Activation of Dioxygen by a Mononuclear Nonheme Iron Complex: Sequential Peroxo, Oxo, and Hydroxo Intermediates.

The activation of dioxygen by FeII(Me3TACN)(S2SiMe2) (1) is reported. Reaction of 1 with O2 at -135 °C in 2-MeTHF generates a thiolate-ligated (peroxo)diiron complex FeIII2(O2)(Me3TACN)2(S2SiMe2)2 (2) that was characterized by UV-vis (λmax = 300, 390, 530, 723 nm), Mössbauer (δ = 0.53, |ΔEQ| = 0.76 mm s-1), resonance Raman (RR) (ν(O-O) = 849 cm-1), and X-ray absorption (XAS) spectroscopies. Complex 2 is distinct from the outer-sphere oxidation product 1ox (UV-vis (λmax = 435, 520, 600 nm), Mössbauer (δ = 0.45, |ΔEQ| = 3.6 mm s-1), and EPR (S = 5/2, g = [6.38, 5.53, 1.99])), obtained by one-electron oxidation of 1. Cleavage of the peroxo O-O bond can be initiated either photochemically or thermally to produce a new species assigned as an FeIV(O) complex, FeIV(O)(Me3TACN)(S2SiMe2) (3), which was identified by UV-vis (λmax = 385, 460, 890 nm), Mössbauer (δ = 0.21, |ΔEQ| = 1.57 mm s-1), RR (ν(FeIV═O) = 735 cm-1), and X-ray absorption spectroscopies, as well as reactivity patterns. Reaction of 3 at low temperature with H atom donors gives a new species, FeIII(OH)(Me3TACN)(S2SiMe2) (4). Complex 4 was independently synthesized from 1 by the stoichiometric addition of a one-electron oxidant and a hydroxide source. This work provides a rare example of dioxygen activation at a mononuclear nonheme iron(II) complex that produces both FeIII-O-O-FeIII and FeIV(O) species in the same reaction with O2. It also demonstrates the feasibility of forming Fe/O2 intermediates with strongly donating sulfur ligands while avoiding immediate sulfur oxidation.

Inactivation of myostatin by photo-oxygenation using catalyst-functionalized peptides.

Inhibition of myostatin is an attractive treatment for muscular dystrophy and other amyotrophic diseases. A myostatin-binding peptide was functionalized by equipped with an on/off switchable photo-oxygenation catalyst. This peptide induces a selective oxygenation of myostatin under near-infrared light, resulting in inactivation of myostatin. This peptide shows several orders of magnitude greater inhibitory effect than the original peptide.

Peculiar Effects of Electromagnetic Millimeter Waves on Tumor Development in BALB/c Mice.

The study examined the effects of millimeter electromagnetic waves at a frequency of 130 GHz corresponding to the molecular absorption and radiation spectra of NO and O2 with the total exposition time of 6 h on tumor morphogenesis in 3- and 6-month-old tumor-prone BALB/c mice of both sexes. In experimental mice exposed to electromagnetic radiation, the development of cancer process was slowed down throughout the observation period; moreover, no macroscopic signs of the tumors were revealed. However, in contrast to control mice, experimental animals demonstrated the formation of pathological reactions reflected by hepatic biochemical indices accompanied by the development of dystrophic and microcirculatory alterations in the liver tissue.

Biological effects of mixed-ion beams. Part 1: Effect of irradiation of the CHO-K1 cells with a mixed-ion beam containing the carbon and oxygen ions.

Carbon and oxygen ions were accelerated simultaneously to estimate the effect of irradiation of living cells with the two different ions. This mixed ion beam was used to irradiate the CHO-K1 cells, and a survival test was performed. The type of the effect of the mixed ion beam on the cells was determined with the isobologram method, whereby survival curves for irradiations with individual ion beams were also used. An additive effect of irradiation with the two ions was found.

Sustained molecular oxygen activation by solid iron doped silicon carbide under microwave irradiation: Mechanism and application to norfloxacin degradation.

