DNA-binding and photocleavage properties of cationic porphyrin-anthraquinone hybrids with different lengths of links

Four cationic porphyrin–anthraquinone (Por–AQ) hybrids differing in lengths of flexible alkyl linkage, 5-[4-(1-N-anthraquinonon-yl)-l-oxophenyl]-10,15,20-tris(N-methylpyridinium-4-yl)porphyrin triiodide, (l = acetyl, pentanoyl, octanoyl, undecanoyl, designed as [AQATMPyP]I₃, [AQPTMPyP]I₃, [AQOTMPyP]I₃ and [AQUTMPyP]I₃, respectively, see Fig. 1), were synthesized and their interactions with DNA were investigated. The results of spectroscopic, denaturation and viscosity measurements suggest that [AQATMPyP]I₃ binds to DNA through non-intercalative mode while the other three hybrids with longer links bind via bis-intercalative mode. Ethidium bromide (EB) competition experiment was carried out to determine the binding constants (K_b) of these compounds for CT DNA, and [AQPTMPyP]I₃ shows the largest K_b among these hybrids. The photocleavage mechanism and wavelength-dependent cleaving abilities of these hybrids to pBR322 plasmid DNA were also comparably investigated.     

Synthesis, characterization and DNA interactions of 5,15-(4-pyridyl)-10,20-(pentafluorophenyl)porphyrin coordinated to two [Ru(bipy)2Cl] groups

A new porphyrin 5,15-(4-pyridyl)-10,20-(pentafluorophenyl)porphyrin (H₂DPDPFPP) and its diruthenium(II) analog ([trans-H₂(DPDPFPP)Ru₂(bipy)₄Cl₂(PF₆)₂]) have been synthesized and characterized. Electronic transitions associated with the porphyrin consist of an intense Soret band near 400 nm and four Q-bands from 500 nm to 650 nm. Coordination of two [Ru(bipy)₂Cl]⁺ groups, where bipy = 2,2′-bipyridine, to the pyridyl nitrogens of the porphyrin give additional electronic transitions associated with the bipy orbitals and metal to ligand charge transfer (MLCT) transitions associated with the Ru(II) and bipy orbitals. Reversible redox couples in the cathodic region occur at E_1/2 = −0.74 V and −1.21 V versus Ag/AgCl reference which are shifted to more positive potentials when the porphyrin is coordinated to the Ru(II) groups. Gel electrophoresis studies with linearized pUC18 indicate an interaction between the metallated porphyrin and DNA which is confirmed by UV/Vis titrations with calf thymus (CT) DNA giving a binding constant of ca. 10⁵ M⁻¹. When buffered, pH 7, solutions of circular plasmid DNA containing the ruthenium porphyrin are irradiated with a 50 W tungsten lamp cleavage of the DNA is observed.     

Tris-ruthenium(II)/copper(II) multimetallic porphyrin: Synthesis, characterization, DNA binding and supercoiled DNA photocleavage studies

The porphyrin, meso-5-(pentafluorophenyl)-10, 15, 20-tris(4-pyridyl)porphyrin has been used to synthesize two new metalloporphyrin complexes. Insertion of copper(II) into the porphyrin center gives the copper(II) porphyrin. Coordination of three [Ru(bipy)₂Cl]⁺ moieties (where bipy = 2,2′-bipyridine) to the pyridyl nitrogens of the copper(II) porphyrin gives the target complex. Electronic transitions associated with the copper(II) porphyrin and the triruthenium copper(II) porphyrin include an intense Soret band and a less intense Q-band in the visible region of the spectrum. An intense π-π∗ transition in the UV region associated with the bipyridyl groups and a metal to ligand charge transfer (MLCT) band appearing as a shoulder to the Soret band are observed for the ruthenated copper(II) porphyrin. Electrochemical properties associated with the multimetallic complex include a redox couple in the cathodic region with E_1/2 = −0.86 V versus Ag/AgCl attributed to the porphyrin and a redox couple in the anodic region E_1/2 = 0.88 V versus Ag/AgCl due to the Ru^III/II couple. DNA titrations indicate the triruthenium copper(II) porphyrin interacts with DNA potentially through a groove binding mechanism. Irradiation of aqueous solutions of the target complex and supercoiled DNA at a 10:1 base pair to complex ratio with visible light above 400 nm indicates that the complex causes nicking of the DNA helix.     

