Macrocyclic Ligand Coordinating Amide-Arm Hydrolysis Reaction Activation in Aqueous Solutions: Tetravalent Uranium Does It Better.

Chelation of lanthanide and actinide cations within a suitable macrocyclic ligand often results in a rigid, kinetically inert, and thermodynamically stable complex. A benchmark for such cation-ligand suitability are cyclen-derived macrocyclic ligands, frequently used as large cation hosts for various applications. Herein, a comprehensive study of the 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane ligand (DOTAM) chelates of U and Ce and their properties in aqueous solutions is presented.

DOTP versus DOTA as Ligands for Lanthanide Cations: Novel Structurally Characterized Ce and Ce Cyclen-Based Complexes and Clusters in Aqueous Solutions.

The coordination and redox chemistry of aqueous Ce macrocyclic compounds were studied by using the ligands DOTA and DOTP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid), respectively). The hydrolysis tendency of the tetravalent cation in the presence of DOTA is shown to result in the formation of a highly ordered, fluorite-like [Ce (O) (OH) (H O) (DOTAH) ] oxo-hydroxo structure both in solution and in the solid state. The lifetime of the analogous species formed in the presence of DOTP was found to be much shorter.

On the reactions of Cu(II/I)ATP complexes with methyl radicals.

The CuATP react with methyl radicals to form methane and methanol, where CuATP reacts with CH in a process that is surprisingly slow. The low-rate constant of this process is attributed to the significant rearrangement of the chelating ligand required for the transient's formation. These results were corroborated by DFT calculations of the relevant compounds.

Reactions of methyl, hydroxyl and peroxyl radicals with the DOTA chelating agent used in medical imaging.

The mechanism of reaction of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) with ·CH, CHO· and ·OH radicals were studied. The radicals were formed in situ radiolytically. The methyl radicals react orders of magnitude slower with DOTA and with M(DOTA) than the hydroxyl radicals.

Oligomers Intermediates in Between Two New Distinct Homonuclear Uranium(IV) DOTP Complexes*.

Two new aqueous U complexes were synthesized by the interaction between the tetravalent uranium cation and the (1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTP) macrocyclic ligand. Two distinct homonuclear complexes were identified; the first was characterized by X-ray crystallography as a unique "out-of-cage", [U(DOTPH ) ] complex, in which the U cation is octa-coordinated to 4 phosphonic arms from each ligand in a square anti-prism geometry, with a C symmetry. The second is the "in-cage" [U(DOTPH )] complex, in which the tetravalent cation is located between the macrocycle O and N planes.

Redox Properties of CeDOTA in Carbonated Aqueous Solutions. A Radiolytic and an Electrochemical Study.

The redox chemistry of CeDOTA in carbonate solutions was studied using electrochemistry and radiolysis techniques (continuous radiolysis and pulse radiolysis). Spectroscopic measurements point out that the species present in the solutions at high bicarbonate concentrations are [CeDOTA(CO)] (or less plausible [CeDOTA(HCO)]) with the carbonate (bicarbonate) anion as the ninth ligand versus [CeDOTA(HO)] present in the absence of bicarbonate. Electrochemical results show a relatively low increase in the thermodynamic stabilization of the redox couple Ce in the presence of carbonate versus its aqueous analogue.

On the Aqueous Chemistry of the U -DOTA Complex.

The 1,4,7,10-tetrazacyclodecane-1,4,7,10-tetraacetic acid (DOTA) aqueous complex of U with H O, OH , and F as axial ligands was studied by using UV/Vis spectrophotometry, ESI-MS, NMR spectroscopy, X-ray crystallography, and electrochemistry. The U -DOTA complex with either water or fluoride as axial ligands was found to be inert to oxidation by molecular oxygen, whereas the complex with hydroxide as an axial ligand slowly hydrolyzed and was oxidized by dioxygen to a diuranate precipitate. The combined data set acquired shows that, although axial substitution of fluoride and hydroxide ligands instead of water does not seem to significantly change the aqueous DOTA complex structure, it has an important effect on the electronic configuration of the complex.

Mechanistic insight into the catalytic inhibition by nitroxides of tyrosine oxidation and nitration.

Background: Nitroxide antioxidants (RNO) protect from injuries associated with oxidative stress. Tyrosine residues in proteins are major targets for oxidizing species giving rise to irreversible cross-linking and protein nitration, but the mechanisms underlying the protective activity of RNO on these processes are not sufficiently clear.

Methods: Tyrosine oxidation by the oxoammonium cation (RN=O) was studied by following the kinetics of RNO formation using EPR spectroscopy.

Direct Observation of Acyl Nitroso Compounds in Aqueous Solution and the Kinetics of Their Reactions with Amines, Thiols, and Hydroxamic Acids.

