A monometallic tri-spin single-molecule magnet based on rare earth radicals

A mononuclear tri-spin single-molecule magnet based on the rare earth radical [Tb(hfac)(3)(NITPhOEt)(2)] (NITPhOEt = 4'-ethoxy-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) has been synthesized, structurally characterized and the alternating current signals show a slow relaxation of magnetization and frequency-dependent signals.

Magnetic Tuning of All-Organic Binary Alloys between Two Stable Radicals

Mixtures of 2-(4,5,6,7-tetrafluorobenzimidazol-2-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (F4BImNN) and 2-(benzi-midazol-2-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (BImNN.) crystallize as solid solutions (alloys) across a wide range of binary compositions. (F4BImNN)(x)(BImNN)((1-x)) with x < 0.8 gives orthorhombic unit cells, while x >= 0.9 gives monoclinic unit cells. In all crystalline samples, the dominant intermolecular packing is controlled by one-dimensional (1D) hydrogen-bonded chains that lead to quasi-1D ferromagnetic behavior. Magnetic analysis over 0.4-300 K indicates ordering with strong 1D ferromagnetic exchange along the chains (J/k = 12-22 K). Interchain exchange is estimated to be 33- to 150-fold weaker, based on antiferromagnetic ordered phase formation below Neel temperatures in the 0.4-1.2 K range for the various compositions. The ordering temperatures of the orthorhombic samples increase linearly as (1 - x) increases from 0.25 to 1.00. The variation is attributed to increased interchain distance corresponding to decreased interchain exchange, when more F4BImNN is added into the orthorhombic lattice. The monoclinic samples are not part of the same trend, due to the different interchain arrangement associated with the phase change.

The impact of carboxy nitroxide antioxidants on irradiated ataxia telangiectasia cells

Three water-soluble carboxy nitroxide antioxidants, 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl, 4-carboxy-2,2,6,6-tetramethylpiperidin-1-yloxyl, and 3-carboxy-2,2,5,5-tetramethylpyrrolidin-1-yloxyl, show significant impact on the postirradiation survival rates of ataxia telangiectasia (A-T) cells compared to normal cells, an assay which represents a model for understanding the impact of ROS damage on the A-T phenotype. The effects of these antioxidants are much more significant than those of vitamin E or Trolox (a water-soluble vitamin E analog), studied using the same cell survival model. (C) 2004 Elsevier Inc. All rights reserved.

The synthesis of novel isoindoline nitroxides bearing water-solubilising functionality

A range of novel tetramethyl- and tetraethylisoindolinenitroxides, possessing aryl-linked carboxylic acids, amines, alcohols and phosphonic acids were prepared. Notably, the chemistry established for the aromatic dibromination of the tetramethylisoindolines was not easily transferred to the corresponding tetraethylisoindoline system. Instead, various tetraethylisoindoline analogues were accessed by the oxidation of methyl groups attached to the aromatic ring to give the carboxylic acids. The increased steric bulk of the tetraethyl structures should limit bio-reduction and these compounds may have potential as antioxidants.