DNA photocleavage activity of cobalt(III) polypyridyl complexes containing dpq ligand

Four cobalt(III) polypyridyl complexes, [Co(phen)_3−n(dpq)_n]³⁺ (phen = 1,10-phenanthroline, dpq = dipyrido[3,2-f:2′,3′-h]-quinoxaline) (n = 0, 1, 2, and 3) were synthesized and the influences of the dpq ligand on the photophysical properties, electrochemical properties, DNA binding affinities, as well as photonuclease activities of the complexes, were examined in detail. The presence of dpq ligand increases the DNA binding affinities of the corresponding complexes remarkably with respect to [Co(phen)₃]³⁺. With the sequential substitution of phen ligand by dpq ligand, the ¹O₂ quantum yields of the corresponding complexes are enhanced greatly. As a result, the photonuclease activities follow the order of [Co(dpq)₃]³⁺ > [Co(phen)(dpq)₂]³⁺ > [Co(phen)₂(dpq)]³⁺ ? [Co(phen)₃]³⁺. It was found all the examined complexes can generate OH upon UV irradiation, and OH is also involved in DNA photocleavage as reactive oxygen species.     

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

Abstract

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 K_b 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,structural characterization,in vitro DNA binding,and antitumor activity properties of Ru(II) compounds containing 2(2,6-dimethoxypyridine-3-yl)-1H-imidazo(4,5-f)[1, 10]phenanthroline

Abstract

The octahedral Ru(II) complexes containing the 2(2,6-dimethoxypyridine-3-yl)-1H-imidazo(4,5-f)[1, 10]phenanthroline ligand of type [Ru(N-N)₂(L)]²⁺, where N-N?=?phen (1,10-phenanthroline) (1), bpy (2,2^'-bipyridine) (2), and dmb (4,4^'-dimethyl-2,2^'-bipyridine) (3); L(dmpip) = (2(2,6-dimethoxypyridine-3-yl)1Himidazo(4,5-f)[1, 10]phenanthroline), have been synthesized and characterized by UV–visible absorption, molar conductivity, elemental analysis, mass, IR, and NMR spectroscopic techniques. The physicochemical properties of the Ru(II) complexes were determined by UV–Vis absorption spectroscopy. The DNA binding studies have been explored by UV–visible absorption, fluorescence titrations, and viscosity measurements. The supercoiled pBR322 DNA cleavage efficiency of Ru(II) complexes 1–3 was investigated. The antimicrobial activity of Ru(II) complexes was done against Gram-positive and Gram-negative microorganisms. The in vitro anticancer activities of all the complexes were investigated by cell viability assay, apoptosis, cellular uptake, mitochondrial membrane potential detection, and semi-quantitative PCR on HeLa cells. The result indicates that the synthesized Ru(II) complexes probably interact with DNA through an intercalation mode of binding with complex 1 having slightly stronger DNA binding affinity and anticancer activity than 2 and 3.     

Mixed-ligand complexes of ruthenium(II) containing new photoactive or electroactive ligands: synthesis, spectral characterization and DNA interactions

