Photo-induced DNA Cleavage Activity Research Articles

Synthesis, characterization, electrochemistry, biological and molecular docking studies of the novel Co(II), Ni(II) and Cu(II) complexes derived from methanethiol bridged (2-((1H-benzo[d]imidazol-2-yl)methylthio)-1H-benzo[d]imidazol-6-yl)(phenyl)methanone

The bio-active Co(II), Ni(II) and Cu(II) complexes derived from new (2-((1H-benzo[d]imidazol-2-yl)methylthio)-1H-benzo[d]imidazol-5-yl)(phenyl)methanone were synthesized in good yield. The structure of these metal complexes have been characterized using IR, Uv–visible, mass spectra,1H NMR, TGA and powder XRD techniques. The spectral data of the Co(II) and Ni(II) complex indicated the tri-dentate bonding mode with the ligand and that of the Cu(II) complex is in bi-dentate bonding mode. The electrocatalytic activity of the Co(II) complex was studied by cyclic voltammeter using modified GCE towards various concentration of dopamine (DA, 3,4-dihydroxyphenethylamine). The obtained Ip value linearly increased with increasing scan rates, indicating the oxidation process of dopamine (DA) which occurred by modified Co(II) complex/GCE through diffusion controlled process. The antimicrobial, antioxidant and cytotoxicity studies of the ligand and its metal complexes were performed, the obtained results showed that the complexes are more potent bio-active as compared with uncoordinated ligand. The DNA binding property of the metal complexes were performed on double strand calf thymus DNA using electronic absorption and fluorescence emission methods, in addition, photo induced DNA cleavage activity also studied on pBR322 DNA. The molecular docking of the Co(II) complex on 6-bp DNA (PDB code: 1Z3F) and C-KIT Tyrosive kinases (TRKs) (PDB code: 1t46), further confirms the inhibition ability of the metal complex. The experimental results and the drug likeness property of the metal complexes suggest the possible applications of metal complex which, could be developed as a potent drug in the near future.

Mitochondria localizing high-spin iron complexes of curcumin for photo-induced drug release

High-spin iron complexes [FeII(L1)(cur)]Cl (1), [FeIII(L2)(cur)]Cl (2) and [FeIII(L3)(cur)] (3), where L1 is tris(2-pyridylmethyl)amine, HL2 is N,N-bis(2-pyridylmethyl)-N-(2-hydroxybenzyl)amine and H2L3 is N,N-dimethyl-N’,N’-bis(4,6-ditertiarybutyl-2-hydroxybenzyl)ethylenediamine and Hcur is curcumin, were synthesized, characterized and their redox-mediated and/or visible light induced release of curcumin, photo-induced DNA cleavage and anticancer activity studied. The molecular structures of 1–3 were optimized from DFT (density functional theory) calculations. The t2g3eg2-iron(III) complexes showed a curcumin based electronic spectral band at ∼ 425 nm in 1:1 DMF/DPBS (Dulbecco's phosphate-buffered saline) and displayed the Fe(III)-Fe(II) redox couple near −0.36 V vs. SCE (saturated calomel electrode) in DMF-0.1 M TBAP (tetrabutylammonium perchlorate). The complexes are avid binders to calf thymus DNA. Complex 1 showed photo-cleavage of pUC19 DNA in visible light of 446 nm forming OH radicals as the reactive oxygen species. The complexes as curcumin carrier showed photo-cytotoxicity in different cell lines on visible light activation. Imaging study showed their subcellular mitochondrial localization.

Monomeric and Dimeric Oxidomolybdenum(V and VI) Complexes, Cytotoxicity, and DNA Interaction Studies: Molybdenum Assisted C═N Bond Cleavage of Salophen Ligands.

