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Accueil > Les équipes > Chemical Biology (ChemBio) > Publications

Publications

publié le , mis à jour le

2021

2020



  • A. Beghennou, K. Passador, A. Passador, V. Corcé, S. Thorimbert, et C. Botuha, « Synthetic Strategy Studies for a Concise Access to Functionalized Pyrano[4,3-b]pyridin-7-ones: An Entry to Semi-Rigid Analogs of Antihistamines », European Journal of Organic Chemistry, vol. 2020, nᵒ 36, p. 5880-5889, sept. 2020.
    Résumé : We report short and efficient syntheses of polyfunctionalized 5,8-dihydro-7H-pyrano[4,3-b]pyridin-7-ones and 1,4-dihydro-3H-pyrano[4,3-c]pyridin-3-ones which can be considered as new aza analogs of 3-isochromanones and as promising scaffolds for medicinal chemistry. Depending on the nature of the substituent, three different and complementary synthetic methodologies were used allowing the introduction of significant diversity in the substituent on the lactone ring of the pyranopyridinones. The selective α-arylation of nitrile (SNAr) and tert-butyl ester enolate (Pd catalyzed) followed by an acidic mediated lactonisation gives access to original C8-functionalized pyrano[4,3-b]pyridin-7-ones and a seleno-mediated cyclization to C1-functionalized pyrano[4,3-c]pyridin-3-ones. We have also applied the outlined synthetic methodologies to the preparation of potential semi-rigid analogs of antihistamines.
    Mots-clés : Antihistamines, CHEMBIO, Pinner reaction, POLE 3, Pyridopyridinones, Seleno-mediated cyclization, δ-Lactone.
    Note Note
    <p>doi: 10.1002/ejoc.202001016</p>


  • B. Bertrand, C. Botuha, J. Forté, H. Dossmann, et M. Salmain, « A bis-chelating (O^N^O)/(N^N) ligand for the synthesis of heterobimetallic Pt(II)/Re(I) complexes: tools for the optimization of a new class of Pt(II) anticancer agents. », Chemistry – A European Journal, vol. 26, nᵒ 56, p. 12846-12861, 2020.
    Résumé : The two independent (O^N^O) and (N^N) coordination sites of a newly synthesized bis 2-(hydroxyphenyl)-1,2,4-triazole platform have been exploited to prepare four monometallic neutral (O^N^O)Pt(II) complexes carrying DMSO, pyridine, triphenylphosphine or N-heterocyclic carbene (NHC) as fourth ligand. Then the second (N^N) coordination site was used to introduce an IR-active rhenium tricarbonyl entity, affording the four corresponding heterobimetallic neutral Pt(II)/Re(I) complexes as well as a cationic Pt(II)/Re(I) derivative. X-ray crystallographic studies showed that distortion of the organic platform occurred to accommodate the coordination geometry of both metal centers. No ligand exchange and no transchelation occurred upon incubation of the Pt(II) complexes in aqueous environment or in the presence of Fe(III), respectively. The ligand and the complexes antiproliferative activity was first screened on the triple negative breast cancer cell line MDA-MB-231. Then the IC 50 of the most active candidates was determined on a wider panel of human cancer cells (MDA-MB-231, MCF-7 and A2780) as well as on a non-tumorigenic cell line (MCF-10F). Low micromolar activities were reached for the complexes carrying a DMSO ligand, making them the first examples of highly active though hydrolytically stable Pt(II) complexes. Finally, the characteristic mid-IR signature of the Re(CO) 3 fragment in the Pt/Re heterobimetallic complexes was used to quantify their uptake in breast cancer cells.
    Mots-clés : cancer, CHEMBIO, CSOB, heterobimetallic, pincer, platinum, POLE 3, rhenium.
    Note Note
    <p>doi: 10.1002/chem.202001752</p>


  • B. Bertrand, G. Gontard, C. Botuha, et M. Salmain, « Pincer-based heterobimetallic Pt(II)/Ru(II), Pt(II)/Ir(III) and Pt(II)/Cu(I) complexes: synthesis and evaluation antiproliferative properties », European Journal of Inorganic Chemistry, vol. 2020, nᵒ 35, p. 3370-3377, sept. 2020.
    Résumé : Platinum pincer-based complexes [(O^N^O)Pt(L)] (L = DMSO, pyridine, triphenylphosphine or 1,3-dimethylbenzimidazol-2-ylidene) carrying an (N^N) coordination site were used as starting materials to synthesize a series of seven cationic heterobimetallic Pt(II)/Ru(II), Pt(II)/Ir(III) and Pt(II)/Cu(I) presenting a [( p- cymene)RuCl] + , a [(Cp*)IrCl] + (Cp* = ? 5 -pentamethylcyclopentadienyl) and a [(NHC iPr )Cu] + (NHC iPr = 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene) moiety respectively. The X-ray structure of one of the bimetallic Pt(II)/Ir(III) complexes showed a distortion of the organic platform to accommodate the coordination geometry of both metal centers as already observed for previous Pt(II)/Re(I) complexes. The antiproliferative activity of the complexes was first screened on the triple negative breast cancer cell line MDA-MB-231. Then the IC 50 of the most active candidates was determined on a wider panel of human cancer cells (MDA-MB-231, MCF-7 and A2780) as well as on a non-tumorigenic cell line (MCF-10A). The most toxic compound, namely the Pt(II)/Cu(I) heterobimetallic complex 4c showed an antiproliferative activity down to the nanomolar level.
    Mots-clés : Bioorganometallic chemistry, cancer, CHEMBIO, heterobimetallic complexes, platinum, POLE 3, Synthesis.
    Note Note
    <p>doi: 10.1002/ejic.202000717</p>


  • L. Cunningham, Y. Wang, C. Nottingham, J. Pagsulingan, G. Jaouen, M. McGlinchey, et P. J. Guiry, « Enantioselective Synthesis of Planar Chiral Ferrocifens that Show Chiral Discrimination in Antiproliferative Activity on Breast Cancer Cells », ChemBioChem, vol. 21, nᵒ 20, p. 2974-2981, 2020.
    Résumé : The design and first enantioselective synthesis of a series of chiral ferrocifens and ferrociphenols was realised via enantioselective palladium-catalysed intramolecular direct C?H bond activation followed by McMurry coupling. Biological evaluation revealed moderate anticancer activities on breast cancer cells and evidence of chiral discrimination between enantiomers. Treatment of these novel ferrocifens with Ag 2 O revealed that these systems are unable to form a neutral quinone methide, yet still demonstrate marked antiproliferative properties versus both the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 cell lines. This bioactivity arises from two mechanisms: Fenton-type chemistry and the anti-estrogenic activity associated with the tamoxifen-like structure.
    Mots-clés : anti-cancer activity, asymmetric synthesis, CHEMBIO, Ferrocene, McMurry coupling, POLE 3.
    Note Note
    <p>doi: 10.1002/cbic.202000311</p>


