Photodynamic activity and photoantimicrobial chemotherapy studies of ferrocene-substituted 2-thiobarbituric acid.

A ferrocene-substituted thiobarbituric acid (FT) has been synthesized to explore its photophysical properties and photodynamic and photoantimicrobial chemotherapy activities. FT has an intense metal-to-ligand charge transfer (MLCT) band at ca. 575 nm. The ferrocene moiety of FT undergoes photooxidation to form a ferrocenium species which in turn produces hydroxyl radical in an aqueous environment, which was confirmed via the bleaching reaction of p-nitrosodimethylaniline (RNO). FT exhibits efficient PDT activity against MCF-7 cancer cells with an IC50 value of 5.6 µM upon irradiation with 595 nm for 30 min with a Thorlabs M595L3 LED (240 mW cm-2). Photodynamic inactivation of Staphylococcus aureus and Escherichia coli by FT shows significant activity with log reduction values of 6.62 and 6.16 respectively, under illumination for 60 min at 595 nm. These results demonstrate that ferrocene-substituted thiobarbituric acids merit further study for developing novel bioorganometallic PDT agents.

LET-Dependent Intertrack Yields in Proton Irradiation at Ultra-High Dose Rates Relevant for FLASH Therapy.

FLASH radiotherapy delivers a high dose (≥10 Gy) at a high rate (≥40 Gy/s). In this way, particles are delivered in pulses as short as a few nanoseconds. At that rate, intertrack reactions between chemical species produced within the same pulse may affect the heterogeneous chemistry stage of water radiolysis. This stochastic process suits the capabilities of the Monte Carlo method, which can model intertrack effects to aid in radiobiology research, including the design and interpretation of experiments. In this work, the TOPAS-nBio Monte Carlo track-structure code was expanded to allow simulations of intertrack effects in the chemical stage of water radiolysis. Simulation of the behavior of radiolytic yields over a long period of time (up to 50 s) was verified by simulating radiolysis in a Fricke dosimeter irradiated by 60Co γ rays. In addition, LET-dependent G values of protons delivered in single squared pulses of widths, 1 ns, 1 µs and 10 µs, were obtained and compared to simulations using no intertrack considerations. The Fricke simulation for the calculated G value of Fe3+ ion at 50 s was within 0.4% of the accepted value from ICRU Report 34. For LET-dependent G values at the end of the chemical stage, intertrack effects were significant at LET values below 2 keV/µm. Above 2 keV/µm the reaction kinetics remained limited locally within each track and thus, effects of intertrack reactions remained low. Therefore, when track structure simulations are used to investigate the biological damage of FLASH irradiation, these intertrack reactions should be considered. The TOPAS-nBio framework with the expansion to intertrack chemistry simulation provides a useful tool to assist in this task.

Ferrocene Functionalized Upconversion Nanoparticle Nanosystem with Efficient Near-Infrared-Light-Promoted Fenton-Like Reaction for Tumor Growth Suppression.

By taking advantage of the efficient Förster resonance energy transfer (FRET) between near-infrared (NIR)-responsive lanthanide-doped upconversion nanoparticles (UCNPs) and Fenton reagent ferrocenyl compounds (Fc), a series of Fc-UCNPs was designed by functionalizing NaYF4:Yb,Tm nanoparticles with Fc1-Fc5 via surface-coordination chemistry. Fc-UCNP-Lipo nanosystems were then constructed by encapsulating Fc-UCNP inside liposomes for efficient delivery. Fc-UCNP can effectively release ·OH via a NIR-promoted Fenton-like reaction. In vitro and in vivo studies of Fc1-UCNP-Lipo confirmed the preferential accumulation in a tumor site followed by an enhanced uptake of cancer cells. After cellular internalization, the released Fc1-UCNP can effectively promote ·OH generation for tumor growth suppression. Such a Fc1-UCNP-Lipo nanosystem exhibits advantages such as easy fabrication, low drug dosage, and no ferrous ion release.