Sustained molecular oxygen activation by iron doped silicon carbide (Fe/SiC) was investigated under microwave (MW) irradiation. The catalytic performance of Fe/SiC for norfloxacin (NOR) degradation was also studied. Rapid mineralization in neutral solution was observed with a pseudo-first-order rate constant of 0.2239 min-1 under 540 W of MW irradiation for 20 min. Increasing Fe/SiC rod and MW power significantly enhanced the degradation and mineralization rate with higher yield of reactive oxygen species (ROS). Fe shell corrosion and subsequent Fe0/II oxidation by molecular oxygen with MW activation was the key factor for NOR degradation through two-electron-transfer by Fe0 under acidic conditions and single-electron-transfer by FeII under neutral-alkaline solution. Removal rate of NOR was significantly affected by solution pH, showing higher degradation rates at both acidic and alkaline conditions. The highest removal efficiencies and rates at alkaline pH values were ascribed to the contribution of bound FeII species on the Fe shell surface due to the hydroxylation of Fe/SiC. ·OH was the main oxidizing specie for NOR degradation, confirmed by density functional theory (DFT) calculations and radical scavenger tests. DFT calculations were conducted on the reaction/activation energies of the transition/final states of NOR/degradation products, combined with intermediate identification with high performance liquid chromatography coupled with a triple-quadruple mass spectrometer (HPLC-MS/MS), the piperazinyl ring was the most reactive site for ·OH attack, followed by further ring-opening and stepwise oxidation. In this study, Fe/SiC were proved to be an excellent catalyst for the treatment of fluoroquinolone antibiotics with MW activation.

Spot Scanning and Passive Scattering Proton Therapy: Relative Biological Effectiveness and Oxygen Enhancement Ratio in Cultured Cells.

PURPOSE: To determine the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and contribution of the indirect effect of spot scanning proton beams, passive scattering proton beams, or both in cultured cells in comparison with clinically used photons. METHODS AND MATERIALS: The RBE of passive scattering proton beams at the center of the spread-out Bragg peak (SOBP) was determined from dose-survival curves in 4 cell lines using 6-MV X rays as controls. Survival of 2 cell lines after spot scanning and passive scattering proton irradiation was then compared. Biological effects at the distal end region of the SOBP were also investigated. The OER of passive scattering proton beams and 6 MX X rays were investigated in 2 cell lines. The RBE and OER values were estimated at a 10% cell survival level. The maximum degree of protection of radiation effects by dimethyl sulfoxide was determined to estimate the contribution of the indirect effect against DNA damage. All experiments comparing protons and X rays were made under the same biological conditions. RESULTS: The RBE values of passive scattering proton beams in the 4 cell lines examined were 1.01 to 1.22 (average, 1.14) and were almost identical to those of spot scanning beams. Biological effects increased at the distal end of the SOBP. In the 2 cell lines examined, the OER was 2.74 (95% confidence interval, 2.56-2.80) and 3.08 (2.84-3.11), respectively, for X rays, and 2.39 (2.38-2.43) and 2.72 (2.69-2.75), respectively, for protons (P<.05 for both cells between X rays and protons). The maximum degree of protection was significantly higher for X rays than for proton beams (P<.05). CONCLUSIONS: The RBE values of spot scanning and passive scattering proton beams were almost identical. The OER was lower for protons than for X rays. The lower contribution of the indirect effect may partly account for the lower OER of protons.

Near infrared radiation protects against oxygen-glucose deprivation-induced neurotoxicity by down-regulating neuronal nitric oxide synthase (nNOS) activity in vitro.

Near infrared radiation (NIR) has been shown to be neuroprotective against neurological diseases including stroke and brain trauma, but the underlying mechanisms remain poorly understood. In the current study we aimed to investigate the hypothesis that NIR may protect neurons by attenuating oxygen-glucose deprivation (OGD)-induced nitric oxide (NO) production and modulating cell survival/death signaling. Primary mouse cortical neurons were subjected to 4 h OGD and NIR was applied at 2 h reoxygenation. OGD significantly increased NO level in primary neurons compared to normal control, which was significantly ameliorated by NIR at 5 and 30 min post-NIR. Neither OGD nor NIR significantly changed neuronal nitric oxide synthase (nNOS) mRNA or total protein levels compared to control groups. However, OGD significantly increased nNOS activity compared to normal control, and this effect was significantly diminished by NIR. Moreover, NIR significantly ameliorated the neuronal death induced by S-Nitroso-N-acetyl-DL-penicillamine (SNAP), a NO donor. Finally, NIR significantly rescued OGD-induced suppression of p-Akt and Bcl-2 expression, and attenuated OGD-induced upregulation of Bax, BAD and caspase-3 activation. These results suggest NIR may protect against OGD at least partially through reducing NO production by down-regulating nNOS activity, and modulating cell survival/death signaling.

Luminescence and photosensitivity of gadolinium labeled hematoporphyrin monomethyl ether.

