DNA Photocleavage Research Articles

Field Detection of Uranyl in Coastal Water of China Using a Portable Device via DNA Photocleavage.

The urgent need for field detection of uranium in seawater is 2-fold: to provide prompt guidance for uranium extraction and to prevent human exposure to nuclear radiation. However, current methods for this purpose are largely hindered by bulky instrumentation, high costs of developed materials, and severe matrix interferences, which limit their further application in the field. Herein, we demonstrated a portable and label-free strategy for the field detection of uranyl in seawater based on the efficient photocleavage of DNA. Further experiments confirmed the generation of ultraviolet (UV) light-induced reactive oxygen species (ROS), such as O2•- and •OH, which fragmented oligomeric DNA in the presence of uranyl and UV light. Detailed studies showed that DNA significantly enhances uranyl absorption in the UV-visible region, leading to the generation of more ROS. A fluorescence system for the selective detection of uranyl in seawater was established by immobilizing two complementary oligonucleotides with the fluorescent dye SYBR Green I. The strategy of UV-induced photocleavage offers high selectivity, excellent interference immunity, and high sensitivity for uranyl, with a detection limit of 6.8 nM. Additionally, the fluorescence can be visually detected using a 3D-printed miniaturized device integrated with a smartphone. This method has been successfully applied to the on-site detection of uranyl in seawater in 18 Chinese coastal cities and along the coast of Hainan Island within 3 min for a single sample. The sample testing and field analysis results indicate that this strategy has promising potential for real-time monitoring of trace uranyl in China's coastal waters. It is expected to be utilized for the rapid assessment of nuclear contamination and nuclear engineering construction.

Photocytoxicity in vitro studies of ruthenium (II) complexes inducing cell death through targeting DNA

Photodynamic therapy (PDT) has been proven to be an important and effective therapy method with good spatial and temporal accuracy in clinical cancer treatment. Among many PDT candidates, Ru(II)-based compounds have received more attention due to their excellent photochemical and photophysical properties, high singlet oxygen (1O2) photogeneration, and DNA affinities. In this study, three ruthenium(II) complexes (RC1, RC2, RC3) have been designed by varying the aromatic plane area of the main ligand to adjust their 1O2 photogeneration, DNA affinities, DNA photodamage, and photocytoxicity. All complexes display no cytotoxicity in the dark against Hela, A549, HepG2, and BEL-7402 cells. RC1 displays no photocytotoxicity against all tumor cells. RC2 and RC3 showed high photocytotoxicity against BEL-7402 cells. The cellular uptake, cell migration, colonies assay, apoptosis analysis, and cell cycle analysis of RC2 and RC3 confirmed that the ruthenium(II) complexes might effectively enter the cancer cells, and lead to BEL-7402 cells apoptosis through DNA damage pathway. DNA photocleavage, DNA binding, and 1O2 measurement experiments demonstrated the DNA damage caused by RC2 and RC3 under light, compared to RC1, might be due to their high DNA affinities, large 1O2 quantum yields, and large lipophilicity by varying the aromatic plane area of the main ligand. Time dependent density functional theory (TDDFT) calculated results further show that two complexes exhibit the photocytotoxicity possibly via type II photoreaction mechanism because of the larger ΔS-T than O2 and strong SOC between Sn and Tm. Hence, rational design of ruthenium(II) complexes by increasing DNA affinities, 1O2 quantum yields and lipophilicity can be regarded as an effective approach for enhanced photodynamic therapy (PDT).

Ru(II) Complexes with Absorption in the Photodynamic Therapy Window: 1O2 Sensitization, DNA Binding, and Plasmid DNA Photocleavage.