Four novel dimeric bis-μ-imido bridged metal-metal bonded oxidomolybdenum(V) complexes [MoV2O2L'21-4] (1-4) (where L'1-4 are rearranged ligands formed in situ from H2L1-4) and a new mononuclear dioxidomolybdenum(VI) complex [MoVIO2L5] (5) synthesized from salen type N2O2 ligands are reported. This rare series of imido-bridged complexes (1-4) have been furnished from rearranged H3L'1-4 ligands, containing an aromatic diimine (o-phenylenediamine) "linker", where Mo assisted hydrolysis followed by -C═N bond cleavage of one of the arms of the ligand H2L1-4 took place. A monomeric molybdenum(V) intermediate species [MoVO(HL'1-4)(OEt)] (Id1-4) was generated in situ. The concomitant deprotonation and dimerization of two molybdenum(V) intermediate species (Id1-4) ultimately resulted in the formation of a bis-μ-imido bridge between the two molybdenum centers of [MoV2O2L'21-4] (1-4). The mechanism of formation of 1-4 has been discussed, and one of the rare intermediate monomeric molybdenum(V) species Id4 has been isolated in the solid state and characterized. The monomeric dioxidomolybdenum(VI) complex [MoVIO2L5] (5) was prepared from the ligand H2L5 where the aromatic "linker" was replaced by an aliphatic diimine (1,2-diaminopropane). All the ligands and complexes have been characterized by elemental analysis, IR, UV-vis spectroscopy, NMR, ESI-MS, and cyclic voltammetry, and the structural features of 1, 2, 4, and 5 have been solved by X-ray crystallography. The DNA binding and cleavage activity of 1-5 have been explored. The complexes interact with CT-DNA by the groove binding mode, and the binding constants range between 103 and 104 M-1. Fairly good photoinduced cleavage of pUC19 supercoiled plasmid DNA was exhibited by all the complexes, with 4 showing the most promising photoinduced DNA cleavage activity of ∼93%. Moreover, in vitro cytotoxic activity of all the complexes was evaluated by MTT assay, which reveals that the complexes induce cell death in MCF-7 (human breast adenocarcinoma) and HCT-15 (colon cancer) cell lines.

Ruthenium(II) complexes of saccharin with dipyridoquinoxaline and dipyridophenazine: Structures, biological interactions and photoinduced DNA damage activity

Ruthenium complexes trans-[Ru(sac)2(dpq)2] (1) and trans-[Ru(sac)2(dppz)2] (2) where sac is artificial sweetener saccharin (o-sulfobenzimide; 1,2-benzothiazole-3(2H)-one1,1-dioxide (Hsac)), dpq = dipyrido[3,2-d:2′,3′-f]quinoxaline and dppz = dipyrido[3,2-a:2′,3′-c]phenazine have been synthesized and thoroughly characterized using various analytical and spectral techniques. Saccharin known to act as carbonic anhydrase IX (CA IX) inhibitor which is a biomarker for highly aggressive and proliferative tumor in hypoxic stress, so inhibition of CA IX is a potential strategy for anticancer chemotherapy. The solid state structures, photophysical properties, photostability, DNA and protein binding affinity, and DNA photocleavage activity were explored. The structural analysis revealed Ru(II) centre is in discrete mononuclear, distorted octahedral {RuN6} coordination geometry with two monoanionic nitrogen donor saccharinate ligands and two neutral bidentate nitrogen donors ligands dpq and dppz. cis-[Ru(sac)2(dppz)2] (cis-2) geometrical isomer was also isolated and structurally characterized by X-ray crystallography. The photo-induced dissociation of monodentate saccharin ligand is observed when irradiated at UV-A light of 365 nm. The complexes show significant binding affinity to the calf thymus DNA (Kb ∼ 105 M−1) through significant intercalation through planar dpq and dppz ligands. Interaction of complexes 1 and 2 with bovine serum albumin (BSA) showed remarkable tryptophan emission quenching (KBSA ∼105 M−1). The complexes showed appreciable photoinduced DNA cleavage activity upon irradiation of low power UV-A light of 365 nm from supercoiled (SC) to its nicked circular (NC) form at micromolar complex concentrations. Photocleavage mechanistic studies in presence of O2 reveals involvement of reactive oxygen species (ROS) mediated through ligand-centered 3ππ* and/or 3MLCT excited states generated upon photoactivation leads to nicking of supercoiled DNA to nicked circular form. In absence of O2, we also observed photocleavage of DNA through formation of photoinduced ligand dissociated Ru-DNA complex involving PACT pathway.