Photodynamic therapy for deep-lying lesions needs an appropriate imaging modality, precise evaluation of tissue oxygen and an effective photosensitizer. Gadolinium based metalloporphyrins Gd(III)-HMME is proposed in this study as a potential multifunctional theranostic agent, as photosensitizer, ratiometric oxygen sensor and MRI contrast agent. The time resolved spectroscopy revealed the luminescence peak of Gd(III)-HMME at 710 and 779 nm with a lifetime of 64 µs in oxygen-free methanol to be phosphorescent. This phosphorescence is strongly dependent on dissolved oxygen concentration. Its intensity in oxygen saturated methanol solution is 21% of that in deoxygenated solution. The singlet oxygen quantum yields ΦΔ of HMME and Gd(III)-HMME in air saturated methanol solution were determined to be 0.79 and 0.40 respectively using comparative spectra method. These phenomena indicate that the oxygen sensibility and production of singlet oxygen of Gd(III)-HMME can fulfill the requirement of PDT treatment.

Revisiting the ultra-high dose rate effect: implications for charged particle radiotherapy using protons and light ions.

OBJECTIVE: To reinvestigate ultra-high dose rate radiation (UHDRR) radiobiology and consider potential implications for hadrontherapy. METHODS: A literature search of cellular UHDRR exposures was performed. Standard oxygen diffusion equations were used to estimate the time taken to replace UHDRR-related oxygen depletion. Dose rates from conventional and novel methods of hadrontherapy accelerators were considered, including spot scanning beam delivery, which intensifies dose rate. RESULTS: The literature findings were that, for X-ray and electron dose rates of around 10(9) Gy s(-1), 5-10 Gy depletes cellular oxygen, significantly changing the radiosensitivity of cells already in low oxygen tension (around 3 mmHg or 0.4 kPa). The time taken to reverse the oxygen depletion of such cells is estimated to be over 20-30 s at distances of over 100 µm from a tumour blood vessel. In this time window, tumours have a higher hypoxic fraction (capable of reducing tumour control), so the next application of radiation within the same fraction should be at a time that exceeds these estimates in the case of scanned beams or with ultra-fast laser-generated particles. CONCLUSION: This study has potential implications for particle therapy, including laser-generated particles, where dose rate is greatly increased. Conventional accelerators probably do not achieve the critical UHDRR conditions. However, specific UHDRR oxygen depletion experiments using proton and ion beams are indicated.

[Mechanism of the biological impact of weak electromagnetic fields and in vitro effects of degassing of blood].

The physical validity of the mechanism proposed by the author is discussed. According to the theory a prolonged exposure to weak electromagnetic fields leads to an enlargement of the micro-bubbles and degassing of bioliquid. Degassing alters the physical and chemical properties of bioliquid that affect some medical and biological indicators. The following changes in some blood parameters during degassing in vitro were analyzed: a decrease in the glucose concentration, an abnormal activation of blood clotting, an increase in the rate of blood cell aggregation, a decrease in the effectiveness of aspirin as an inhibitor of platelet aggregation and the slowing of indirect anticoagulants. All of this evidences a possible correlation between the increasing electromagnetic pollution and the risk of cardiovascular disease.

Quantification of hydroxyl radical-derived oxidation products in peptides containing glycine, alanine, valine, and proline.

Proteins are a major target for oxidation due to their abundance and high reactivity. Despite extensive investigation over many years, only limited quantitative data exist on the contributions of different pathways to the oxidation of peptides and proteins. This study was designed to obtain quantitative data on the nature and yields of oxidation products (alcohols, carbonyls, hydroperoxides, fragment species) formed by a prototypic oxidant system (HO(•)/O(2)) on small peptides of limited, but known, amino acid composition. Peptides composed of Gly, Ala, Val, and Pro were examined with particular emphasis on the peptide Val-Gly-Val-Ala-Pro-Gly, a repeat motif in elastin with chemotactic activity and metalloproteinase regulation properties. The data obtained indicate that hydroperoxide formation occurs nonrandomly (Pro > Val > Ala > Gly) with this inversely related to carbonyl yields (both peptide-bound and released). Multiple alcohols are generated at both side-chain and backbone sites. Backbone fragmentation has been characterized at multiple positions, with sites adjacent to Pro residues being of major importance. Summation of the product concentrations provides clear evidence for the occurrence of chain reactions in peptides exposed to HO(•)/O(2), with the overall product yields exceeding that of the initial HO(•) generated.

Photosynthetic response of clusterbean chloroplasts to UV-B radiation: energy imbalance and loss in redox homeostasis between Q(A) and Q(B) of photosystem II.