Two Ru(II) complexes, [Ru(pydppn)(bim)(py)]2+ [2; pydppn = 3-(pyrid-2'-yl)-4,5,9,16-tetraaza-dibenzo[a,c]naphthacene; bim = 2,2'-bisimidazole; py = pyridine] and [Ru(pydppn)(Me4bim)(py)]2+ [3; Me4bim = 2,2'-bis(4,5-dimethylimidazole)], were synthesized and characterized, and their photophysical properties, DNA binding, and photocleavage were evaluated and compared to [Ru(pydppn)(bpy)(py)]2+ (1; bpy = 2,2'-bipyridine). Complexes 2 and 3 exhibit broad 1MLCT (metal-to-ligand charge transfer) transitions with maxima at ∼470 nm and shoulders at ∼525 and ∼600 nm that extend to ∼800 nm. These bands are red-shifted relative to those of 1, attributed to the π-donating ability of the bim and Me4bim ligands. A strong signal at 550 nm is observed in the transient absorption spectra of 1-3, previously assigned as arising from a pydppn-centered 3ππ* state, with lifetimes of ∼19 μs for 1 and 2 and ∼270 ns for 3. A number of methods were used to characterize the mode of binding of 1-3 to DNA, including absorption titrations, thermal denaturation, relative viscosity changes, and circular dichroism, all of which point to the intercalation of the pydpppn ligand between the nucleobases. The photocleavage of plasmid pUC19 DNA was observed upon the irradiation of 1-3 with visible and red light, attributed to the sensitized generation of 1O2 by the complexes. These findings indicate that the bim ligand, together with pydppn, serves to shift the absorption of Ru(II) complexes to the photodynamic therapy window, 600-900 nm, and also extend the excited state lifetimes for the efficient production of cytotoxic singlet oxygen.

Photodynamic Therapy with Targeted Release of Boron-Dipyrromethene Dye from Cobalt(III) Prodrugs in Red Light.

Boron-dipyrromethene (BODIPY) dyes are promising photosensitizers for cellular imaging and photodynamic therapy (PDT) owing to their excellent photophysical properties and the synthetically tunable core. Metalation provides a convenient way to overcome the drawbacks arising from their low aqueous solubility. New photo-/redox-responsive Co(III) prodrug chaperones are developed as anticancer PDT agents for efficient cellular delivery of red-light-active BODIPY dyes. The photobiological activity of heteroleptic Co(III) complexes derived from tris(2-pyridylmethyl)amine (TPA) and acetylacetone-conjugated PEGylated distyryl BODIPY (HL1) or its dibromo analogue (HL2), [CoIII(TPA)(L1/L2)](ClO4)2 (1 and 2), are investigated. The Co(III)/Co(II) redox potential is tuned using the Co(III)-TPA scaffold. Complex 1 displays the in vitro release of BODIPY on red light irradiation. Complex 2, having good singlet oxygen quantum yield (ΦΔ ∼ 0.28 in DMSO), demonstrates submicromolar photocytotoxicity to HeLa cancer cells (IC50 ≈ 0.23 μM) while being less toxic to HPL1D normal cells in red light. Cellular imaging using the emissive complex 1 shows mitochondrial localization and significant penetration into the HeLa tumor spheroids. Complex 2 shows supercoiled DNA photocleavage activity and apoptotic cell death through phototriggered generation of reactive oxygen species. The Co(III)-BODIPY prodrug conjugates exemplify new type of phototherapeutic agents with better efficacy than the organic dyes alone in the phototherapeutic window.

Synthesis of 2-Amino-N'-aroyl(het)arylhydrazides, DNA Photocleavage, Molecular Docking and Cytotoxicity Studies against Melanoma CarB Cell Lines.