Studies of the radiation chemistry and grafting of a fluoropolymer

The radiation chemistry and the grafting of a fluoropolymer, poly(tetrafluoroethylene-coperfluoropropyl vinyl ether) (PFA), was investigated with the aim of developing a highly stable grafted support for use in solid phase organic chemistry (SPOC). A radiation-induced grafting method was used whereby the PFA was exposed to ionizing radiation to form free radicals capable of initiating graft copolymerization of styrene. To fully investigate this process, both the radiation chemistry of PFA and the grafting of styrene to PFA were examined. Radiation alone was found to have a detrimental effect on PFA when irradiated at 303 K. This was evident from the loss in the mechanical properties due to chain scission reactions. This meant that when radiation was used for the grafting reactions, the total radiation dose needed to be kept as low as possible. The radicals produced when PFA was exposed to radiation were examined using electron spin resonance spectroscopy. Both main-chain (–CF2–C.F–CF2-) and end-chain (–CF2–C.F2) radicals were identified. The stability of the majority of the main-chain radicals when the polymer was heated above the glass transition temperature suggested that they were present mainly in the crystalline regions of the polymer, while the end-chain radicals were predominately located in the amorphous regions. The radical yield at 77 K was lower than the radical yield at 303 K suggesting that cage recombination at low temperatures inhibited free radicals from stabilizing. High-speed MAS 19F NMR was used to identify the non-volatile products after irradiation of PFA over a wide temperature range. The major products observed over the irradiation temperature 303 to 633 K included new saturated chain ends, short fluoromethyl side chains in both the amorphous and crystalline regions, and long branch points. The proportion of the radiolytic products shifted from mainly chain scission products at low irradiation temperatures to extensive branching at higher irradiation temperatures. Calculations of G values revealed that net crosslinking only occurred when PFA was irradiated in the melt. Minor products after irradiation at elevated temperatures included internal and terminal double bonds and CF3 groups adjacent to double bonds. The volatile products after irradiation at 303 K included tetrafluoromethane (CF4) and oxygen-containing species from loss of the perfluoropropyl ether side chains of PFA as identified by mass spectrometry and FTIR spectroscopy. The chemical changes induced by radiation exposure were accompanied by changes in the thermal properties of the polymer. Changes in the crystallinity and thermal stability of PFA after irradiation were examined using DSC and TGA techniques. The equilibrium melting temperature of untreated PFA was 599 K as determined using a method of extrapolation of the melting temperatures of imperfectly formed crystals. After low temperature irradiation, radiation- induced crystallization was prevalent due to scission of strained tie molecules, loss of perfluoropropyl ether side chains, and lowering of the molecular weight which promoted chain alignment and hence higher crystallinity. After irradiation at high temperatures, the presence of short and long branches hindered crystallization, lowering the overall crystallinity. The thermal stability of the PFA decreased with increasing radiation dose and temperature due to the introduction of defect groups. Styrene was graft copolymerized to PFA using -radiation as the initiation source with the aim of preparing a graft copolymer suitable as a support for SPOC. Various grafting conditions were studied, such as the total dose, dose rate, solvent effects and addition of nitroxides to create “living” graft chains. The effect of dose rate was examined when grafting styrene vapour to PFA using the simultaneous grafting method. The initial rate of grafting was found to be independent of the dose rate which implied that the reaction was diffusion controlled. When the styrene was dissolved in various solvents for the grafting reaction, the graft yield was strongly dependent of the type and concentration of the solvent used. The greatest graft yield was observed when the solvent swelled the grafted layers and the substrate. Microprobe Raman spectroscopy was used to map the penetration of the graft into the substrate. The grafted layer was found to contain both poly(styrene) (PS) and PFA and became thicker with increasing radiation dose and graft yield which showed that grafting began at the surface and progressively penetrated the substrate as the grafted layer was swollen. The molecular weight of the grafted PS was estimated by measuring the molecular weight of the non-covalently bonded homopolymer formed in the grafted layers using SEC. The molecular weight of the occluded homopolymer was an order of magnitude greater than the free homopolymer formed in the surrounding solution suggesting that the high viscosity in the grafted regions led to long PS grafts. When a nitroxide mediated free radical polymerization was used, grafting occurred within the substrate and not on the surface due to diffusion of styrene into the substrate at the high temperatures needed for the reaction to proceed. Loading tests were used to measure the capacity of the PS graft to be functionialized with aminomethyl groups then further derivatized. These loading tests showed that samples grafted in a solution of styrene and methanol had superior loading capacity over samples graft using other solvents due to the shallow penetration and hence better accessibility of the graft when methanol was used as a solvent.

The application of profluorescent nitroxides to detect reactive oxygen species derived from combustion-generated particulate matter: Cigarette smoke – a case study

Reactive oxygen species (ROS) and related free radicals are considered to be key factors underpinning the various adverse health effects associated with exposure to ambient particulate matter. Therefore, measurement of ROS is a crucial factor for assessing the potential toxicity of particles. In this work, a novel profluorescent nitroxide, BPEAnit, was investigated as a probe for detecting particle-derived ROS. BPEAnit has a very low fluorescence emission due to inherent quenching by the nitroxide group, but upon radical trapping or redox activity, a strong fluorescence is observed. BPEAnit was tested for detection of ROS present in mainstream and sidestream cigarette smoke. In the case of mainstream cigarette smoke, there was a linear increase in fluorescence intensity with an increasing number of cigarette puffs, equivalent to an average of 101 nmol ROS per cigarette based on the number of moles of the probe reacted. Sidestream cigarette smoke sampled from an environmental chamber exposed BPEAnit to much lower concentrations of particles, but still resulted in a clearly detectible increase in fluorescence intensity with sampling time. It was calculated that the amount of ROS was equivalent to 50 ± 2 nmol per mg of particulate matter; however, this value decreased with ageing of the particles in the chamber. Overall, BPEAnit was shown to provide a sensitive response related to the oxidative capacity of the particulate matter. These findings present a good basis for employing the new BPEAnit probe for the investigation of particle-related ROS generated from cigarette smoke as well as from other combustion sources.

Oxidative potential of logwood and pellet burning particles assessed by a novel profluorescent nitroxide probe

This study reports the potential toxicological impact of particles produced during biomass combustion by an automatic pellet boiler and a traditional logwood stove under various combustion conditions using a novel profluorescent nitroxide probe BPEAnit. This probe is weakly fluorescent, but yields strong fluorescence emission upon radical trapping or redox activity. Samples were collected by bubbling aerosol through an impinger containing BPEAnit solution, followed by fluorescence measurement. The fluorescence of BPEAnit was measured for particles produced during various combustion phases, at the beginning of burning (cold start), stable combustion after refilling with the fuel (warm start) and poor burning conditions. For particles produced by the logwood stove under cold-start conditions significantly higher amounts of reactive species per unit of particulate mass were observed compared to emissions produced during a warm start. In addition, sampling of logwood burning emissions after passing through a thermodenuder at 250oC resulted in an 80-100% reduction of the fluorescence signal of BPEAnit probe, indicating that the majority of reactive species were semivolatile. Moreover, the amount of reactive species showed a strong correlation with the amount of particulate organic material. This indicates the importance of semivolatile organics in particle-related toxicity. Particle emissions from the pellet boiler, although of similar mass concentration, were not observed to lead to an increase in fluorescence signal during any of the combustion phases.

