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

Iron(III) complexes [Fe(L)(2)]Cl (1-3), where L is monoanionic N-salicylidene-arginine (sal-argH for 1), hydroxynaphthylidene-arginine (nap-argH for 2) and N-salicylidene-lysine (sal-lysH for 3), were prepared and their DNA binding and photo-induced DNA cleavage activity studied. Complex 3 as its hexafluorophosphate salt [Fe(sal-lysH)(2)](PF6)center dot 6H(2)O (3a) was structurally characterized by single crystal Xray crystallography. The crystals belonged to the triclinic space group P-1. The complex has two tridentate ligands in FeN2O4 coordination geometry with two pendant cationic amine moieties. Complexes 1 and 2 with two pendant cationic guanidinium moieties are the structural models for the antitumor antibiotics netropsin. The complexes are stable and soluble in water. They showed quasi-reversible Fe(III)/Fe(II) redox couple near 0.6 V in H2O-0.1 M KCl. The high-spin 3d(5)-iron(III) complexes with mu(eff) value of similar to 5.9 mu(B) displayed ligand-to-metal charge transfer electronic band near 500 mm in Tris-HCl buffer. The complexes show binding to Calf Thymus (CT) DNA. Complex 2 showed better binding propensity to the synthetic oligomer poly(dA)center dot poly(dT) than to CT-DNA or poly(dG)center dot poly(dC). All the complexes displayed chemical nuclease activity in the presence of 3-mercaptopropionic acid as a reducing agent and cleaved supercoiled pUC19 DNA to its nicked circular form. They exhibited photo-induced DNA cleavage activity in UV-A light and visible light via a mechanistic pathway that involves the formation of reactive hydroxyl radical species. (C) 2010 Elsevier Inc. All rights reserved.

Ternary Iron(III) complex showing photocleavage of DNA in the photodynamic therapy window

A new ternary iron(III) complex [FeL(dpq)] containing dipyridoquinoxaline (dpq) and 2,2-bis(3,5-di-tert-butyl-2-hydroxybenzyl)aminoacetic acid (H3L) is prepared and structurally characterized by X-ray crystallography. The high-spin complex with a FeN3O3 core shows a quasi-reversible iron(III)/iron(II) redox couple at -0.62 V (vs SCE) in DMF/0.1 M TBAP and a broad visible band at 470 nm in DMF/Tris buffer. Laser photoexcitation of this phenolate (L)-to-iron(III) charge-transfer band at visible wavelengths including red light of >= 630 nm leads to cleavage of supercoiled pUC19 DNA to its nicked circular form via a photoredox pathway forming hydroxyl radicals.

Biosorption of iron(III) from aqueous solutions using the husk of Cicer arientinum

Iron is a major pollutant released as a by-product during several industrial operations especially during acid mining of metal ores. In this paper, the use of Bengal gram husk (husk of channa dal, Cicer arientinum) in the biosorption of Fe(III) from aqueous solutions is discussed. Parameters like agitation time, adsorbent dosage and pH were studied at different Fe(Ill) concentrations. The adsorption data fit well with Langmuir and Freundlich isotherm models. The adsorption capacity (q(max)) calculated from the Langmuir isotherm was 72.16 mg of Fe(III)/g of the biosorbent at an initial pH of 2.5. Desorption Studies were performed at different concentrations of hydrochloric acid showing that quantitative recovery of the metal ion is possible. The infrared spectra of the biomass before and after treatment with Fe(III), revealed that hydroxyl, carboxyl and amide bonds are involved in the uptake of Fe(III) ions.