The effects of ultraviolet-B (UV-B: 280-320 nm) radiation on the photosynthetic pigments, primary photochemical reactions of thylakoids and the rate of carbon assimilation (P(n)) in the cotyledons of clusterbean (Cyamopsis tetragonoloba) seedlings have been examined. The radiation induces an imbalance between the energy absorbed through the photophysical process of photosystem (PS) II and the energy consumed for carbon assimilation. Decline in the primary photochemistry of PS II induced by UV-B in the background of relatively stable P(n), has been implicated in the creation of the energy imbalance(.) The radiation induced damage of PS II hinders the flow of electron from Q(A) to Q(B) resulting in a loss in the redox homeostasis between the Q(A) to Q(B) leading to an accumulation of Q(A)(-). The accumulation of Q(A)(-) generates an excitation pressure that diminishes the PS II-mediated O(2) evolution, maximal photochemical potential (F(v)/F(m)) and PS II quantum yield (Φ(PS II)). While UV-B radiation inactivates the carotenoid-mediated protective mechanisms, the accumulation of flavonoids seems to have a small role in protecting the photosynthetic apparatus from UV-B onslaught. The failure of protective mechanisms makes PS II further vulnerable to the radiation and facilitates the accumulation of malondialdehyde (MDA) indicating the involvement of reactive oxygen species (ROS) metabolism in UV-B-induced damage of photosynthetic apparatus of clusterbean cotyledons.

The effect of added O(2) on the transmittance and radiation resistance of radiation resistant glasses.

One method of hardening optical glasses against radiation-induced darkening has been to add CeO(2) to the batch composition. In the present investigation we prepared a series of lanthanum crown glasses with varying degrees of CeO(2) additions and melted them at 1,400 °C with and without bubbling oxygen gas. We examined the influence of added oxygen on the optical transmissions of these glasses in the spectral range 460 to 760 nm following gamma irradiations ranging from 10 to 250 krad. The results showed that dose-for-dose the radiation-induced optical attenuations of the oxidized glasses were greater than for the glasses without added O(2).

Effective bacterial inactivation using low temperature radio frequency plasma.

Staphylococcus aureus is one of the most common pathogens responsible for hospital-acquired infections. In this study, S. aureus was exposed to 13.56MHz radiofrequency (RF) plasma generated by two different gases namely nitrogen and nitrogen-oxygen mixture and their sterilization efficacies were compared. Nitrogen plasma had a significant effect on sterilization due to generation of ultraviolet (UV) radiation. However, the addition of 2% oxygen showed enhanced effect on the sterilization of bacteria through nitric oxide (NO) emission and various reactive species. The presence of these reactive species was confirmed by optical emission spectroscopy (OES). Scanning electron microscopy (SEM) analysis was carried out to study the morphological changes of bacteria after plasma treatment. From the SEM results, it was observed that the bacterial cells treated by N(2)-O(2) mixture plasma were severely damaged. As a result, a log(10) reduction factor of 6 was achieved using N(2)-O(2) plasma after 5min treatment with 100W RF power.

Iron-doped Pt-TiO2 nanotubes for photo-catalytic water splitting.

In this work we report on the photo-catalytic performance of phase-pure and iron-doped anatase and rutile nanotubes, produced via a sol-gel process using pristine carbon nanotubes as templates. The encapsulated iron residues can be used to in situ dope the TiO(2) nanotubes without phase separation. The anatase and rutile nanotubes were further impregnated with platinum crystals with a uniform dispersion and an average size of approximately 2 nm. The materials showed dramatically improved activities for the photo-catalytic splitting of water compared to commercial TiO(2) with similar surface area (up to two orders of magnitudes), due to their higher illumination area, extended absorption range and reduced electron-hole recombination rate. The homogeneous dispersion of platinum nanoparticles further increased the hydrogen evolution rate for anatase nanotubes by a factor of seven in comparison to that for the pristine material, thus proving the great potential for commercial applications.

Oxygen dependence of two-photon activation of zinc and copper phthalocyanine tetrasulfonate in Jurkat cells.