Diacylhydrazine bridged anthranilic acids with aryl and heteroaryl domains have been synthesized as the open flexible scaffold of arylamide quinazolinones in order to investigate flexibility versus rigidity towards DNA photocleavage and sensitivity. Most of the compounds have been synthesized via the in situ formation of their anthraniloyl chloride and subsequent reaction with the desired hydrazide and were obtained as precipitates, in moderate yields. All compounds showed high UV-A light absorption and are eligible for DNA photocleavage studies under this "harmless" irradiation. Despite their reduced UV-B light absorption, a first screening indicated the necessity of a halogen at the p-position in relation to the amine group and the lack of an electron-withdrawing group on the aryl group. These characteristics, in general, remained under UV-A light, rendering these compounds as a novel class of UV-A-triggered DNA photocleavers. The best photocleaver, the compound 9, was active at concentrations as low as 2 μΜ. The 5-Nitro-anthranilic derivatives were inactive, giving the opposite results to their related rigid quinazolinones. Molecular docking studies with DNA showed possible interaction sites, whereas cytotoxicity experiments indicated the iodo derivative 17 as a potent cytotoxic agent and the compound 9 as a slight phototoxic compound.

Exploring the phototoxicity of GSH-resistant 2-(5,6-dichloro-1H-benzo[d]imidazol-2-yl)quinoline-based Ir(III)-PTA complexes in MDA-MB-231 cancer cells.

Metal complexes play a crucial role in photo-activated chemotherapy (PACT), which has recently been used to treat specific disorders. Triple-negative breast cancer has an enormously high rate of relapse due to the existence and survival of cancer stem cells (CSCs) characterized by increased amounts of glutathione (GSH). Hence, designing a phototoxic molecule is an enticing area of research to combat triple-negative breast cancer (TNBC) via GSH depletion and DNA photocleavage. Herein, we focus on the application of PTA and non-PTA Ir(III) complexes for phototoxicity in the absence and presence of GSH against MDA-MB-231 TNBC cells. Between these two complexes, [Cp*IrIII(DD)PTA]·2Cl (DDIRP) exhibited better phototoxicity (IC50 ∼ 2.80 ± 0.52 μM) compared to the non-PTA complex [Cp*IrIII(DD)Cl]·Cl (DDIR) against TNBC cells because of the high GSH resistance power of the complex DDIRP. The significant potency of the complex DDIRP under photo irradiation in both normoxia and hypoxia conditions can be attributed to selective transportation, high cellular permeability and uptake towards the nucleus, GSH depletion by GSH-GSSG conversion, the ability of strong DNA binding including intercalation, and oxidative stress. The strong affinity to serum albumin, which serves as a carrier protein, aids in the transport of the complex to its target site while preventing glutathione (GSH) deactivation. Consequently, the complex DDIRP was developed as a suitable phototoxic complex in selective cancer therapy, ruling over the usual chemotherapeutic drug cisplatin and the PDT drug Photofrin. The ability of ROS generation under hypoxic conditions delivers this complex as a hypoxia-efficient selective metallodrug for the treatment of TNBC.

Iridium(III)-based minor groove binding complexes as DNA photocleavage agents.

Transition metal complexes containing the qtpy ligand (2':4,4'':4',4'''-quaterpyridyl) are known to be DNA intercalators or minor groove binders. In this study, new tricationic iridium(III) complexes of qtpy are reported. Both [Ir(bpy)2(qtpy)]3+1 and [Ir(phen)2(qtpy)]3+2 display good water solubility as chloride salts. The complexes possess high-energy excited states, which are quenched in the presence of duplex DNA and even by the mononucleotides guanosine monophosphate and adenosine monophosphate. Further studies reveal that although the complexes bind to quadruplex DNA, they display a preference for duplex structures, which are bound with an order of magnitude higher affinities than their isostructural dicationic RuII-analogues. Detailed molecular dynamics simulations confirm that the complexes are groove binders through the insertion of, predominantly, the qtpy ligand into the minor groove. Photoirradiation of 1 in the presence of plasmid DNA confirms that this class of complexes can function as synthetic photonucleases by cleaving DNA.

New Tridentate Ligand Affords a Long-Lived 3MLCT Excited State in a Ru(II) Complex: DNA Photocleavage and 1O2 Production.

