DNA Photocleavage Activity Research Articles

A ruthenium(ii) arene complex showing emission enhancement and photocleavage activity towards DNA from singlet and triplet excited states respectively

The emission enhancement behavior and photocleavage activity of a ruthenium(II) arene complex, [(η(6)-p-cymene)Ru(dppn)(py)](2+) (1) (dppn = 4,5,9,16-tetraaza-dibenzo[a,c]naphthacene, py = pyridine), towards DNA were compared with [(η(6)-p-cymene)Ru(bpy)(py)](2+) (2), [Ru(bpy)2(dppz)](2+) (3) and [Ru(bpy)2(dppn)](2+) (4) (bpy = 2,2'-bipyridine, dppz = dipyrido-[3,2-a:2',3'-c]phenazine). It was found that 1 emits fluorescence from the dppn-based ligand-centered (LC) singlet excited state and generates singlet oxygen ((1)O2) from the dppn-based LC triplet excited state. As a result, 1 displays emission enhancement behavior and photocleavage activity towards DNA simultaneously. In contrast, 3 is the most classical DNA light switch but shows poor DNA photocleavage activity, while 4 is an efficient DNA photocleaver but cannot report DNA binding by luminescence enhancement. An increased cytotoxicity against human lung carcinoma cells A549 by about 10-fold was also observed for 1 upon visible light activation. These intriguing properties result from the unique combination of the Ru(II) arene and dppn subunits.

Photocytotoxic lanthanide complexes

Lanthanide complexes have recently received considerable attention in the field of therapeutic and diagnostic medicines. Among many applications of lanthanides, gadolinium complexes are used as magnetic resonance imaging (MRI) contrast agents in clinical radiology and luminescent lanthanides for bioanalysis, imaging and sensing. The chemistry of photoactive lanthanide complexes showing biological applications is of recent origin. Photodynamic therapy (PDT) is a non-invasive treatment modality of cancer using a photosensitizer drug and light. This review primarily focuses on different aspects of the chemistry of lanthanide complexes showing photoactivated DNA cleavage activity and cytotoxicity in cancer cells. Macrocyclic texaphyrin-lanthanide complexes are known to show photocytotoxicity with the PDT effect in near-IR light. Very recently, non-macrocyclic lanthanide complexes are reported to show photocytotoxicity in cancer cells. Attempts have been made in this perspective article to review and highlight the photocytotoxic behaviour of various lanthanide complexes for their potential photochemotherapeutic applications.

Selective cleavage of DNA at guanosine bases which locate in DNA non-duplex portions within duplexes by ruthenium(II) complexes

Ruthenium complexes are well known for their high affinity and reactivity with DNA. There are so many reports about the interactions of ruthenium complexes and duplex DNA. However, their effects on other DNA structures are poorly studied. In this paper, the photo-activated DNA cleavage by two ruthenium(II) complexes was researched. It was found that these complexes can selectively act on the guanosine bases located in DNA non-duplex portions which were contained in the well matched duplex structures. The mechanism was also studied and considered to be a singlet oxygen oxidation. Through the molecular modeling experiment, we proposed that the strong interaction of complexes with non-duplex DNA structure cause the structural selectivity of DNA cleavage. The research show great future prospects of these ruthenium complexes to be used in anticancer drug development and nucleic acid structure research.

Photoactivated DNA cleavage and anticancer activity of pyrenyl-terpyridine lanthanide complexes

Lanthanide(III) complexes [Ln(R-tpy)(acac)(NO3)2] (Ln = La(III) in 1, 2; Gd(III) in 4, 5) and [Ln(py–tpy)(sacac)(NO3)2] (Ln = La(III), 3; Gd(III), 6), where R-tpy is 4′-phenyl-2,2′:6′,2″-terpyridine (ph–tpy in 1, 4), 4′-(1-pyrenyl)-2,2′:6′,2″-terpyridine (py–tpy in 2, 3, 5 and 6), acac is acetylacetonate and sacac is 4-hydroxy-6-{4-[(β-d-glucopyranoside)oxy]phenyl}hex-3,5-dien-2-onate, were prepared to study their DNA photocleavage activity and photocytotoxicity. Complexes [La(ph-tpy)(acac)(EtOH)(NO3)2] (1a) and [Gd(ph–tpy)(acac)(NO3)2] (4) were characterized by X-ray crystallography. The 1:1 electrolytic complexes bind to calf thymus DNA. The py–tpy complexes cleave pUC19 DNA and exhibit remarkable photocytotoxicity in HeLa cells in UV-A light of 365 nm with apoptotic cell death (IC50: ∼40 nM in light, >200 μM in dark). Confocal microscopy using HeLa cells reveal primarily cytosolic localization of the complexes.