A profluorescent azaphenalene nitroxide for nitroxide-mediated polymerization

A novel nitroxide-mediated polymerization (NMP) control agent; 1,1,3,3-tetramethyl-2,3-dihydro-2-azaphenalen-2-yloxyl (TMAO), was used in the free-radical polymerization of styrene. The conversion of styrene during NMP was studied using FT-Raman spectroscopy and the effectiveness of TMAO as a NMP control agent was assessed by GPC analysis. Fidelity of the TMAO-alkoxyamine end-group on the synthesized polymers was confirmed by GPC, UV-Vis and fluorescence spectroscopic analyses. Comparison to the well known NMP control agent, TEMPO was made. TMAO showed control of molecular weight approaching that of TEMPO. Attempts to improve the properties of TMAO as an NMP control agent by synthesizing an analogue with bulkier substituents around the nitroxide did not generate the target molecule but demonstrated some of the interesting chemistry of the azaphenalene ring system

The evaluation of new and isotopically labeled isoindoline nitroxides and an azaphenalene nitroxide for EPR oximetry

Isoindoline nitroxides are potentially useful probes for viable biological systems, exhibiting low cytotoxicity, moderate rates of biological reduction and favorable Electron Paramagnetic Resonance (EPR) characteristics. We have evaluated the anionic (5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl; CTMIO), cationic (5-(N,N,N-trimethylammonio)-1,1,3,3-tetramethylisoindolin-2-yloxyl iodide, QATMIO) and neutral (1,1,3,3-tetramethylisoindolin-2-yloxyl; TMIO) nitroxides and their isotopically labeled analogs ((2)H(12)- and/or (2)H(12)-(15)N-labeled) as potential EPR oximetry probes. An active ester analogue of CTMIO, designed to localize intracellularly, and the azaphenalene nitroxide 1,1,3,3-tetramethyl-2,3-dihydro-2-azaphenalen-2-yloxyl (TMAO) were also studied. While the EPR spectra of the unlabeled nitroxides exhibit high sensitivity to O(2) concentration, deuteration resulted in a loss of superhyperfine features and a subsequent reduction in O(2) sensitivity. Labeling the nitroxides with (15)N increased the signal intensity and this may be useful in decreasing the detection limits for in vivo measurements. The active ester nitroxide showed approximately 6% intracellular localization and low cytotoxicity. The EPR spectra of TMAO nitroxide indicated an increased rigidity in the nitroxide ring, due to dibenzo-annulation.

Generation of profluorescent isoindoline nitroxides using click chemistry

Novel profluorescent nitroxides bearing a triazole linker between the coumarin fluorophore and an isoindoline nitroxide were prepared in good yields using the coppercatalyzed azide�alkyne 1,3-dipolar cycloaddition reaction (CuAAC). Nitroxides containing 7-hydroxy and 7-diethylamino substitution on their coumarin rings displayed significant fluorescence suppression, and upon reaction with methyl radicals, normal fluorescence emission was returned. The fluorescence emission for the 7-hydroxycoumarin nitroxide and its diamagnetic analogue was found to be strongly influenced by pH with maximal fluorescence emission achieved in basic solution. Solvent polarity was also shown to affect fluorescence emission. The significant difference in fluorescence output between the nitroxides and their corresponding diamagnetic analogues makes these compounds ideal tools for monitoring processes involving free-radical species.

Two-Photon Fluorescence Microscopy Imaging of Cellular Oxidative Stress Using Profluorescent Nitroxides

A range of varying chromophore nitroxide free radicals and their nonradical methoxyamine analogues were synthesized and their linear photophysical properties examined. The presence of the proximate free radical masks the chromophore’s usual fluorescence emission, and these species are described as profluorescent. Two nitroxides incorporating anthracene and fluorescein chromophores (compounds 7 and 19, respectively) exhibited two-photon absorption (2PA) cross sections of approximately 400 G.M. when excited at wavelengths greater than 800 nm. Both of these profluorescent nitroxides demonstrated low cytotoxicity toward Chinese hamster ovary (CHO) cells. Imaging colocalization experiments with the commercially available CellROX Deep Red oxidative stress monitor demonstrated good cellular uptake of the nitroxide probes. Sensitivity of the nitroxide probes to H2O2-induced damage was also demonstrated by both one- and two-photon fluorescence microscopy. These profluorescent nitroxide probes are potentially powerful tools for imaging oxidative stress in biological systems, and they essentially “light up” in the presence of certain species generated from oxidative stress. The high ratio of the fluorescence quantum yield between the profluorescent nitroxide species and their nonradical adducts provides the sensitivity required for measuring a range of cellular redox environments. Furthermore, their reasonable 2PA cross sections provide for the option of using two-photon fluorescence microscopy, which circumvents commonly encountered disadvantages associated with one-photon imaging such as photobleaching and poor tissue penetration.