François Lambert

Electrochemical Functionalization of Carbon Surfaces by Aromatic Azide or Alkyne Molecules: A Versatile Platform for Click Chemistry

The electrochemical reduction of phenylazide or phenylacetylene diazonium salts leads to the grafting of azido or ethynyl groups onto the surface of carbon electrodes. In the presence of copper(I) catalyst, these azide- or alkyne-modified surfaces react efficiently and rapidly with compounds bearing an acetylene or azide function, thus forming a covalent 1,2,3-triazole linkage by means of click chemistry. This was illustrated with the surface coupling of ferrocenes functionalized with an ethynyl or azido group and the biomolecule biotin terminated by an acetylene group.

Arenethiolatocopper(I) complexes as homogeneous catalysts for Michael addition reactions

Arenethiolatocopper(I) complexes are shown to be efficient homogeneous catalysts in Michael addition reactions of several Grignard reagents to acyclic enones; the addition products are formed with excellent chemoselectivity (>99%) and good enantioselectivity (76% e.e.).

A rhenium tris-carbonyl derivative as a single core multimodal probe for imaging (SCoMPI) combining infrared and luminescent properties

A rhenium tris-carbonyl derivative has been designed to couple infrared and luminescent detection in cells. Both spectroscopies are consistent with one another; they point out the reliability of the present SCoMPI (for Single Core Multimodal Probe for Imaging) for bimodal imaging and unambiguously indicate a localization at the Golgi apparatus in MDA-MB-231 breast cancer cells.

On the way to chiral copper(I) arenethiolate catalysts for the enantioselective conjugate addition of methyl lithium and methyl magnesium iodide to benzylideneacetone

Selective conjugate addition (0 % enantiomeric excess (e.e.)) of organo- arenethiolatocuprates (from methyl lithium and 23 l-(R)-(dimethylamino)ethyl)phenyl- thiolatocopper(I), CuSAr*) to benzylideneacetone (BA) is found up to a LiMe/CuSAr* ratio of 2/l indicating the potential of the chiral SAr*-anion as non-transferable group; at higher ratios only 1,2-addition occurs. Reactions of methyl magnesium iodide with BA in the presence of a catalvtic amount of CuSAr* (9 mol%) result in exclusive conjugate addition with 57% e.e..

Amine conformational change and spin conversion induced by metal-assisted ligand oxidation: from the seven-coordinate iron(II)–TPAA complex to the two oxidized iron(II)–(py)3tren isomers. Characterization, crystal structures, and density functional study

Abstract The tripodal heptadentate ligand TPAA (TPAA=tris[ N -(2-pyridylmethyl)-2-aminoethyl]amine) is found to undergo an iron(II)-assisted oxidative dehydrogenation with its three amine functions oxidized into three imine groups, giving the tripodal potentially heptadentate ligand (py) 3 tren ((py) 3 tren=tris[ N -(2-pyridylmethyl)-2-iminoethyl]amine). This oxidative process induces structural changes and spin conversion in the three identified iron(II) complexes, Fe–TPAA complex ( 1 ), Fe–py3tren complexes ( 2 ) and ( 3 ). X-ray crystallographic studies revealed differences in the coordination geometry of the bridging nitrogen atom and shifts in the coordination number from seven to six. Complex 1 is seven-coordinate and is characterized by a pyramidal environment of the tripodal centered nitrogen and a short N tripodal Fe distance equal to 2.504 A. Complex 3 is hexa-coordinate with a planar environment of the centered nitrogen located at 3.435 A from iron(II) and therefore not bound to the iron. Complex 2 which is an isomeric form of complex 3 is found to be a structural intermediate between complexes 2 and 3 with a pseudo-coordination of six as shown by the N tripodal Fe distance equal to 2.754 A. Electronic changes were recognized from NMR studies in solution and EPR and SQUID measurements of susceptibilities in solid state. Complex 1 is high-spin with the S =2 state characterized by a g factor equal to 2.25. Complex 3 is low-spin but its isomer, the intermediate complex 2 exhibits a temperature-dependent spin conversion from the S =2 high-spin form at room temperature to a lower spin that we provisionally identify as a S =1 intermediate spin form. DFT Becke3LYP calculations were carried out on the two isomeric complexes 2 and 3 . The planar complex was found to be 3.2 kcal mol −1 more stable than the pyramidal isomer, in agreement with the experiment.

