Bruno Faure

Visible light-driven O2 reduction by a porphyrin-laccase system.

Several recent studies have shown that the combination of photosensitizers with metalloenzymes can support a light-driven multielectron reduction of molecules such as CO(2) or HCN. Here we show that the association of the zinc tetramethylpyridinium porphyrin (ZnTMPyP(4+)) photosensitizer with the multicopper oxidase (MCO) laccase allows to link the oxidation of an organic molecule to the four electrons reduction of dioxygen into water. The enzyme is photoreduced within minutes with porphyrin/enzyme ratio as low as 1:40. With a 1:1 ratio, the dioxygen consumption rate is 1.7 μmol L(-1) s(-1). Flash photolysis experiments support the formation of the triplet excited state of ZnTMPyP(4+) which reduces the enzyme to form a radical cation of the porphyrin with a k(ET) ≈ 10(7) s(-1) M(-1). The long-lived triplet excited state of the ZnTMPyP(4+) (τ(0) = 0.72 ms) accounts for a substantial electron-transfer quantum yield, φ(ET) = 0.35. Consequently, the enzyme-dependent photo-oxidation of the electron donor occurs with a turnover of 8 min(-1) for the one-electron oxidation process, thereby supporting the suitability of such enzyme/sensitizer hybrid systems for aerobic photodriven transformations on substrates. This study is the first example of a phorphyrin-sensitized four-electron reduction of an enzyme of the MCO family, leading to photoreduction of dioxygen into water.

Use of new chiral tricoordinated phosphorus borane complexes in enantioselective borane reduction of ketones: Complexes structure and mechanistic studies

New tricoordinated phosphorus borane complexes were synthesized and their use as catalysts in enantioselective borane reduction of prochiral aromatic and aliphatic ketones was investigated. The structure of (2R,5S)-2-o-anisyl-3-oxa-1-aza phosphabicyclo[3.3.0]octane—borane complex 1b and (2R,5S)-2,3-diphenyl-1,3-diazaphosphabicyclo[3.3.0]octane—borane complex 6a was established by X-ray diffraction analysis. A relationship has been established between the structure of the oxazaphospholidine borane complexes and the enantioselectivity obtained in the reduction of acetophenone, both with 2 mol% and one equivalent of the catalyst. Among the different oxazaphospholidine borane complexes tested, only the complexes 1–3, including 3-oxa-l-azaphosphabicyclo[3.3.0]octane and 3-oxa-l-azaphosphabicyclo[4.3.0]nonane moieties, were efficient catalysts. A rational mechanism is proposed according to the experimental results, especially from a deuterium labelling study.

Binding of 2-Hydroxypyridine-N-oxide on Dicopper(II) Centers: Insights into Tyrosinase Inhibition Mechanism by Transition-State Analogs

2-Hydroxypyridine-N-oxide (HOPNO) is described as a new and efficient transition-state analog (TS-analog) inhibitor for the mushroom tyrosinase with an IC(50) = 1.16 microM and a K(I) = 1.8 microM. Using the binuclear copper(II) complex [Cu(2)(BPMP)(mu-OH)](ClO(4))(2) (2) known as a functional model for the tyrosinase catecholase activity, we isolated and fully characterized a 1:1 (2)/OPNO adduct in which the HOPNO is deprotonated and chelates only one Cu-atom of the binuclear site in a bidentate mode. On the basis of these results, a structural model for the tyrosinase inhibition by HOPNO is proposed.

A new 31P NMR method for the enantiomeric excess determination of diols and secondary diamines with C2 symmetry

Abstract A new reagent for the determination of enantiomeric excess of chiral diols and diamines with C2 symmetry is described. This derivatizing agent easily prepared from PCl3 and (1R,2S,5R)-(−)-menthol allows an accurate analysis of the diastereomeric derivatives by 31P NMR spectroscopy.

Application of AMPP-Pd catalysts in an unusual asymmetric allylic coupling reaction of 1-trimethylsilyl vinyl magnesium bromide.

Abstract Unusual palladium catalyzed allylation of a silylated Grignard reagent by cyclohexenyl acetate gives in high yields a versatile synthon, 3-(1-trimethyisilyl vinyl) cyclohexene; use of chiral AMPP ligands results in e.e. up to 33 %.

Enantioselective borane reduction of ketones catalyzed by a chiral oxazaphospholidine borane complex

Abstract The borane complex of (2R,4S)-2-phenyl-1,3,2- oxazaphospholidine 2 was readily synthetized. This complex can be used as catalyst in enantioselective reduction of ketones in toluene, with BH3:THF (or BH3:SMe2) as reducing agent. The catalytic reduction of iso-propyl methyl ketone yields (R)-3-methyl-2-butanol in 92% e.e. and 100% conversion. Reduction of different ketones under stoichiometric conditions gives the corresponding alcohols in e.e. = 99%.