Synthesis, circular dichroism, DNA cleavage and singlet oxygen photogeneration of 4-amidinophenyl porphyrins

5,10,15,20-tetrakis(4-amidinophenyl)porphyrin (Por 1), its Zn complex (Por 2) and its conjugate with a tetraphenylporphyrin to form a bisporphyrin (Por 3) were prepared. The monomeric Por 1 and Por 2 showed both intercalative and external binding with DNA whereas only external DNA binding was seen in the bisporphyrin, Por 3 by circular dichroism and UV-vis. The DNA photocleavage activities of these porphyrins followed the order: Por 1 ~ Por 2 > Por 3, which did not correlate with their measured 1O2 production rates. It suggests 4-amidinophenylporphyrins are promising new photodynamic therapeutic agents.

Synthesis, Fluorescence and DNA Photocleavage Activity of Phenothiazine-Corrole Gallium(III) Complexes

Phenothiazine(PTZ)-corrole dyads 1-3 and their gallium(III) complexes 4-6 have been synthesized and characterized.The steady-state absorption and emission spectra and the time-resolved fluorescence decay profiles have been measured in toluene.The radiative and nonradiative rate constants have been obtained from the fluorescence quantum yields and monoexponential fluorescence lifetimes.The absorption spectra revealed that the gallium(III) corrole dyads exhibit stronger Soret bands and Q bands than free base corrole dyads.The fluorescence quantum yields of 1-3 are 0.156,0.134,and 0.139,and the radiative rate constants are 4.02×107,3.47×107,and 2.89×107 s-1,respectively.The fluorescence quantum yields of 4-6 are 0.502,0.443,and 0.494,and the radiative rate constants are 20.9×107,16.78×107,and 21.11×107 s-1,which are obviously higher than those of the corresponding free base corroles.The lifetimes of 4-6 are 2.40,2.64,and 2.34 ns,respectively,which are somewhat shorter than those of the corresponding free base corroles.Agarose gel electrophoresis shows that these gallium(III) corrole dyads could cleave supercoiled DNA(form I) to give nicked-circular DNA(form II) under irradiation.

Oxovanadium(iv) based hypocrellin B complexes with enhanced photodynamic activity

Hypocrellin B (HB), a naturally occurring photosensitizer, has been extensively and intensively studied as a promising photodynamic therapy (PDT) agent. In this work, three new oxovanadium(IV) complexes were designed and synthesized with HB as a bridging ligand and phen (1,10-phenanthroline, complex 1), tmp (3,4,7,8-tetramethyl-1,10-phenanthroline, complex 2) and dpq (dipyrido[3,2-f:2'3'-h]quinoxaline, complex 3) as terminal ligands. The use of a diimine terminal ligand avoids the formation of polymeric complexes and ensures the three VO(2+)-HB complexes possess a definite molecular formula and molecular weight to meet the single component requirement for an ideal PDT agent. Compared to HB, the VO(2+)-HB complexes exhibit improved water solubility, enhanced absorptivity in the phototherapeutic window, increased binding affinity toward dsDNA, and similar singlet oxygen quantum yield, therefore advanced DNA photocleavage activity. Both the DNA binding constants and photo nuclease activities of the complexes follow the order 2 (tmp) > 3 (dpq) > 1 (phen), demonstrating the importance of the binding affinity to biomolecules, which improves the bioavailability of reactive oxygen species. Our work opens a new avenue for the development of HB-based PDT agents.

