Photocytotoxic Oxidovanadium(IV) Complexes of Polypyridyl Ligands Showing DNA-Cleavage Activity in Near-IR Light

Oxidovanadium(IV) complexes VO(pyphen)(L)]Cl2 (1, 2) and VO(pydppz)(L)]Cl2 (3, 4), where L is 1,10-phenanthroline (phen in 1 and 3) and dipyrido3,2-a:2',3'-c]phenazine (dppz in 2 and 4) are prepared and characterized. The crystal structure of VO(pyphen)(phen)](ClO4)2 (1a) shows a six-coordinate VN5O geometry with a VO2+ moiety in which the polypyridyl ligand binds in a meridional fashion and the phen ligand displays a chelating binding mode with an N-donor site trans to the oxidovanadyl group. The complexes show a dd band within 720-750 nm in DMF. The one-electron paramagnetic complexes are 1:2 electrolytes in DMF. The complexes exhibit an irreversible VIV/VIII redox response near -0.85 V vs. SCE in DMF/0.1 M TBAP. The complexes bind to calf thymus (ct) DNA giving Kb values within 7.5 x 104 to 1.1 x 106 M1. The complexes show poor chemical nuclease activity in the dark and exhibit significant DNA-photocleaving activity in near-IR light of 705 and 785 nm forming .OH radicals. Complexes 2-4 show remarkable photocytotoxicity in HeLa cancer cells. FACS analysis of the HeLa cells treated with complex 4 shows cell death as highlighted by the sub G1 peak. Propidium iodide staining data indicate apoptosis as the primary mode of cell death.

Cellular uptake and remarkable photocytotoxicity of pyrenylter pyridine oxovanadium(IV) complexes of dipyridophenazine bases

Pyrenylterpyridine (pytpy) oxovanadium(IV) complexes VO(pytpy)(L)]Cl-2 (1-6) of the dipyridophenazine bases (L), viz., dipyrido-6,7,8,9-tetrahydrophenazine (dpqC in 1), dipyrido3,2-a:2',3'-c]phenazine-2-carboxylic acid (dppzc in 2), dipyrido3,2-a:2',3'-c]phenazine-11-sulfonic acid (dppzs in 3), 7-aminodipyrido3,2-a:2',3'-c]phenazine (dppza in 4), benzo-i]dipyrido3,2-a:2',3'-c]phenazine (dppn in 5) and dipyrido3,2-a:2',3'-c]phenazine (dppz in 6) were prepared, characterized and their DNA binding, photocleavage activity and photocytotoxicity studied. The complexes which showed a d-d band near 750 nm in DMF are efficient binders to calf thymus DNA (K-b: 3.2 x 10(5)-2.9 x 10(6) M-1). The complexes showed significant pUC19 DNA cleavage in near-IR light of 785 nm forming center dot OH radicals and photocytotoxicity in HeLa cells in visible light with the benzo-i] dipyrido3,2-a:2',3'-c]phenazine complex 5 showing a remarkably low IC50 value of 0.036 mu M. Flow-cytometric analysis shows a high sub-G1 phase cell cycle arrest in HeLa cells by the complexes on photo-irradiation. The photocytotoxicity correlates well with the hydrophobicity, photosensitizing ability and DNA binding propensity of the complexes. (C) 2012 Elsevier B.V. All rights reserved.

Photoactivated DNA cleavage and anticancer activity of oxovanadium(IV) complexes of curcumin

Oxovanadi um(IV) complexes VO(Fc-pic)(acac)](ClO4) (1), VO(Fc-pic)(cur)](ClO4) (2), VO(Ph-pic)(acac)](ClO4) (3) and VO(Ph-pic)(cur)](ClO4) (4), where Fc-pic and Ph-pic are ferrocenylmethyl-bis-(2-pyridylmethylamine) (in 1, 2) and bis-(2-pyridylmethyl)benzylamine (in 3, 4), respectively, acac is acetylacetonate anion (in 1, 3) and cur is curcumin anion (in 2, 4) were prepared, characterized and their photo-induced DNA cleavage and anticancer activity studied. The crystal structure of 1 as its PF6 salt (1a) shows the presence of a VO2+ moiety in VO3N3 coordination geometry. The complexes show a d-d band at similar to 790 nm in DMF and display V(IV)/V(III) redox couple near -1.45 V vs. SCE in DMF-0.1 M TBAP. The complexes are avid binders to calf thymus DNA. Complex 2 efficiently photo-cleaves plasmid DNA in near-IR light of 785 nm forming (OH)-O-center dot radicals. The curcumin complexes show photocytotoxicity in HeLa cancer cells in visible light of 400-700 nm with significant cellular uptake within 4 h of incubation time.