Mixed-ligand ruthenium(II) complexes of three photoactive ligands, viz., (E)-1-[2-(4-methyl-2-pyridyl)-4-pyridyl]-2-(1-naphthyl)-1-ethene (mppne), (E)-1-(9-anthryl)-2-[2-(4-methyl-2-pyridyl)-4-pyridyl]-1-ethene (mppae) and (E)-1-[2-(4-methyl-2-pyridyl)-4-pyridyl]-2-(1-pyrenyl)-1-ethene (mpppe), in which a 2,2′-bipyridyl unit is linked via an ethylinic linkage to either a naphthalene, an anthracene or a pyrene chromophore and three electroactive ligands, viz., 4-(4-pyridyl)-1,2-benzenediol (catpy), 5,6-dihydroxy-1,10-phenanthroline (catphen) and 1,2-benzenediol (cat), were synthesized in good to moderate yields. Complexes [Ru(bpy)₂(mppne)]²⁺ (bpy is 2, 2′–bipyridyl), [Ru(bpy)₂(mppae)]²⁺, [Ru(bpy)₂(mpppe)]²⁺, [Ru(bpy)₂(sq-py)]⁺, [Ru(bpy)₂(sq-phen)]⁺ and [Ru(phen)₂(bsq)]⁺ (phen is 1,10-phenanthroline) were fully characterized by elemental analysis, IR, ¹H NMR, fast-atom bombardment or electron-impact mass, UV–vis and cyclic voltammetric methods. In the latter three complexes, the ligands catpy, catphen and cat are actually bound to the metal center as the corresponding semiquinone species, viz., 4-(4-pyridyl)-1,2-benzenedioleto(+I) (sq-py), 1,10-phenanthroline-5,6-dioleto(+I) (sq-phen) and 1,2-benzenedioleto(+I) (bsq), thus making the overall charge of the complexes formally equal to + 1 in each case. These three complexes are electron paramagnetic resonance active and exhibit an intense absorption band between 941 and 958 nm owing to metal-to-ligand charge transfer (MLCT, d _Ru→π*_sq) transitions. The other three ruthenium(II) complexes containing three photoactive ligands, mppne, mppae and mpppe, exhibit MLCT (d _Ru→π*_bpy ) bands in the 454–461-nm region and are diamagnetic. These can be characterized by the ¹H NMR method. [Ru(bpy)₂(mppne)]²⁺, [Ru(bpy)₂(mppae)]²⁺ and [Ru(bpy)₂(mpppe)]²⁺ exhibit redox waves corresponding to the Ru^III/Ru^II couple along with the expected ligand (bpy and substituted bpy) based ones in their cyclic and differential pulse voltammograms (CH₃CN, 0.1 M tetrabutylammonium hexafluorophosphate)—corresponding voltammograms of [Ru(bpy)₂(sq-py)]⁺, [Ru(bpy)₂(sq-phen)]⁺ and [Ru(phen)₂(bsq)]⁺ are mainly characterized by waves corresponding to the quinone/semiquinone (q/sq) and semiquinone/1,2-diol (sq/cat) redox processes. The results of absorption and fluorescence titration as well as thermal denaturation studies reveal that [Ru(bpy)₂(mppne)]²⁺ and [Ru(bpy)₂(mppae)]²⁺ are moderate-to-strong binders of calf thymus DNA with binding constants ranging from 10⁵ to 10⁶ M⁻¹. Under the identical conditions of drug and light dose, the DNA (supercoiled pBR 322) photocleavage activities of these two complexes follow the order:[Ru(bpy)₂(mppne)]²⁺>[Ru(bpy)₂(mppae)]²⁺, although the emission quantum yields follow the reverse order. The other ruthenium(II) complexes containing the semiquinone-based ligands are found to be nonluminescent and inefficient photocleavage agents of DNA. However, experiments shows that [Ru(bpy)₂(sq)]⁺-based complexes oxidize the sugar unit and could be used as mild oxidants for the sugar moiety of DNA. Possible explanations for these observations are presented.Electronic Supplementary Material Supplementary material is available for this article at .     

