Eric Maimon

The reduction of a nitroxide spin label as a probe of human blood antioxidant properties.

The kinetics of reduction of the radical R ”, 5-dimethylaminonaphthalene-1-sulfonyl-4-amino-2,2,6,6-tetramethyl-1-piperidine-oxyl, by blood and its components were studied using the EPR technique. The results demonstrate that R ” is adsorbed to the outer surface of the membrane and does not penetrate into the erythrocytes. A series of control experiments in PBS demonstrate that ascorbate is the only natural reducing agent that reacts with R ” . The observed first order rate of disappearance of the nitroxide radical, k , is: k blood > k eryth > k plasma and k blood ; k eryth + k plasma . The results demonstrate that: The erythrocytes catalyze the reduction of R ” by ascorbate. The rate of reduction of the radical is high though it does not penetrate the cells. In human erythrocytes there is an efficient electron transfer route through the cell membrane. The study points out that R ” is a suitable spin label for measuring the reduction kinetics and antioxidant capacity in blood as expressed by reduction by ascorbate.

Comproportionation and redox catalyzed isomerization of Cu(II)(1R,4S,8R,11S-1,4,8,11-tetramethyl-1,4,8,11-tetraaza-cyclotetradecane)2+ in aqueous solutions

Abstract The complex Cu(II)(1R,4S,8R,11S-tmc)2+ comproportionates and isomerizes in the presence of excess of ligand and Cu° in alkaline aqueous solutions to yield Cu(II)(1R,4R,8S,1S-tmc)2+. The visible and EPR spectra of the two complexes as well as their electrochemical properties are reported. The complexes Cu(II)(1R,4R,8S,11S-tmc)(ClO4)2 and [Cu(II)(1R,4S,8R,11S-tmc)]2N3(ClO4)3 were isolated and crystallographically characterized.

Liposome-based delivery of a boron-containing cholesteryl ester for high-LET particle-induced damage of prostate cancer cells: A boron neutron capture therapy study

Abstract Purpose: The efficacy of a boron-containing cholesteryl ester compound (BCH) as a boron neutron capture therapy (BNCT) agent for the targeted irradiation of PC-3 human prostate cancer cells was examined. Materials and methods: Liposome-based delivery of BCH was quantified with inductively coupled plasma-mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). Cytotoxicity of the BCH-containing liposomes was evaluated with neutral red, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), and lactate dehydrogenase assays. Colony formation assays were utilized to evaluate the decrease in cell survival due to high-linear energy transfer (LET) particles resulting from 10B thermal neutron capture. Results: BCH delivery by means of encapsulation in a lipid bilayer resulted in a boron uptake of 35.2 ± 4.3 μg/109 cells, with minimal cytotoxic effects. PC-3 cells treated with BCH and exposed to a 9.4 × 1011 n/cm2 thermal neutron fluence yielded a 20–25% decrease in clonogenic capacity. The decreased survival is attributed to the generation of high-LET α particles and 7Li nuclei that deposit energy in densely ionizing radiation tracks. Conclusion: Liposome-based delivery of BCH is capable of introducing sufficient boron to PC-3 cells for BNCT. High-LET α particles and 7Li nuclei generated from 10B thermal neutron capture significantly decrease colony formation ability in the targeted PC-3 cells.

Tautomerism in N-confused porphyrins as the basis of a novel fiber-optic humidity sensor

It is shown that N-confused porphyrins exhibit tautomerism not only in organic solvents, as already reported, but also after incorporation in dry/humid Nafion films. This allows the development of a new fiber-optic humidity sensor which exhibits long-term stability and a linear response over the humidity range 0 to at least 4000 ppm.

Nitroxides catalytically inhibit nitrite oxidation and heme inactivation induced by H2O2, nitrite and metmyoglobin or methemoglobin.

Stable nitroxide radicals have multiple biological effects, although the mechanisms underlying them are not fully understood. Their protective effect against oxidative damage has been mainly attributed to scavenging deleterious radicals, oxidizing reduced metal ions and reducing oxyferryl centers of heme proteins. Yet, the potential of nitroxides to protect heme proteins against inactivation while suppressing or enhancing their catalytic activities has been largely overlooked. We have studied the effect of nitroxides, including TPO (2,2,6,6-tetramethylpiperidin-N-oxyl), 4-OH-TPO, 4-oxo-TPO and 3-carbamoyl proxyl, on the peroxidase-like activity of metmyoglobin (MbFeIII) and methemoglobin (HbFeIII) using nitrite as an electron donor by following heme absorption, H2O2 consumption, O2 evolution and nitrite oxidation. The results demonstrate that the peroxidase-like activity is accompanied by a progressive heme inactivation where MbFeIII is far more resistant than HbFeIII. Nitroxides convert the peroxidase-like activity into catalase-like activity while inhibiting heme inactivation and nitrite oxidation in a dose-dependent manner. The nitroxide facilitates H2O2 dismutation, yet none of its reactions with any of the intermediates formed in these systems is rate-determining, and therefore its effect on the rate of the catalysis is hardly dependent on the kind of the nitroxide derivative and its concentration. The nitroxide at µM concentrations range catalytically inhibits nitrite oxidation, and consequently prevents tyrosine nitration induced by heme protein/H2O2/nitrite due to its fast oxidation by •NO2 forming the respective oxoammonium cation, which is reduced back to the nitroxide by H2O2 and by superoxide radical. The nitroxides are superior over common antioxidants, which their reaction with •NO2 always yields secondary radicals leading eventually to consumption of the antioxidant. A mechanism is proposed, and the kinetic simulations fit very well the experimental data in the case of MbFeIII where most of the rate constants of the reactions involved are independently known.