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

Oxidovanadium(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 V-IV/V-III 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 M and a three-fold increase in MCF-7 cells with an IC50 of 5.4 M compared with complex 2. Both 2 and 3 were non-toxic in the dark.

Mitochondria targeting Photocytotoxic Oxidovanadium( IV) Complexes of Curcumin and ( Acridinyl) dipyridophenazine in Visible Light

Oxidovanadium(IV) complexes, VO(acac)(L)Cl] (1), VO(cur)(L)Cl] (2), and VO(scur)(L)Cl] (3) {acac = acetylacetonate, cur = curcumin monoanion, scur = diglucosylcurcumin monoanion, L = 11-(9-acridinyl)dipyrido3, 2-a:2',3'-c]phenazine (acdppz)}, were prepared and characterized. The complexes are non-electrolytic in DMF and 1:1 electrolytic in aqueous DMF. The one-electron paramagnetic complexes showed a d-d band near 725 nm in aqueous DMF and green emission near 520 nm in aqueous DMSO. The complexes exhibited an irreversible V-IV/V-III redox response near -0.85 V versus SCE in aqueous DMF. The complexes showed good binding strengths to calf thymus DNA (K-b: 3.1x10(5)-9.6x10(5) M-1) and efficient pUC19 DNA photocleavage activity in red light of 705 and 785 nm by singlet oxygen (O-1(2)) pathway. Complexes 1 and 2 exhibited significant photocytotoxicity (IC50: 0.1-1.0 M) in visible light (400-700 nm) with low dark toxicity (IC50: >20 M) in HeLa and HaCaT cells. Complex 3 was cytotoxic in both light and dark. DNA ladder formation experiments indicated cell death via apoptotic pathway. Confocal microscopy done with 1 and 2 revealed primarily cytosolic localization of the complexes with significant presence of the complex in the mitochondria as evidenced from the imaging data using mitotracker red.

Oxovanadium(IV) complexes of curcumin for cellular imaging and mitochondria targeted photocytotoxicity

Oxovanadium(IV) complexes VO(R-tpy)(cur)](ClO4) (1, 2) of curcumin (Hcur) and terpyridine ligands (R-tpy) where R is phenyl (phtpy in 1) or p-triphenylphosphonium methylphenyl bromide (C6H4CH2PPh3Br) (TPP-phtpy in 2) were prepared and characterized and their DNA photocleavage activity, photocytotoxicity and cellular localization in cancer cells (HeLa and MCF-7) were studied. Acetylacetonate (acac) complexes VO(R-tpy)(acac)](ClO4) of phtpy (3) and TPP-phtpy (4) were prepared and used as the control species. These complexes showed efficient cleavage of pUC19 DNA in visible light of 454 nm and near-IR light of 705 rim. Complexes 1 and 2 showed significant photocytotoxicity in visible light of 400-700 nm. FACS analysis showed sub-G1/G0 phase cell-cycle arrest in cancer cells when treated with 1 and 2 in visible light in comparison with the dark controls. Fluorescence microscopic studies revealed specific localization of the p-triphenylphosphonium complex 2 in the mitochondria of MCF-7 cancer cells whereas no such specificity was observed for complex 1.

Oxovanadium(IV) catecholates of terpyridine bases for cellular imaging and photocytotoxicity in red light