  • D. Jamroz, N. Fischer-Durand, M. Palusiak, S. Wojtulewski, S. Jarzyński, M. Stępniewska, M. Salmain, et B. Rudolf, « Inverse electron-demand Diels-Alder (iEDDA) bioorthogonal conjugation of half-sandwich transition metallocarbonyl entities to a model protein », Applied Organometallic Chemistry, vol. 34, nᵒ 4, p. e5507, 2020.
    Résumé : Novel transition metallocarbonyl complexes carrying a norbornene or an oxanorbornene group were synthesized by [4 + 2] cycloaddition between the organometallic maleimide dienophiles and cyclopentadiene or furan, respectively. The oxanorbornene adduct was obtained as a mixture of endo and exo isomers as confirmed by X-ray diffraction and NMR spectroscopy. The (oxa)norbornene groups further provided convenient chemical reporters to carry out inverse electron demand Diels-Alder (iEDDA) reactions with tetrazine derivatives. Detailed kinetic studies with a model tetrazine revealed that faster rates of reaction were determined with both isomers of the oxanorbornene complex with respect to the norbornene complexes. Eventually, incorporation of metallocarbonyl entities into bovine serum albumin equipped with tetrazine handles was achieved as shown by IR spectroscopy of the protein conjugates.
    Mots-clés : bioconjugation, CHEMBIO, iEDDA, metallocarbonyl complex, norbornene, POLE 3, tetrazine.
    Note Note
    <p>doi: 10.1002/aoc.5507</p>


  • Š. Nováková Lachmanová, L. Pospíšil, J. Šebera, B. Talbi, M. Salmain, et M. Hromadová, « Electrochemical characterization of the artificial metalloenzyme papain-[(η6-arene)Ru(1,10-phenanthroline)Cl]+ », Journal of Electroanalytical Chemistry, vol. 859, p. 113882, 2020.
    Résumé : Electrochemical properties were studied for [(η6-arene)Ru(1,10-phenanthroline)Cl]Cl (arene = C6H5(CH2)2NHCOCH2Cl) organometallic complex 1, protein Papain PAP and its conjugate with organometallic complex 1-PAP. The latter can serve as an artificial metalloenzyme with catalytic activity in transfer hydrogenation. This work demonstrates that AC voltammetry and electrochemical impedance spectroscopy can be used as fast tools to screen the catalytic ability of 1-PAP electrochemically by studies of the catalytic hydrogen evolution reaction (HER). Proteins are known to catalyze this process, but we have shown that additional HER signal associated with the catalytic activity of 1 is observed for its conjugate with Papain 1-PAP.
    Mots-clés : Artificial metalloenzyme, CHEMBIO, Electrochemical admittance and impedance techniques, Papain, POLE 3, Ruthenium(II) complexes.


  • V. Pellas, D. Hu, Y. Mazouzi, Y. Mimoun, J. Blanchard, C. Guibert, M. Salmain, et S. Boujday, « Gold Nanorods for LSPR Biosensing: Synthesis, Coating by Silica, and Bioanalytical Applications », Biosensors, vol. 10, nᵒ 10, p. 146, 2020.
    Résumé : Nanoparticles made of coinage metals are well known to display unique optical properties stemming from the localized surface plasmon resonance (LSPR) phenomenon, allowing their use as transducers in various biosensing configurations. While most of the reports initially dealt with spherical gold nanoparticles owing to their ease of synthesis, the interest in gold nanorods (AuNR) as plasmonic biosensors is rising steadily. These anisotropic nanoparticles exhibit, on top of the LSPR band in the blue range common with spherical nanoparticles, a longitudinal LSPR band, in all respects superior, and in particular in terms of sensitivity to the surrounding media and LSPR-biosensing. However, AuNRs synthesis and their further functionalization are less straightforward and require thorough processing. In this paper, we intend to give an up-to-date overview of gold nanorods in LSPR biosensing, starting from a critical review of the recent findings on AuNR synthesis and the main challenges related to it. We further highlight the various strategies set up to coat AuNR with a silica shell of controlled thickness and porosity compatible with LSPR-biosensing. Then, we provide a survey of the methods employed to attach various bioreceptors to AuNR. Finally, the most representative examples of AuNR-based LSPR biosensors are reviewed with a focus put on their analytical performances.
    Mots-clés : CHEMBIO, gold nanorods, localized surface plasmon resonance (LSPR), POLE 3, silica coating, surface functionalization.



  • J. P. Rada, J. Forté, G. Gontard, V. Corcé, M. Salmain, et N. A. Rey, « Isoxazole-Derived Aroylhydrazones and Their Dinuclear Copper(II) Complexes Show Antiproliferative Activity on Breast Cancer Cells with a Potentially Alternative Mechanism Of Action », ChemBioChem, vol. 21, nᵒ 17, p. 2474-2486, 2020.
    Résumé : Abstract This paper reports the design, synthesis and cytotoxicity studies of two new isoxazole-derived aroylhydrazone ligands and their dinuclear copper(II) complexes. Compounds were fully characterized by various spectroscopic and analytical techniques. The molecular structures of four derivatives were confirmed by X-ray crystallography. The stability of the ligands and the complexes in aqueous medium was monitored spectroscopically. Both the ligands and the complexes were shown to interact with calf thymus DNA (ct-DNA). Additionally, structures containing a phenol pendant arm were significantly more cytotoxic than those carrying a pendant pyridine substituent, reaching sub-micromolar IC50 values on the triple-negative human breast cancer cell line MDA-MB-231. The metal chelation and transchelation ability of the compounds towards FeII, FeIII and ZnII ions was explored as a possible mechanism of action of these compounds.
    Mots-clés : antitumor agents, aroylhydrazonic ligands, CHEMBIO, copper(II) complexes, cytotoxicity, DNA, POLE 3.
    Note Note
    <p>doi: 10.1002/cbic.202000122</p>


  • R. Ramos, J. M. Zimbron, S. Thorimbert, L. - M. Chamoreau, A. Munier, C. Botuha, A. Karaiskou, M. Salmain, et J. Sobczak-Thépot, « Insights into the antiproliferative mechanism of (C^N)-chelated half-sandwich iridium complexes », Dalton Transactions, 2020.
    Résumé : Transition metal-based anticancer compounds, as alternative to platinum derivatives, are raising scientific interest as they may present distinct although poorly understood mechanisms of action. We used a structure-activity relationship-based methodology to investigate the chemical and biological features of a series of ten (C^N)-chelated half-sandwich iridiumIII complexes of the general formula [IrCp*(phox)Cl], where (phox) is a 2-phenyloxazoline ligand forming a 5-membered metallacycle. This series of compounds undergoes a fast exchange of their chlorido ligand once solubilised in DMSO. They were cytotoxic to HeLa cells with IC50 values in the micromolar range and induced a rapid activation of caspase-3, an apoptosis marker. In vitro, the oxidative power of all the complexes towards NADH was highlighted but only the complexes bearing substituents on the oxazoline ring were able to produce H2O2 at the micromolar range. However, we demonstrated using a powerful HyPer protein redox sensor-based flow cytometry assay that most complexes rapidly raised intracellular levels of H2O2. Hence, this study shows that oxidative stress can partly explain the cytotoxicity of these complexes on the HeLa cell line and gives a first entry to their mechanism of action
    Mots-clés : CHEMBIO, POLE 3.