Two new complexes, [Ru(tpy)(qdppz)](PF6)2 (1; qdppz = 2-(quinolin-8-yl)dipyrido[3,2-a:2',3'-c]phenazine, tpy = 2,2':6',2″-terpyridine) and [Ru(qdppz)2](PF6)2 (2), were investigated for their potential use as phototherapeutic agents through their ability to photosensitize the production of singlet oxygen, 1O2, upon irradiation with visible light. The complexes exhibit strong Ru(dπ) → qdppz(π*) metal-to-ligand charge transfer (MLCT) absorption with maxima at 485 and 495 nm for 1 and 2 in acetone, respectively, red-shifted from the Ru(dπ) → tpy(π*) absorption at 470 nm observed for [Ru(tpy)2]2+ (3) in the same solvent. Complexes 1 and 3 are not luminescent at room temperature, but 3MLCT emission is observed for 2 with maximum at 690 nm (λexc = 480 nm) in acetone. The lifetimes of the 3MLCT states of 1 and 2 were measured using transient absorption spectroscopy to be ∼9 and 310 ns in methanol, respectively, at room temperature (λexc = 490 nm). The bite angle of the qdppz ligand is closer to octahedral geometry than that of tpy, resulting in the longer lifetime of 2 as compared to those of 1 and 3. Arrhenius treatment of the temperature dependence of the luminescence results in similar activation energies, Ea, from the 3MLCT to the 3LF (ligand-field) state for the two complexes, 2520 cm-1 in 1 and 2400 cm-1 in 2. However, the pre-exponential factors differ by approximately two orders of magnitude, 2.3 × 1013 s-1 for 1 and 1.4 × 1011 s-1 for 2, which, together with differences in the Huang-Rhys factors, lead to markedly different 3MLCT lifetimes. Although both 1 and 2 intercalate between the DNA bases, only 2 is able to photocleave DNA owing to its 1O2 production upon irradiation with ΦΔ = 0.69. The present work highlights the profound effect of the ligand bite angle on the electronic structure, providing guidelines for extending the lifetime of 3MLCT Ru(II) complexes with tridentate ligands, a desired property for a number of applications.

Structural Characterization of Zinc(II)/Cobalt(II) Complexes of Chiral N-(Anthracen-9-yl)methyl-N,N-bis(2-picolyl)amine and Evaluation of DNA Photocleavage Activity.

We designed and synthesized a chiral ligand N-(anthracen-9-ylmethyl)-1-(pyridin-2-yl)-N-(pyridin-2-ylmethyl)ethanamine (APPE) DNA photocleavage agent to investigate the effects of chirality of bis(2-picolyl)amine on the DNA photocleavage activity of metal complexes. The structures of ZnII and CoII complexes in APPE were analyzed via X-ray crystallography and fluorometric titration. APPE formed metal complexes with a 1 : 1 stoichiometry in both the crystalline and solution states. Fluorometric titration was used to show that the ZnII and CoII association constants of these complexes (log Kas) were 4.95 and 5.39, respectively. The synthesized complexes were found to cleave pUC19 plasmid DNA when irradiated at 370 nm. The DNA photocleavage activity of the ZnII complex was higher than that of the CoII complex. The absolute configuration of the methyl-attached carbon did not affect DNA cleavage activity and, unfortunately, an achiral APPE derivative without the methyl group (ABPM) was found to perform DNA photocleavage more effectively than APPE. One reason for this may be that the methyl group suppressed the structural flexibility of the photosensitizer. These results will be useful for the design of new photoreactive reagents.

Click synthesis, antimicrobial, DNA photocleavage and computational studies of oxindole-tethered 1H-1,2,3-triazoles.