Cooperative oxidation of edta by Ni(III) and dioxygen. A pulse radiolysis study

Abstract The oxidation of the edta ligand in the Ni III edta − complex in the presence of dioxygen obeys a second order dependence on [Ni III (edta) − ] and a first order dependence on [O 2 ], k =(2.0±0.4)×10 8 dm 6 mol −2 s −1 , indicating a cooperative mechanism of oxidation in which one molecule of dioxygen and two Ni III (edta) − complexes are involved.

Mechanism of reaction of alkyl radicals with (NiIIL)2+ complexes in aqueous solutions

The reactions of methyl radicals, *CH3, with the macrocyclic complexes Ni(II)L(1-5) (L(1-5) = cyclam derivatives, vide infra) and Ni(II)edta in aqueous solutions were studied. Methyl radicals react with all these nickel complexes, forming intermediates with Ni(III)-C sigma-bonds. The L(m)Ni(III)-CH3 complexes are formed in equilibria processes with relatively fast forward rate constants of k(f) > 1 x 10(8) M(-1) s(-1) (except in the case of NiL2-trans I cyclam, where the reaction is slower). In all cases the decomposition of the transient complexes occurs via the homolytic cleavage of the metal-carbon sigma-bond. When the homolysis is relatively slow, an isomerisation process of the transient is also observed with the exception of NiL2, where no isomerisation was observed. The results suggest that the strength of the Ni(III)-CH3sigma-bond is mainly affected by steric hindrance.

Mechanistic studies on the role of [CuII(CO3)n]2-2n as a water oxidation catalyst: Carbonate as a non-innocent ligand

Recently it was reported that copper bicarbonate/carbonate complexes are good electro-catalysts for water oxidation. However, the results did not enable a decision whether the active oxidant is a CuIII or a CuIV complex. Kinetic analysis of pulse radiolysis measurements coupled with DFT calculations point out that CuIII (CO3 )n3-2n complexes are the active intermediates in the electrolysis of CuII (CO3 )n2-2n solution. The results enable the evaluation of E°[(CuIII/II (CO3 )n )aq ]≈1.42 V versus NHE at pH 8.4. This redox potential is in accord with the electrochemical report. As opposed to literature suggestions for water oxidation, the present results rule out single-electron transfer from CuIII (CO3 )n3-2n to yield hydroxyl radicals. Significant charge transfer from the coordinated carbonate to CuIII results in the formation of C2 O62- by means of a second-order reaction of CuIII (CO3 )n3-2n . The results point out that carbonate stabilizes transition-metal cations at high oxidation states, not only as a good sigma donor, but also as a non-innocent ligand.

H/D kinetic isotope effect as a tool to elucidate the reaction mechanism of methyl radicals with glycine in aqueous solutions.

The H/D kinetic isotope effect (KIE) for the reaction of methyl radicals with glycine in aqueous solutions at pH 10.6 equals 16 ± 3. This result proves that the methyl radical abstracts a hydrogen atom from the methylene group of glycine and not an electron from the unpaired couple on the nitrogen atom. The rate constant of the reaction of methyl radicals with glycine at pH 7.0 is orders of magnitude smaller than that at pH 10.6.

Electron exchange columns through entrapment of a nickel cyclam in a sol-gel matrix.

An electron exchange column (analogous to ion exchange columns) was developed using the unique redox properties of the nickel-tetraazamacrocyclic complexes (nickel cyclam [Ni(II)L(1)](2+)) and nickel-trans-III-meso-5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane, ([Ni(II)L(2)](2+)), and the physical and chemical stability of the ceramic materials using the sol-gel process to entrap the complexes. The entrapment by the biphasic sol-gel method is based on non-covalent bonds between the matrix and the complex; therefore the main problem was leaching. Parameters controlling the leaching were investigated. Redox cycles with the reducing agent ascorbic acid, and persulfate as the oxidizing agent were performed.