Vestibular Asymmetry as the Cause of Idiopathic Scoliosis: A Possible Answer from Xenopus

Human idiopathic scoliosis is characterized by severe deformations of the spine and skeleton. The occurrence of vestibular-related deficits in these patients is well established but it is unclear whether a vestibular pathology is the common cause for the scoliotic syndrome and the gaze/posture deficits or if the latter behavioral deficits are a consequence of the scoliotic deformations. A possible vestibular origin was tested in the frog Xenopus laevis by unilateral removal of the labyrinthine endorgans at larval stages. After metamorphosis into young adult frogs, X-ray images and three-dimensional reconstructed micro-computer tomographic scans of the skeleton showed deformations similar to those of scoliotic patients. The skeletal distortions consisted of a curvature of the spine in the frontal and sagittal plane, a transverse rotation along the body axis and substantial deformations of all vertebrae. In terrestrial vertebrates, the initial postural syndrome after unilateral labyrinthectomy recovers over time and requires body weight-supporting limb proprioceptive information. In an aquatic environment, however, this information is absent. Hence, the lesion-induced asymmetric activity in descending spinal pathways and the resulting asymmetric muscular tonus persists. As a consequence the mostly cartilaginous skeleton of the frog tadpoles progressively deforms. Lack of limb proprioceptive signals in an aquatic environment is thus the element, which links the Xenopus model with human scoliosis because a comparable situation occurs during gestation in utero. A permanently imbalanced activity in descending locomotor/posture control pathways might be the common origin for the observed structural and behavioral deficits in humans as in the different animal models of scoliosis.

Sugars to Control Ligand Shape in Metal Complexes: Conformationally Constrained Glycoligands with a Predetermination of Stereochemistry and a Structural Control

In coordination chemistry, ligand shape can be used to tune properties, such as metal selectivity, coordination number, electronic structure, redox potential, and metal center stereochemistry including coordination helicates formation, and also to generate cavities for encapsulation. The results presented in this article indicate that two epimeric glycoligands (3 and 4) based on the conformationally restrained xylo- and ribo-1,2-O-isopropylidenefurano scaffolds are preorganized in water through pi-pi stacking due to hydrophobic interactions, as evidenced from excimer observation. The structure obtained in the solid state for one of the Cu(II) complexes (5) is chiral, with an original helical chirality arising from the coiling of the two ligands around the Cu-Cu axis. It shows an unusual double-deck type structure, with pi-pi interaction between two triazoyl-pyridyl rings and with a small cavity between the two Cu(II) ions able to host a bridging water molecule, as suggested by electron paramagnetic resonance. The Cu(II) complex from the epimeric ligand (6) shows similar properties with a mirror-image CD spectrum in the d-d region of the Cu(II). There is a predetermination of chirality at the metal center by the glycoligand induced by the C3 configuration, 6 and 5 being pseudoenantiomers. Interestingly, the stereochemistry at the metal center is here controlled by the combination of pi-stacking and chiral backbone.