Aim: To obtain new hybrids derived from isatin and triazole. Materials & methods: A series of oxindole-1-H-1,2,3-triazole hybrids (4a-l) were synthesized from 3-sulfenylated N-propargylated oxindoles and organic azides employing Cu(I)-catalyzed azide-alkyne cycloaddition. These compounds were evaluated in vitro for antimicrobial activity by the standard serial dilution method and DNA photocleavage activity. Results: Antimicrobial assay revealed that compounds 4l and 4f exhibited promising efficacy against Candida albicans and Rhizopus oryzae, respectively, with aminimum inhibitory concentrationvalue of 0.0008μmol/mL. Compounds 4h and 4k completely degraded plasmid DNA. Further molecular docking of compounds with 1KZN (4j and 4k) and 5TZ1 (4h and 4l) revealed good binding interactions. Conclusion: Results of the current research can help in the development of new antimicrobial agents with high efficacy.

Study on antitumor activity of three ruthenium arene complexes in vitro

Three ruthenium arene complexes, namely {[(η6-p-cymene)Ru(Cl)]2(dpb)}(PF6)2 (1), [(η6-p-cymene)Ru(dpb)Cl](PF6) (2) and [(η6-p-cymene) Ru(dpb)py](PF6) (3) (dpb = 2,3-bis(2-pyridyl)benzo-quinoxaline, py = pyridine), were synthesized and their antitumor properties were introduced. Complexes 1-3 were characterized by 1H NMR, MS, and elemental analysis. As a binuclear ruthenium structure, the absorption of metal ligand electron transfer (MLCT) of 1 extended to 700 nm. Complex 1 was significantly hydrolyzed under dark conditions. The cytotoxicity in vitro study showed that complexes 1 and 2 are more toxic to human lung cancer cells (A549) and human cervial cancer cells (Hela) than cisplatin. Moreover, there was almost no cross-resistance between complex 1-2 and cisplatin. Under the irradiation at 478 nm, complexes 1-3 all produced singlet oxygen (1O2), and the 1O2 quantum yield of complex 1 in PBS is the highest among complexes 1-3. Complex 1 also produced 1O2 under 600 nm light irradiation. DNA gel electrophoresis showed that 1 caused the photocleavage of plasmid DNA. The hydrolysis rate of complex 1 was accelerated under light (λ > 600 nm). And the phototoxicity of complex 1 to Hela cells under light (λ > 600 nm) was much greater than its dark toxicity, which may be due to its generation of 1O2 and the promotion of its hydrolysis under long-wave light irradiation.

More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

Photodynamic therapy (PDT) uses a combination of photosensitizers (PSs), light sources, and reactive oxygen species (ROS) to damage only the desired target and keep normal tissues from being hurt. The dark cytotoxicity (chemotoxicity) of PSs, leading to whole-body damage in the absence of irradiation, is a major limiting factor in PDT. How to simultaneously increase ROS generation and decrease dark cytotoxicity is an essential challenge that must be resolved in PS research. In this study, a series of homoligand polypyridyl ruthenium complexes (HPRCs) containing three singlet oxygen (1O2)-generating ligands (L) in a single molecule ([Ru(L)3]2+) have been constructed. Compared to the heteroligand complexes [Ru(bpy)2(L)]2+ where bpy is 2,2'-bipyridine, the 1O2 quantum yield under infrared two-photon irradiation and the DNA photocleavage effect of the HPRCs are significantly enhanced with two more ligands L. The intraligand triplet excited states transition played an important role in the activation of oxygen. The HPRCs target the mitochondria but not the nuclei, generating 1O2 intracellularly under irradiation of visible or infrared light. Ru1 exhibits high phototoxicity and low dark cytotoxicity toward human malignant melanoma cells in vitro. Moreover, HPRCs have minimal cytotoxicity to human normal liver cells, suggesting their potential as antitumor PDT reagents with more security. This study may provide inspiration for the structural design of potent PS for PDT.

