Fabrice Thomas

X‐Ray Structures of Copper(II) and Nickel(II) Radical Salen Complexes: The Preference of Galactose Oxidase for Copper(II)

Organic radicals are normally extremely reactive, and often nonselective and toxic species. They are found in a number of proteins, some of which are involved in essential processes such as photosynthesis and DNA synthesis. Nature has therefore nicely succeeded in domesticating them and taking advantage of their high reactivity. Galactose oxidase (GO, Scheme 1), which catalyzes aerobic oxidation of primary

Calcein as a Fluorescent Probe for Ferric Iron APPLICATION TO IRON NUTRITION IN PLANT CELLS

The recent use of calcein (CA) as a fluorescent probe for cellular iron has been shown to reflect the nutritional status of iron in mammalian cells (Breuer, W., Epsztejn, S., and Cabantchik, Z. I. (1995) J. Biol. Chem. 270, 24209–24215). CA was claimed to be a chemosensor for iron(II), to measure the labile iron pool and the concentration of cellular free iron(II). We first study here the thermodynamic and kinetic properties of iron binding by CA. Chelation of a first iron(III) involves one aminodiacetic arm and a phenol. The overall stability constant log β111 of FeIIICAH is 33.9. The free metal ion concentration is pFeIII = 20.3. A (FeIII)2 CA complex can be formed. A reversible iron(III) exchange from FeIIICAH to citrate and nitrilotriacetic acid is evidenced when these ligands are present in large excess. The kinetics of iron(III) exchange by CA is compatible with metabolic studies. The low reduction potential of FeIIICAH shows that the ferric form is highly stabilized. CA fluorescence is quenched by 85% after FeIIIchelation but by only 20% using FeII. Real time iron nutrition by Arabidopsis thaliana cells has been measured by fluorimetry, and the iron buffer FeIIICAH + CA was used as source of iron. As a siderophore, FeIIICAH promotes cell growth and regreening of iron-deficient cells more rapidly than FeIIIEDTA. We conclude that CA is a good chemosensor for iron(III) in cells and biological fluids, but not for Fe(II). We discuss the interest of quantifying iron buffers in biochemical studies of iron, in vitro as well as in cells.

Intramolecularly hydrogen-bonded versus copper(II) coordinated mono- and bis-phenoxyl radicals.

Ligands bearing two salicylidene imine moieties substituted in ortho and para positions by tert-butyl groups have been electrochemically oxidized into mono- and bis-phenoxyl radicals. The process involves an intramolecular proton coupled to electron transfer and affords a radical in which the oxygen atom is hydrogen-bonded to a protonated ammonium or iminium group. A weak intramolecular dipolar interaction exists between the two phenoxyl moieties in the bis-radical species. The copper(II) complexes of these ligands have been characterized and electrochemically oxidized. The mono-phenoxyl radical species are X-band EPR silent. The bis-phenoxyl radical species exhibits a (S= 3/2) ground state: it arises from a ferromagnetic exchange coupling between the two spins of the radicals and that of the copper(II) when the spacer is rigid enough; a flexible spacer such as ethylidene induces decomplexation of at least one phenoxyl group. Metal coordination is more efficient than hydrogen-bonding to enhance the chemical stability of the mono-phenoxyl radicals.

Reversible double oxidation and protonation of the non-innocent bridge in a nickel(II) salophen complex.

Substitution on the aromatic bridge of a nickel(II) salophen complex with electron-donating dimethylamino substituents creates a ligand with three stable, easily and reversibly accessible oxidation states. The one-electron-oxidized product is characterized as a nickel(II) radical complex with the radical bore by the central substituted aromatic ring, in contrast to other nickel(II) salen or salophen complexes that oxidize on the phenolate moieties. The doubly oxidized product, a singlet species, is best described as having an iminobenzoquinone bridge with a vinylogous distribution of bond lengths between the dimethylamino substituents. Protonation of the dimethylamino substituents inhibits these redox processes on the time scale of cyclovoltammetry, but electrolysis and chemical oxidation are consistent with deprotonation occurring concomitantly with electron transfer to yield the mono- and dioxidized species described above.

Influence of Electron-Withdrawing Substituents on the Electronic Structure of Oxidized Ni and Cu Salen Complexes

Nickel (Ni(Sal(CF3))) and copper (Cu(Sal(CF3))) complexes of an electron-poor salen ligand were prepared, and their one-electron oxidized counterparts were studied using an array of spectroscopic and theoretical methods. The electrochemistry of both complexes exhibited quasi-reversible redox processes at higher potentials in comparison to the M(Sal(R)) (R = (t)Bu, OMe, NMe2) analogues, in line with the electron-withdrawing nature of the para-CF3 substituent. Chemical oxidation, monitored by ultraviolet-visible-near-infrared (UV-vis-NIR) spectroscopy, afforded their corresponding one-electron oxidized products. Ligand-based oxidation was observed for [Ni(Sal(CF3))](+•), as evidenced by sharp NIR transitions in the UV-vis-NIR spectrum and a broad isotropic signal at g = 2.067 by solution electron paramagnetic resonance (EPR) spectroscopy. Such sharp NIR transitions observed for [Ni(Sal(CF3))](+•) are indicative of a delocalized electronic structure, which is in good agreement with electrochemical measurements and density functional theory (DFT) calculations. In addition, the increased Lewis acidity of [Ni(Sal(CF3))](+•), evident from the EPR g-value and DFT calculations, was further quantified by the binding affinity of axial ligands to [Ni(Sal(CF3))](+•). For [Cu(Sal(CF3))](+), an intense ligand-to-metal charge transfer band at 18 700 cm(-1) in the UV-vis-NIR spectrum was observed, which is diagnostic for the formation of a Cu(III) species [J. Am. Chem. Soc., 2008, 130, 15448-15459]. The Cu(III) character for [Cu(Sal(CF3))](+) is further confirmed by (19)F NMR analysis. Taken together, these results show that the electron-deficient salen ligand H2Sal(CF3) increases the Lewis acidity of the coordinating metal center.