Ruthenium(II) complexes: structure, DNA-binding, photocleavage, antioxidant activity, and theoretical studies

Two triazine-containing ruthenium(II) complexes, [Ru(dmb)2(pdpt)](ClO4)2 (dmb = 4,4′-dimethyl-2,2′-bipyridine, pdpt = 3-(pyridine-2-yl)-5,6-diphenyl-as-triazine) (1) and [Ru(dmb)2(pdtp)](ClO4)2 (pdtp = 3-(pyridine-2-yl)-as-triazino[5,6-f]phenanthrene) (2), were synthesized and characterized by elemental analysis, ES-MS, 1H NMR, UV-Vis spectra, and cyclic voltammetry; the crystal structure of 2 was determined by X-ray diffraction. DNA-binding behaviors of both complexes were studied by absorption titration, thermal denaturation, and viscosity measurements. The photoactivated DNA cleavage of plasmid pBR322 in the presence of 1 and 2 was explored through gel electrophoresis. Antioxidant activities of the two complexes against hydroxyl radical (•OH) were also investigated. The results indicate that the DNA-binding affinity of 2 is much greater than that of 1, and that 2 binds to calf thymus DNA by intercalation, but 1 binds in partial intercalation, with π–π stacking on the DNA surface. Experimental findings made through analysis of the CV, absorption spectra, X-ray crystal structure, and the DNA-binding properties were compared with those of theoretical studies using density functional calculations.

Ferrocene‐Conjugated Oxidovanadium(IV) Complexes as Potent Near‐IR Light Photocytotoxic Agents

AbstractFerrocene‐conjugated oxidovanadium(IV) complexes [VO(Fc‐tpy)(B)](ClO4)2 (1–4) and [VO(Ph‐tpy)(dppz)](ClO4)2 (5) as a control [Fc = (η5‐C5H4)FeII(η5‐C5H5), Fc‐tpy = 4′‐ferrocenyl‐2,2′:6′,2″‐terpyridine, Ph‐tpy = 4′‐phenyl‐2,2′:6′,2″‐terpyridine, B = heterocyclic base: 2,2′‐bipyridine (bpy in 1), 1,10‐phenanthroline (phen in 2), dipyridoquinoxaline (dpq in 3), dipyridophenazine (dppz in 4)] were prepared and their DNA binding, DNA photocleavage activity and photocytotoxicity studied. The crystal structure of [VO(Fc‐tpy)(bpy)](PF6)2·3Me2CO shows a vanadyl group in six‐coordinate VIVON5 coordination geometry, in which Fc‐tpy and bpy display tridentate meridional and bidentate N‐donor axial–equatorial binding modes, respectively. The one‐electron paramagnetic complexes exhibit a charge‐transfer band near 590 nm in DMF. The VIV/VIII redox couple in 1–4 appears near –0.7 V, whereas the Fc moiety shows a response near 0.6 V vs. SCE in DMF/0.1 M TBAP. The complexes are good binders to calf thymus DNA with Kb values of 104–106 M–1. DNA melting and viscometric data suggest groove and/or partial intercalative DNA binding of the complexes. Complexes 3–5 display DNA photocleavage activity in near‐IR light of 785 nm. Complex 4 shows significant photocytotoxicity in visible light (400–700 nm) in HeLa cells with low dark toxicity.

Copper(II) chloride mediated synthesis and DNA photocleavage activity of 1-aryl/heteroaryl-4-substituted-1,2,4-triazolo[4,3- a]quinoxalines

A new class of photonucleases, 1-aryl/heteroaryl-4-substituted-1,2,4-triazolo[4,3- a]quinoxalines ( 4) was synthesized in a facile and efficient manner via copper(II) chloride mediated oxidative intramolecular cyclization of 2-(arylidenehydrazino)-3-substituted-quinoxalines ( 3). DNA cleavage potency of compounds 4a– d (40 μg each) was quantitatively evaluated on supercoiled plasmid ΦX174 under UV irradiation (312 nm, 15 W) without any additive. Compound 4c was found to be the most efficient DNA photocleaver which had converted supercoiled DNA (form I) into the relaxed DNA (form II) at 30 μg and the DNA photocleavage activity increases with increase in concentration of 4c.