One Stone Two Birds: Zr-Fc Metal-Organic Framework Nanosheet for Synergistic Photothermal and Chemodynamic Cancer Therapy.

Metal-organic frameworks (MOFs) have been identified as promising materials for the delivery of therapeutics to cure cancer owing to their intrinsic porous structure. However, in a majority of cases, MOFs act as only a delivery cargo for anticancer drugs while little attention has been focused on the utilization of their intriguing physical and chemical properties for potential anticancer purposes. Herein for the first time, an ultrathin (16.4 nm thick) ferrocene-based MOF (Zr-Fc MOF) nanosheet has been synthesized for synergistic photothermal therapy (PTT) and Fenton reaction-based chemodynamic (CDT) therapy to cure cancer without additional drugs. The Zr-Fc MOF nanosheet acts not only as an excellent photothermal agent with a prominent photothermal conversion efficiency of 53% at 808 nm but also as an efficient Fenton catalyst to promote the conversion of H2O2 into hydroxyl radical (•OH). As a consequence, an excellent therapeutic performance has been achieved in vitro as well as in vivo through this combinational effect. This work aims to construct an "all-in-one" MOF nanoplatform for PTT and CDT treatments without incorporating any additional therapeutics, which may launch a new era in the investigation of MOF-based synergistic therapy platforms for cancer therapy.

Ferrocene-catalyzed heterogeneous Fenton-like degradation mechanisms and pathways of antibiotics under simulated sunlight: A case study of sulfamethoxazole.

Readily-available and efficient catalyst is essential for activating oxidants to produce reactive species for deeply remediating water bodies contaminated by antibiotics. In this study, Ferrocene (Fc) was introduced to establish a heterogeneous photo-Fenton system for the degradation of sulfonamide antibiotics, taking sulfamethoxazole as a representative. Results showed that the removal of sulfamethoxazole was effective in Fc-catalyzed photo-Fenton system. Electron spin resonance and radical scavenging experiments verified that there was a photoindued electron transfer process from Fc to H2O2 and dissolved oxygen resulting in the formation of OH that was primarily responsible for the degradation of sulfamethoxazole. The reactions of OH with substructure model compounds of sulfamethoxazole unveiled that aniline moiety was the preferable reaction site of sulfamethoxazole, which was verified by the formation of hydroxylated product and the dimer of sulfamethoxazole in Fc-catalyzed photo-Fenton system. This heterogeneous photo-Fenton system displayed an effective degradation efficiency even in a complex water matrices, and Fc represented a long-term stability by using the catalyst for multiple cycles. These results demonstrate that Fc-catalyzed photo-Fenton oxidation may be an efficient approach for remediation of wastewater containing antibiotics.

Iron oxide-mediated semiconductor photocatalysis vs. heterogeneous photo-Fenton treatment of viruses in wastewater. Impact of the oxide particle size.

The photo-Fenton process is recognized as a promising technique towards microorganism disinfection in wastewater, but its efficiency is hampered at near-neutral pH operating values. In this work, we overcome these obstacles by using the heterogeneous photo-Fenton process as the default disinfecting technique, targeting MS2 coliphage in wastewater. The use of low concentrations of iron oxides in wastewater without H2O2 (wüstite, maghemite, magnetite) has demonstrated limited semiconductor-mediated MS2 inactivation. Changing the operational pH and the size of the oxide particles indicated that the isoelectric point of the iron oxides and the active surface area are crucial in the success of the process, and the possible underlying mechanisms are investigated. Furthermore, the addition of low amounts of Fe-oxides (1mgL-1) and H2O2 in the system (1, 5 and 10mgL-1) greatly enhanced the inactivation process, leading to heterogeneous photo-Fenton processes on the surface of the magnetically separable oxides used. Additionally, photo-dissolution of iron in the bulk, lead to homogeneous photo-Fenton, further aided by the complexation by the dissolved organic matter in the solution. Finally, we assess the impact of the presence of the bacterial host and the difference caused by the different iron sources (salts, oxides) and the Fe-oxide size (normal, nano-sized).