  • M. Salmain, N. Fischer-Durand, et B. Rudolf, « Bioorthogonal Conjugation of Transition Organometallic Complexes to Peptides and Proteins: Strategies and Applications », European Journal of Inorganic Chemistry, vol. 2020, nᵒ 1, p. 21-25, 2020.
    Résumé : The advent of bioorthogonal chemistry has revolutionized the common practices in protein bioconjugation and contributed to a large extent to the development of chemical biology, a discipline aimed at studying biological/biochemical processes/events in their natural setting (living cells, whole organisms) using dedicated chemical tools. This minireview intends to provide an up-to-date overview on the various bioorthogonal strategies implemented for the conjugation of transition organometallic entities to peptides, peptide nucleic acids and proteins with a focus on targeted applications, i.e. fluorescence- or radio-labeling for imaging, controlled delivery of therapeutic agents and bioanalysis.
    Mots-clés : CHEMBIO, Click chemistry, Cycloaddition, Ferrocene, Manganese, Peptide nucleic acids, POLE 3.
    Note Note
    <p>doi: 10.1002/ejic.201900810</p>
    Note Note
    <p>doi: 10.1002/ejic.201900810</p>


  • S. Topin-Ruiz, A. Mellinger, E. Lepeltier, C. Bourreau, J. Fouillet, J. Riou, G. Jaouen, L. Martin, C. Passirani, et N. Clere, « p722 ferrocifen loaded lipid nanocapsules improve survival of murine xenografted-melanoma via a potentiation of apoptosis and an activation of CD8+ T lymphocytes », International Journal of Pharmaceutics, p. 120111, nov. 2020.
    Résumé : Metastatic melanoma is a malignant tumor with a poor prognosis. Recent new therapeutics improved the survival of patients at a metastatic stage. However, the low response rate to immunotherapy, explained in part by resistance to apoptosis, needs to develop new strategies. The ferrocifen family represents promising bioorganometallic molecules for melanoma treatment since they show potent anticancer properties. The aim of this study is (i) to evaluate the benefits of a strategy involving encapsulated p722 in lipid nanocapsules (LNC) in B16F10 melanoma mice models and (ii) to compare the beneficial effects with an existing therapy such as anti-CTLA4 mAb. Interestingly, LNC-p722 induces a significant decrease of melanoma cell viability. In vivo data shows a significant improvement in the survival rate and a slower tumor growth with p722-loaded LNC in comparison with anti-CTLA4 mAb. Western blots confirm that LNC-p722 potentiates intrinsic apoptotic pathway. Treatment with LNC-p722 significantly activates CD8+ T lymphocytes compared to treatment with anti-CTLA4 mAb. This study uncovers a new therapeutic strategy with encapsulated p722 to prevent B16F10 melanoma growth and to improve survival of treated mice.
    Mots-clés : apoptosis, CD8 T lymphocytes, CHEMBIO, Ferrocifen, metastatic melanoma, POLE 3.


  • K. Wu, B. Pudasaini, J. Y. Park, S. Top, G. Jaouen, M. - H. Baik, et W. E. Geiger, « Oxidation of Cymantrene-Tagged Tamoxifen Analogues: Effect of Diphenyl Functionalization on the Redox Mechanism », Organometallics, vol. 39, nᵒ 5, p. 679–687, 2020.
    Résumé : The oxidations of 1,1′-di-p-anisolyl-2-cymantrenylbutene (3b) and 1,1′-di-p-hydroxyphenyl-2-cymantrenylbutene (3c) were investigated by electrochemical and spectroscopic experiments and by density functional theory (DFT) calculations. Both compounds undergo a reversible one-electron oxidation followed closely by a partially chemically reversible second oxidation (E1/2 values vs ferrocene: 0.60 and 0.74 V for 3b; 0.63 and 0.78 V for 3c). In comparison to the nonphenyl-functionalized parent, 1,1′-diphenyl-2-cymantrenylbutene (3a), 3b,c have lower and more closely spaced oxidation potentials and more rapid follow-up reactions of their dications, 3b2+ and 3c2+. Shifts in the calculated charge distributions of the neutral compounds and their singly and doubly oxidized products corroborated trends in the measured shifts of Mn–CO νCO frequencies in assigning the redox sites primarily to the diarylbutene fragment. Upon removal of electrons, the lost charge density is partially compensated by the polarizable cymantrenyl tag. The half-lives of the dications 3b2+ and 3c2+ are about 10 s at room temperature in dichloromethane/0.05 M [NBu4][B(C6F5)4]. Their follow-up reactions are initiated by loss of a proton either from a hydroxyl group or from the CH2 group of the diarylbutene unit, giving rise to two products having quinone methide structures. Although the initial oxidation sites of cymantrene-tagged diarylbutenes are primarily ligand based and those of ferrocene-tagged diarylbutenes are metal-based, the ultimate oxidation products of their p-OH- or p-OMe-functionalized derivatives are very similar.
    Mots-clés : CHEMBIO, POLE 3.
    Note Note
    <p>doi: 10.1021/acs.organomet.9b00822</p>


  • L. Zhang, Y. Mazouzi, M. Salmain, B. Liedberg, et S. Boujday, « Antibody-Gold Nanoparticle Bioconjugates for Biosensors: Synthesis, Characterization and Selected Applications », Biosensors and Bioelectronics, vol. 165, p. 112370, oct. 2020.
    Résumé : Antibody-Gold nanoparticle (Ab-AuNP) bioconjugates are widely used in the field of biosensing. This prompted researchers to set up various strategies to conjugate antibodies to gold nanoparticles. Optimal conjugation is of critical importance, as the Ab-AuNP bioconjugates should be stable while maintaining the ability of the antibody to recognize and bind its corresponding antigen. All the same, a high coverage of antibodies on AuNPs is a key-step to build up a sensitive biosensor, but an ideal coverage requires to be perfectly balanced with the orientation and accessibility of the conjugated antibodies. In this review, we intend to provide the reader with the key elements allowing for mastering the conjugation of Ab to AuNP and rationalizing, at the molecular level, the mechanisms involved together with the expected antibody coverages and orientations. We will focus on IgG-type antibodies conjugated to spherical AuNPs as these bioconjugates are the most commonly used ones for biosensors. First, we report an exhaustive survey of the methods of conjugation, via strategies of physisorption and chemisorption. Then we provide a critical restitution of the relevant strategies allowing the quantification of antibodies coverage on gold nanoparticles either through direct analysis of the bioconjugates or indirect analysis of the supernatant. In the last part, we review and discuss selected applications of these Ab-AuNP bioconjugates in optical biosensing.
    Mots-clés : CHEMBIO, Fluorescence, Gold nanoparticles, Immunoglobulin G, Ligand quantification, Localized surface plasmon resonance (LSPR), POLE 3, Surface enhanced Raman scattering (SERS).

2019



  • « 15 Silicates in Photocatalysis », in Photocatalysis in Organic Synthesis, 2019ᵉ éd., Stuttgart: Thieme Verlag, 2019, p. 427.
    Résumé : Thieme E-Books & E-Journals
    Mots-clés : CHEMBIO, MACO, POLE 1, POLE 3.