Luminescence Modulations of Rhenium Tricarbonyl Complexes Induced by Structural Variations

Octahedral d(6) low-spin Re(I) tricarbonyl complexes are of considerable interest as noninvasive imaging probes and have been deeply studied owing to their biological stability, low toxicity, large Stokes shifts, and long luminescence lifetimes. We reported recently the bimodal IR and luminescence imaging of a Re(I) tricarbonyl complex with a Pyta ligand (4-(2-pyridyl)-1,2,3-triazole) in cells and labeled such metal-carbonyl complexes SCoMPIs for single-core multimodal probes for imaging. Re(I) tricarbonyl complexes have unique photophysical properties allowing for their unequivocal detection in cells but also present some weaknesses such as a very low luminescence quantum yield in aqueous medium. Further optimizations would thus be desirable. We therefore developed new Re(I) tricarbonyl complexes prepared from different ancillary ligands. Complexes with benzothiadiazole-triazole ligands show interesting luminescent quantum yields in acetonitrile and may constitute valuable luminescent metal complexes in organic media. A series of complexes with bidentate 1-(2-quinolinyl)-1,2,3-triazole (Taquin) and 1-(2-pyridyl)-1,2,3-triazole (Tapy) ligands bearing various 4-substituted alkyl side chains has been designed and synthesized with efficient procedures. Their photophysical properties have been characterized in acetonitrile and in a H2O/DMSO (98/2) mixture and compared with those of the parent Quinta- and Pyta-based complexes. Tapy complexes bearing long alkyl chains show impressive enhancement of their luminescent properties relative to the parent Pyta complex. Theoretical calculations have been performed to further characterize this new class of rhenium tricarbonyl complexes. Preliminary cellular imaging studies in MDA-MB231 breast cancer cells reveal a strong increase in the luminescence signal in cells incubated with the Tapy complex substituted with a C12 alkyl chain. This study points out the interesting potential of the Tapy ligand in coordination chemistry, which has been so far underexploited.

Detection of an estrogen derivative in two breast cancer cell lines using a single core multimodal probe for imaging (SCoMPI) imaged by a panel of luminescent and vibrational techniques

3-Methoxy-17α-ethynylestradiol or mestranol is a prodrug for ethynylestradiol and the estrogen component of some oral contraceptive formulations. We demonstrate here that a single core multimodal probe for imaging - SCoMPI - can be efficiently grafted onto mestranol allowing its tracking in two breast cancer cell lines, MDA-MB-231 and MCF-7 fixed cells. Correlative imaging studies based on luminescence (synchrotron UV spectromicroscopy, wide field and confocal fluorescence microscopies) and vibrational (AFMIR, synchrotron FTIR spectromicroscopy, synchrotron-based multiple beam FTIR imaging, confocal Raman microspectroscopy) spectroscopies were consistent with one another and showed a Golgi apparatus distribution of the SCoMPI-mestranol conjugate in both cell lines.

Influence of the Side‐Chain Length on the Cellular Uptake and the Cytotoxicity of Rhenium Triscarbonyl Derivatives: A Bimodal Infrared and Luminescence Quantitative Study

Rhenium triscarbonyl complexes fac-[Re(CO)3 (N^N)] with appropriate ancillary N^N ligands are relevant for fluorescent bio-imaging. Recently, we have shown that [Re(CO)3 ] cores can also be efficiently mapped inside cells using their IR signature and that they can thus be used in a bimodal approach. To describe them we have coined the term SCoMPIs for single-core multimodal probes for imaging. In the context of the use of these SCoMPIs in bio-imaging, the questions of their cellular uptake and cytotoxicity are critical. We report here a series of compounds derived from the [Re(CO)3 Cl(pyta)] core (pyta=4-(2-pyridyl)-1,2,3-triazole). The pyta ligand is of interest because it can be easily functionalized. Aliphatic side chains (C4 , C8 , and C12 ) were appended to this core. A correlative study involving IR and luminescence was performed to monitor and quantify their cellular internalization. We studied the relationship between lipophilicity (log P(o/w)), cytotoxicity (IC50 ), and cellular uptake, and we showed that both uptake and cytotoxicity increase with the length of the side chain, with a higher uptake for the C12 derivative. This study stresses the distinction that has to be made between apparent toxicity, determined as an incubation concentration IC50 , and intrinsic toxicity. Indeed, the intrinsic toxicity of a compound can remain hidden if it is not cell permeable. Therefore it must be kept in mind that IC50 values are composite values, reflecting both cellular uptake and intrinsic toxicity.