Oxovanadium(IV) catecholates of terpyridyl bases, viz. VO(cat)(L)] (L - phtpy, 1; stpy, 2) and VO(dopa-NBD)(L)] (L = phtpy, 3; stpy, 4), where cat is benzene-1,2-diolate, dopa-NBD is 4-(2-(4-nitrobenzoc]1,2,5]oxadiazol-7-ylamino)ethyl)benzene-1,2-di olate, phtpy is (4'-phenyl)-2,2':6',2 `'-terpyridine and stpy is (2,2':6',2 `'-terpyridin-4'-oxy)ethyl-beta-D-glucopyranoside, were prepared and characterized, and their DNA binding, DNA photo-cleavage activity, photocytotoxicity in red light (600-720 nm), cellular uptake and intracellular localization behaviour were studied. The complexes showed an intense ligand-to-metal charge transfer (LMCT) band at similar to 500 nm. The sugar appended complexes 2 and 4 showed significant uptake into the cancer cells. The dopa-NBD complexes 3 and 4 showing green emission were used for cellular imaging. The complexes showed diffused cellular localization mainly in the cytosol and to a lesser extent into the nucleus as evidenced from the confocal microscopy study. Complexes 1-4 showed significant photocytotoxicity in the PDT spectral window giving low IC50 values, while remaining relatively non-toxic in dark.

Photoactivated cytotoxicity of ferrocenyl-terpyridine oxovanadium(IV) complexes of curcuminoids

Oxovanadium(IV) complexes, viz. VO(Fc-tpy)(Curc)](ClO4) (1), VO(Fc-tpy)(bDHC)](ClO4) (2), VO(Fc-tpy)(bDMC)](ClO4) (3) and VO(Ph-tpy)(Curc)](ClO4) (4), of 4'-ferrocenyl-2,2':6',2 `'-terpyridine (Fc-tpy) and 4'-phenyl-2,2':6',2 `'-terpyridine (Ph-tpy) and monoanionic curcumin (Curc), bis-dehydroxycurcmin (bDHC) and bis-demethoxycurcumin (bDMC) were prepared, characterized and their photo-induced DNA cleavage activity and photocytotoxicity in visible light studied. The ferrocenyl complexes 1-3 showed an intense metal-to-ligand charge transfer band near 585 nm in DMF and displayed Fc(+)/Fc and V(IV)/V(III) redox couples near 0.65 V and -1.05 V vs. SCE in DMF-0.1 M TBAP. The complexes as avid binders to calf thymus DNA showed significant photocleavage of plasmid DNA in red light of 647 nm forming (OH)-O-center dot radicals. The complexes showed photocytotoxicity in HeLa and Hep G2 cancer cells in visible light of 400-700 nm with low dark toxicity. ICP-MS and fluorescence microscopic studies exhibited significant cellular uptake of the complexes within 4 h of treatment with complexes. The treatment with complex 1 resulted in the formation of reactive oxygen species inside the HeLa cells which was evidenced from the DCFDA assay. (C) 2014 Elsevier Masson SAS. All rights reserved.

Remarkable Selectivity and Photo-Cytotoxicity of an Oxidovanadium(IV) Complex of Curcumin in Visible Light

Oxidovanadium(IV) complexes of 2-(2'-pyridyl)-1,10-phenanthroline (pyphen), viz. VO(pyphen)(acac)](ClO4) (1), VO(pyphen)(anacac)](ClO4) (2) and VO(pyphen)(cur)](ClO4) (3), where acac is acetylacetonate (in 1), anacac is anthracenylacetylacetonate (in 2) and cur is curcumin monoanion (in 3) were synthesized, characterized and their photo-induced DNA cleavage activities and photo-cytotoxicities studied. The complexes are 1: 1 electrolytes in DMF. The one-electron paramagnetic complexes show a d-d band near 760 nm in DMF. Complexes 2 and 3 are blue and green emissive, respectively, in DMSO. The complexes exhibit irreversible V-IV/V-III reductive responses near -1.1 V and V-V/V-IV oxidative responses near 0.85 V vs. SCE in DMF-0.1 M TBAP. Complexes 2 and 3 display significant and selective photo-cytotoxicity upon irradiation with visible light giving an IC50 value of about 5 mu M against HeLa and MCF-7 cancer cells; they are significantly less-toxic against normal 3T3 control cells and in the absence of light. Complex 1 was used as a control. Both cytosolic and nuclear localization of the complexes were observed on the basis of fluorescence imaging. The complexes, avid binders to calf thymus (ct) DNA, were found to photocleave supercoiled pUC19 DNA upon irradiation with near-IR light (785 nm) by generating hydroxyl radical (OH) as the reactive oxygen species (ROS). Cell death events noted with HeLa and MCF-7 cell lines likely are attributable to apoptotic pathways involving light-assisted generation of intracellular ROS.

