Mechanism Of Radical Generation Research Articles

A light-driven enzymatic enantioselective radical acylation.

Enzymes are recognized as exceptional catalysts for achieving high stereoselectivities1-3, but their ability to control the reactivity and stereoinduction of free radicals lags behind that of chemical catalysts4. Thiamine diphosphate (ThDP)-dependent enzymes5 are well-characterized systems that inspired the development of N-heterocyclic carbenes (NHCs)6-8 but have not yet been proved viable in asymmetric radical transformations. There is a lack of a biocompatible and general radical-generation mechanism, as nature prefers to avoid radicals that may be harmful to biological systems9. Here we repurpose a ThDP-dependent lyase as a stereoselective radical acyl transferase (RAT) through protein engineering and combination with organophotoredox catalysis10. Enzyme-bound ThDP-derived ketyl radicals are selectively generated through single-electron oxidation by a photoexcited organic dye and then cross-coupled with prochiral alkyl radicals with high enantioselectivity. Diverse chiral ketones are prepared from aldehydes and redox-active esters (35 examples, up to 97% enantiomeric excess (e.e.)) by this method. Mechanistic studies reveal that this previously elusive dual-enzyme catalysis/photocatalysis directs radicals with the unique ThDP cofactor and evolvable active site. This work not only expands the repertoire of biocatalysis but also provides a unique strategy for controlling radicals with enzymes, complementing existing chemical tools.

Mechanisms of Radical Formation on Chemically Modified Graphene Oxide under Near Infrared Irradiation.

In this work, the mechanisms of radical generation on different functionalized graphene oxide (GO) conjugates under near-infrared (NIR) light irradiation are investigated. The GO conjugates are designed to understand how chemical functionalization can influence the generation of radicals. Both pristine and functionalized GO are irradiated by a NIR laser, and the production of different reactive oxygen species (ROS) is investigated using fluorimetry and electron paramagnetic resonance to describe the type of radicals present on the surface of GO. The mechanism of ROS formation involves a charge transfer from the material to the oxygen present in the media, via the production of superoxide and singlet oxygen. Cytotoxicity and effects of ROS generation are then evaluated using breast cancer cells, evidencing a concentration dependent cell death associated to the heat and ROS. The study provides new hints to understand the photogeneration of radicals on the surface of GO upon near infrared irradiation, as well as, to assess the impact on these radicals in the context of a combined drug delivery system and phototherapeutic approach. These discoveries open the way for a better control of phototherapy-based treatments employing graphene-based materials.

Enhanced hydroxyl radical generation by human leukocytes exposed to bacterial diamines highlighting immunomodulatory effect of microbial metabolites

Recently, there have been increasing an interest to study a role of polyamines in intercellular interactions, especially in the focus of inflammation, where accumulation of such polycations is observed. In this regard, products of microbial origin cadaverine and putrescine are of particular attention. The role of polyamines as scavengers of free radicals has been described, but no data of their effect on the leukocyte radical-producing activity have been obtained so far. The aim of the investigation was to study features of hydroxyl radical generation by human leukocytes exposed to microbe-derived polyamines. Materials and methods. Peripheral venous blood samples were obtained from 20 healthy donors. To assess radical production, a luminol-dependent chemiluminescence reaction was carried out with blood leukocytes pre-incubated with cadaverine (0.01 M) and putrescine (0.01 M), measured on a Luminoskan Ascent Thermo Labsystems luminometer (USA) for 180 min. For statistical analysis, an integral chemiluminescence index was used for the entire measurement period (RLU). Results and discussion. It was shown that cadaverine has a stimulating effect on the leukocyte potential to produce radicals (averaged area under the curve is 6.70.7 r.u., p 0.05). Putrescine had little effect on the radical-producing activity of human cells (2.80.4 r.u., p 0.05). This might be due to the direct influence of polycations on the mechanisms of radical generation, as well as increased activity of leukocyte diamine oxidase catalyzing the conversion of diamines into aminoaldehyde, which is accompanied by the release of hydrogen peroxide reacting with luminol. In addition, the enzyme inactivates other compounds, such as histamine leading to formation of a less pronounced clinical picture. Polyamines, particularly cadaverine and putrescine, can be referred to the factors remodeling the metabolic activity of the host leukocytes, which is aimed at maintaining the viability and increasing the number of microorganisms. Conclusion. Thus, cadaverine and putrescine produced by microorganisms, depending on the conditions of the microenvironment, might be evidently considered as mediators of the mild or asymptomatic course of inflammatory diseases, which contributes to underlying persistent potential of bacteria.