Lysosome directed red light photodynamic therapy using glycosylated iron-(III) conjugates of boron-dipyrromethene

To overcome the drawbacks associated with chemotherapeutic and porphyrin-based photodynamic therapy (PDT) agents, the use of BODIPY (boron-dipyrromethene) scaffold has gained prominence in designing a new generation of photosensitizers-cum-cellular imaging agents. However, their poor cell permeability and limited solubility in aqueous medium inhibits the in-vitro application of their organic form. This necessitates the development of metal-BODIPY conjugates with improved physiological stability and enhanced therapeutic efficacy. We have designed two iron(III)-BODIPY conjugates, [Fe(L1/2)(L3)Cl] derived from benzyl-dipicolylamine and its glycosylated analogue along with a BODIPY-tagged catecholate. The complexes showed intense absorption bands (ε ∼ 55,000 M−1 cm−1) and demonstrated apoptotic PDT activity upon red-light irradiation (30 J/cm2, 600–720 nm). The complex with singlet oxygen quantum yield value of ∼0.34 gave sub-micromolar IC50 (half-maximal inhibitory concentration) value (∼0.08 μM) in both HeLa and H1299 cancer cells with a photocytotoxicity index value of >1200. Both the complexes were found to have significantly lower cytotoxic effects in non-cancerous HPL1D (human peripheral lung epithelial) cells. Singlet oxygen was determined to be the prime reactive oxygen species (ROS) responsible for cell damage from pUC19 DNA photo-cleavage studies, 1,3-diphenylisobenzofuran and SOSG (Singlet Oxygen Sensor Green) assays. Cellular imaging studies showed excellent fluorescence from complex 2 within 4 h, with localization in lysosomes. Significant drug accumulation into the core of 3D multicellular tumor spheroids was observed within 8 h from intense in-vitro emission. The complexes exemplify iron-based targeted PDT agents and show promising results as potential transition metal-based drugs for ROS mediated red light photocytotoxicity with low dosage requirement.

Exploration of the DNA Photocleavage Activity of O-Halo-phenyl Carbamoyl Amidoximes: Studies of the UVA-Induced Effects on a Major Crop Pest, the Whitefly Bemisia tabaci

The DNA photocleavage effect of halogenated O-carbamoyl derivatives of 4-MeO-benzamidoxime under UVB and UVA irradiation was studied in order to identify the nature, position, and number of halogens on the carbamoyl moiety that ensure photoactivity. F, Cl, and Br-phenyl carbamate esters (PCME) exhibited activity with the p-Cl-phenyl derivative to show excellent photocleavage against pBR322 plasmid DNA. m-Cl-PCME has diminished activity, whereas the presence of two halogen atoms reduced DNA photocleavage. The substitution on the benzamidoxime scaffold was irrelevant to the activity. The mechanism of action indicated function in the absence of oxygen, probably via radicals derived from the N-O bond homolysis of the carbamates and in air via hydroxyl radicals and partially singlet oxygen. The UVA-vis area of absorption of the nitro-benzamidoxime p-Cl-PCMEs allowed for the investigation of their potential efficacy as photopesticides under UVA irradiation against the whitefly Bemisia tabaci, a major pest of numerous crops. The m-nitro derivative exhibited a moderate specificity against the adult population. Nymphs were not affected. The compound was inactive in the dark. This result may allow for the development of lead compounds for the control of agricultural insect pests that can cause significant economic damage in crop production.

Biotin and boron-dipyrromethene-tagged platinum(IV) prodrug for cellular imaging and mito-targeted photocytotoxicity in red light.