Novel iron phenanthroline-based photosensitizers for antimicrobial PDT: synthesis, DNA binding and photo-induced DNA cleavage activity

The chemistry of Fe(II) complexes showing efficient light-induced DNA cleavage activity, binding propensity to calf thymus DNA and antibacterial photodynamic therapy has been summarized in this article. Complexes of formulation [Fe(mqt)(B)2](PF6)(1)–(3), where mqt is 2-thiol-4-methylquinoline and B is N,N-donor heterocyclic base, viz. 1,10-phenanthroline, dipyrido[3,2-d:2′,3′-f]quinoxaline and dipyrido[3,2-a:2′,3′-c]phenazine 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 1.9 × 103, 3.4 × 104 and 8.1 × 104 M−1, respectively. The experimental results suggest these complexes interact with DNA through groove-binding mode. The complexes show significant photocleavage of supercoiled DNA proceeds via a type-II process forming singlet oxygen as the reactive species. Antimicrobial photodynamic therapy was studied using photodynamic antimicrobial chemotherapy assay against Escherichia coli and all complexes exhibited significant reduction in bacterial growth on photoirradiation.

Ternary Eu(iii) and Tb(iii) β-diketonate complexes containing chalcones: photophysical studies and biological outlook

Ternary Eu(iii) and Tb(iii) β-diketonate complexes containing chalcones were studied for their structures, photophysical properties, interactions with DNA and serum protein, and photo-induced DNA cleavage activity.

Photo-induced DNA cleavage by zinc-substituted myoglobin with a redesigned active center

Artificial nucleases were constructed by the redesign of the heme center in myoglobin (Mb) and replacement of the native heme with zinc protoporphyrin (ZnPP), which exhibit tunable photo-induced DNA cleavage activity.

Binding interactions with biological targets and DNA photocleavage activity of Pr(III) and Nd(III) complexes of dipyridoquinoxaline

Two new lanthanide(III) complexes [Ln(dpq)(DMF)2(NO3)3], where Ln=Pr (1), Nd (2), dpq=dipyrido[3,2-d:2′,3′-f]quinoxaline, DMF=N,N-dimethylformamide were synthesized, characterized by various spectroscopic methods and single crystal X-ray crystallography. They were studied for their DNA and protein binding and photo-induced DNA cleavage activity. The complexes displays ten-coordinate [LnN2O8] bicapped dodecahedron coordination geometry from a bidentate N,N-donor dpq ligand, two DMF and three bidentate NO3- anions. The complexes 1 and 2 showed intense ligand centered absorption bands ∼300–350nm originated from n/π→π∗ transition from dipyridoquinoxaline (dpq). The binding interaction of complexes studied with UV–vis spectroscopy, competitive displacement of ethidium bromide and isothermal titration calorimetry (ITC) shows that the complexes display efficient binding affinity to calf thymus DNA with binding constant (Kb) of ∼104M−1 suggesting groove binding or partial intercalation of complexes to CT-DNA. The complexes display favorable binding affinity to bovine serum albumin (BSA) protein with binding constant (KBSA) of ∼105M−1. Both the complexes efficiently cleave supercoiled (SC) DNA to its nicked circular (NC) form at UV-A light of 365nm at 10μM via formation of singlet oxygen (1O2) and hydroxyl radical (OH) species under physiological condition in a type-II and photoredox pathway.

Oxidovanadium(v) complexes of aroylhydrazones incorporating heterocycles: synthesis, characterization and study of DNA binding, photo-induced DNA cleavage and cytotoxic activities

The interaction of four neutral oxidovanadium(v) complexes with DNA and their cytotoxic activities have been reported.