Singlet quenching of tetraphenylporphyrin and its metal derivatives by iron(III) coordination compounds

The quenching of fluorescence of the free-base tetraphenylporphyrin, H2TPP, and its metal derivatives, MgTPP and ZnTPP by diverse iron(III) complexes, [Fe(CN)6]3−, Fe(acac)3, [Fe(mnt)2]−, Fe(Salen)Cl, [Fe4S4(SPh)4]2−·, FeTPPCl and [Fe(Cp)2]+ has been studied both in homogeneous medium (CH3CN) and micellar media, SDS., CTAB and Triton X-100. The quenching efficiencies are analysed in terms of diffusional encounters and it has been possible to separate static quenching components. The quenching constants are dependent on the nature of the ligating atoms around iron(III) and also on the extent of π-conjugation of the ligands. The quenching mechanism has been investigated using steady-state irradiation experiments. Evidence for oxidative quenching by iron(III) complexes was obtained, though the spin multiplicities of the excited electronic states of iron(III) complexes permit both energy and electron transfer mechanisms for quenching of the singlet excited state of the porphyrins.

Differential pulse polarographic determination of trace levels of iron(III) by using the catalytic current

Trace of iron(III) are determined by differential pulse polarography in a medium of sodium hydroxide and sodium bromate using the catalytic current. Various cations do not interfere. The relative standard deviation is 2%.

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), 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) and benzoi]dipyridro3,2-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 center dot 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 IC50 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 DAFT 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.

Iron(III) Chloride-Catalysed Aerobic Reduction of Olefins using Aqueous Hydrazine at Ambient Temperature

A chemoselective reduction of olefins and acetylenes is demonstrated by employing catalytic amounts of ferric chloride hexahydrate (FeCl3 center dot 6H(2)O) and aqueous hydrazine (NH2NH2 center dot H2O) as hydrogen source at room temperature. The reduction is chemoselective and tolerates a variety of reducible functional groups. Unlike other metal-catalysed reduction methods, the present method employs a minimum amount of aqueous hydrazine (1.5-2 equiv.). Also, the scope of this method is demonstrated in the synthesis of ibuprofen in aqueous medium.

Biotin-conjugated tumour-targeting photocytotoxic iron(III) complexes

Iron(III) complexes FeL(B)] (1-4) of a tetradentate phenolate-based ligand (H3L) and biotin-conjugated dipyridophenazine bases (B), viz. 7-aminodipyrido 3,2-a: 2',3'-c]-phenazine (dppza in 1), (N-dipyrido3,2-a: 2',3'-c]-phenazino) amidobiotin (dppzNB in 2), dipyrido 3,2-a: 2',3'-c]-phenazine-11-carboxylic acid (dppzc in 3) and 2-((2-biotinamido) ethyl) amidodipyrido 3,2-a: 2',3'-c]-phenazine (dppzCB in 4) are prepared, characterized and their interaction with streptavidin and DNA and their photocytotoxicity and cellular uptake in various cells studied. The high-spin iron(III) complexes display Fe(III)/Fe(II) redox couple near -0.7V versus saturated calomel electrode in dimethyl sulfoxide-0.1M tetrabutylammonium perchlorate. The complexes show non-specific interaction with DNA as determined from the binding studies. Complexes with appended biotin moiety show similar binding to streptavidin as that of free biotin, suggesting biotin conjugation to dppz does not cause any loss in its binding affinity to streptavidin. The photocytotoxicity of the complexes is tested in HepG2, HeLa and HEK293 cell lines. Complex 2 shows higher photocytotoxicity in HepG2 cells than in HeLa or HEK293, forming reactive oxygen species. This effect is attributed to the presence of overexpressed sodium-dependent multi-vitamin transporters in HepG2 cells. Microscopic studies in HepG2 cells show internalization of the biotin complexes 2 and 4 essentially occurring by receptor-mediated endocytosis, which is similar to that of native biotin and biotin fluorescein isothiocyanate conjugate.

