophoresis indicate effective cleavage of supercoiled plasmid DNA into its nicked form by all the complexes and even to its linear form in presence of 9.

Conventional and microwave-assisted synthesis, characterization, DFT calculations, in vitro DNA binding and cleavage studies of potential chemotherapeutic diorganotin(IV) mandelates

Diorganotin(IV) complexes of the general formulae {[R2Sn(L)]2O}(R=Me (1), n-Bu (2), and n-Oct (3); L=anion of mandelic acid) and {[R2Sn(L)]2Cl2}(R=Ph (4)) have been synthesized by conventional thermal method (1a–3a), except 4a and by microwave-assisted reactions (1b–4b). The elemental analysis, IR, NMR (1H, 13C and 119Sn) and ESI-MS/DART-mass spectral studies revealed that dimeric 1:1 complexes with SnOSn bridges (1–3) are formed possessing distorted trigonal bipyramidal geometry around the Sn atoms, except 4b which exhibits octahedral geometry with SnClSn bridges. The proposed geometries have been validated by density functional theory calculations. Thermal behavior of 1b–4b, studied by using thermogravimetry (TG), differential thermal analysis (DTA) and derivative thermogravimetric (DTG) techniques, indicated that all except 4b are stable up to 200°C. In vitro interaction studies of 1b–4b with CT-DNA were performed by UV–Vis, fluorescence titrations and results suggest that the complexes are binding to DNA via an intercalative mode. The binding affinity and quenching ability were quantified in terms of intrinsic binding constant (Kb) (3.74×104M−1, 2b; >3.67×104M−1, 4b; >3.03×104M−1, 3b; >0.72×104M−1, 1b) and Stern-Volmer quenching constant (Ksv) (2.16×105, 2b; >1.73×105, 4b; >1.66×1053b; >1.51×105, 1b) which showed high binding affinity of 2b with CT-DNA. The cleavage studies of 1b–4b with pBR322 plasmid DNA was ascertained by agarose gel electrophoresis. They exhibited effective cleavage of supercoiled plasmid DNA into its nicked form (1b, 3b, 4b) and even into its linear form in presence of 2b.

Interaction of RuIII(EDTA) with cellular thiols and O2: biological implications thereof

Reaction of [RuIII(EDTA)(CyS)]2− (edta4− = ethylenediaminetetraacetate; CySH = cysteine) with molecular oxygen (O2) has been studied as a function of pH (4.0–8.0) and cysteine concentration (0.2–2.0 mM) at room temperature (25 °C). Biological activities of the [Ru(EDTA)]/CySH/O2 system pertaining to cleavage of supercoiled plasmid DNA to its nicked open circular form has been explored in this work. Results are discussed in regard to the reaction of the ruthenium(III)-complex with molecular oxygen) and a working mechanism is proposed for the biological activities of the ruthenium(III)-complex in the presence of O2.

Ligand effect and cooperative role of metal ions on the DNA cleavage efficiency of mono and binuclear Cu(II) macrocyclic ligands complexes

Two binuclear Cu(II) complexes of N-functionalized macrocycle ligands, namely 1,3-bis(1,4,7-triaza-1-cyclonomyl)propane and 1-(3-(1,4,7-triazonan-1-yl)propyl)-1,4,7,10-tetraazacyclo-dodecane, were synthesized and their ability to hydrolyze the cleavage of supercoiled plasmid DNA (pBR322) was compared with that of structurally related non-functionalized mononuclear Cu(II) complexes. The former, binuclear Cu(II) complex with the symmetrical ligand exhibited enhanced double-strand cleavage activity compared to the other three complexes at the same [Cu2+] concentration. In contrast, the latter binuclear complex with unsymmetrical macrocylic ligand did not give rise to double-strand DNA cleavage. The linear DNA formation induced by the mononuclear Cu(II) 1,4,7,10-tetraazacyclo-dodecane complex was realized via a non-random double-stranded scission process. The differential cleavage activity is discussed in relation to dimer formation, effective cooperation and coordination environment of the metal center. The hydrolytic cleavage by the copper complexes without H2O2 is supported by evidence from an anaerobic reaction, free radical quenching, and nitro blue tetrazolium assay. In contrast, both the binuclear complexes cleaved supercoiled DNA efficiently to Form III (linearized DNA) in the presence of H2O2, indicating that nuclearity is a crucial parameter in oxidative cleavage. The radical scavenger inhibition study and nitro blue tetrazolium assay suggested the involvement of H2O2 and superoxide ions in the oxidative cleavage of DNA by the binuclear complexes.