Enhanced 4-chlorophenol Degradation under Visible and Solar Radiation through TiO2/g-C3N4 Z-Scheme Heterojunction

The efficient remediation of the persistent organic pollutant known as 4-chlorophenol (4CP) in aqueous effluent presents a challenge for a wide array of industries due to its elevated toxicity and resistance to natural degradation processes. This study proposes the development of a hybrid photocatalyst composed of titanium dioxide (TiO2) and graphitic carbon nitride (g-C3N4), aiming to increase the efficiency of photocatalytic degradation of 4CP under solar and visible radiation through the formation of Z-scheme heterojunction between the semiconductors. The results showed that the synthesis of the TiO2/g-C3N4 binary material was successful by X-ray diffractometry and infrared spectrometry. Furthermore, the addition of g-C3N4 to TiO2 led to optical and morphological modifications, such as the pore volume increase and gap energy of TiO2/g-C3N4. Concerning the photocatalytic evaluation, the main results indicate that photocatalytic activity under visible radiation of the TiO2/g-C3N4 improved by 44.8% compared to pure TiO2, whereas an improvement of 30.5% was obtained under simulated solar radiation. This improvement in efficiency was further corroborated by chronoamperometry tests, which demonstrated a higher photocurrent generation for the TiO2/g-C3N4. The radical generation mechanism suggested the creation of an effective Z-scheme heterojunction between the semiconductors, as the formation of both hydroxyl and superoxide radicals was observed.

Broken-Symmetry Density Functional Theory Analysis of the Ω Intermediate in Radical S-Adenosyl-l-methionine Enzymes: Evidence for a Near-Attack Conformer over an Organometallic Species.

Radical S-adenosyl-l-methionine (SAM) enzymes are found in all domains of life and catalyze a wide range of biochemical reactions. Recently, an organometallic intermediate, Ω, has been experimentally implicated in the 5'-deoxyadenosyl radical generation mechanism of the radical SAM superfamily. In this work, we employ broken-symmetry density functional theory to evaluate several structural models of Ω. The results show that the calculated hyperfine coupling constants (HFCCs) for the proposed organometallic structure of Ω are inconsistent with the experiment. In contrast, a near-attack conformer of SAM bound to the catalytic [4Fe-4S] cluster, in which the distance between the unique iron and SAM sulfur is ∼3 Å, yields HFCCs that are all within 1 MHz of the experimental values. These results clarify the structure of the ubiquitous Ω intermediate and suggest a paradigm shift reversal regarding the mechanism of SAM cleavage by members of the radical SAM superfamily.

Degradation of Oxytetracycline by Persulfate Activation Using a Magnetic Separable Iron Oxide Catalyst Derived from Hand-Warmer Waste

Oxytetracycline (OTC) is a tetracycline antibiotic that is widely used in the drug therapy and livestock industry and may threaten human health and ecosystems when released into the environment. In this study, a catalyst was prepared from hand-warmer waste using a simple magnetic separation method. The prepared hand-warmer waste catalyst (HWWC) was used as a persulfate (PS) activator for OTC removal. Characterization methods, such as X-ray diffraction and scanning electron microscopy–energy dispersive X-ray spectrometry, were used to investigate the crystal structure, surface morphology, and weight ratios of the elements in the HWWC. The degradation efficiency of OTC in the presence of the catalyst and PS was studied, and the radical generation mechanism of the catalyst was investigated. The removal ratio of OTC by PS activation was greater than 99% for a reaction time of 24 min at a pH of 6. The effects of the HWWC dosage, PS concentration, and solution pH on OTC degradation were also investigated. The reuse test revealed that HWWC can be reused for eight cycles with great stability. These results suggest that PS activation using hand-warmer waste can be an efficient strategy for the degradation of antibiotics.

Oxidative Stress and Low-Grade Inflammation in Polycystic Ovary Syndrome: Controversies and New Insights.