Carbohydrate-Appended Tumor Targeting Iron(III) Complexes Showing Photocytotoxicity in Red Light

Glucose-appended photocytotoxic iron(III) complexes of a tridentate Schiff base phenolate ligand Fe(bpyag) (L)] (NO3) (1-3), where bpyag is N,N-bis(2- pyridylmethyl)-2-aminoethyl-beta-D-glucopyranoside and H2L is 3-(2-hydroxyphenylimino)-1-phenylbutan-1-one (H(2)phap) in 1, 3-(2-hydroxyphenylimino)-9-anthrylbutan-1-one (H(2)anap) 2, and 3- (2-hydroxyphenylimino)-1-pyrenylbutan-1-one (H(2)pyap) in 3, were synthesized and characterized. The complex Fe(dpma)(anapn(NO3) (4), having bis-(2-pyridylmethyl)benzylamine (dpma), in which the glucose moiety of bpyag is substituted by a phenyl group, was used as a control, and the complex Fe(dpma)(anap)](PF6) (4a) was structurally characterized by X-ray crystallography. The structure shows a FeN4O2 core in a distorted octahedral geometry. The high-spin iron(III) complexes with magnetic moment value of similar to 5.9 mu(B) showed a low-energy phenolate-to-Fe(III) charge-transfer (CT) absorption band as a shoulder near 500 nm with a tail extending to 700 nm and an irreversible Fe(III)-Fe(II) redox couple near -0.6 V versus saturated calomel electrode. The complexes are avid binders to calf thymus DNA and showed photocleavage of supercoiled pUC19 DNA in red (647 nm) and green (532 nm) light. Complexes 2 and 3 displayed significant photocytotoxicity in red light, with an IC50 value of similar to 20 mu M in HeLa and HaCaT cells, and no significant toxicity in dark. The cell death is via an apoptotic pathway, by generation of reactive oxygen species. Preferential internalization of the carbohydrate-appended complexes 2 and 3 was evidenced in HeLa cells as compared to the control complex 4. A 5-fold increase in the cellular uptake was observed for the active complexes in HeLa cells. The photophysical properties of the complexes are rationalized from the density functional theory calculations.

Iron(III) benzhydroxamates of dipicolylamines for photocytotoxicity in red light and cellular imaging

Benzhydroxamate (BHA) iron(III) complexes Fe(BHA)(L)ClICI (I, 2)], where L is (phenyl)dipicolylamine (phdpa in I) and (pyrenyl)dipicolylamine (pydpa in 2), were prepared and their photocytotoxicity in visible (400-700 nm) and red (600-720 nm) light was studied. Complex 1 was structurally characterized by X-ray crystallography. The complexes have high-spin iron(III) centers. Complex 2, with a pyrenyl fluorophore, was used for cellular imaging, showing both mitochondrial and nuclear localization in the fluorescence microscopic study. The complex exhibited photocytotoxicity in red light in HeLa cancer cells, giving IC50 value of 24.4(+/- 0.4) pM, but remained essentially non-toxic in the dark. The involvement of reactive oxygen species and an apoptotic nature of cell death were observed from the cellular studies. (C) 2014 Elsevier Ltd. All rights reserved.

Iron(III) Catecholates for Cellular Imaging and Photocytotoxicity in Red Light

Iron(III) complexes Fe(L)(L') (NO3)]-in which L is phenyl-N, N-bis(pyridin-2-yl) methyl]methanamine (1), (anthracen-9-yl)N, N-bis(pyridin-2-yl) methyl] methanamine (2), (pyreny-1-yl)-N, N-bis(pyridin- 2-yl) methyl] methanamine (3-5), and L' is catecholate (1-3), 4-tert-butyl catecholate (4), and 4-(2-aminoethyl)benzene- 1,2-diolate (5)-were synthesized and their photocytotoxic proper-ties examined. The five electron-paramagnetic complexes displayed a FeIII/ Fe-II redox couple near similar to 0.4 V versus a saturated calomel electrode (SCE) in DMF/0.1m tetrabutylammonium perchlorate (TBAP). They showed unpre-cedented photocytotoxicity in red light (600-720 nm) to give IC50-15 mm in various cell lines by means of apoptosis to generate reactive oxygen species. They were ingested in the nucleus of HeLa and HaCaT cells in 4 h, thereby interacting favorably with calf thymus (ct)-DNA and photocleaving pUC19 DNA in red light of 785 nm to form hydroxyl radicals.