A platinum(IV) prodrug, cis,cis,trans-[Pt(NH3)2Cl2(biotin)(L)] (1), derived from cisplatin, where HL is the PEGylated red-light active boron-dipyrromethene (BODIPY) ligand, was synthesized, characterized and its photocytotoxicity evaluated. The complex showed a near-IR absorption band at 653 nm (ε ∼9.19 × 104 M-1 cm-1) in dimethyl sulfoxide and Dulbecco's phosphate-buffered saline (1 : 1 v/v) at pH 7.2. When excited at 630 nm, it showed an emission band at 677 nm in DMSO with a fluorescence quantum yield of 0.13. The 1,3-diphenylisobenzofuran titration experiment gave a singlet oxygen quantum yield (ΦΔ) of ∼0.32. A mechanistic DNA photocleavage study revealed singlet oxygen as the reactive oxygen species (ROS). The complex with biotin and PEGylated-distyryl-BODIPY showed significantly higher cellular uptake in A549 cancer cells as compared to non-cancerous Beas-2B cells from flow cytometry, indicating selectivity towards cancer cells. A dichlorodihydrofluorescein diacetate assay showed cellular ROS generation. Confocal images revealed predominant internalization in the mitochondria. The prodrug showed remarkable photodynamic therapy (PDT) activity in cancerous A549 and multidrug-resistant MDA-MB-231 cells with a high photocytotoxicity index value (half-maximal inhibitory concentration (IC50): 0.61-1.54 μM in red light), while being non-toxic in the dark. The chemo-PDT activity was significantly less in non-tumorigenic lung epithelial cells (Beas-2B). The prodrug effectively triggered cellular apoptosis, which was confirmed by the Annexin V-FITC/propidium iodide assay, and the alteration of the mitochondrial membrane potential was substantiated by the JC-1 dye assay. The β-tubulin immunofluorescence assay confirmed that incubating the cells with a light-treated complex resulted in the rapture of the cytoskeletal structure and the formation of apoptotic bodies. The results demonstrate that the prodrug triggered apoptosis via DNA damage, a reduction in mitochondrial function and disruption of the cytoskeletal framework.

Bis-pyrimidine Derivatives: Synthesis and Impact of Olefinic/Aromatic Linkers on Antimicrobial and DNA Photocleavage Activity

Bis-pyrimidine Derivatives: Synthesis and Impact of Olefinic/Aromatic Linkers on Antimicrobial and DNA Photocleavage Activity

Ferrocenyl chalcone armed macrocyclic tet a‐based cobalt(II) and copper(II) complexes: DNA photocleavage activity and photocytotoxicity

Ferrocenyl chalcone armed ‘tet a’ macrocyclic cobalt(II) and copper(II) complexes (1) and (2) were synthesised and characterised by various physico‐chemical methodologies. The complexes exhibit Co(II)/Co(I) and Cu(II)/Cu(I) redox couple (quasi‐reversible) with E1/2 value of −0.82 and −0.82 V, respectively. Complex 1 is oxidised as quasi‐reversible two‐electron transfer processes with oxidation potential of E1pa = 0.64 and E1pc = 0.68 V, and complex 2 with oxidation potential of E1pa = 0.62 and E1pc = 0.66 V over 0.37 V of ferrocene was observed. The above scenario is indicating the positive charge destabilisation of mono‐ and dications originating a challenging condition for ferrocene oxidation. The DNA binding abilities of both the complexes (1 and 2) with calf thymus DNA (CT‐DNA) were investigated by spectroscopic studies (absorption/fluorescence) and electrochemical methods. Absorption spectral studies revealed that complexes 1 and 2 bind with CT‐DNA by partial intercalative mode of binding with Kb values of 1.04 × 106 and 7.29 × 105 M−1, respectively. Chemical nuclease activity is exhibited moderately in these complexes generating singlet oxygen (1O2) species and acting as effective photocleavers of pUC19 DNA in the red light region. As irradiated by red light, their cytotoxicity toward MDA‐MB‐231 displays a typical increase in cytotoxicity values. In comparing the dark and red light irradiated cell, MDA‐MB‐231 cells that were exposed to red light exhibited significant morphological alternations. Cell morphological studies were confirmed the morphological changes with dual staining by using AO/EB, Hoechst 33342 and PI against MDA‐MB‐231 cells. Furthermore, complexes 1 and 2 have less toxicity on Artemia nauplii even at higher concentrations, indicating that the synthesised complexes 1 and 2 are biocompatible.