Anti-oxidative and DNA Protecting Effects of Flavonoids-rich Scutellaria Lateriflora

Scutellaria lateriflora (American skullcap), a native plant of North America, has been used by Americans and Europeans as a nerve tonic for more than 200 years. In vivo studies have shown anxiolytic activity ofS. lateriflora in animals and humans. However, the neuroprotective mechanisms ofS. lateriflora are not fully understood. Oxidative stress plays a vital role in the neurodegenerative and neuropsychiatric diseases such as anxiety, Alzheimer's disease, depression, and Parkinson's disease. Bioactive compounds present in various medicinal plants neutralize or scavenge toxic free radicals and thus suppress oxidative stress. Therefore, the objective of this study was to investigate the antioxidant effects of S. lateriflora. The antioxidant potential of aqueous or ethanolic extracts of S. lateriflora was determined in mouse brain tissue using various biochemical assays. Protective effects of S. lateriflora against oxidative stress induced DNA fragmentation was determined using plasmid DNA. The ethanolic and aqueous extracts scavenged the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. The ethanolic extract reduced tert-butyl peroxide-induced reactive oxygen species (ROS) and lipid peroxides in the mouse brain homogenates. Furthermore, the ethanolic extract of S. lateriflora protected hydrogen peroxide-UV induced cleavage of supercoiled plasmid DNA. In conclusion, S. lateriflora exhibited significant antioxidant effects. The current findings posit S. lateriflora as one of the potential experimental herbal drugs that should be screened for its therapeutic potential against various oxidative stress associated mental disorders.

Cleavage of Supercoiled Plasmid DNA by Phenanthroline–Polyamine Conjugates as a Metal-free Artificial Nuclease

Abstract In this study, phenanthroline–polyamine conjugates have been synthesized. The conjugates bind to DNA and hydrolyze it in the absence of any metal and reducing agent under physiological conditions.

The reactivity of macrocyclic Fe(II) paraCEST MRI contrast agents towards biologically relevant anions, cations, oxygen or peroxide

The reactivity of four macrocyclic Fe(II) complexes (L1–L4) is studied with the goal of developing paramagnetic chemical exchange saturation transfer (paraCEST) magnetic resonance imaging (MRI) contrast agents for in vivo studies. (L1 = 1,4,7-tris(carbamoylmethyl)-1,4,7-triazacyclononane; L2 = 1,4,7-tris[(5-methyl-2-pyridyl)methyl]-1,4,7-triazacyclononane; L3 = 1,4,7-tris[(2-pyridyl)methyl]-1,4,7-triazacyclononane; L4 = 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane). The Fe(II) complexes remain intact in the presence of 25mM carbonate, 0.40mM phosphate and 100mM NaCl for 12h at 37°C, consistent with their moderately high formation constants (log K=13.5, 19.2, 7.50 for [Fe(L1)]2+, [Fe(L3)]2+ and [Fe(L4)]2+, respectively). [Fe(L4)]2+, [Fe(L2)]2+ and [Fe(L3)]2+ do not dissociate over 12h in the presence of excess Cu(II) at 37°C. None of the complexes show appreciable redox cycling as measured by consumption of ascorbate in the presence of oxygen, corresponding to their highly stabilized Fe(II) oxidation state (Eo=860, 930, 970, and 800mV versus NHE for [Fe(L1)]2+, [ [Fe(L2)]2+, [Fe(L3)]2+ and [Fe(L4)]2+. None of the Fe(II) complexes produce appreciable amounts of hydroxyl radical in the presence of peroxide and ascorbate as shown by limited hydroxylation of benzoate. Fe(II) complexes of L1, L2, and L3 show 25–28% cleavage of supercoiled plasmid DNA in the presence of peroxide and ascorbate over 2h at 37°C while [Fe(L4)]2+ shows 6% cleavage.

A copper(II) complex of 1,4,7-triazacyclononane featuring acetate pendant: an efficient DNA cleavage agent

A new water-soluble copper(II) complex, Cu(TACNA)Br · 0.375H2O (1) [TACNA = 1,4,7-triazacyclononane-N-acetate], has been synthesized to serve as artificial nucleases. The X-ray crystal structure of 1 indicates that one bromide and an oxygen from acetate pendant coordinate to copper(II) in addition to the nitrogen atoms in the TACN macrocycle, resulting in a five-coordinate complex with square-pyramidal geometry. The interaction of 1 with calf thymus DNA (ct-DNA) has been investigated by UV absorption and fluorescence spectroscopies, and the mode of ct-DNA binding for 1 has been proposed. In the absence of external agents, supercoiled plasmid DNA cleavage by 1 was performed under aerobic condition; the influences on DNA cleavage of different complex concentrations and reaction times were also studied. The cleavage of plasmid DNA likely involves oxidative mechanism.

Enantioselective cleavage of supercoiled plasmid DNA catalyzed by chiral macrocyclic lanthanide(III) complexes

The enantiomers of the Sm (III), Eu (III) and Yb (III) complexes [LnL(NO 3) 2](NO 3) of a chiral hexaazamacrocycle were tested as catalysts for the hydrolytic cleavage of supercoiled plasmid DNA. The catalytic activity was remarkably enantioselective; while the [LnL SSSS (NO 3) 2](NO 3) enantiomers promoted the cleavage of plasmid pBR322 from the supercoiled form (SC) to the nicked form (NC), the [LnL RRRR (NO 3) 2](NO 3) enantiomers were inactive. Kinetics of plasmid DNA hydrolysis was also investigated by agarose electrophoresis and it indicated typical single-exponential cleavage reaction. The hydrolytic mechanism of DNA cleavage was confirmed by the successful ligation of hydrolysis product by T4 ligase. The NMR study of the solutions of the complexes in various buffers indicated that the complexes exist as monomeric cationic complexes [LnL(H 2O) 3] 3 + in slightly acidic solutions and as dimeric cationic complexes [Ln 2L 2(μ-OH) 2(H 2O) 2] 4 + in slightly basic 8 mM solutions, with the latter form being a possible catalyst for hydrolysis of phosphodiester bonds.