Photodynamic therapy (PDT), the use of light-activated drugs, is a promising treatment of cancer as well as several nonmalignant conditions. However, the efficacy of one-photon (1-gamma) PDT is limited by hypoxia, which can prevent the production of the cytotoxic singlet oxygen ((1)O(2)) species, leading to tumor resistance to PDT. To solve this problem, we propose an irradiation protocol based on a simultaneous, two-photon (2-gamma) excitation of the photosensitizer (Ps). Excitation of the Ps triplet state leads to an upper excited triplet state T(n) with distinct photochemical properties, which could inflict biologic damage independent of the presence of molecular oxygen. To determine the potential of a 2-gamma excitation process, Jurkat cells were incubated with zinc or copper phthalocyanine tetrasulfonate (ZnPcS(4) or CuPcS(4)). ZnPcS(4) is a potent (1)O(2) generator in 1-gamma PDT, while CuPcS(4) is inactive under these conditions. Jurkat cells incubated with either ZnPcS(4) or CuPcS(4) were exposed to a 670 nm continuous laser (1-gamma PDT), 532 nm pulsed-laser light (2-gamma PDT), or a combination of 532 and 670 nm (2-gamma PDT). The efficacy of ZnPcS(4) to photoinactivate the Jurkat cells decreased as the concentration of oxygen decreased for both the 1-gamma and 2-gamma protocols. In the case of CuPcS(4), cell phototoxicity was measured only following 2-gamma irradiation, and its efficacy also decreased at a lower oxygen concentration. Our results suggest that for CuPcS(4) the T(n) excited state can be populated after 2-gamma irradiation at 532 nm or the combination of 532 and 670 nm light. Dependency of phototoxicity upon aerobic conditions for both 1-gamma and 2-gamma PDT suggests that reactive oxygen species play an important role in 1-gamma and 2-gamma PDT.

A ground-based radio frequency inductively coupled plasma apparatus for atomic oxygen simulation in low Earth orbit.

A radio frequency (rf) inductively coupled plasma apparatus has been developed to simulate the atomic oxygen environment encountered in low Earth orbit (LEO). Basing on the novel design, the apparatus can achieve stable, long lasting operation, pure and high density oxygen plasma beam. Furthermore, the effective atomic oxygen flux can be regulated. The equivalent effective atomic oxygen flux may reach (2.289-2.984) x 10(16) at.cm(2) s at an oxygen pressure of 1.5 Pa and rf power of 400 W. The equivalent atomic oxygen flux is about 100 times than that in the LEO environment. The mass loss measured from the polyimide sample changes linearly with the exposure time, while the density of the eroded holes becomes smaller. The erosion mechanism of the polymeric materials by atomic oxygen is complex and involves initial reactions at the gas-surface interface as well as steady-state material removal.

Kerma coefficients for neutron scattering on 12C and 16O at 96 MeV.

Recently, many new applications of fast neutrons are emerging or under development, like dose effects due to cosmic ray neutrons for airplane crew, fast neutron cancer therapy, studies of electronics failure induced by cosmic ray neutrons and accelerator-driven incineration of nuclear waste and energy production technologies. In radiation treatment, the kerma (Kinetic energy release in matter) coefficient, which describes the average energy transferred from neutrons to charged particles, is widely used. The kerma coefficient can be calculated from microscopic nuclear data. Nuclear data above 20 MeV are rather scarce, and more complete nuclear data libraries are needed in order to improve the understanding of the processes occurring on a cellular level. About half the dose in human tissue due to fast neutrons comes from proton recoils in neutron-proton (np) scattering, 10-15% from nuclear recoils due to elastic and inelastic neutron scattering and the remaining 35-40% from neutron-induced emission of light ions. Experimental data on elastic and inelastic neutron scattering at 96 MeV from (12)C and (16)O have been obtained recently at The Svedberg Laboratory in Uppsala, Sweden. These data are shown to be relevant for the determination of nuclear recoil kerma coefficients from elastic and inelastic neutron scattering at intermediate energies.

Light charged-particle production in 96 MeV neutron-induced reactions on carbon and oxygen.

In recent years, an increasing number of applications involving fast neutrons have been developed or are under consideration, e.g. radiation treatment of cancer, neutron dosimetry at commercial aircraft altitudes, soft-error effects in computer memories, accelerator-driven transmutation of nuclear waste and energy production and determination of the response of neutron detectors. Data on light-ion production in light nuclei such as carbon, nitrogen and oxygen are particularly important in calculations of dose distributions in human tissue for radiation therapy at neutron beams, and for dosimetry of high-energy neutrons produced by high-energy cosmic radiation interacting with nuclei (nitrogen and oxygen) in the atmosphere. When studying neutron dose effects, it is especially important to consider carbon and oxygen, since they are, by weight, the most abundant elements in human tissue. Preliminary experimental double-differential cross sections of inclusive light-ion (p, d, t, (3)He and alpha) production in carbon induced by 96-MeV neutrons have been presented. Energy spectra were measured at eight laboratory angles: 20, 40, 60, 80, 100, 120, 140 and 160 degrees. Measurements were performed at The Svedberg Laboratory (TSL), Uppsala, using the dedicated MEDLEY experimental setup. The authors have earlier reported experimental double-differential cross sections of inclusive light-ion production in oxygen. In this paper, the deduced kerma coefficients for oxygen has been presented and compared with reaction model calculations.