Remarkable photocytotoxicity in hypoxic HeLa cells by a dipyridophenazine copper(II) Schiff base thiolate

Copper(II) complexes [Cu(satp)(L)] ( 1– 3) of a Schiff base thiolate (salicylidene-2-aminothiophenol, H 2satp) and phenanthroline bases (L), viz. 1,10-phenanthroline (phen in 1), dipyrido[3,2- d:2′,3′- f]quinoxaline (dpq in 2) and dipyrido[3,2- a:2′,3′- c]phenazine (dppz in 3), were prepared, characterized and their anaerobic DNA photocleavage activity and hypoxic photocytotoxicity studied. The redox active complexes show the Cu(II)–Cu(I) couple near − 0.5 V for 1 and near 0.0 V vs. SCE (saturated calomel electrode) for 2 and 3. The one-electron paramagnetic complexes (~ 1.85 μ B) are avid DNA binders giving K b values within 1.0 × 10 5 − 8.0 × 10 5 M − 1 . Thermal melting and viscosity data along with molecular docking calculations suggest DNA groove and/or partial intercalative binding of the complexes. The complexes show anaerobic DNA cleavage activity in red light under argon via type-I pathway, while DNA photocleavage in air proceeds via hydroxyl radical pathway. The DFT (density functional theory) calculations reveal a thyil radical pathway for the anaerobic DNA photocleavage activity and suggest the possibility of generation of a transient copper(I) species due to bond breakage between the copper and sulfur to generate the thyil radical. An oxidation of the copper(I) species is likely by oxygen in an aerobic medium or by the buffer medium in an anaerobic condition. Complex 3 exhibits significant photocytotoxicity in HeLa cells (IC 50 = 8.3(± 1.0) μM) in visible light, while showing lower dark toxicity (IC 50 = 17.2(± 1.0) μM). A significant reduction in the dark toxicity is observed under hypoxic cellular conditions (IC 50 = 30.0(± 1.0) μM in dark), while retaining its photocytotoxicity (IC 50 = 8.0(± 1.0) μM).

Ruthenium(II) Polypyridyl Complexes: Synthesis and Studies of DNA Binding, Photocleavage, Cytotoxicity, Apoptosis, Cellular Uptake, and Antioxidant Activity

Two ruthenium (II) complexes [Ru(dmb)2(APIP)](ClO4)2 (APIP=2-(2-aminophenyl)imidazo[4,5-f ][1,10]phenanthroline, dmb=4,4'-dimethyl-2,2'-bipyridine; 1) and [Ru(dmb)2(HAPIP)](ClO4)2 (HAPIP=2-(2-hydroxyl-4-aminophenyl)imidazo[4,5-f ][1,10]phenanthroline; 2) were synthesized and characterized. DNA binding was investigated by electronic absorption titration, luminescence spectra, thermal denaturation, viscosity measurements, and photocleavage. The DNA binding constants for complexes 1 and 2 were 4.20 (±0.14)×10(4) and 5.45 (±0.15)×10(4) M(-1). The results suggest that these complexes partially intercalate between the base pairs. The cytotoxicity of complexes 1 and 2 was evaluated by MTT assay. Cellular uptake was observed under fluorescence microscopy; complexes 1 and 2 can enter into the cytoplasm and accumulate in the nuclei. Apoptosis and the antioxidant activity against hydroxyl radicals (•OH) were also explored.

Structure−Activity Relationship of Photocytotoxic Iron(III) Complexes of Modified Dipyridophenazine Ligands