Significant photocytotoxic effect of an iron(III) complex of a Schiff base ligand derived from vitamin B-6 and thiosemicarbazide in visible light

Iron(III)-Schiff base complexes, namely, Fe(tsc-py)(2)](NO3) (1), Fe(tsc-acpy)(2)](NO3) (2) and Fe(tsc-VB6)(2)](NO3) (3), where tsc-py, tsc-acpy and tsc-VB6 are the respective Schiff bases derived from thiosemicarbazide (tsc) and pyridine-2-aldehyde (tsc-py), 2-acetyl pyridine (tsc-acpy) and vitamin B-6 (pyridoxal, tsc-VB6), have been prepared, structurally characterized and their photocytotoxicity studied in cancer HeLa cells. The single crystal X-ray structures of the complexes 1 and 2 show a distorted octahedral geometry formed by the FeN4S2 core. The low-spin and 1 : 1 electrolytic complexes display a broad absorption band in the visible region. Complexes 1 and 2, without any VB6 moiety are not cytotoxic under light or dark conditions. Complex 3 is significantly photocytotoxic under visible light of 400-700 nm giving an IC50 value of 22.5 mu M in HeLa cells with no dark toxicity (IC50 > 100 mu M). The photo-induced cell death is attributable to apoptotic pathways involving photo-assisted generation of intracellular ROS. The observed photocytotoxicity of complex 3 could be the result of its better photosensitizing property combined with its enhanced uptake into cancer cells via a VB6 transporting membrane carrier (VTC) mediated diffusion pathway due to the presence of the VB6 moiety compared to the two non-vitamin B-6 analogues, complexes 1 and 2.

Iron(III) Complexes of a Pyridoxal Schiff Base for Enhanced Cellular Uptake with Selectivity and Remarkable Photocytotoxicity

Iron(III) complexes of pyridoxal (vitamin B6, VB6) or salicylaldehyde Schiff bases and modified dipicolylamines, namely, Fe(B)(L)](NO3) (15), where B is phenyl-N,N-bis((pyridin-2-yl)methyl)methanamine (phbpa in 1), (anthracen-9-yl)-N,N-bis((pyridin-2-yl)methyl)methanamine (anbpa in 2, 4) and (pyren-1-yl)-N,N-bis((pyridin-2-yl)methyl)methanamine (pybpa in 3, 5) (H2L1 is 3-hydroxy-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylp yridine (13) and H2L2 is 2-(2-hydroxyphenyl-imino)methyl]phenol), were prepared and their uptake in cancer cells and photocytotoxicity were studied. Complexes 4 and 5, having a non-pyridoxal Schiff base, were prepared to probe the role of the pyridoxal group in tumor targeting and cellular uptake. The PF6 salt (1a) of complex 1 is structurally characterized. The complexes have a distorted six-coordinate FeN4O2 core where the metal is in the +3 oxidation state with five unpaired electrons. The complexes display a ligand to metal charge transfer band near 520 and 420 nm from phenolate to the iron(III) center. The photophysical properties of the complexes are explained from the time dependent density functional theory calculations. The redox active complexes show a quasi-reversible Fe(III)/Fe(II) response near -0.3 V vs saturated calomel electrode. Complexes 2 and 3 exhibit remarkable photocytotoxicity in various cancer cells with IC50 values ranging from 0.4 to 5 mu M with 10-fold lower dark toxicity. The cell death proceeded by the apoptotic pathway due to generation of reactive oxygen species upon light exposure. The nonvitamin complexes 4 and 5 display 3-fold lower photocytotoxicity compared to their VB6 analogues, possibly due to preferential and faster uptake of the vitamin complexes in the cancer cells. Complexes 2 and 3 show significant uptake in the endoplasmic reticulum, while complexes 4 and 5 are distributed throughout the cells without any specific localization pattern.