The pathophysiology of Polycystic Ovary Syndrome (PCOS) is quite complex and different mechanisms could contribute to hyperandrogenism and anovulation, which are the main features of the syndrome. Obesity and insulin-resistance are claimed as the principal factors contributing to the clinical presentation; in normal weight PCOS either, increased visceral adipose tissue has been described. However, their role is still debated, as debated are the biochemical markers linked to obesity per se. Oxidative stress (OS) and low-grade inflammation (LGI) have recently been a matter of researcher attention; they can influence each other in a reciprocal vicious cycle. In this review, we summarize the main mechanism of radical generation and the link with LGI. Furthermore, we discuss papers in favor or against the role of obesity as the first pathogenetic factor, and show how OS itself, on the contrary, can induce obesity and insulin resistance; in particular, the role of GH-IGF-1 axis is highlighted. Finally, the possible consequences on vitamin D synthesis and activation on the immune system are briefly discussed. This review intends to underline the key role of oxidative stress and low-grade inflammation in the physiopathology of PCOS, they can cause or worsen obesity, insulin-resistance, vitamin D deficiency, and immune dyscrasia, suggesting an inverse interaction to what is usually considered.

Addition of Heteroatom Radicals to endo-Glycals †

Radical reactions have found many applications in carbohydrate chemistry, especially in the construction of carbon–carbon bonds. The formation of carbon–heteroatom bonds has been less intensively studied. This mini-review will summarize the efforts to add heteroatom radicals to unsaturated carbohydrates like endo-glycals. Starting from early examples, developed more than 50 years ago, the importance of such reactions for carbohydrate chemistry and recent applications will be discussed. After a short introduction, the mini-review is divided in sub-chapters according to the heteroatoms halogen, nitrogen, phosphorus, and sulfur. The mechanisms of radical generation by chemical or photochemical processes and the subsequent reactions of the radicals at the 1-position will be discussed. This mini-review cannot cover all aspects of heteroatom-centered radicals in carbohydrate chemistry, but should provide an overview of the various strategies and future perspectives.

Global ab initio exploration of potential energy surfaces for radical generation in the initial stage of benzene oxidation.

The potential energy surfaces (PESs) of benzene oxidation by molecular oxygen were explored using the anharmonic downward distortion following (ADDF) and artificial force induced reaction (AFIR) methods of the global reaction route mapping (GRRM) strategy. The reaction mechanism of benzene activation by initial molecular oxygen depends on the combustion temperature. At high temperature, the benzene molecule could be oxidized by abstracting hydrogen atoms and form the radical fragments, C6H5 and OOH. However, before reaching its auto-ignition point, the formation of a singlet bridging peroxide molecule C6H6O2 from the triplet reactants via electronic non-adiabatic transition will play a critical role in the increase of the combustion temperature by the generation of initial free radicals. Bridging peroxide C6H6O2 could isomerize to other stable isomers by a consecutive series of oxygen and hydrogen atom transfers. Importantly, these C6H6O2 isomers are vital sources of free radical generation in the initial stage of benzene oxidation. Free radicals, such as OOH, O, and OH, could be generated during the further oxidation of these oxygenated hydrocarbon species C6H6O2 due to the presence of active groups or sp3-C–H bonds.

62 - Generation of superoxide radical by human cytochrome b5 reductase is modulated by cytochrome b5

Cytochrome b5 reductase (CYB5R) plays a central role in many diverse metabolic reactions by coupling NAD(P)H oxidation to reduction of proteins, such as cytochrome b5 (CYB5). Together, CYB5R and CYB5 transfer electrons to terminal oxidases, such as the mitochondrial amidoxime reducing component (mARC) or hemoglobin. Previous studies have demonstrated that nitric oxide (NO) production by the mARC/CYB5/CYB5R system is quenched by molecular oxygen (O2) and suggested that superoxide radical production was involved, as the addition of Cu,Zn-superoxide(SOD1) dismutase partially recovered NO production. Flavin proteins are known to generate superoxide, suggesting that the CYB5R was the likely site of superoxide radical production. However, the direct formation of superoxide by human CYB5R had not been studied. Here, studies were performed to understand the related mechanisms of radical generation by CYB5R in the absence and presence of CYB5. Electron paramagnetic resonance (EPR) spin trapping studies using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) were performed with CYB5R and NADH. An EPR spectrum corresponding to the superoxide radical adduct of DMPO (DMPO-OOH) was obtained. This EPR signal was quenched by the addition of the SOD1. The amount of DMPO-OOH formed from the oxidation of NADH by the CYB5R increased with NADH concentration. Importantly, the formation of DMPO-OOH was abrogated in the presence of CYB5. Spectral kinetics demonstrate that NADH consumption is O2-dependent, as no NADH consumption was observed in the absence of O2. From these results, we propose a mechanism in which NADH-reduced CYB5R catalyzes superoxide radical formation. Our results demonstrate that human CYB5R catalyzes the O2-dependent oxidation of NADH to generate superoxide radical. Additionally, CYB5 may protect biological targets from oxidative damage, by inhibiting CYB5R superoxide radical production. The ability of CYB5R to catalyze superoxide radical production in response to O2 has potential pathophysiological implications for the ischemia/reperfusion induced damages, endothelial dysfunction, and cardiovascular and neurological diseases.