Synthesis, structure, DNA binding and DNA cleavage activity of oxovanadium(IV) N-salicylidene-S-methyldithiocarbazate complexes of phenanthroline bases

Ternary oxovanadium(IV) complexes [VO(salmdtc)(B)] (1-3), where salmdtc is dianionic N-salicylidene-S-methyldithiocarbazate and B is N,N-donor phenanthroline bases like 1,10-phenanthroline (phen, 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 2) and dipyrido[3,2-a:2′,3′-c]phenazine (dppz, 3), are prepared, characterized and their DNA binding and DNA cleavage activity studied. Complex 3 is structurally characterized by single-crystal X-ray crystallography. The molecular structure shows the presence of a vanadyl group in six-coordinate VN₃O₂S coordination geometry. The S-methyldithiocarbazate Schiff base acts as a tridentate NSO-donor ligand in a meridional binding mode. The N,N-donor heterocyclic base displays a chelating mode of binding with an N-donor site trans to the vanadyl oxo-group. The complexes show a d-d band in the range of 675-707 nm in DMF. They exhibit an irreversible oxidative cyclic voltammetric response near 0.9 V due to the V(V)/V(IV) couple and a quasi-reversible reductive V(IV)/V(III) redox couple near −1.0 V vs. SCE in DMF-0.1 M TBAP. The complexes show good binding propensity to calf thymus DNA giving binding constant values in the range of 7.4 × 10⁴-2.3 × 10⁵ M⁻¹. The thermal denaturation and viscosity binding data suggest DNA surface and/or groove binding nature of the complexes. The complexes show poor chemical nuclease activity in dark in the presence of 3-mercaptopropionic acid (MPA) or hydrogen peroxide. The dpq and dppz complexes show efficient DNA cleavage activity in UV-A light of 365 nm via a type-II mechanistic pathway involving formation of singlet oxygen (¹O₂) as the reactive species.     

New insights in the DNA-[Cr(phen)2(dppz)] binding and photocleavage properties by the complex with an intercalating ligand

Due to the key role of DNA in cell life and pathological processes, the design of specific chemical nucleases, DNA probes and alkylating agents is an important research area for the development of new therapeutic agents and tools in Biochemistry. Hence, the interaction of small molecules with DNA has attracted in particular a great deal of attention.The aim of this study was to investigate the ability of [Cr(phen)₂(dppz)]³⁺ to associate with DNA and to characterize it as photocleavage reagent for Photodynamic Therapy (PDT).Chromium(III) complex [Cr(phen)₂(dppz)]³⁺, (dppz = dipyridophenazine, phen = 1,10-phenanthroline), where dppz is a planar bidentate ligand with an extended π system, has been found to bind strongly to double strand oligonucleotides (ds-oligo) and plasmid DNA with intrinsic DNA binding constants, K_b, of (3.9 ± 0.3) × 10⁵ M⁻¹ and (1.1 ± 0.1) × 10⁵ M⁻¹, respectively. The binding properties to DNA were investigated by UV-visible (UV-Vis) absorption spectroscopy and electrophoretic studies. UV-Vis absorption data provide clearly that the chromium(III) complex interacts with DNA intercalatively. Competitive binding experiments show that the enhancement in the emission intensity of ethidium bromide (EthBr) in the presence of DNA was quenched by [Cr(phen)₂(dppz)]³⁺, indicating that the Cr(III) complex displaces EthBr from its binding site in plasmid DNA. Moreover, [Cr(phen)₂(dppz)]³⁺, non-covalently bound to DNA, promotes the photocleavage of plasmid DNA under 457 nm irradiation. We also found that the irradiated Cr(III)-plasmid DNA association is able to impair the transforming capacity of bacteria. These results provide evidence confirming the responsible and essential role of the excited state of [Cr(phen)₂(dppz)]³⁺ for damaging the DNA structure. The combination of DNA, [Cr(phen)₂(dppz)]³⁺ and light, is necessary to induce damage. In addition, assays of the photosensitization of transformed bacterial suspensions suggest that Escherichia coli may be photoinactivated by irradiation in the presence of [Cr(phen)₂(dppz)]³⁺. In sum, our results allow us to postulate the [Cr(phen)₂(dppz)]³⁺ complex as a very attractive candidate for DNA photocleavage with potential applications in Photodynamic Therapy (PDT).     

Antibacterial,tyrosinase, and DNA photocleavage studies of some triazolylnucleosides

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.     