Evaluation of the cell cytotoxicity and DNA/BSA binding and cleavage activity of some dioxidovanadium(V) complexes containing aroylhydrazones

Three dioxidovanadium(V) complexes [VO2L1–3] (1–3) [HL1=1-napthoyl hydrazone of 2-acetyl pyridine, HL2=2-furoyl hydrazone of 2-acetyl pyridine and H2L3=isonicotinoyl hydrazone of 2-hydroxy benzaldehyde] have been reported. All the complexes were characterized by various spectroscopy (IR, UV-visible and NMR) and the molecular structures of 1 and 2 were characterized by single crystal X-ray diffraction technique. Structural report established five-coordinate geometries, distorted toward square pyramidal for each of 1 and 2, based on a tridentate -O,N,N coordinating anion and two oxido–O atoms. The experimental results show that the complexes interact with calf–thymus DNA (CT-DNA) possibly by a groove binding mode, with binding constants of ~105M−1. All complexes show good photo-induced cleavage of pUC19 supercoiled plasmid DNA with complex 1 showing the highest photo-induced DNA cleavage activity of ~68%. 1–3 also exhibit moderate binding affinity in the range of 103–104M−1 towards bovine serum albumin (BSA), while all the complexes show good photo-induced BSA cleavage activity. Moreover the antiproliferative activity of all these complexes was studied, which reveal all compounds are significantly cytotoxic towards the HeLa cell line.

Synthesis, singlet-oxygen photogeneration, two-photon absorption, photo-induced DNA cleavage and cytotoxic properties of an amphiphilic β-Schiff-base linked Ru(II) polypyridyl–porphyrin conjugate

A novel porphyrin–polypyridyl ruthenium(II) conjugate (TPP–Ru), in which the ruthenium(II) polypyridyl moiety is linked to the β-position of the tetraphenylporphyrin via a Schiff base linkage, has been synthesized and characterized by 1H NMR, HRMS and UV–visible spectroscopy. The relative singlet oxygen quantum yield and two-photon absorption cross-section of this conjugate, together with its photo-induced DNA cleavage and cytotoxic activities were measured. The results show that the amphiphilic ruthenium(II) polypyridyl–porphyrin conjugate is an effective DNA photocleavage agent, with potential application in one- and two-photon absorption anti-cancer photodynamic therapy.

Mitochondria‐Targeted Photoinduced Anticancer Activity of Oxidovanadium(IV) Complexes of Curcumin in Visible Light

AbstractOxidovanadium(IV) complexes [VO(py‐aebmz)(B)]Cl (1, 2) and [VO(napth‐py‐aebmz)(cur)]Cl [3; py‐aebmz = 2‐(1H‐benzimidazol‐2‐yl)‐N‐(pyridin‐2‐ylmethylene)ethanamine, HB = acetylacetone (Hacac, 1) and curcumin (Hcur, 2), napth‐py‐aebmz = naphthalimide conjugated to py‐aebmz ] have been prepared, characterized and their photoinduced DNA cleavage activities and photocytotoxicities studied. Complexes 1–3 each exhibited an irreversible cyclic voltammetric response of the VIV/VIII redox couple at around –0.85 V versus SCE in dmf/0.1 M tbap. The complexes showed DNA photocleavage activity in visible light of 454, 530 and 647 nm through hydroxyl radical and singlet oxygen pathways. Fluorescence microscopy data suggest mitochondrial localization of complex 3 bearing a naphthalimide with a two‐fold increase in photocytotoxicity in HaCaT cells with an IC50 value of 6.3 μM and a three‐fold increase in MCF‐7 cells with an IC50 of 5.4 μM compared with complex 2. Both 2 and 3 were non‐toxic in the dark.

Syntheses and structural investigation of some alkali metal ion-mediated LV(V)O2(-) (L(2-) = tridentate ONO ligands) species: DNA binding, photo-induced DNA cleavage and cytotoxic activities.