Near-Infrared Light-Initiated Molecular Superoxide Radical Generator: Rejuvenating Photodynamic Therapy against Hypoxic Tumors.

Hypoxia, a quite universal feature in most solid tumors, has been considered as the "Achilles' heel" of traditional photodynamic therapy (PDT) and substantially impairs the overall therapeutic efficacy. Herein, we develop a near-infrared (NIR) light-triggered molecular superoxide radical (O2-•) generator (ENBS-B) to surmount this intractable issue, also reveal its detailed O2-• action mechanism underlying the antihypoxia effects, and confirm its application for in vivo targeted hypoxic solid tumor ablation. Photomediated radical generation mechanism study shows that, even under severe hypoxic environment (2% O2), ENBS-B can generate considerable O2-• through type I photoreactions, and partial O2-• is transformed to high toxic OH· through SOD-mediated cascade reactions. These radicals synergistically damage the intracellular lysosomes, which subsequently trigger cancer cell apoptosis, presenting a robust hypoxic PDT potency. In vitro coculture model shows that, benefiting from biotin ligand, ENBS-B achieves 87-fold higher cellular uptake in cancer cells than normal cells, offering opportunities for personalized medicine. Following intravenous administration, ENBS-B is able to specifically target to neoplastic tissues and completely suppresses the tumor growth at a low light-dose irradiation. As such, we postulated this work will extend the options of excellent agents for clinical cancer therapy.

Enhanced adsorption and catalytic oxidation of ciprofloxacin on hierarchical CuS hollow nanospheres@N-doped cellulose nanocrystals hybrid composites: Kinetic and radical generation mechanism studies

In this study, a new hybrid catalyst/adsorbent, CuS hollow nanospheres@N-doped CNCs hybrid composites, was synthesized and demonstrated to be highly efficient for enhanced adsorptive removal and catalytic oxidation of ciprofloxacin (CIP) in the presence of PMS (peroxymonosulfate) as an oxidant in aqueous solution. A comprehensive characterization was performed to identify as-prepared materials. The efficiency of the new nanocomposites was compared to untreated CNCs and N-doped CNCs at the same conditions that the fabricated nanocomposites removed CIP with higher efficiency. Kinetic studies showed that CIP degradation follows first order reaction kinetics and it was remarkably faster when using CuS hollow nanospheres@N-doped CNCs hybrid composites as a catalyst (>68 times using only PMS). PMS activation mechanism and CIP oxidation was clarified by utilizing electron paramagnetic resonance (EPR) studies. The results showed that both of OH and SO4− radicals were generated and played crucial roles in CIP degradation. Regarding the adsorption process, the efficiency of the process was in agreement with specific surface area (SSA) order indicating domination of SSA on the adsorption process.