DNA binding,prominent photonuclease activity and antibacterial PDT of cobalt(II) complexes of phenanthroline based photosensitizers

Abstract

The chemistry of Co(II) complexes showing efficient light induced DNA cleavage activity, binding propensity to calf thymus DNA and antibacterial PDT is summarized in this article. Complexes of formulation [Co(mqt)(B)₂]ClO₄ 1–3 where mqt is 4-methylquinoline-2-thiol and B is N,N-donor heterocyclic base, viz. 1,10-phenanthroline (phen 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq 2) and dipyrido[3,2-a:2′,3′-c]phenazine (dppz 3) have been prepared and characterized. The DNA-binding behaviors of these three complexes were explored by absorption spectra, viscosity measurements and thermal denaturation studies. The DNA binding constants for complexes 1, 2 and 3 were determined to be 1.6?×?10³?M^?1, 1.1?×?10⁴?M^?1 and 6.4?×?10⁴?M^?1 respectively. The experimental results suggest that these complexes interact with DNA through groove binding mode. The complexes show significant photocleavage of supercoiled (SC) DNA proceeds via a type-II process forming singlet oxygen as the reactive species. Antimicrobial photodynamic therapy was studied using photodynamic antimicrobial chemotherapy (PACT) assay against E. coli and all complexes exhibited significant reduction in bacterial growth on photoirradiation.     

Sequence/structure selective thermal and photochemical cleavage of yeast-tRNAPhe by UO

The uranyl(VI) ion, UO, cleaves yeast tRNA^Phe both thermally and photochemically. Photochemical cleavage takes place at all positions but exhibits maxima at G₁₀, G₁₈, G₃₀, A₃₈, C₄₉ and A₆₂. Furthermore, in the presence of stoichiometric concentrations of citrate, the cleavage is generally suppressed except that strong cleavage at positions G₁₀ and C₄₈–U₅₀ persists, indicating the presence of a high-affinity metal-ion binding site. It is proposed that these photocleavage sites reflect the tertiary structure of the yeast tRNA^Phe molecule in terms of D-loop/T-loop interaction and anticodon loop conformation and that uranyl-mediated photocleavage of RNA may be used as a probe of RNA tertiary structure, and in particular for identifying binding sites for divalent metal ions. Thus a high-affinity metal-ion binding site is inferred in the Rcentral pocket' formed by the D-loop, the T-loop and the acceptor stem.     

Iron(III) Schiff base complexes of arginine and lysine as netropsin mimics showing AT-selective DNA binding and photonuclease activity

Iron(III) complexes [Fe(L)₂]Cl (1-3), where L is monoanionic N-salicylidene-arginine (sal-argH for 1), hydroxynaphthylidene-arginine (nap-argH for 2) and N-salicylidene-lysine (sal-lysH for 3), were prepared and their DNA binding and photo-induced DNA cleavage activity studied. Complex 3 as its hexafluorophosphate salt [Fe(sal-lysH)₂](PF₆)·6H₂O (3a) was structurally characterized by single crystal X-ray crystallography. The crystals belonged to the triclinic space group P-1. The complex has two tridentate ligands in FeN₂O₄ coordination geometry with two pendant cationic amine moieties. Complexes 1 and 2 with two pendant cationic guanidinium moieties are the structural models for the antitumor antibiotics netropsin. The complexes are stable and soluble in water. They showed quasi-reversible Fe(III)/Fe(II) redox couple near 0.6 V in H₂O-0.1 M KCl. The high-spin 3d⁵-iron(III) complexes with μ_eff value of ∼5.9 μ_B displayed ligand-to-metal charge transfer electronic band near 500 nm in Tris-HCl buffer. The complexes show binding to Calf Thymus (CT) DNA. Complex 2 showed better binding propensity to the synthetic oligomer poly(dA)·poly(dT) than to CT-DNA or poly(dG)·poly(dC). All the complexes displayed chemical nuclease activity in the presence of 3-mercaptopropionic acid as a reducing agent and cleaved supercoiled pUC19 DNA to its nicked circular form. They exhibited photo-induced DNA cleavage activity in UV-A light and visible light via a mechanistic pathway that involves the formation of reactive hydroxyl radical species.     