Efficient double-strand cleavage of DNA mediated by Zn(ii)-based artificial nucleases

Two water-soluble zinc complexes, [Zn(L)Cl(2)] (1) and [Zn(2)(L)(2)(μ-C(2)O(4))(H(2)O)(2)]·(ClO(4))(2)·CH(3)OH (2) (L = N,N-bis(2-pyridylmethyl)methylamine), were prepared to serve as nuclease mimics. The complexes were characterized by X-ray, IR and UV-vis spectroscopy as well as ESI-MS. The electrospray mass spectrum of 2 in solution indicates that dinuclear ion [Zn(2)(L)(2)(μ-C(2)O(4))(ClO(4))](+) (3) is the active species. UV-Vis absorption and fluorescence spectroscopy studies show that the complexes partially intercalate to CT-DNA. In the absence of reducing agent, supercoiled plasmid DNA cleavage by the complexes 1 and 3 was performed and the hydrolytic mechanism was demonstrated by adding standard radical scavengers.

Synthesis, Crystal Structure, DNA Binding, and Hydrolytic Cleavage Activity of a Manganese(II) Complex

AbstractA new trinuclear manganese(II) complex {[MnCl(bpma)]2[Mn(μ‐Cl)4(H2O)2]}·CH3CN (1) [bpma = N,N‐bis(2‐pyridylmethyl)methylamine] has been synthesized and structurally characterized by X‐ray crystallography. The variable temperature‐dependent susceptibility measurement (2–300 K) of 1 reveals a weak antiferromagnetic interaction between the manganese ions through the dichlorido bridging ligands, with J = –0.46 cm–1, g = 1.99. The electrospray ionization mass spectrum of 1 in solution indicates that the dinuclear [Mn2(bpma)2Cl2(H2O)(OH)]+ ion is the active species. In the absence of a reducing agent, supercoiled plasmid DNA cleavage by the active species was performed and its hydrolytic mechanism was demonstrated with radical scavengers, anaerobic reaction, and T4 ligase. The pseudo‐Michaelis–Menten kinetic parameters (kcat., KM) were calculated to be 1.11 h–1 and 6.65 × 10–4 M for the dinuclear species.

DNA cleavage by the Cu(ii) complex of the DNA-intercalating 9-bis(pyridin-2-ylmethyl)aminobenzo[b]quinolizinium

The synthesis and the investigation of the Cu(II)-binding, the DNA-binding, and the DNA-damaging properties of a conjugate between the benzo[b]quinolizinium ion and the bis(pyridin-2-ylmethyl)amino receptor are presented. Photometric and fluorimetric titrations as well as CD spectroscopic analysis reveal that the 9-bis(pyridin-2-ylmethyl)aminobenzo[b]quinolizinium ligand intercalates into DNA (K(b) = 1.9 x 10(4) M(-1)) and exhibits a high selectivity towards complexation of Cu(2+) in water (K(b) = 4.3 x 10(4) M(-1)). This combination of functionalities allows to localize Cu(2+) in close proximity of DNA, where these metal ions induce efficient DNA damage, as shown by the single-strand cleavage of supercoiled plasmid DNA. Notably, the DNA cleavage does not require additional reagents nor light.

Synthesis and characterization of a new series of unsymmetrical macrocyclic binuclear vanadyl(IV) complexes: Electrochemical, antimicrobial, DNA binding and cleavage studies

A new series of unsymmetrical macrocyclic binuclear bis-phenoxo bridged oxidovanadium(IV) complexes have been synthesized and characterized by elemental and spectral techniques. A cyclic voltammetric investigation of these binuclear V IVO complexes evidenced that two successive quasi-reversible one electron transfer reduction waves ( E 1 pc = −0.54 to −0.67 V, E 2 pc = −0.80 to −0.85 V) are obtained. In the positive potential region (+0.50 to +1.00 V) two quasi-reversible oxidation couples are observed for all the complexes. The first one electron oxidation is observed around ( E 1 pc ) +0.63 to +0.78 V and the second around ( E 2 pc ) +0.82 to +0.97 V. The ESR spectra of all the binuclear V IVO complexes showed a single broad-band resonance at ca. g = 1.97–2.11 with the half field signal at 1500G ( M = ±2), which suggest magnetic interactions between two V IVO ions through the phenolate bridge. DNA binding experiments show that the aromatic diimine containing macrocyclic V IVO complexes display better DNA interactions than the aliphatic diimine containing V IVO analogues. These complexes significantly promote the oxidative cleavage of supercoiled plasmid DNA under physiological conditions in the presence of H 2O 2. All the complexes show noticeable growth inhibition of some plant pathogenic fungal species and human pathogenic bacterial species.