Chloramphenicol removal by zero valent iron activated peroxymonosulfate system: Kinetics and mechanism of radical generation

Zero valent iron (Fe0) was used as a catalyst to activate peroxymonosulfate (PMS) for removal of chloramphenicol (CAP). About 95.2% of 10 mg/L CAP was removed by 0.2 mM peroxymonosulfate and 0.5 g/L Fe0 at neutral pH, with little Fe3+ leaching. The degradation reactions well followed a pseudo-first-order kinetics pattern (R2 > 0.95). The production of hydroxyl radicals (OH) and sulfate radicals (SO4−) was directly identified in in-situ Electron paramagnetic resonance (EPR) tests with 0.1 M 5,5-dimethyl-1-pyrrolidine N-oxide (DMPO) and indirectly identified through quenching tests. The second order rate constant between CAP and SO4− was ascertained to be 6.18 × 1010 M−1 s−1 in competition reaction. According to SEM and XRD analysis, the average diameter of catalyst was elevated to be about 88 nm after use. Possible mechanisms on the radical generation were proposed based on the results of EPR and XPS analyses. It emerged that the cycle of Fe2+-Fe3+ on the Fe0 was answerable for the OH and SO4− generation, and iron sulfate layer was assembled on the Fe0 following exposure to peroxymonosulfate compared to the FeOOH layer present on the fresh Fe0. While the presence of common anions including Cl−, CO32−, Fe2+, Cu2+ and Mn2+ will inhibit the degradation of CAP in Fe0/PMS system. Besides, Fe0/PMS pre-oxidation before chlorine or chloramine engendered in a sharp increment in the concentration of disinfection by-products (DBPs) precursors. The results manifested that Fe0/PMS was effective in CAP removal at neutral pH, whereas it should be more cautiously investigated when combined with chlorine disinfection.

A Fe(II)/citrate/UV/PMS process for carbamazepine degradation at a very low Fe(II)/PMS ratio and neutral pH: The mechanisms

A novel Fe(II)/citrate/UV/PMS process for degrading a model micropollutant, carbamazepine (CBZ), at a low Fe(II)/PMS ratio and neutral pH has been proposed in this study, and the mechanisms of radical generation in the system was explored. With a UV dose of 302.4 mJ/cm2, an initial pH of 7, and CBZ, PMS, Fe(II) and citrate at initial concentrations of 10, 100, 12 and 26 μM, respectively, the CBZ degradation efficiency reached 71% in 20 min in the Fe(II)/citrate/UV/PMS process, which was 4.7 times higher than that in either the citrate/UV/PMS or Fe(II)/citrate/PMS process. The enhanced CBZ degradation in the Fe(II)/citrate/UV/PMS process was mainly attributed to the continuous activation of PMS by the UV-catalyzed regenerated Fe(II) from a Fe(III)-citrate complex, [Fe3O(cit)3H3]2-, which not only maintained Fe(III) soluble at neutral pH, but also increased 6.6 and 2.6 times of its molar absorbance and quantum yield as compared to those of ionic Fe(III), respectively. In the Fe(II)/citrate/UV/PMS process, the SO4•– produced from the fast reaction between PMS and the initially-added Fe(II) contributed 11% of CBZ degradation. The PMS activation by the UV radiation and regenerated Fe(II) contributed additional 14% and 46% of CBZ removal, respectively. The low iron and citrate doses and the fast radical generation at neutral pH make the Fe(II)/citrate/UV/PMS process suitable for degrading recalcitrant organic compounds in potable water.

Mechanisms on the Impacts of Alkalinity, pH, and Chloride on Persulfate-Based Groundwater Remediation.

Persulfate (S2O82-)-based in situ chemical oxidation (ISCO) has gained more attention in recent years due to the generation of highly reactive and selective sulfate radical (SO4•-). This study examined the effects of important groundwater chemical parameters, i.e., alkalinity, pH, and chloride on benzene degradation via heterogeneous persulfate activation by three Fe(III)- and Mn(IV)-containing aquifer minerals: ferrihydrite, goethite, and pyrolusite. A comprehensive kinetic model was established to elucidate the mechanisms of radical generation and mineral surface complexation. Results showed that an increase of alkalinity up to 10 meq/L decreased the rates of persulfate decomposition and benzene degradation, which was associated with the formation of unreactive surface carbonato complexes. An increase in pH generally accelerated persulfate decomposition due to enhanced formation of reactive surface hydroxo complexation. A change in the chloride level up to 5 mM had a negligibly effect on the reaction kinetics. Kinetics modeling also suggested that SO4•- was transformed to hydroxyl radical (HO•) and carbonate radical (CO3•-) at higher pHs. Furthermore, the yields of two major products of benzene oxidation, i.e., phenol and aldehyde, were positively correlated with the branching ratio of SO4•- reacting with benzene, but inversely correlated with that of HO• or CO3•-, indicating that SO4•- preferentially oxidized benzene via pathways involving fewer hydroxylation steps compared to HO• or CO3•-.