Eight alkali metal ion-mediated dioxidovanadium(v), [{V(V)O2L(1-6)}A(H2O)n]∝, complexes for A = Li(+), Na(+), K(+) and Cs(+), containing tridentate aroylhydrazonate ligands coordinating via ONO donor atoms, are described. All the synthesised ligands and the metal complexes were successfully characterised by elemental analysis, IR, UV-Vis and NMR spectroscopy. X-ray crystallographic investigation of 3, 5-7 shows the presence of distorted NO4 coordination geometries for LVO2(-) in each case, and varying μ-oxido and/or μ-aqua bridging with interesting variations correlated with the size of the alkali metal ions: with small Li(+), no bridging-O is found but four ion aggregates are found with Na(+), chains for K(+) and finally, layers for Cs(+). Two (5) or three-dimensional (3, 6 and 7) architectures are consolidated by hydrogen bonding. The dioxidovanadium(v) complexes were found to exhibit DNA binding activity due to their interaction with CT-DNA by the groove binding mode, with binding constants ranging from 10(3) to 10(4) M(-1). Complexes 1-8 were also tested for DNA nuclease activity against pUC19 plasmid DNA which showed that 6 and 7 had the best DNA binding and photonuclease activity; these results support their good protein binding and cleavage activity with binding constants ranging from 10(4) to 10(5) M(-1). Finally, the in vitro antiproliferative activity of all complexes was assayed against the HeLa cell line. Some of the complexes (2, 5, 6 and 7) show considerable activity compared to commonly used chemotherapeutic drugs. The variation in cytotoxicity of the complexes is influenced by the various functional groups attached to the aroylhydrazone derivative.

DNA binding, nuclease activity, DNA photocleavage and cytotoxic properties of Cu(II) complexes of N-substituted sulfonamides

Ternary copper(II) complexes [Cu(NST)2(phen)] (1) and [Cu(NST)2(NH3)2]·H2O (2) [HNST=N-(4,5-dimethylthiazol-2-yl)naphthalene-1-sulfonamide] were prepared and characterized by physico-chemical techniques. Both 1 and 2 were structurally characterized by X-ray crystallography. The crystal structures show the presence of a distorted square planar CuN4 geometry in which the deprotonated sulfonamide, acting as monodentate ligand, binds to the metal ion through the thiazole N atom. Both complexes present intermolecular π–π stacking interactions between phenanthroline rings (compound 1) and between naphthalene rings (compound 2). The interaction of the complexes with CT DNA was studied by means of thermal denaturation, viscosity measurements and fluorescence spectroscopy. The complexes display good binding propensity to the calf thymus DNA giving the order: 1>2. Complex 1, which has a higher capability for binding to DNA, showed better nuclease activity than 2 in the presence of ascorbate/H2O2. Both the kinetics and the mechanism of the DNA cleavage reaction were investigated. Furthermore, complex 1 showed efficient photo-induced DNA cleavage activity on irradiation with UV light in the absence of any external reagent. The UV light induced DNA cleavage follows a photo-redox pathway with generation of hydroxyl radicals as reactive species. In addition, the cytotoxic properties of both complexes (1 and 2) were evaluated in human cancer cells (HeLa, Caco-2 and MDA-468). The low IC50 values, in particular those against Caco-2, have indicated that the compounds can be considered as promising chemotherapeutic agents.

Design and Synthesis of a Functional Derivative of the Triazinium Cation and Its Rhodium Complex that Shows Photoinduced DNA Cleavage Activity and Photocytotoxicity

AbstractThe design and synthesis of an intensely blue rhodium(III) complex [3]+ of a new N,N‐donor ligand, 8‐(quinolin‐8‐ylamino)pyrido[2,1‐c][1,2,4]benzotriazin‐11‐ium, [2]+, which contains a planar pendant triazinium arm, is described. Structural characterization for [3]+ was carried out by using various spectroscopic techniques and single‐crystal X‐ray crystallography. The organometallic rhodium(III) compound shows a ligand‐based reversible reduction at –0.65 V. The electrochemically reduced compound displays a single‐line EPR spectrum that signifies the formation of ligand‐based free radicals. Compound [3]+ shows a binding propensity to calf thymus DNA to give a Kapp value of 6.05 × 105 M–1. The parent triazinium salt, pyrido[2,1‐c][1,2,4]benzotriazin‐11‐ium [1]+ and the ligand salt [2]+ exhibit photoinduced cleavage of DNA in UV‐A light, whereas the reference Rh complex [3]+ photocleaves DNA with red light (647.1 nm). The compounds show photonuclease activities under both aerobic and anaerobic conditions. Mechanistic investigations under aerobic conditions with several inhibitors indicate the formation of hydroxyl radicals by means of a photoredox pathway. Under anaerobic conditions, it is believed that a photoinduced oxidation of DNA mechanism is operative. Compound [3]+ exhibits photocytotoxicity in HeLa cervical cancer cells to give IC50 values of (12 ± 0.9) μM in UV‐A light at 365 nm and (31.4 ± 1.1) μM in the dark.