  • A. Cartier, E. Levernier, V. Corcé, T. Fukuyama, A. - L. Dhimane, C. Ollivier, I. Ryu, et L. Fensterb

    ank, « Carbonylation of Alkyl Radicals Derived from Organosilicates through Visible-Light Photoredox Catalysis », Angewandte Chemie International Edition, vol. 58, nᵒ 6, p. 1789-1793, 2019.
    Résumé : Primary, secondary, and tertiary alkyl radicals formed by the photocatalyzed oxidation of organosilicates underwent efficient carbonylation with carbon monoxide (CO) to give a variety of unsymmetrical ketones. This study introduces the possibility of radical carbonylation under a photooxidative regime.
    Mots-clés : carbonylation, CHEMBIO, MACO, photocatalysis, POLE 1, POLE 3, radicals, silicates, three-component reactions.


  • L. Chang, S. Thorimbert, et L. Dechoux, « The bio-based methyl coumalate involved Morita–Baylis–Hillman reaction », Organic & Biomolecular Chemistry, vol. 17, nᵒ 10, p. 2784-2791, 2019.
    Résumé : We report the first use of renewable, bio-based, non-hazardous feedstock methyl coumalate (MC) in organocatalyzed Morita–Baylis–Hillman (MBH) reactions. This atom-economical pathway employs inexpensive Et3N as a catalyst in ethanol. Synthon MC efficiently constructs C–C bonds with various imines and aldehydes in moderate to good yields. This catalytic process is triggered via an unprecedented 1,6-conjugated addition, as opposed to the classical MBH reaction. Moreover, this methodology expands Morita–Baylis–Hillman donor capabilities to a 2-pyrone derivative for the first time. MBH adducts described herein could be applied to the synthesis of fine chemicals with biologically active structural cores, such as diphenylmethanol, hydroisobenzofurans, and hydroisoindoles.
    Mots-clés : CHEMBIO, POLE 3.


  • T. Dallagi, M. Saidi, G. Jaouen, et S. Top, « Synthesis and biodistribution of 1-[2-(cyclopentadienyltricarbonyltechnetium-99m)-2-oxo-ethoxy-phenyl]-1,2-di- (p-hydroxyphenyl)but-1-ene for tumor imaging », Journal of Organometallic Chemistry, vol. 891, p. 1-6, 2019.
    Résumé : The high incidence and mortality of breast cancer and other estrogen receptor related tumors motivates efforts to develop innovative imaging probes to effectively diagnose, evaluate the extent of the tumor, and predict the efficacy of treatments while concurrently and selectively delivering anticancer agents to the cancer tissues. In the present study, 1-[2-(cyclopentadienyltricarbonyltechnetium-99m)-2-oxo-ethoxy-phenyl]-1,2-di-(p-hydroxyphenyl)but-1-ene was prepared and investigated as a potential agent for imaging estrogen receptors (ERs) in associated tumors. The compound was obtained in high radiochemical purity and radiochemical yields. The biodistribution of the radioactive compound in mature female rats showed an ER-mediation in the ovarian target tissues as the uptake was reduced by a blocking dose of estradiol. The nonspecific uptake in muscle was relatively low.
    Mots-clés : Biodistribution, CHEMBIO, Estrogen receptor, POLE 3, SPECT, Tc radiolabelling, Tumor, Tumor imaging.


  • N. Fischer-Durand, D. Lizinska, V. Guérineau, B. Rudolf, et M. Salmain, « ‘Clickable’ cyclopentadienyl iron carbonyl complexes for bioorthogonal conjugation of mid-infrared labels to a model protein and PAMAM dendrimer », Applied Organometallic Chemistry, vol. 33, nᵒ 4, p. e4798, 2019.
    Résumé : Owing to the intrinsic limitations of the conventional bioconjugation methods involving native nucleophilic functions of proteins, we sought to develop alternative approaches to introduce metallocarbonyl infrared labels onto proteins on the basis of the [3?+?2] dipolar azide-alkyne cycloaddition (AAC). To this end, two cyclopentadienyl iron dicarbonyl (Fp) complexes carrying a terminal or a strained alkyne handle were synthesized. Their reactivity was examined towards a model protein and poly (amidoamine) (PAMAM) dendrimer, both carrying azido groups. While the copper (I)-catalysed azide-alkyne cycloaddition (CuAAC) proceeded smoothly with the terminal alkyne metallocarbonyl derivative, labelling by strain-promoted azide-alkyne cycloaddition (SPAAC) was less successful in terms of final coupling ratios. Infrared spectral characterization of the bioconjugates showed the presence of two bands in the 2000?cm?1 region, owing to the stretching vibration modes of the carbonyl ligands of the Fp entities.
    Mots-clés : bioconjugation, CHEMBIO, copper (I)-catalysed azide-alkyne cycloaddition, infrared spectroscopy, metallocarbonyl complex, POLE 3, strain-promoted azide-alkyne cycloaddition.
    Note Note
    <p>doi: 10.1002/aoc.4798</p>


  • F. Fus, Y. Yang, S. Lee, S. Top, M. Carriere, A. Bouron, A. Pacureanu, J. Da Silva, M. Salmain, A. Vessieres, P. Cloetens, G. Jaouen, et S. Bohic, « Intracellular localization of an osmocenyl-tamoxifen derivative in breast cancer cells revealed by synchrotron radiation X-ray fluorescence nanoimaging », Angewandte Chemie, vol. 58, nᵒ 11, p. 3461-3465, janv. 2019.
    Résumé : We have recently developed a series of tamoxifen-like metallocifens of the group-8 metals (Fe, Ru and Os) with strong antiproliferative activity on the triple negative breast cancer cells (MDA-MB-231). This property, not observed for the organic analog 4-hydroxytamoxifen, has been associated with the unique redox behavior of metallocenic moieties, readily affording reactive quinone methides in cancer cells. To shed light on the mechanism of action of these molecules, synchrotron radiation X-ray fluorescence (SR-XRF) nanoimaging studies were performed on cells exposed to osmocenyl-tamoxifen (Oc-OH-Tam) to disclose its intracellular distribution using osmium as an intrinsic reporter. High resolution mapping of the lipophilic Oc-OH-Tam in cells, revealed its preferential accumulation in the endomembrane system encompassing endoplasmic reticulum, nuclear envelope and vesicular structures. This is consistent with the ability of the amino nitrogen chain of the compounds to be protonated at physiological pH and responsible for electrostatic interactions between Oc-OH-Tam and membranes. We propose a comprehensive scenario that provides new insight into the cellular behavior and activation of Oc-OH-Tam and advances the understanding of its mechanism of action.
    Mots-clés : bioorganometallic chemistry, breast cancer cells, CHEMBIO, elemental tomography, osmium, POLE 3, synchrotron X-ray fluorescence.
    Note Note
    <p>doi: 10.1002/ange.201812336</p>