Mechanochemical Synthesis, Characterization and Biological Exploration of Pyrimidinethione based ligands

The mechanochemical synthesis of 1-(4-Nitro phenylamino)-4,4,6-trimethyl-3,4-dihydro pyrimidine-2-(1H)- thione (Hnppt) based ligand and its metal complexes with Cu(II), Co(II), Ni(II), Mn(II), Cd(II), Pd(II) has been achieved. The synthesized ligand and its coordination complexes were evaluated for antibacterial ability and DNA photocleavage potential by using plasmid DNA. Ligand(Hnppt) was prepared and then it was allowed to chelate with different transition metals in 1:2 metal ligand ratio. All the complexes were then characterized by IR, Mass, NMR, magnetic moment, electronic spectra like spectroscopic techniques. 1H NMR data of complexes reveals that coordination occurs via nitrogen atom with the loss of a proton and IR data confirms that the thione sulphur of ligand participates in coordination with metal. Electronic spectral data revealed the octahedral and square planar geometry of coordination complexes. The formation of 2:1 ligand to metal stoichiometry was confirmed by mass spectra. It was observed that metal complexes possess good level of antibacterial and DNA cleaving potential than the ligand.

Synthesis, characterization, DNA photocleavage, in silico and in vitro DNA/BSA binding properties of novel hexahydroquinolines

A simple, and efficient procedure has been developed for the synthesis of novel 2-(4-(hexahydroquinolin-4-yl)phenoxy)-N-arylacetamides and thieno[3′,2′:5,6]pyrimido[1,2-a]quinolines via Michael addition reaction of cyclic enaminones with various 2-(4-(2,2-dicyanovinyl)phenoxy)-N-arylacetamides in the presence of a basic catalyst. The interaction of the compounds with DNA and bovine serum albumin (BSA) was investigated. DNA photocleavage ability was evaluated by agarose gel electrophoresis in UV-A (356 nm). Through inhibitor studies of the most active compounds 5h and 12d, we found that reactive oxygen species play a major role in photocleavage. Molecular docking methods were also used to model the binding of the compound to DNA and BSA, and good agreement was found between experimental and theoretical results. All of these findings suggest that the compounds could be used as a photodynamic therapy agent due to their nucleic acid interactions and photobiological or photochemical properties.

Comparative Studies on DNA-Binding Mechanisms between Enantiomers of a Polypyridyl Ruthenium(II) Complex.

A pair of ruthenium(II) complex enantiomers, Δ- and Λ-[Ru(bpy)2MBIP]2+ (bpy = 2,2'-bipyridine, MBIP = 2-(3-bromophenyl)imidazo[5,6-f]phenanthroline), were designed, synthesized, and characterized. Comparative studies between the enantiomers on their binding behaviors to calf thymus DNA (CT-DNA) were conducted using UV-visible, fluorescence, and circular dichroism spectroscopies, viscosity measurements, isothermal titration calorimetry, a photocleavage experiment, and molecular simulation. The experimental results indicated that both the enantiomers spontaneously bound to CT-DNA through intercalation stabilized by the van der Waals force or the hydrogen bond and driven by enthalpy and that Δ-[Ru(bpy)2MBIP]2+ intercalated into DNA more deeply than Λ-[Ru(bpy)2MBIP]2+ did and exhibited a better DNA photocleavage ability. Molecular simulation further indicated that Δ-[Ru(bpy)2MBIP]2+ more preferentially intercalated between the base pairs of CT-DNA to the major groove, and Λ-[Ru(bpy)2MBIP]2+ more favorably intercalated to the minor groove. These research findings should be very helpful to the understanding of the stereoselectivity mechanism of DNA-bindings of metal complexes, and be useful for the design of novel metal-complex-based antitumor drugs with higher efficacy and lower toxicity.