Acyl nitroso compounds or nitrosocarhonyls (RC(O)N═O) are reactive short-lived electrophiles, and their hydrolysis and reactions with nucleophiles produce HNO. Previously, direct detection of acyl nitroso species in nonaqueous media has been provided by time-resolved infrared spectroscopy demonstrating that its half-life is about 1 ms. In the present study hydroxamic acids (RC(O)NHOH) are oxidized electrochemically in buffered aqueous solutions (pH 5.

Nitrogen Dioxide Reaction with Nitroxide Radical Derived from Hydroxamic Acids: The Intermediacy of Acyl Nitroso and Nitroxyl (HNO).

Hydroxamic acids (RC(O)NHOH) form a class of compounds that display interesting chemical and biological properties The chemistry of RC(O)NHOH) is associated with one- and two-electron oxidations forming the respective nitroxide radical (RC(O)NHO) and acyl nitroso (RC(O)N═O), respectively, which are relatively unstable species. In the present study, the kinetics and mechanism of the NO reaction with nitroxide radicals derived from acetohydroxamic acid, suberohydroxamic acid, benzohydroxamic acid, and suberoylanilide hydroxamic acid have been studied in alkaline solutions. Ionizing radiation was used to generate about equal yields of these radicals, demonstrating that the oxidation of the transient nitroxide radical by NO produces HNO and nitrite at about equal yields.

Mechanistic Studies on the Role of [Cu (CO ) ] 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 Cu or a Cu complex. Kinetic analysis of pulse radiolysis measurements coupled with DFT calculations point out that Cu (CO ) complexes are the active intermediates in the electrolysis of Cu (CO ) solution.

The role of carbonate in electro-catalytic water oxidation by using Ni(1,4,8,11-tetraazacyclotetradecane).

NiL are good electro-catalysts for water oxidation in phosphate or carbonate buffers. The results point out that the active oxidizing agents are L(X)NiOH, where X = POH or COH formed from LNiXvia a mechanism involving an acid catalyzed O-P or O-C bond heterolysis. Carbonate behaves differently from phosphate as it is a non-innocent ligand and it can be oxidized.

Mechanism of HRP-catalyzed nitrite oxidation by HO revisited: Effect of nitroxides on enzyme inactivation and its catalytic activity.

The peroxidative activity of horseradish peroxidase (HRP) undergoes progressive inactivation while catalyzing the oxidation of nitrite by HO. The extent of inactivation increases as the pH increases, [nitrite] decreases or [HO] increases, and is accompanied by a loss of the Soret peak of HRP along with yellow-greenish coloration of the solution. HRP-catalyzed nitrite oxidation by HO involves not only the formation of compounds I and II as transient heme species, but also compound III, all of which in turn, oxidize nitrite yielding NO.

Nitroxides protect horseradish peroxidase from HO-induced inactivation and modulate its catalase-like activity.

Background: Horseradish peroxidase (HRP) catalyzes HO dismutation while undergoing heme inactivation. The mechanism underlying this process has not been fully elucidated. The effects of nitroxides, which protect metmyoglobin and methemoglobin against HO-induced inactivation, have been investigated.

Nitroxides catalytically inhibit nitrite oxidation and heme inactivation induced by HO, 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.

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.

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.

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.

Covalent binding of a nickel macrocyclic complex to a silica support: towards an electron exchange column.

Ni(II)L(2), L(2) = 1-propyl-1,3,5,8,12-pentaazacyclotetradecane, was covalently bound to a silica support. This complex can be reversibly oxidized to the corresponding Ni(III) complex. The latter complex is relatively long lived.

The "Fenton like" reaction of MoO43- involves two H2O2 molecules.

Surprisingly the oxidation of MoO4(3-) by H2O2 involves two H2O2 molecules. It is proposed that generally when the reaction of a reducing agent with H2O2, to form a single electron oxidized product and a hydroxyl radical, is endothermic the reaction involves more than one H2O2 molecule.

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.

On the mechanism of reduction of maleate and fumarate by Ni(I)(1,4,8,11-tetraazacyclotetradecane)+ in aqueous solutions.

Ni(I)(1,4,8,11-tetraazacyclotetradecane)(+), Ni(I)L(+), was produced in neutral aqueous solutions by radiolytic techniques. The mechanism and kinetics of the reaction of Ni(I)L(+) with maleate and fumarate were studied applying pulse-radiolysis and analysis of the final products. Surprisingly the mechanisms of reduction of maleate and fumarate differ considerably.

Superoxide dismutase activity of corrole metal complexes.

The first report regarding SOD activity of metallocorroles, investigated via the combination of the cytochrome C assay, pulse radiolysis, and electrochemistry, is used for identifying the main criteria needed for achieving good performance, as well as for elucidating mechanistic aspects of their action.

Mechanism of reaction of alkyl radicals with (Ni(II)L)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).