Iron(III) complexes [FeL(B)] (1-5) of a tetradentate trianionic phenolate-based ligand (L) and modified dipyridophenazine bases (B), namely, dipyrido-6,7,8,9-tetrahydrophenazine (dpqC in 1), dipyrido[3,2-a:2',3'-c]phenazine-2-carboxylic acid (dppzc in 2), dipyrido[3,2-a:2',3'-c]phenazine-11-sulfonic acid (dppzs in 3), 7-aminodipyrido[3,2-a:2',3'-c]phenazine (dppza in 4) and benzo[i]dipyrido[3,2-a:2',3'-c]phenazine (dppn in 5), have been synthesized and their photocytotoxic properties studied along with their dipyridophenazine analogue (6). The complexes have a five electron paramagnetic iron(III) center, and the Fe(III)/Fe(II) redox couple appears at about -0.69 V versus SCE in DMF-0.1 M TBAP. The physicochemical data also suggest that the complexes possess similar structural features as that of its parent complex [FeL(dppz)] with FeO3N3 coordination in a distorted octahedral geometry. The DNA-complex and protein-complex interaction studies have revealed that the complexes interact favorably with the biomolecules, the degree of which depends on the nature of the substituents present on the dipyridophenazine ring. Photocleavage of pUC19 DNA by the complexes has been studied using visible light of 476, 530, and 647 nm wavelengths. Mechanistic investigations with inhibitors show formation of HO(•) radicals via a photoredox pathway. Photocytotoxicity study of the complexes in HeLa cells has shown that the dppn complex (5) is highly active in causing cell death in visible light with sub micromolar IC(50) value. The effect of substitutions and the planarity of the phenazine moiety on the cellular uptake are quantified by determining the total cellular iron content using the inductively coupled plasma-optical emission spectrometry (ICP-OES) technique. The cellular uptake increases marginally with an increase in the hydrophobicity of the dipyridophenazine ligands whereas complex 3 with dppzs shows very high uptake. Insights into the cell death mechanism by the dppn complex 5, obtained through DAPI nuclear staining in HeLa cells, reveal a rapid programmed cell death mechanism following photoactivation of complex 5 with visible light. The effect of substituent on the DNA photocleavage activity of the complexes has been rationalized from the theoretical studies.

In vitro photobiochemical characterization of sulfobutylether-β-cyclodextrin formulation of bufexamac

The present study aimed to modulate the photoreactivity of bufexamac, with a focus on photostability and phototoxicity, by forming an inclusion complex with sulfobutylether-β-cyclodextrin (SBECD). The photobiochemical properties of bufexamac were evaluated by reactive oxygen species (ROS) assay and using in vitro photogenotoxic assessment tools. To assess the inclusion properties of SBECD complex with bufexamac, a UV absorption spectroscopic study was also carried out. The influence of SBECD on the photoreactivity of bufexamac was analyzed by ROS assay and photostability test. From the photobiochemical data, superoxide generation from irradiated bufexamac indicated its photoreactivity; however, the photogenotoxic risk of bufexamac was negligible owing to low DNA-binding affinity and DNA-photocleaving activity. SBECD complex of bufexamac was formed, and the association constant of the complex was calculated to be 620 M −1. On the basis of the photochemical data on bufexamac co-existing with SBECD, ROS generation from irradiated bufexamac (200 μM) was inhibited by SBECD at concentrations of over 20 μM. The degradation constant of bufexamac in SBECD was decreased ca. 30% compared with that of bufexamac, suggesting improvement of its photostability. The phototoxic risk of bufexamac might be attenuated by SBECD complexation, and cyclodextrin inclusion complexes might be a useful approach for modulating the phototoxicity of drugs.

Terpyridine Oxovanadium(IV) Complexes of Phenanthroline Bases for Cellular Imaging and Photocytotoxicity in HeLa Cells

AbstractOxovanadium(IV) complexes [VO(N‐N‐N)(N‐N)](NO3)2 (1–4) of (4′‐phenyl)‐2,2′:6′,2″‐terpyridine (ph‐tpy in 1 and 2) or (4′‐pyrenyl)‐2,2′:6′,2″‐terpyridine (py‐tpy in 3 and 4) having N‐N as 1,10‐phenanthroline (phen in 1 and 3) or dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz in 2 and 4) are prepared and characterized. The crystal structure of 1 has VO2+ group in VN5O coordination geometry. The terpyridine ligand coordinates in a meridional binding mode. The phen ligand 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 710–770 nm in aqueous DMF (4:1 v/v). The complexes exhibit an irreversible VIV/VIII redox response near –1.0 V vs. SCE in aqueous DMF/0.1 M KCl. The complexes bind to CT DNA giving Kb values within 3.5 × 105 to 1.2 × 106 M–1. The complexes show poor chemical nuclease activity in dark. Complexes 2–4 show photonuclease activity in UV‐A light of 365 nm forming 1O2 and ·OH. Complex 4 shows DNA photocleavage activity at near‐IR light of 785 nm forming ·OH radicals. Complexes 2 and 4 show significant photocytotoxicity in HeLa cancer cells. Uptake of the complexes in HeLa cells, studied by fluorescence imaging, show predominantly cytosolic localization inside the cells.