  • L. Guyon, E. Lepeltier, J. - C. Gimel, B. Calvignac, F. Franconi, N. Lautram, A. Dupont, C. Bourgaux, P. Pigeon, P. Saulnier, G. Jaouen, et C. Passirani, « Importance of Combining Advanced Particle Size Analysis Techniques To Characterize Cell-Penetrating Peptide–Ferrocifen Self-Assemblies », The Journal of Physical Chemistry Letters, vol. 10, nᵒ 21, p. 6613-6620, oct. 2019.
    Mots-clés : CHEMBIO, POLE 3.
    Note Note
    <p>doi: 10.1021/acs.jpclett.9b01493</p>


  • N. Illy, V. Corcé, J. Zimbron, V. Molinié, M. Labourel, G. Tresset, J. Degrouard, M. Salmain, et P. Guégan, « pH-Sensitive Poly(ethylene glycol)/Poly(ethoxyethyl glycidyl ether) Block Copolymers: Synthesis, Characterization, Encapsulation, and Delivery of a Hydrophobic Drug », Macromolecular Chemistry and Physics, vol. 220, nᵒ 16, p. 1900210, 2019.
    Résumé : Abstract Curcumin is a natural polyphenolic compound known for its numerous pharmacological properties. However, its low water solubility and instability at neutral pH are serious drawbacks preventing its use as an oral drug. Well-defined amphiphilic poly(ethylene glycol)-block-poly(ethoxyethyl glycidyl ether) (PEG-b-PEEGE) block copolymers carrying acid-labile acetal groups are synthesized by anionic ring-opening polymerization and investigated as potential pH-sensitive nano-carriers for delivery of curcumin to cancer cells. The nanoparticles, resulting from copolymer self-assembly in aqueous media, are characterized by dynamic light scattering and cryo-transmission electron microscopy. The nanoparticles? stabilities are evaluated in three different phosphate buffers (pH = 7.2, 6.4, and 5.3). The stability decreases at lower pH and a complete disappearance of the nanoparticles is noticed after 4 days at pH 5.3. Curcumin is encapsulated in hydrophobic core of mPEG40-b-PEEGE25 nanoparticles allowing significant enhancements of curcumin solubility in water and lifetime at neutral pH. In vitro curcumin release is studied at different pH by UV-spectroscopy and high-performance liquid chromatography (HPLC). The cytotoxicity of curcumin and curcumin encapsulated in micelles is evaluated by cell viability 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay on MDA-MB-231 human breast cancer cells.
    Mots-clés : amphiphilic polyethers, anionic-ring opening polymerization, CHEMBIO, curcumin encapsulation, pH-sensitive copolymers, POLE 3, POLE 4, POLYMERES, self-assembly.
    Pièce jointe Full Text PDF 1.8 Mo (source)
    Note Note
    <p>doi: 10.1002/macp.201900210</p>


  • S. H. Z. Lee, F. Chau, S. Top, G. Jaouen, A. Vessières, E. Labbé, et O. Buriez, « New mechanistic insights into osmium-based tamoxifen derivatives », Electrochimica Acta, vol. 302, p. 130-136, 2019.
    Résumé : The electrochemical behavior of osmociphenol (3, Oc-OH), an organometallic osmium-based anticancer drug candidate, has been investigated by cyclic voltammetry in the absence and presence of lutidine used as a base model. Osmociphenol exhibited spontaneous deprotonation of the phenol function upon oxidation of the osmocene moiety due to its high acidity. In the presence of lutidine, a base-dependent and different electrochemical behavior was observed at low scan rates indicating a second oxidation step leading to the corresponding cationic quinone methide precursor (3b+). However, compared to ruthenocene derivatives, the stability of 3b+ prevented its conversion into quinone methide as the final and stable complex. Despite differences in their oxidative processes, osmociphenol and ruthenociphenol derivatives exhibit similar biological activities.
    Mots-clés : Anti-cancer, Bioorganometallic, CHEMBIO, Cyclic voltammetry, Osmium, POLE 3, Tamoxifen.


  • C. Lévêque, E. Levernier, V. Corcé, L. Fensterbank, M. Malacria, et C. Ollivier, « Photoredox Catalysis, an Opportunity for Sustainable Radical Chemistry », in Advanced Green Chemistry, vol. Volume 6, World Scientific, 2019, p. 49-121.
    Résumé : The following sections are included: List of Abbreviations Introduction The Photoredox Catalysis as an Alternative Nature as a Source of Inspiration Artificial Redox Photocatalysts Photophysical Properties Principle of Photoredox Catalysis Formation of Carbon Centered Radicals Merging Photoredox and Organometallic Catalysis for Cross-Coupling Reactions Context Radical Trapping by Transition Metals Cobalt Nickel Copper Genesis of the Photoredox/Transition Metal Dual Catalysis: Ruthenium and Palladium Towards Photoredox/Transition Metal Dual Catalysis Processes Processes without Radical Formation: Catalysis of Redox Steps Processes with Radical Formation: Catalysis of Downstream Steps Conclusion Acknowledgments References
    Mots-clés : CHEMBIO, MACO, POLE 1, POLE 3.
    Note Note
    <p>doi:10.1142/9789811210587_0003</p>


  • E. Levernier, V. Corcé, L. - M. Rakotoarison, A. Smith, M. Zhang, S. Ognier, M. Tatoulian, C. Ollivier, et L. Fensterbank, « Cross coupling of alkylsilicates with acyl chlorides via photoredox/nickel dual catalysis: a new synthesis method for ketones », Organic Chemistry Frontiers, vol. 6, nᵒ 9, p. 1378-1382, avr. 2019.
    Résumé : Photoredox/nickel dual catalysis using easily oxidized bis-catecholato hypercoordinated silicon derivatives as radical sources and acyl chlorides as electrophiles allows a new method of formation of dialkyl and alkyl-aryl ketones as well as dibenzyl ketones which are less easily accessed. Flow chemistry can be used.
    Mots-clés : CHEMBIO, MACO, POLE 1, POLE 3.
    Pièce jointe Version soumise 654.1 ko (source)


  • A. Loiseau, V. Asila, G. Boitel-Aullen, M. Lam, M. Salmain, et S. Boujday, « Silver-Based Plasmonic Nanoparticles for and Their Use in Biosensing », Biosensors, vol. 9, nᵒ 2, p. 78, 2019.
    Résumé : The localized surface plasmon resonance (LSPR) property of metallic nanoparticles is widely exploited for chemical and biological sensing. Selective biosensing of molecules using functionalized nanoparticles has become a major research interdisciplinary area between chemistry, biology and material science. Noble metals, especially gold (Au) and silver (Ag) nanoparticles, exhibit unique and tunable plasmonic properties; the control over these metal nanostructures size and shape allows manipulating their LSPR and their response to the local environment. In this review, we will focus on Ag-based nanoparticles, a metal that has probably played the most important role in the development of the latest plasmonic applications, owing to its unique properties. We will first browse the methods for AgNPs synthesis allowing for controlled size, uniformity and shape. Ag-based biosensing is often performed with coated particles; therefore, in a second part, we will explore various coating strategies (organics, polymers, and inorganics) and their influence on coated-AgNPs properties. The third part will be devoted to the combination of gold and silver for plasmonic biosensing, in particular the use of mixed Ag and AuNPs, i.e., AgAu alloys or Ag-Au core@shell nanoparticles will be outlined. In the last part, selected examples of Ag and AgAu-based plasmonic biosensors will be presented.
    Mots-clés : alloy, biosensors, CHEMBIO, coating, core@shell, LSPR, POLE 3, silver nanoparticles, synthesis.