Electrocatalytic O2 Reduction at a Bio-inspired Mononuclear Copper Phenolato Complex Immobilized on a Carbon Nanotube Electrode

An original copper-phenolate complex, mimicking the active center of galactose oxidase, featuring a pyrene group was synthesized. Supramolecular pi-stacking allows its efficient and soft immobilization at the surface of a Multi-Walled Carbon Nanotube (MWCNT) electrode. This MWCNT-supported galactose oxidase model exhibits a 4 H(+)/4 e(-) electrocatalytic activity towards oxygen reduction at a redox potential of 0.60 V vs. RHE at pH 5.

Synthesis and iron(III) complexing ability of CacCAM, a new analog of enterobactin possessing a free carboxylic anchor arm. Comparative studies with TRENCAM

A new tricatecholate, CacCAM, has been synthesized by attachment of three catecholamide subunits to a CO2H-functionalized triamine backbone. The solution coordination chemistry of the ligand and its iron(III) complex have been investigated by potentiometric, spectroscopic and kinetic methods. The results are compared to those obtained with TRENCAM, which possesses the same catecholamide subunits, but a TREN [tris(2-aminoethyl)-amine] backbone. The stability constant (log β110=42.9, pFe=27.5) is close to that of TRENCAM (log β110=43.6, pFe=27.8), showing that a change of backbone does not significantly alter the iron chelating ability of the ligand. Kinetics of iron exchange between Fe(III)–EDTA and CacCAM or TRENCAM involves similar rate constants (16±1 and 14±2 M−1 s−1, respectively). EPR data show that the iron(III) does not have the same distorted rhombic geometry in the two complexes. Fe(III)–CacCAM has been tested as a source of iron in nutritional experiments with Arabidopsis thaliana plant cells: its efficiency is good, comparable to that of Fe(III)–EDTA, the most widely used iron complex for plant nutrition.

Interaction of polycationic Ni(II)-salophen complexes with G-quadruplex DNA.

A series of nine Ni(II) salophen complexes involving one, two, or three alkyl-imidazolium side-chains was prepared. The lengths of the side-chains were varied from one to three carbons. The crystal structure of one complex revealed a square planar geometry of the nickel ion. Fluorescence resonance energy transfer melting of G-quadruplex structures in the presence of salophen complex were performed. The G-quadruplex DNA structures were stabilized in the presence of the complexes, but a duplex DNA was not. The binding constants of the complexes for parallel and antiparallel G-quadruplex DNA, as well as hairpin DNA, were measured by surface plasmon resonance. The compounds were selective for G-quadruplex DNA, as reflected by equilibrium dissociation constant KD values in the region 0.1-1 μM for G-quadruplexes and greater than 2 μM for duplex DNA. Complexes with more and shorter side-chains had the highest binding constants. The structural basis for the interaction of the complexes with the human telomeric G-quadruplex DNA was investigated by computational studies: the aromatic core of the complex stacked over the last tetrad of the G-quadruplex with peripherical cationic side chains inserted into opposite grooves. Biochemical studies (telomeric repeat amplification protocol assays) indicated that the complexes significantly inhibited telomerase activity with IC50 values as low as 700 nM; the complexes did not significantly inhibit polymerase activity.

Ligand‐Centered Redox Activity in Cobalt(II) and Nickel(II) Bis(phenolate)–Dipyrrin Complexes

One for all: a trianionic ligand containing the biologically relevant moieties phenolate and porphyrin was designed and synthesized. One-electron oxidation of the nickel and cobalt complexes of these ligands affords an unprecedented and highly stable hybrid porphyrinyl-phenoxyl radical bound to the metal center. Two-electron oxidation of these complexes leads to the M(2+) -(close-shell two-electron oxidized ligand) species.

Stable Anilinyl Radicals Coordinated to Nickel: X-ray Crystal Structure and Characterization

Two anilinosalen and a mixed phenol-anilinosalen ligands involving sterically hindered anilines moieties were synthesized. Their nickel(II) complexes 1, 2, and 3 were prepared and characterized. They could be readily one-electron oxidized (E(1/2)=-0.30, -0.26 and 0.10 V vs. Fc(+)/Fc, respectively) into anilinyl radicals species [1](+), [2](+), and [3](+), respectively. The radical complexes are extremely stable and were isolated as single crystals. X-ray crystallographic structures reveal that the changes in bond length resulting from oxidation do not exceed 0.02 Å within the ligand framework in the symmetrical [1](+) and [2](+). No quinoid bond pattern was present. In contrast, larger structural rearrangements were evidenced for the unsymmetrical [3](+), with shortening of one C(ortho)-C(meta) bond. Radical species [1](+) and [2](+) exhibit a strong absorption band at around 6000 cm(-1) (class III mixed valence compounds). This band is significantly less intense than [3](+), consistent with a rather localized anilinyl radical character, and thus a classification of this species as class II mixed-valence compound. Magnetic and electronic properties, as well as structural parameters, have been computed by DFT methods.