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.

Synthesis, DNA Binding, DNA Photocleavage and Antimicrobial Activity of [Co(bpy)2DMHBT]3+, [Co(dmb)2DMHBT]3+ and [Co(phen)2DMHBT]3+ Complexes

ABSTRACT Cobalt(III) polypyridyl complexes of the type [Co(bpy)2DMHBT]3+, [Co(dmb)2DMHBT]3+ and [Co(phen)2DMHBT]3+ (where DMHBT = 11,13-dimethyl-13H-4,5,9,11,14-hexa aza-benzo[b] triphenylene-10,12-dione; bpy = 2,2′-bipyridine; dmb = 4,4′-dimethyl-2,2′-bipyridine; phen = 1,10-phenanthroline) have been synthesized and fully characterized by elemental analysis, IR, UV-Visible spectra, 1H, 13C-NMR and Mass spectra. The results of absorption and emission titrations as well as thermal temperature and Viscosity measurement studies reveal that [Co(bpy)2DMHBT]3+, [Co(dmb)2DMHBT]3+, and [Co(phen)2DMHBT]3+ are moderate to strong binders of Calf Thymus DNA. An experimental result indicates that the three complexes can intercalate in to DNA base pairs. Under the identical conditions the super-coiled pBR 322 DNA photo-cleavage activities of these three cobalt(III) complexes follow the order:[Co(phen)2DMHBT]3+ > [Co(bpy)2DMHBT]3+ > [Co(dmb)2DMHBT]3+. These complexes are also found to have good antimicrobial activity.

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.

Impact of metal on the DNA photocleavage activity and cytotoxicity of ferrocenyl terpyridine 3d metal complexes

Ferrocenyl terpyridine 3d metal complexes and their analogues, viz. [M(Fc-tpy)(2)](ClO(4))(2) (1-4), [Zn(Ph-tpy)(2)](ClO(4))(2) (5) and [Zn(Fc-dpa)(2)]X(2) (X = ClO(4), 6; PF(6), 6a), where M = Fe(II) in 1, Co(II) in 2, Cu(II) in 3 and Zn(II) in 4, Fc-tpy is 4'-ferrocenyl-2,2':6',2''-terpyridine, Ph-tpy is 4'-phenyl-2,2':6',2''-terpyridine and Fc-dpa is ferrocenyl-N,N-dipicolylmethanamine, are prepared and their DNA binding and photocleavage activity in visible light studied. Complexes 2, 4, 5 and 6a that are structurally characterized by X-ray crystallography show distorted octahedral geometry with the terpyridyl ligands binding to the metal in a meridional fashion, with Fc-dpa in 6a showing a facial binding mode. The Fc-tpy complexes display a charge transfer band in the visible region. The ferrocenyl (Fc) complexes show a quasi-reversible Fc(+)-Fc redox couple within 0.48 to 0.66 V vs. SCE in DMF-0.1 M TBAP. The DNA binding constants of the complexes are ∼10(4) M(-1). Thermal denaturation and viscometric data suggest DNA surface binding through electrostatic interaction by the positively charged complexes. Barring the Cu(II) complex 3, the complexes do not show any chemical nuclease activity in the presence of glutathione. Complexes 1-4 exhibit significant plasmid DNA photocleavage activity in visible light via a photoredox pathway. Complex 5, without the Fc moiety, does not show any DNA photocleavage activity. The Zn(II) complex 4 shows a significant PDT effect in HeLa cancer cells giving an IC(50) value of 7.5 μM in visible light, while being less toxic in the dark (IC(50) = 49 μM).

Planar triazinium cations from VO2+-assisted ring cyclizations: a remarkably efficient thiazole species for nuclear staining, PDT and anaerobic photocleavage of DNA

Planar triazinium cationic species, from VO(2+)-assisted cyclization of 1-(2-thiazolylazo)-2-naphthol, shows efficient DNA intercalative binding, visible light-induced anaerobic plasmid DNA photocleavage activity and photocytotoxicity in HeLa and MCF-7 cancer cells by an apoptotic pathway with selective localization of the compound in the nucleus as evidenced from the nuclear staining and confocal imaging.