Photocytotoxic oxovanadium(IV) complexes of ferrocenyl-terpyridine and acetylacetonate derivatives

Oxovanadium(IV) complexes VO(Fc-tpy)(acac)](ClO4) (1), VO(Fc-tpy)(nap-acac)](ClO4) (2), VO(Fc-tpy)(py-acac)](ClO4) (3) and VO(Ph-tpy)(py-acac)](ClO4) (4) of 4'-ferroceny1-2,2':6',2 `'-terpyridine (Fc-tpy) and 4'-phenyl-2,2':6',2 `'-terpyridine (Ph-tpy) having monoanionic acetylacetonate (acac), naphthylacetylacetonate (nap-acac) or pyrenylacetylacetonate (py-acac) ligand were prepared, characterized and their photocytotoxicity in visible light studied. The ferrocenyl complexes 1-3 showed an intense charge transfer band near 585 nm in DMF and displayed Fc(+)/Fc and V(IV)/V(III) redox couples near 0.66 V and -0.95 V vs. SCE in DMF-0.1 M TBAP. The complexes as avid binders to calf thymus DNA showed significant photocleavage of plasmid DNA in green light (568 nm) forming center dot OH radicals. The complexes that are photocytotoxic in HeLa and MCF-7 cancer cells in visible light (400-700 nm) with low dark toxicity remain nontoxic in normal fibroblast 3T3 cells. ICP-MS and fluorescence microscopic studies show significant cellular uptake of the complexes. Photo-irradiation of the complexes causes apoptotic cell death by ROS as evidenced from the DCFDA assay. (C) 2015 Elsevier Masson SAS. All rights reserved.

Photoinduced DNA Crosslink Formation by Dichloridooxidovanadium(IV) Complexes of Polypyridyl Bases

Oxidovanadium(IV) complexes VO(pyphen)Cl-2] (1) and VO(pydppz)Cl-2] (2), where pyphen is 2-(2-pyridyl)-1,10-phenanthroline and pydppz is 3-(pyridin-2-yl)dipyrido3,2-a:2,3-c]phenazine, show remarkable photoinduced DNA crosslinking ability and photocytotoxicity. The complexes are non-electrolytes in DMF, 1:1 electrolytes in 20% aqueous DMF, and 1:2 electrolytes in 20% aqueous DMF upon photoirradiation with visible light of 400-700 nm. The paramagnetic complexes, which have one unpaired electron, show a d-d band near 780 nm in aqueous DMF. The IR data suggest a V=O moiety trans to a V-N bond. Complex VO(pydppz)Cl-2] (2), as a novel photoinducible nuclear ds-DNA crosslinking agent, shows visible-light-induced cytotoxicity in HeLa and MCF-7 cancer cells by an apoptotic pathway, giving IC50 values of 0.87 +/- 0.07 and 1.4 +/- 0.2 M, respectively, while being essentially nontoxic (IC50 > 40 M) in the dark and less toxic in normal MCF-10A cells.

Peftjauawybast, king of Nen-nesut : genealogy, art history, and the chronology of late libyan Egypt

This paper argues in detail for the identification of Peftjauawybast, King of Nen-nesut (fl. 728/720 BC ), with Peftjauawybast, High Priest of Ptah in Memphis (fl. c. 790–780 BC2), known from the Apis stela of year 28 of Shoshenq III. This identification ties in with a significant lowering of the accepted dates for the kings from Shoshenq III, Osorkon III and Takeloth III to Shoshenq V, and the material culture associated with them. Such a shift seems to be supported by stylistic and genealogical evidence. As a consequence, it is further suggested that the Master of Shipping at Nen-nesut, Pediese i, was perhaps related by descent and marriage to the family of the High Priests of Memphis and King Peftjauawybast.

Socioeconomic impacts of National Parks: a case study from the North-east of England

[EN] Enforcement of rural policy measures within National Parks may have a particular importance as they may contribute to reach socioeconomic objectives devised for such areas. So this paper approaches as case study the application of a relevant rural development measure in the Northumberland National Park (NNP) –England, North East— over the period 2000-2008 in order to explore whether NNP makes any difference in terms of enforcing rural policy measures. The main research findings indicate that NNP may have some sort of positive impact on rural development, but support relying on tourism monoculture may be a background reason for undesired negative consequences.