  • A. Loiseau, L. Zhang, D. Hu, M. Salmain, Y. Mazouzi, R. Flack, B. Liedberg, et S. Boujday, « Core–Shell Gold/Silver Nanoparticles for Localized Surface Plasmon Resonance-Based Naked-Eye Toxin Biosensing », ACS Applied Materials & Interfaces, vol. 11, nᵒ 50, p. 46462-46471, déc. 2019.
    Résumé : The localized surface plasmon resonance (LSPR) phenomenon provides a versatile property for biodetection. Herein, this unique feature was employed to build a homogeneous optical biosensor to detect staphylococcal enterotoxin A (SEA) in solution down to very low levels by naked-eye readout. If the initial position of the LSPR band is located in the cyan region, even a small red shift (∼2–3 nm) induced by a refractive index change close to the surface of nanoparticles (NPs) could make the light absorption transit from cyan to green and become visually detectable via a concomitant change in the complementary colors. In this work, we aimed at synthesizing two types of NPs based on compositionally complex core–shell NPs—Ag shells on AuNPs (Au@AgNPs) and Ag inside gold nanoshells (Ag@AuNPs). By controlling the thickness of the shells and their surface chemistry with anti-SEA antibody (Ab), the LSPR band was tuned to near 495 and 520 nm for Ag@AuNPs and Au@AgNPs, respectively. The two particle systems were subsequently applied to spectroscopically and visually detect anti-SEA Ab–SEA interactions. Upon the addition of SEA, large red shifts of the LSPR band were observed spectroscopically and the limits of detection (LODs) were estimated to be 0.2 and 0.4 nM for Au@AgNPs and Ag@AuNPs, respectively. Although the two sets of NPs gave almost identical LODs, the Ag@AuNPs whose initial position of the LSPR band was tuned in the cyan to green region (∼500 nm) displayed a substantially more distinct color change from orange to red, as revealed by the naked eye. We foresee significant potential to this strategy in medical diagnostics and environmental monitoring, especially when basic laboratory infrastructure is sparse or nonexistent.
    Mots-clés : CHEMBIO, POLE 3.
    Note Note
    <p>doi: 10.1021/acsami.9b14980</p>


  • F. Tonolo, M. Salmain, V. Scalcon, S. TOP, P. Pigeon, A. Folda, B. Caron, M. J. McGlinchey, R. - A. Toillon, A. Bindoli, G. Jaouen, A. Vessieres, et M. P. Rigobello, « Small Structural Differences Between Two Ferrocenyl Diphenols Determine Large Discrepancies of Reactivity and Biological Effects », ChemMedChem, vol. 14, nᵒ 19, p. 1717-1726, sept. 2019.
    Résumé : Ferrocenyl diphenol complexes 1, [1,1-bis(4?-hydroxyphenyl)-2-ferrocenyl-but-1-ene], and Z-2, [1,2-bis(4?-hydroxyphenyl)-1-ferrocenyl-but-1-ene], differing by the relative position of the two phenolic substituents, display dramatically different antiproliferative activities on cancer cells (1 being by far more cytotoxic than 2). In this paper our goal is to decipher the origin of this difference by comparing their reactivity and biological behaviour. In terms of common behaviour we found that 1 and 2 are both very efficient inhibitors of thioredoxin reductase (TrxR) in vitro after oxidation by the HRP/H2O2 system. However, as 1 is only a moderate inhibitor of TrxR in MDA-MB-231 cells, TrxR is probably not a major target responsible for the cytotoxicity of 1. In terms of difference we noted that 1 induces a significant redox imbalance characterized by lipid peroxidation and thiol oxidation and a moderate decrease of the mitochondrial membrane potential in breast cancer cells while 2 has almost no effect. These results underline the importance of the trans configuration in the ferrocenyl /double bond / phenol motif, which is present in 1 but not in Z-2 that exists only in a cis configuration.
    Mots-clés : Bioorganometallic chemistry, cancer, CHEMBIO, iron, lipid peroxidation, POLE 3, Thioredoxin Reductase.
    Note Note
    <p>doi: 10.1002/cmdc.201900430</p>


  • A. Vessieres, « CHAPTER 3 Iron Compounds as Anticancer Agents », in Metal-based Anticancer Agents, The Royal Society of Chemistry, 2019, p. 62-90.
    Résumé : Many ferrocene complexes have been prepared for their oncological potential. Some derive from molecules with known biological effects (taxanes, podophyllotoxine, artemisine, SAHA, etc.) while others are synthetic molecules selected for their cytotoxic effects (N-alkylaminoferrocenes and ferrocenyl alkylpyridinium). Although these complexes have received a great deal of attention, the field of iron metallodrugs is not limited to them. A number of inorganic complexes of iron(ii) and iron(iii) with possible anticancer effects have also been published, although research into their biological effects is often only at an early stage. This chapter also includes iron chelators, molecules that are administered in non-metallic form but whose cytotoxic species are their coordination complexes of iron generated in vivo. The most emblematic molecule of this family is bleomycin, used as an anticancer agent in many chemotherapies. To these can be added the iron chelates originally synthesized to treat iron overload, some of which have been shown to possess interesting anticancer properties. They have been, and continue to be, the subject of many clinical trials, whether alone or in combination. Thus, the area of iron metallodrugs includes molecules with very different structures and reactivity, studied from a number of different perspectives, but focused on increasing the number of molecules at our disposal for combatting cancer.
    Mots-clés : CHEMBIO, POLE 3.


  • Y. Wang, P. Pigeon, S. Top, J. García, C. Troufflard, I. Ciofini, M. J. McGlinchey, et G. Jaouen, « Atypical lone pair-π interaction with quinone methides in a series of imido-ferrociphenol anticancer drug candidates », Angewandte Chemie International Edition, vol. 58, nᵒ ja, p. 8421-8425, 2019.
    Résumé : Ferrociphenols, especially those possessing a heterocycle at the terminus of an aliphatic chain, display strong anticancer activity via a novel redox mechanism that generates active metabolites such as quinone methides (QMs). X-ray crystallography and UV-Vis spectroscopy reveal that the specific lone pair (lp)-π interaction between a carbonyl group of the imide and the quinone motif of the QM plays an important role in the exceptional cytotoxic behaviour of their imido-ferrociphenol precursors. This intramolecular lp-π interaction markedly enhanced the stability of the QMs and lowered the pKa values of the corresponding phenolates. As the first example of such a non-covalent interaction that stabilizes QMs remotely, it not only expands the scope of the lp-π interaction in supramolecular chemistry, but also represents a new mode of stabilization of a QM. This unprecedented application of lp-π interactions in imido-ferrociphenol anticancer drug candidates may also have great potential in drug discovery and organocatalyst design.
    Mots-clés : antitumor agents, bioorganometallics, CHEMBIO, ferrocifen, non-covalent interactions, POLE 3, quinones.
    Note Note
    <p>doi: 10.1002/anie.201902456</p>
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    Z. Xia, V. Corcé, F. Zhao, C. Przybylski, A. Espagne, L. Jullien, T. L. Saux, Y. Gimbert, H. Dossmann, V. Mouriès-Mansuy, C. Ollivier, et L. Fensterbank, « Photosensitized oxidative addition to gold( i ) enables alkynylative cyclization of o -alkylnylphenols with iodoalkynes », Nature Chemistry, vol. 11, nᵒ 9, p. 797-805, sept. 2019.
    Résumé : Studies into gold-catalysed cross-coupling reactions have expanded over recent decades; however, oxidative addition to gold(i) complexes remains challenging. Now it has been shown that a dual catalytic transformation involving iridium photosensitization to trigger oxidative addition to organogold intermediates enables C(sp2)–C(sp) cross-coupling reactions that are useful for the alkynylation of benzofurans.
    Mots-clés : CHEMBIO, CSOB, MACO, POLE 1, POLE 3.
    Pièce jointe Full Text PDF 1.8 Mo (source)