The Fricke dosimeter as an absorbed dose to water primary standard for Ir-192 brachytherapy.

The aim of this project was to develop an absorbed dose to water primary standard for Ir-192 brachytherapy based on the Fricke dosimeter. To achieve this within the framework of the existing TG-43 protocol, a determination of the absorbed dose to water at the reference position, D(r0,θ0), was undertaken. Prior to this investigation, the radiation chemical yield of the ferric ions (G-value) at the Ir-192 equivalent photon energy (0.380 MeV) was established by interpolating between G-values obtained for Co-60 and 250 kV x-rays.An irradiation geometry was developed with a cylindrical holder to contain the Fricke solution and allow irradiations in a water phantom to be conducted using a standard Nucletron microSelectron V2 HDR Ir-192 afterloader. Once the geometry and holder were optimized, the dose obtained with the Fricke system was compared to the standard method used in North America, based on air-kerma strength.Initial investigations focused on reproducible positioning of the ring-shaped holder for the Fricke solution with respect to the Ir-192 source and obtaining an acceptable type A uncertainty in the optical density measurements required to yield the absorbed dose. Source positioning was found to be reproducible to better than 0.3 mm, and a careful cleaning and control procedure reduced the variation in optical density reading due to contamination of the Fricke solution by the PMMA holder. It was found that fewer than 10 irradiations were required to yield a type A standard uncertainty of less than 0.5%.Correction factors to take account of the non-water components of the geometry and the volume averaging effect of the Fricke solution volume were obtained from Monte Carlo calculations. A sensitivity analysis showed that the dependence on the input data used (e.g. interaction cross-sections) was small with a type B uncertainty for these corrections estimated to be 0.2%.The combined standard uncertainty in the determination of absorbed dose to water at the reference position for TG-43 (1 cm from the source on the transverse axis, in a water phantom) was estimated to be 0.8% with the dominant uncertainty coming from the determination of the G-value. A comparison with absorbed dose to water obtained using the product of air-kerma strength and the dose rate constant gave agreement within 1.5% for three different Ir-192 sources, which is within the combined standard uncertainties of the two methods.

A feasibility study of Fricke dosimetry as an absorbed dose to water standard for 192Ir HDR sources.

High dose rate brachytherapy (HDR) using 192Ir sources is well accepted as an important treatment option and thus requires an accurate dosimetry standard. However, a dosimetry standard for the direct measurement of the absolute dose to water for this particular source type is currently not available. An improved standard for the absorbed dose to water based on Fricke dosimetry of HDR 192Ir brachytherapy sources is presented in this study. The main goal of this paper is to demonstrate the potential usefulness of the Fricke dosimetry technique for the standardization of the quantity absorbed dose to water for 192Ir sources. A molded, double-walled, spherical vessel for water containing the Fricke solution was constructed based on the Fricke system. The authors measured the absorbed dose to water and compared it with the doses calculated using the AAPM TG-43 report. The overall combined uncertainty associated with the measurements using Fricke dosimetry was 1.4% for k = 1, which is better than the uncertainties reported in previous studies. These results are promising; hence, the use of Fricke dosimetry to measure the absorbed dose to water as a standard for HDR 192Ir may be possible in the future.

Ferrocenyl-L-amino acid copper(II) complexes showing remarkable photo-induced anticancer activity in visible light.