Potential Contribution of Antioxidant Mechanism in the Defensive Effect of Lycopene Against Partial Sciatic Nerve Ligation Induced Behavioral, Biochemical and Histopathological Modification in Wistar Rats.

Neuropathic pain is a severe and unbearable condition which arises due to activation of peripheral nociceptors after tissue damage, neuropathic pain is caused from anomalous physiology of central or peripheral nervous system and it may not be related to the ongoing tissue damage or inflammation. Involvement of oxidative damage has been reported in the pathophysiology of neuropathic pain. The purpose of this study was to examine the effect of lycopene to quench the free radicals produced as a result of the increased oxidative stress in neuropathic pain. Neuropathic pain was induced in wistar rats by partial sciatic nerve ligation. The effect was evaluated by assessing various behavioral parameters (thermal hyperalgesia, cold hyperalgesia), biochemical parameters (lipid peroxidation, reduced glutathione, superoxide dismutase and catalase) as well as histopathological parameters in sciatic nerve. During the experiment group of 8 rats each was administered drugs once daily intraperitonealy (I.P.) and naïve groups, sham group and sciatic nerve ligated group were treated with vehicle for the duration of 14 days. Partial sciatic nerve ligation (PSNL) significantly caused thermal hyperalgesia, cold hyperalgesia and oxidative damage compared to normal and sham groups. Daily administration of lycopene (25 mg/kg, 50 mg/kg) and gabapentin (100 mg/kg) considerably reversed hyperalgesia, cold hyperalgesia and attenuated oxidative stress when compared to control group. There was significant histological improvement in the in the architecture of myelinated and unmyelinated fibers. The results indicated that free radical generation mechanism might be involved in PSNL induced behavior, biochemical and histopathological changes in wistar rats.

Advanced Oxidation Processes (AOPs) in Wastewater Treatment

Advanced oxidation processes (AOPs) were first proposed in the 1980s for drinking water treatment and later were widely studied for treatment of different wastewaters. During the AOP treatment of wastewater, hydroxyl radicals (OH·) or sulfate radicals (SO4 ·−) are generated in sufficient quantity to remove refractory organic matters, traceable organic contaminants, or certain inorganic pollutants, or to increase wastewater biodegradability as a pre-treatment prior to an ensuing biological treatment. In this paper, we review the fundamental mechanisms of radical generation in different AOPs and select landfill leachate and biologically treated municipal wastewater as model wastewaters to discuss wastewater treatment with different AOPs. Generally, the treatment efficiencies rely heavily upon the selected AOP type, physical and chemical properties of target pollutants, and operating conditions. It would be noted that other mechanisms, besides hydroxyl radical or sulfate radical-based oxidation, may occur during the AOP treatment and contribute to the reduction of target pollutants. Particularly, we summarize recent advances in the AOP treatment of landfill leachate, as well as advanced oxidation of effluent organic matters (EfOM) in biologically treated secondary effluent (BTSE) for water reuse.

Abstract 3337: Titanium peroxide nanoparticles enhance antitumor efficacy through reactive oxygen species in pancreatic cancer radiation therapy