Molecular docking,QSAR properties and DNA/BSA binding,anti-proliferative studies of 6-methoxy benzothiozole imine base and its metal complexes

Abstract

The molecular and QSAR (Quantitative Structure–Activity Relationship) properties of title compound 2-((6-Methoxybenzo[d]thiazol-2-ylimino)methyl)-6-ethoxyphenol (HL) were evaluated employing HyperChem 7.5 tools. The interaction of the 1a–1e complexes of HL with calf thymus DNA (CT-DNA) was investigated by absorption titrations, Fluorescence quenching and viscosity measurements. The experimental data suggest that these complexes bind to CT-DNA through an intercalative mode, wherein DNA-binding affinity of 1e is found to be greater compared to other complexes. The tryptophan emission-quenching with bovine serum albumin (BSA) experiment revealed stronger binding of 1e than other complexes in the hydrophobic region of protein. The photocleavage of plasmid pBR322 DNA investigated in the presence of the title complexes inferred conversion of supercoiled form of DNA plasmid to circular nicked form. Free-radical scavenging activity studies of HL and its metal complexes determined by their interaction with the stable free-radical DPPH have shown promising antioxidant property. Further cytotoxicity studies with HeLa and MCF-7 cell lines indicated that the compounds can efficiently inhibit the cell proliferation in a dose dependent manner. The DAPI staining assay studies revealed the higher potency of 1e to induce apoptosis. Abbreviations BSA Bovine serum albumin protein

CT-DNA Calf thymus DNA

DMSO Dimethyl sulfoxide

DAPI 4′,-6-Diamidino-2-phenylindole dihydrochloride

ESI–MS Electrospray ionization mass spectrometry

IC₅₀ Half-maximal inhibitory concentration

MBTYE 2-((6-methoxybenzo[d]thiazol-2-ylimino) methyl)-6-ethoxyphenol

MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

PBS Phosphate-buffered saline

Tris Tris(hydroxymethyl)aminomethane

Communicated by Ramaswamy H. Sarma     

Synthesis, DNA-binding and photocleavage studies of ruthenium complexes [Ru(bpy)2(mitatp)] and [Ru(bpy)2(nitatp)]

Two new ruthenium complexes [Ru(bpy)₂(mitatp)](ClO₄)₂1 and [Ru(bpy)₂(nitatp)](ClO₄)₂2 (bpy = 2,2′-bipyridine, mitatp = 5-methoxy-isatino[1,2-b]-1,4,8,9-tetraazatriphenylene, nitatp = 5-nitro-isatino[1,2-b]-1,4,8,9-tetraazatriphenylene) have been synthesized and characterized by elemental analysis, ¹H NMR, mass spectrometry and cyclic voltammetry. Spectroscopic and viscosity measurements proved that the two Ru(II) complexes intercalate DNA with larger binding constants than that of [Ru(bpy)₂(dppz)]²⁺ (dppz = dipyrido[3,2-a:2′,3′-c]phenazine) and possess the excited lifetime of microsecond scale upon binding to DNA. Both complexes can efficiently photocleave pBR322 DNA in vitro under irradiation. Singlet oxygen (¹O₂) was proved to contribute to the DNA photocleavage process, the ¹O₂ quantum yields was determined to be 0.43 and 0.36 for 1 and 2, respectively. Moreover, a photoinduced electron transfer mechanism was also found to be involved in the DNA cleavage process.     