Ferrocene-conjugated copper(ii) complexes [Cu(Fc-aa)(aip)](ClO4) () and [Cu(Fc-aa)(pyip)](ClO4) () of l-amino acid reduced Schiff bases (Fc-aa), 2-(9-anthryl)-1H-imidazo[4,5-f][1,10]phenanthroline (aip) and 2-(1-pyrenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (pyip), where Fc-aa is ferrocenylmethyl-l-tyrosine (Fc-Tyr in , ), ferrocenylmethyl-l-tryptophan (Fc-Trp in , ) and ferrocenylmethyl-l-methionine (Fc-Met in , ), were prepared and characterized, and their photocytotoxicity was studied (Fc = ferrocenyl moiety). Phenyl analogues, viz. [Cu(Ph-Met)(aip)](ClO4) () and [Cu(Ph-Met)(pyip)](ClO4) (), were prepared and used as control compounds. The bis-imidazophenanthroline copper(ii) complexes, viz. [Cu(aip)2(NO3)](NO3) () and [Cu(pyip)2(NO3)](NO3) (), were also prepared and used as controls. Complexes having a redox inactive cooper(ii) center showed the Fc(+)-Fc redox couple at ∼0.5 V vs. SCE in DMF-0.1 mol [Bu(n)4N](ClO4). The copper(ii)-based d-d band was observed near 600 nm in DMF-Tris-HCl buffer (1 : 1 v/v). The ferrocenyl complexes showed low dark toxicity, but remarkably high photocytotoxicity in human cervical HeLa and human breast adenocarcinoma MCF-7 cancer cells giving an excellent photo-dynamic effect while their phenyl analogues were inactive. The photo-exposure caused significant morphological changes in the cancer cells when compared to the non-irradiated ones. The photophysical processes were rationalized from the theoretical studies. Fluorescence microscopic images showed and localizing predominantly in the endoplasmic reticulum (ER) of the cancer cells, thus minimizing any undesirable effects involving nuclear DNA.

Mineralization of wastewater from the pharmaceutical industry containing chloride ions by UV photolysis of H2O2/Fe(II) and ultrasonic irradiation.

The mineralization of pharmaceutical wastewater containing chloride ions using a UV/H2O2/Fe(II) process was studied. The addition of Fe(II) to the UV/H2O2 system did not improve the degradation efficiency due to inhibition of the photo-Fenton reaction, at acid pH, in the presence of chloride ions in these wastewaters. The increase of pH from 2 to 7 increased the degree of mineralization under UV photolysis of H2O2 because more HO radicals are available by HOCl dissociation reaction. Under the selected operation conditions ([H2O2]o = 11,500 ppm, [Fe(II)] = 0 ppm, [TOC]o = 125 ppm and pH = 7), 100% of TOC removal was attained in 120 min. A significant synergistic effect of combining photolysis (UV/H2O2) and sonolysis was observed. Sonophotolysis (UV/H2O2/ultrasound) technique significantly increased the degree of mineralization (100% TOC removal in 90 min using 6500 ppm H2O2) when compared with each individual process. Sonochemical reaction was favored by the presence of chloride ions since the concentration of contaminants at the gas-liquid interface increased. Free radicals reaction was the controlling mechanism in the UV/H2O2/ultrasound system. HO radicals were the main oxidative intermediate species in the process, although hydroperoxyl radicals (HO2) also played a role. The contribution of thermal-pyrolytic reaction (in gas-phase) to sonophotolysis process was negligible.

A study of hydrogen peroxide chemistry and photochemistry in tea stain solution with relevance to clinical tooth whitening.

OBJECTIVE: Tooth whitening using hydrogen peroxide is a complex process, and there is still some controversy about the roles of pH, temperature, chemical activators, and the use of light irradiation. In this work the basic interactions between whitening agents and stain molecules are studied in simple solutions, thus avoiding the physics of diffusion and light penetration in the tooth to give clarity on the basic chemistry which is occurring. METHOD: The absorbance of tea stain solution at 450 nm was measured over a period of 40 min, with various compositions of whitening agent added (including hydrogen peroxide, ferrous gluconate and potassium hydroxide) and at the same time the samples were subjected to blue light (465 nm) or infra-red light (850 nm) irradiation, or alternatively they were heated to 37°C. RESULTS: It is shown that the reaction rates between chromogens in the tea solution and hydrogen peroxide can be accelerated significantly using ferrous gluconate activator and blue light irradiation. Infra red irradiation does not increase the reaction rate through photochemistry, it serves only to increase the temperature. Raising the temperature leads to inefficiency through the acceleration of exothermic decomposition reactions which produce only water and oxygen. CONCLUSION: By carrying out work in simple solution it was possible to show that ferrous activators and blue light irradiation significantly enhance the whitening process, whereas infra red irradiation has no significant effect over heating. The importance of controlling the pH within the tooth structure during whitening is also demonstrated.