Stereoselective synthesis of (Rp)-benzylphenyl-[2-(S)-bromomethylpyrrolidine-1-yl]phosphine oxide from (S)-(+)-prolinol by the Michaelis–Arbuzov reaction: application in the synthesis of a chiral hybrid phosphine–phosphine oxide ligand

The chiral oxazaphospholidine (2) derived from (S)-(+)-prolinol reacts with benzyl bromide in a stereoselective Michaelis–Arbuzov reaction to give (3), an ideal precursor for the synthesis of the chiral hybrid phosphine–phosphine oxide ligand (5).

Supramolecular complexes involving non-symmetric viologen cations and hexacyanoferrate(II) anions. A spectroscopic, crystallographic and computational study

We have investigated spectrally, crystallographically as well as computationally the charge transfer complexes involving newly synthesized N-aryl-N′-methyl non-symmetric viologens (AMVs) and hexacyanoferrate(II) (HCF) anions. The supramolecular binding of AMVs and HCF was studied in solution and in the crystal state for one of the obtained complexes. Substituent effects on the electron affinities of the dicationic AMVs, determined using Mullikens theory [R. S. Mulliken, J. Am. Chem. Soc., 1952, 74, 811–824] were quantified. The structure of one of the AMV//FeII(CN)6 pairs solved through Single-Crystal X-ray Diffraction (SCXRD), provided insights for the supramolecular binding of the anionic and cationic counterparts and the role of lattice water molecules. Supramolecular binding in solution, studied with the use of NMR spectroscopy, is in agreement with the results obtained in the solid state.

Electrochemical Water Oxidation and Stereoselective Oxygen Atom Transfer Mediated by a Copper Complex

Water oxidation by copper-based complexes to form dioxygen has attracted attention in recent years, with the aim of developing efficient and cheap catalysts for chemical energy storage. In addition, high-valent metal-oxo species produced by the oxidation of metal complexes in the presence of water can be used to achieve substrate oxygenation with the use of H2 O as an oxygen source. To date, this strategy has not been reported for copper complexes. Herein, a copper(II) complex, [(RPY2)Cu(OTf)2 ] (RPY2=N-substituted bis[2-pyridyl(ethylamine)] ligands; R=indane; OTf=triflate), is used. This complex, which contains an oxidizable substrate moiety (indane), is used as a tool to monitor an intramolecular oxygen atom transfer reaction. Electrochemical properties were investigated and, upon electrolysis at 1.30 V versus a normal hydrogen electrode (NHE), both dioxygen production and oxygenation of the indane moiety were observed. The ligand was oxidized in a highly diastereoselective manner, which indicated that the observed reactivity was mediated by metal-centered reactive species. The pH dependence of the reactivity was monitored and correlated with speciation deduced from different techniques, ranging from potentiometric titrations to spectroscopic studies and DFT calculations. Water oxidation for dioxygen production occurs at neutral pH and is probably mediated by the oxidation of a mononuclear copper(II) precursor. It is achieved with a rather low overpotential (280 mV at pH 7), although with limited efficiency. On the other hand, oxygenation is maximum at pH 8-8.5 and is probably mediated by the electrochemical oxidation of an antiferromagnetically coupled dinuclear bis(μ-hydroxo) copper(II) precursor. This constitutes the first example of copper-centered oxidative water activation for a selective oxygenation reaction.

Reactivity of dinuclear copper(II) complexes towards melanoma cells: Correlation with its stability, tyrosinase mimicking and nuclease activity

In this work, the influence of two new dinuclear copper(II) complexes in the viability of melanoma cells (B16F10 and TM1MNG3) was investigated, with the aim of verifying possible correlations between their cytotoxicity and their structure. One of the complexes had a polydentate dinucleating amine-imine ligand (complex 2), and the other a tridentate imine and a diamine-bridging ligand (complex 4). The analogous mononuclear copper(II) species (complexes 1 and 3, respectively) were also prepared for comparative studies. Crystal structure determination of complex 2 indicated a square-based pyramidal geometry around each copper, coordinated to three N atoms from the ligand and the remaining sites being occupied by either solvent molecules or counter-ions. Complex 4 has a tetragonal geometry. Interactions of these complexes with human albumin protein (HSA) allowed an estimation of their relative stabilities. Complementary studies of their reactivity towards DNA indicated that all of them are able of causing significant oxidative damage, with single and double strand cleavages, in the presence of hydrogen peroxide. However, nuclease activity of the dinuclear species was very similar and much higher than that of the corresponding mononuclear compounds. Although complex 2, with a more flexible structure, exhibits a much higher tyrosinase activity than complex 4, having a more rigid environment around the metal ion, both complexes showed comparable cytotoxicity towards melanoma cells. Corresponding mononuclear complexes showed to be remarkably less reactive as tyrosinase mimics as well as cytotoxic agents. Moreover, the dinuclear complexes showed higher cytotoxicity towards more melanogenic cells. The obtained results indicated that the structure of these species is decisive for its activity towards the malignant tumor cells tested.