Synthesis, crystal structures, DNA binding and cleavage activity of l-glutamine copper(II) complexes of heterocyclic bases

Ternary l-glutamine (l-gln) copper(II) complexes [Cu(l-gln)(B)(H₂O)](X) (B = 2,2′-bipyridine (bpy), , 1; B = 1,10-phenanthroline (phen), , 2) and [Cu(l-gln)(dpq)(ClO₄)] (3) (dpq, dipyridoquinoxaline) are prepared and characterized by physicochemical methods. The DNA binding and cleavage activity of the complexes have been studied. Complexes 1-3 are structurally characterized by X-ray crystallography. The complexes show distorted square pyramidal (4+1) CuN₃O₂ coordination geometry in which the N,O-donor amino acid and the N,N-donor heterocyclic base bind at the basal plane with a H₂O or perchlorate as the axial ligand. The crystal structures of the complexes exhibit chemically significant hydrogen bonding interactions besides showing coordination polymer formation. The complexes display a d-d electronic band in the range of 610-630 nm in aqueous-dimethylformamide (DMF) solution (9:1 v/v). The quasireversible cyclic voltammetric response observed near −0.1 V versus SCE in DMF-TBAP is assignable to the Cu(II)/Cu(I) couple. The binding affinity of the complexes to calf thymus (CT) DNA follows the order: 3 (dpq) > 2 (phen) ? 1 (bpy). Complexes 2 and 3 show DNA cleavage activity in dark in the presence of 3-mercaptopropionic acid (MPA) as a reducing agent via a mechanistic pathway forming hydroxyl radical as the reactive species. The dpq complex 3 shows efficient photo-induced DNA cleavage activity on irradiation with a monochromatic UV light of 365 nm in absence of any external reagent. The cleavage efficiency of the DNA minor groove binding complexes follows the order: 3 > 2 ? 1. The dpq complex exhibits photocleavage of DNA on irradiation with visible light of 647.1 nm. Mechanistic data on the photo-induced DNA cleavage reactions reveal the involvement of singlet oxygen (¹O₂) as the reactive species in a type-II pathway.     

Enhanced uranyl photocleavage across the minor groove of all (A/T)4 sequences indicates a similar narrow minor groove conformation

The uranyl(VI)-mediated photocleavage of a Drew–Dickerson sequence oligonucleotide (5′-dGATCACGCGAATTCGCGT) either as the (self-complementary) duplex or cloned into the BamH1 site of pUC19 has been studied. At pH 6.5 in acetate buffer relatively enhanced photocleavage is observed at the 3′-end of the AATT sequence corresponding to maximum cleavage across the minor groove in the A/T tract. Thus maximum cleavage correlates with minimum minor groove width in the crystal structure and also with the largest electronegative potential according to computations. Using plasmid constructs with cloned inserts of the type [CGCG(A/T₄)]_n, we also analysed all possible sequence combinations of the (A/T)₄ tract and in all cases we observed maximum uranyl-mediated photocleavage across the minor groove in the (A/T)₄ tract without any significant differences between the various sequences. From these results we infer that DNA double helices of all (A/T)₄ sequences share the same narrow minor groove helix conformation.     

Chloroplast and mitochondrial DNA composition of triploid and tetraploid somatic hybrids between Lycopersicon esculentum and Solanum tuberosum

The chloroplast (cp) DNA type and mitochondrial (mt) DNA composition of 17 somatic hybrids between a cytoplasmic albino tomato and monoploid potato (A7-hybrids) and 18 somatic hybrids between a nitrate reductase-deficient tomato and monoploid potato (C7-hybrids) were analyzed. Thirteen A7-hybrids and 9 C7-hybrids were triploids (with one potato genome); the other hybrids were tetraploid. As expected, all A7-hybrids contained potato cpDNA. Of the C7-hybrids 7 had tomato cpDNA, 10 had potato cpDNA and 1 hybrid contained both tomato and potato cpDNA. The mtDNA composition of the hybrids was analyzed by hybridization of Southern blots with four mtDNA-specific probes. The mtDNAs in the hybrids had segregated independently from the cpDNAs. Nuclear DNA composition (i.e. one or two potato genomes) did not influence the chloroplast type in the C7-hybrids, nor the mtDNA composition of A7- or C7-hybrids. From the cosegregation of specific mtDNA fragments we inferred that both tomato and potato mtDNAs probably have a coxII gene closely linked to 18S+5S rRNA genes. In tomato, atpA, and in potato, atp6 seems to be linked to these mtDNA genes.