  • L. Zhang, P. Chen, A. Loiseau, D. Brouri, S. Casale, M. Salmain, S. Boujday, et B. Liedberg, « Spatially Controlled Reduction and Growth of Silver in Hollow Gold Nanoshell Particles », The Journal of Physical Chemistry C, vol. 123, nᵒ 16, p. 10614-10621, 2019.
    Résumé : Spatially controlled reactions at the nanoscale have attracted increasing interest for fundamental chemistry and for the engineering of novel functional materials. Herein, we demonstrate that pH-triggered reduction of silver ions preferentially occurs at the inner walls of porous and citrate-capped gold nanoshell (AuNS) particles. The reaction initially relies on the presence of sacrificial silver ions inside the AuNS particles as well as in the surrounding preparation solution, and it proceeds upon external addition of silver ions until a solid silver core is formed inside the AuNS particles. Subsequent reduction of silver occurs on the external surface of the solidified AuNS, resulting in a layered and compositionally complex nanoparticle containing both silver and gold. Growth experiments performed in the dark, under white light illumination, as well as near resonance suggest that the reduction reaction is not guided by a plasmonic field enhancement effect. This is in contrast to the recently proposed hot spot mechanism of silver reduction at the rim of nanoholes in a periodic gold array. Our observations point toward a confinement process that proceeds via a continuous supply of silver ions that diffuse from the external solution through the porous shell into the inner volume of the AuNS particles where they become reduced.
    Mots-clés : CHEMBIO, POLE 3.
    Note Note
    <p>doi: 10.1021/acs.jpcc.8b11864</p>


  • L. Zhang, D. Hu, M. Salmain, B. Liedberg, et S. Boujday, « Direct quantification of surface coverage of antibody in IgG-Gold nanoparticles conjugates », Talanta, vol. 204, p. 875-881, nov. 2019.
    Résumé : It is of paramount importance to be able to accurately quantify surface coverage of antibodies on gold nanoparticles (AuNP) so as to optimise the sensitivity of AuNP-based immunosensors. Herein, we developed a fluorescence-based method to directly quantify rabbit immunoglobulin G (IgG) used as antibody model bound to AuNP. Rabbit IgG was first labelled with fluorescein-5-isothiocyanate (FITC) prior to conjugation to AuNP via either physisorption or chemisorption. IgG-conjugated AuNP were treated with NaCN to dissolve the AuNP and restore the fluorescence emission that was quenched in the presence of the metallic colloids, followed by quantification of fluorescein by spectrofluorimetry. This direct assay gave about 4 IgG bound to each 15-nm diameter AuNP for both immobilization strategies. This surface coverage value was in good agreement with that determined from the theoretical value calculated from the Localized Surface Plasmon Resonance (LSPR) band shift. For comparison, we also applied two indirect methods based on the quantitation of excess IgG remaining in the supernatant using fluorescence assay or enzyme-linked immunosorbent assay (ELISA). The indirect assays, either fluorescence or ELISA, commonly used to assess the antibody coverage on AuNP, overestimated the IgG surface coverage to a large extent, since up to 3 to 4 times higher coverages were measured. Therefore, the direct fluorescence method reported in this paper appears as a valuable method for quantification of surface coverage of antibody on AuNP.
    Mots-clés : Adsorption, CHEMBIO, Fluorescence, Gold nanoparticles, Immunoglobulin G (IgG), POLE 3, Quantification.


  • L. Zhang, M. Salmain, B. Liedberg, et S. Boujday, « Naked Eye Immunosensing of Food Biotoxins Using Gold Nanoparticle-Antibody Bioconjugates », ACS Applied Nano Materials, vol. 2, nᵒ 7, p. 4150-4158, 2019.
    Résumé : Colorimetric immunoassays using gold nanoparticles (AuNP) form a special class of assays where AuNP act as a transducer to monitor binding events between an antigen and an antibody. Indeed, AuNP display unique optical properties that can been exploited in various ways to develop biosensors. One of the most striking properties of colloidal AuNP (and more generally of noble metal nanomaterials) is their extremely high extinction coefficient in the visible range of the spectrum owing to the localized surface plasmon resonance (LSPR) phenomenon. This feature makes AuNP detectable down to very low concentrations by absorption spectroscopy or even by the naked eye. Herein we took advantage of the high detectability of AuNP to design a solid-phase, sandwich-type, colorimetric immunosensor aiming at the detection of staphylococcal enterotoxin A (SEA). A test zone comprised of a polyclonal anti-SEA antibody was created at the surface of amino-functionalized glass slides via high affinity binding to covalently immobilized Protein A. The same antibody was conjugated to 13 nm diameter AuNP to afford the nanoimmunoprobe. After the glass slides were successively exposed to SEA and AuNP-antibody bioconjugate, a distinct red spot appeared at the detection zone from as low as 1 ng SEA in buffer. Quantification of SEA in the 10–500 ng/mL range was established using a benchtop UV–visible spectrometer by integration of the LSPR band centered at 530 nm. Eventually, this biosensor was applied to the detection of SEA in milk with a limit of detection of 1.5 ng/mL.
    Mots-clés : CHEMBIO, POLE 3.
    Note Note
    <p>doi: 10.1021/acsanm.9b00598</p>

2018



  • C. K. Barik, R. Ganguly, Y. Li, C. Przybylski, M. Salmain, et W. K. Leong, « Embedding a Ruthenium-Based Structural Mimic of the [Fe]-Hydrogenase Cofactor into Papain », Inorganic Chemistry, vol. 57, nᵒ 19, p. 12206-12212, sept. 2018.
    Mots-clés : CHEMBIO, CSOB, POLE 3.

  • M. Ben Haddada, M. Salmain, et S. Boujday, « Gold colloid-nanostructured surfaces for enhanced piezoelectric immunosensing of staphylococcal enterotoxin A », Sensors and Actuators B: Chemical, vol. 255, nᵒ 2, p. 1604-1613, 2018.