Optimization of hydrous ferrous sulfate dehydration by microwave heating using response surface methodology.

The work relates to assessing the ability of the microwave for dehydration of large amount of waste hydrous ferrous sulfate generated from the titanium pigment process industry. The popular process optimization tool of response surface methodology with central composite design was adopted to estimate the effect of dehydration. The process variables were chosen to be power input, duration of heating and the bed thickness, while the response variable being the weight loss. An increase in all the three process variables were found to significantly increase the weight loss, while the effect of interaction among the parameters were found to be insignificant. The optimized process conditions that contribute to the maximum weight loss were identified to be a power input of 960 W, duration of heating of 14 min and bed thickness of 5 cm, resulting in a weight loss of 31.44%. The validity of the optimization process was tested with the repeat runs at optimized conditions.

Gamma/neutron dose evaluation using Fricke gel and alanine gel dosimeters to be applied in boron neutron capture therapy.

Gel dosimetry has been studied mainly for medical applications. The radiation induced ferric ions concentration can be measured by different techniques to be related with the absorbed dose. Aiming to assess gamma/thermal neutrons dose from research reactors, Fricke gel and alanine gel solutions produced at IPEN using 300 bloom gelatin were mixed with Na(2)B(4)O(7) salt, and the mixtures were irradiated at the beam hole #3 of the IEA-R1 research reactor, (BH#3) adapted to BNCT studies, and the dose-response was evaluated using spectrophotometry technique.

Fricke gel-layer dosimetry in high dose-rate brachytherapy.

The aim of this study was to evaluate the reliability of Fricke gel-layer dosimeters for the measurement of in-phantom dose distributions produced by a ((192))Ir brachytherapy source. The doses obtained were compared to measurements performed with thermoluminescent dosimeters and treatment planning calculations. Fricke gel-layer dosimeters have proven to be a promising tool to measure three-dimensional dose distributions in high dose-rate brachytherapy.

Photoinduced spin transition for Iron(II) compounds with liquid-crystal properties.

The iron(II) compounds [Fe(3Cn-L)2(NCS)2] (n = 6 (1), n = 8 (2), n = 10 (3), n = 12 (4), n = 14 (5), n = 16 (6), n = 18 (7), n = 20 (8), and n = 22 (9)) were synthesized and their physical properties characterized by polarizing optical microscopy, differential scanning calorimetry, and powder X-ray analysis, where 3Cn-L denotes bidentate Schiff-base ligands formed from the corresponding aniline derivatives and pyridine-2-carboxyaldehyde. The iron(II) compounds 4-8 exhibited crystal to liquid-crystal transitions at 318, 334, 345, 338, and 347 K, respectively. Variable-temperature magnetic susceptibility measurements revealed that the compounds 1-9 exhibit spin-crossover behavior between the high-spin and low-spin states and a photoinduced spin transition from a low-spin state to a metastable high-spin state. Therefore, the iron(II) compounds 4-8 can undergo spin-crossover and photoinduced spin transition as well as have liquid-crystal properties all in a single molecule. Compounds with multifunctions are important in the development of molecular switches and optical materials.

Growth morphology and spectroscopy of multiwall carbon nanotubes synthesized by pyrolysis of iron phthalocyanine.