A Copper Complex, ghn‐12, as a sensitization of DNA to UVA offers potential for a novel photochemotherapy

Photochemotherapy is a modern therapy modality, based upon the application of a photosensitizing agent onto the tissue followed by illumination with light sources, which is a proven therapeutic strategy for a number of non‐malignant hyperproliferative skin diseases and various cancers. The aim of the present study is to investigate a new synthesis copper complex (ghn‐12, Chemical Formula: C53H39ClCuN8O5) as a potent photocytotoxic agent. Photoinduced DNA cleavage activity, cell cytotoxicity, cell cycle distribution and apoptosis assay are used to investigate the effect of ghn‐12 on therapeutic applications. Ghn‐12 induced supercoiled pUC19 DNA cleavage from supercoiled to nicked circular form at a low‐power monochromatic UV‐A light of 365 nm. Flow cytometry analysis revealed that photoinduced ghn‐12 sensitized squamous cell carcinoma (SCC15) cells to arrest in the G0/G1 and S‐G2/M phases of the cell cycle with a concomitantly significant increase in the sub‐G1 cell population, indicating cell death by apoptosis. This photoinduced apoptosis process was accompanied by activation of caspase‐3 expression and FITC Annexin V staining after SCC15 cells treated with ghn‐12. Our data suggest that a new photosensitizing compound, ghn‐12, exhibiting light‐induced cleavage of double‐stranded DNA and causing apoptosis of squamous cell carcinoma. Ghn‐12 is a potential therapeutic reagent. Research support by grant from the National Science Council, Taiwan Grant NSC99‐2314‐B‐384 ‐002 ‐MY3.

Photo-induced DNA cleavage activity and remarkable photocytotoxicity of lanthanide(iii) complexes of a polypyridyl ligand

Lanthanide(III) complexes [Ln(pyphen)(acac)(2)(NO(3))] (1, 2), [Ln(pydppz)(acac)(2)(NO(3))] (3, 4) and [La(pydppz)(anacac)(2)(NO(3))] (5), where Ln is La(III) (in 1, 3, 5) and Gd(III) (in 2, 4), pyphen is 6-(2-pyridyl)-1,10-phenanthroline, pydppz is 6-(2-pyridyl)-dipyrido[3,2-a:2',3'-c]phenazine, anacac is anthracenylacetylacetonate and acac is acetylacetonate, were prepared, characterized and their DNA photocleavage activity and photocytotoxicity studied. The crystal structure of complex 2 displays a GdO(6)N(3) coordination. The pydppz complexes 3-5 show an electronic spectral band at ~390 nm in DMF. The La(III) complexes are diamagnetic, while the Gd(III) complexes are paramagnetic with seven unpaired electrons. The molar conductivity data suggest 1 : 1 electrolytic nature of the complexes in aqueous DMF. They are avid binders to calf thymus DNA giving K(b) in the range of 5.4 × 10(4)-1.2 × 10(6) M(-1). Complexes 3-5 efficiently cleave supercoiled DNA to its nicked circular form in UV-A light of 365 nm via formation of singlet oxygen ((1)O(2)) and hydroxyl radical (HO˙) species. Complexes 3-5 also exhibit significant photocytotoxic effect in HeLa cancer cells giving respective IC(50) value of 0.16(±0.01), 0.15(±0.01) and 0.26±(0.02) μM in UV-A light of 365 nm, while they are less toxic in dark with an IC(50) value of >3 μM. The presence of an additional pyridyl group makes the pydppz complexes more photocytotoxic than their dppz analogues. FACS analysis of the HeLa cells treated with complex 4 shows apoptosis as the major pathway of cell death. Nuclear localization of complex 5 having an anthracenyl moiety as a fluorophore is evidenced from the confocal microscopic studies.