Abstract Purpose: Pancreatic cancer is a highly lethal disease and notoriously resistant to many types of cytotoxic chemotherapy and radiotherapy. A novel strategy should be explored for these radioresistant tumors. We originally synthesized a titanium peroxide nanoparticle (TiOxNP) which had a distinct ability to produce reactive oxygen species (ROS) upon X-ray irradiation (IR). Here, the characterization and efficacy of TiOxNP as radiosensitizer for pancreatic cancer therapy were investigated. Methods: TiOxNPs were synthesized from anatase titanium oxide nanoparticles (TiO2NPs) by H2O2 processing and coated by polyacrylic acid. The ability of TiOxNPs to enhance ROS generation upon X-ray irradiation (IR) was tested by using 3′-(p-Aminophenyl) fluorescein and several antioxidants. A xenograft mouse model using the human pancreatic cancer cell line MIAPaCa-2 was used to evaluate the cytotoxic effects of a combination of TiOxNPs and IR in vivo. MIAPaCa-2 cells were injected subcutaneously into the hind legs of immunodeficient BALB/c mice. Seven days after injection, the tumor was treated with a TiOxNP suspension injected directly into the tumor and application of 5 Gy of IR. Tumor size and health of the mice were monitored for 43 days after the treatment. Induction of apoptosis was evaluated by immunohistochemistry using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining. We also characterized TiOxNPs by ESR and XAFS analyses. Results: ROS generation was enhanced dramatically by TiOxNPs in a concentration- and radiation dose- dependent manner compared to enhancement by TiO2NPs. At the highest concentration of TiOxNPs, ROS generation upon an irradiation dose of 30 Gy was enhanced by a factor of more than 10. Also, ROS generated by TiOxNPs upon IR were scavenged by vitamin C or glutathione. Growth inhibition of the tumor in the group receiving both TiOxNP and IR was significantly greater than single treatment subgroups (P < 0.05). The number of apoptotic cells was also significantly higher in the combination group (P < 0.05). Histologically, large pools of TiOxNPs around tumor cells and small amounts inside the tumor cells were observed. No mice died within a 43-day observation period or showed any apparent body weight loss. In the ESR spectra, some signals were observed for TiOxNPs. The spectral shapes of Ti K-edge X-ray absorption near edge structure, spectra were the same among the mineral anatase, TiO2NPs and TiOxNPs. Conclusions: TiOxNPs induced remarkable ROS production upon IR. They were safe and effective in a xenograft mouse model using engrafted human pancreatic cancer cells. Further studies would be necessary to elucidate a mechanism of radical generation and long-term toxicity, however our study shows that TiOxNPs are promising radiosensitizers for application in pancreatic cancer therapy. Citation Format: Masao Nakayama, Ryohei Sasaki, Toru Mukohara, Chiaki Ogino, Kenta Morita, Mitsuo Umetsu, Satoshi Ohara, Kazuyoshi Sato, Chiya Numako, Seiichi Takami, Akihiko Kondo. Titanium peroxide nanoparticles enhance antitumor efficacy through reactive oxygen species in pancreatic cancer radiation therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3337. doi:10.1158/1538-7445.AM2015-3337

A new magnetic nano zero-valent iron encapsulated in carbon spheres for oxidative degradation of phenol

In this study, magnetic carbon encapsulated nano iron hybrids (nano Fe0/Fe3C@CS) were synthesized via a novel one-pot hydrothermal method followed by self-reduction in N2 atmosphere. The structural, morphological, and physicochemical properties of the samples were thoroughly investigated by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), N2 sorption isotherms and thermogravimetric analysis–differential scanning calorimetry (TGA–DSC). Catalytic performance of the as-synthesized nanoparticles was tested in activation of oxone® for phenol degradation in aqueous solutions. Superior catalytic performance was observed by complete removal of 20ppm phenol within 10min. The formation of Fe3C was found to contribute to a better stability and magnetic separation of Fe0/Fe3C@CS in its repeated uses. Both electron paramagnetic resonance (EPR) and classic quenching tests were carried out to investigate the mechanism of radical generation and evolution in phenol oxidation. Different from Co- and Mn-based catalysts in generation of sulfate radicals, Fe0/Fe3C@CS selectively induced hydroxyl radicals for phenol degradation.

Thioxanthone Hydroquinone-O,O′-diacetic Acid: Photoinitiator or Photostabilizer?

A photoinitiator for free-radical polymerization based on a thioxanthone chromophore containing two acetic acid functions was synthesized and characterized. Photophysical studies such as fluorescence, phosphorescence, and laser flash photolysis in addition to photopolymerization of acrylates were performed to elucidate the radical generation mechanism involving intramolecular electron transfer from the triplet state followed by decarboxylation. We found that the position of the acetic acid substituent is critical for the photoreactivity. In most solvents and acrylic monomers, if the acetic acid functionality is at the 1-position, the singlet excited states are deactivated rapidly before electron transfer can occur, resulting in negligible photoreactivity. The excited-state deactivation probably involves intramolecular H-bonding deactivation. The intramolecular H-bonding is disrupted by solvents that support intermolecular H-bonding, such as DMF and DMSO, leading to efficient intramolecular photoreaction.