Carbon nanotubes (CNTs) were synthesized by Chemical Vapor Deposition (CVD) from the pyrolytic decomposition of Iron Phthalocyanine (FePc) molecules, on SiO2/Si(111) substrates in the presence of a hydrogen flow. FePc molecules contribute simultaneously both to the formation of the precursor Fe nanoparticles and also as a Carbon source. Different experimental conditions were examined. Samples were characterized by scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, and inverse photoemission. The resulting samples are highly oriented multiwall carbon nanotubes films, with heights in the range between: 4 and 20 microm. The tubes diameter is strongly dependent on growth temperature. Our experimental results show evidence of a transition in the growth mechanism, from a tip growth to a base growth mode, as the decomposition temperature is increased. Preliminary spectroscopic measurements performed on these MWCNTs, show the unoccupied density of states has several resonances close to Fermi level, related both to the graphene electronic structure and the formation of the tube.

Dose imaging with gel-dosemeter layers: optical analysis and dedicated software.

In radiotherapy involving thermal and epithermal neutrons, the knowledge of dose distributions, with separation of the contribution of each secondary radiation component, is of utmost importance. Layers of Fricke-Xylenol-Orange-infused gel dosemeters give the possibility of achieving such requirements because, owing to the layer-geometry, enriching or depleting the gel matrix of suitable isotopes does not sensibly alter neutron transport. The dosimetry method has been critically re-examined with the aim of improving its suitability to boron neutron capture therapy (BNCT) requirements, as it applies to the protocol of measurement and analysis, the sensitivity of the method and the range of the linearity of the dosemeters. Software has been developed and studied to obtain automatically the images of the various dose components with the established separation procedure.

Ion diffusion modelling of Fricke-agarose dosemeter gels.

In Fricke-agarose gels, an accurate determination of the spatial dose distribution is hindered by the diffusion of ferric ions. In this work, a model was developed to describe the diffusion process within gel samples of finite length and, thus, permit the reconstruction of the initial spatial distribution of the ferric ions. The temporal evolution of the ion concentration as a function of the initial concentration is derived by solving Fick's second law of diffusion in two dimensions with boundary reflections. The model was applied to magnetic resonance imaging data acquired at high spatial resolution (0.3 mm) and was found to describe accurately the observed diffusion effects.

Optical imaging of dose distributions in Fricke gels.

Ferrous-sulphate infused gels, or 'Fricke gels', encounter great interest in the field of radiation dosimetry, due to their potential for 3D radiation dose mapping. Typically, magnetic resonance (MR) relaxation rates are determined in these systems in order to derive the absorbed dose. However, when large concentration gradients are present, diffusion effects before and during the MR imaging may not be negligible. In these cases, optical techniques may represent a viable alternative. This paper describes research aimed at measuring 3D dose distributions in a Fricke-xylenol orange gel by measuring optical density with a CCD camera. This method is inexpensive and fast. A series of early experiments is described, in which optical density profiles were measured with a commercial microdensitometer for film dosimetry. The light box of the device was modified to work at 567 nm, close to the maximum absorbance of the ferric ion-xylenol orange complex. Under these conditions, the gel shows linearity with dose and high sensitivity.

Dosimetry of soft x-rays in thin liquid layers.

Very thin material layers (<100 microm) partially absorb ionizing radiation of low energy. When irradiating monolayer cell cultures from above, attention must be paid to absorption by the medium. Frequently, the volume of the nutrient medium is variable, and this leads to differences in the radiation doses delivered to the cells. In the present work these conditions were investigated for x-rays of energies between 13 kV and 100 kV in comparison with 60Co gamma rays using chemical dosimetry to measure the absorption by liquid layers between 25 microm and 500 microm thick. When the dose as measured with the ionization chamber was held constant, the dose absorbed in the Fricke solution was shown to increase with decreasing thickness of the layer of liquid because of a dose gradient. The effect of the dose gradient disappeared, however, in thick liquid layers of the Fricke solution by mixing during spectrophotometry. Secondary (photoeffect and Compton) electrons produced in air or filters are responsible for this effect in plastic petri dishes where back scattering at the interface does not occur. This interpretation is suggested by the same results of an analogous experimental setup using gamma rays with a 5-mm-thick Perspex plate. This dose increase in very thin layers, however, could not be verified by irradiating monolayer cells in poured-out plastic petri dishes because the secondary electrons are already absorbed in the remaining liquid film above the cells.