Synthesis, DNA binding, photo-induced DNA cleavage and cell cytotoxicity studies of a family of light rare earth complexes

A family of light rare earth complexes, [RE(acac)3(dpq)] (RE=La (1), Ce (2), Pr (3), Nd (4), Sm (5)) and [RE(acac)3(dppz)].CH3OH (RE=La (6), Ce (7), Pr (8), Nd (9), Sm (10) viz. acetylacetonate (acac), dipyrido[3,2-d:20,30-f]quinoxaline (dpq), dipyrido[3,2-a:20,30-c] phenazine (dppz)), have been synthesized and structurally characterized. Binding interactions of these complexes with CT-DNA and their photo-induced DNA cleavage activity with pBR 322 DNA are also investigated. These complexes have strong DNA binding interaction (Kb≈105M−1 and Kapp≈105M−1)and the binding propensity to CT-DNA decrease with the order: dppz complexes>dpq complexes. Furthermore, DNA photocleavage experiments indicate that these complexes are efficient DNA cleaving agents in UV-A (365nm) and ambient light in the absence of any external reagents. Hydroxyl radical (HO•) and singlet oxygen (1O2) are the major cleavage active species from the machanistic studies. Moreover, cell cytotoxicity studies of these complexes on HeLa, K562 and MDA-MB-231 cells indicate that they have the potential to act as effective metal-based anti-cancer drugs.

Schiff base oxovanadium(IV) complexes of phenanthroline bases showing DNA photocleavage activity at near-IR light and photocytotoxicity

Oxovanadium(IV) complexes [VO(L)(B)](ClO 4) ( 1– 3) of N-2-pyridylmethylidine-2-hydroxyphenylamine (HL) Schiff base and phenanthroline bases (B), viz. 1,10-phenanthroline (phen in 1), dipyrido[3,2- d:2′,3′- f]quinoxaline (dpq in 2) or dipyrido[3,2- a:2′,3′- c]phenazine (dppz in 3), were prepared, characterized and their DNA binding property, photo-induced DNA cleavage activity and photocytotoxicity in HeLa cells studied. The crystal structure of 1 shows the presence of a VO 2+ moiety in VO 2N 4 coordination geometry. The complexes show a d– d band at ∼830 nm in DMF. The complexes display an oxidative V(V)–V(IV) response near 0.5 V versus SCE and a reductive V(IV)/V(III) response near −0.65 V in DMF −0.1 M TBAP. The complexes that are avid binders to CT DNA giving K b values within 7.1 × 10 4 to 3.2 × 10 5 M −1, do not show any significant chemical nuclease activity in presence of 3-mercaptopropionic acid or glutathione. The dpq and dppz complexes are photocleavers of pUC19 DNA in UV-A light of 365 nm forming both 1O 2 and ·OH radicals and in near-IR light of 785 nm forming ·OH radicals. The dppz complex exhibits photocytotoxicity in visible light in HeLa cells (IC 50 = 6.8 μM). Flow-cytometric study on this complex shows a high sub-G1 phase in light compared to dark indicating PDT effect.

DNA Photocleavage and Cytotoxic Properties of Ferrocene Conjugates

AbstractFerrocenyl conjugates 2‐ferrocenylimidazophenanthroline (1) and 2‐ferrocenylimidazophenanthrene (2) were prepared, characterized, and their photoinduced DNA cleavage and photocytotoxic activity were studied. 2‐Phenylimidazophenanthroline (3) was used as a control species. Compound 2 was characterized by X‐ray crystallography. The interaction of the compounds with double‐stranded calf thymus DNA (CT DNA) was studied. The compounds show good binding affinity to CT DNA with Kb values of approximately 105 M–1. Thermal denaturation data suggest the groove binding nature of the compounds. The redox‐active compounds show poor chemical nuclease activity in the presence of hydrogen peroxide and glutathione (GSH). Compound 1 exhibits significant DNA photocleavage activity in visible light of 476 and 532 nm. Compound 3 shows only moderate DNA cleavage activity. The positive effect of the ferrocenyl moiety is demonstrated by the DNA photocleavage data. Mechanistic investigations reveal the formation of superoxide as well as hydroxyl radicals as the active species. The photocytotoxicity of the compounds in HeLa cells was studied upon irradiation with visible light (400–700 nm). Compound 1 shows efficient photocytotoxic activity with an IC50 value of 13 μM, while compounds 2 and 3 are less active with IC50 values of >50 and 22 μM, respectively.