  • B. Bertrand, K. Passador, C. Goze, F. Denat, E. Bodio, et M. Salmain, « Metal-based BODIPY derivatives as multimodal tools for life sciences », Coordination Chemistry Reviews, vol. 358, p. 108-124, 2018.
    Résumé : Nowadays, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene – better known as BODIPY – is at the forefront of fluorophores for life sciences. Indeed, its high brightness, its tunable excitation and emission wavelengths along with its high chemical and photochemical stability draw more and more the interest of researchers. In the last decade, chemists have taken advantage of the versatility of the synthesis of BODIPY to design sophisticated objects. This review focuses on the different recent studies dealing with the conception of metal-based-BODIPY derivatives for medical purposes. More precisely, emphasis is put on the use of BODIPY derivatives for the elaboration of BODIPY-based theranostics, multimodal imaging probes, and photodynamic therapy sensitizers.
    Mots-clés : Bimodal imaging, BODIPY, CHEMBIO, Fluorescence, Metal-based drugs, Photodynamic therapy, POLE 3, Theranostics.


  • N. Chahin, L. A. Uribe, A. M. Debela, S. Thorimbert, B. Hasenknopf, M. Ortiz, I. Katakis, et C. K. O'Sullivan, « Electrochemical primer extension based on polyoxometalate electroactive labels for multiplexed detection of single nucleotide polymorphisms », Biosensors and Bioelectronics, vol. 117, p. 201-206, 2018.
    Résumé : Polyoxymetalates (POMs) ([SiW11O39{Sn(CH2)2CO)}]4- and [P2W17O61{Sn(CH2)2CO)}]6-) were used to modify dideoxynucleotides (ddNTPs) through amide bond formation, and applied to the multiplexed detection of single nucleotide polymorphisms (SNPs) in an electrochemical primer extension reaction. Each gold electrode of an array was functionalised with a short single stranded thiolated DNA probe, specifically designed to extend with the POM-ddNTP at the SNP site to be interrogated. The system was applied to the simultaneous detection of 4 SNPs within a single stranded 103-mer model target generated using asymmetric PCR, highlighting the potential of POM-ddNTPs for targeted, multiplexed SNP detection. The four DNA bases were successfully labelled with both ([SiW11O39{Sn(CH2)2CO)}]4- and [P2W17O61{Sn(CH2)2CO)}]6-), and [SiW11O39{Sn(CH2)2CO)}]4- demonstrated to be the more suitable due to its single oxidation peak, which provides an unequivocal signal. The POM-ddNTP enzymatically incorporated to the DNA anchored to the surface was visualised by AFM using gold coated mica. The developed assay has been demonstrated to be highly reproducible, simple to carry out and with very low non-specific background signals. Future work will focus on applying the developed platform to the detection of SNPs associated with rifampicin resistance in real samples from patients suffering from tuberculosis.
    Mots-clés : CHEMBIO, Electrochemical primer extension reaction (éPEX), GOBS, Multiplexed electrochemical detection, POLE 3, Polyoxometalate-labelled ddNTPs, SNP detection.


  • L. Chang, N. Klipfel, L. Dechoux, et S. Thorimbert, « A solvent-free, base-catalyzed domino reaction towards trifluoromethylated benzenes from bio-based methyl coumalate », Green Chemistry, vol. 20, nᵒ 7, p. 1491-1498, 2018.
    Résumé : A novel, efficient, and environmentally compatible method for CF3-substituted benzene production is reported. It sources a bio-based feedstock, employs tBuOK as a catalyst, and is solvent-free. This regioselective approach provides various trifluoromethyl benzenes in good to excellent yields, without any extra oxidant or special care. CO2 and water are the only byproducts of this process, and the reaction conditions can scale up to gram quantities. The transformation involves an unprecedented tBuOK-catalyzed domino process, and features Michael addition/6[small pi]-electrocyclic ring opening/[1,5]-H shift/carba-6[small pi]-electrocyclic ring closure/decarboxylative aromatization reactions.
    Mots-clés : CHEMBIO, POLE 3.


  • M. V. Cherrier, P. Amara, B. Talbi, M. Salmain, et J. C. Fontecilla-Camps, « Crystallographic evidence for unexpected selective tyrosine hydroxylations in an aerated achiral Ru–papain conjugate », Metallomics, vol. 10, nᵒ 10, p. 1452-1459, 2018.
    Résumé : The X-ray structure of an aerated achiral Ru–papain conjugate has revealed the hydroxylation of two tyrosine residues found near the ruthenium ion. The most likely mechanism involves a ruthenium-bound superoxide as the reactive species responsible for the first hydroxylation and the resulting high valent Ru(iv)O species for the second one.
    Mots-clés : CHEMBIO, POLE 3.


  • de Jesús Cázares-Marinero José, Przybylski Cédric, et Salmain Michèle, « Proteins as Macromolecular Ligands for Metal-Catalysed Asymmetric Transfer Hydrogenation of Ketones in Aqueous Medium », European Journal of Inorganic Chemistry, vol. 2018, nᵒ 12, p. 1383-1393, 2018.
    Résumé : Biohybrid catalysts resulting from the dative anchoring of half-sandwich organometallic complexes [M(arene)(H2O)x(Cl)y]n+ (M = RuII, arene = ?6-benzene, p-cymene or mesitylene; M = IrIII, RhIII, arene = ?5-Cp*; x = 1?3, y = 0?2, n = 0?2) to bovine beta-lactoglobulin (?LG) or hen egg white lysozyme showed unprecedented behaviour. These constructs were shown to catalyse the asymmetric transfer hydrogenation of aryl ketones in water with sodium formate as hydrogen donor at a much faster rate than the complexes alone. Full conversion of the benchmark substrate 2,2,2-trifluoroacetophenone was reached with an ee of 86?% for the most selective biohybrid. Surprisingly, even the crude biohybrid gave a good ee despite the presence of non-protein-bound metal species in the reaction medium. Other aryl ketones were reduced in the same way, and the highest ee was obtained for ortho-substituted acetophenone derivatives. Furthermore, treatment of ?LG with dimethyl pyrocarbonate resulted in a noticeable decrease of the activity and selectivity of the biohybrid, indicating that the sole accessible histidine residue (His146) was probably involved in the coordination and activation of Ru(benzene). This work underscores that protein scaffolds are efficient chiral ligands for asymmetric catalysis. The use of sodium formate instead of dihydrogen makes this approach safe, inexpensive and environmentally friendly.
    Mots-clés : Artificial metalloenzymes, Asymmetric catalysis, CHEMBIO, CSOB, Hydrogenation, Mass spectrometry, POLE 3, Ruthenium.
    Note Note
    <p>doi: 10.1002/ejic.201701359</p>


  • J. Elloumi-Mseddi, S. Mnif, N. Akacha, B. Hakim, P. Pigeon, G. Jaouen, S. Top, et S. Aifa, « Selective cytotoxicity of arene tricarbonylchromium towards tumour cell lines », Journal of Organometallic Chemistry, vol. 862, p. 7-12, 2018.
    Mots-clés : 50% inhibitory concentration, CHEMBIO, Cytotoxicity, Inorganic chromium (VI), Organometallics, POLE 3, Tricarbonylchromium, Tumour cell lines.


  • F. Fus, Y. Yang, H. Z. S. Lee, S. Top, M. Carriere, A. Bouron, A. Pacureanu, J. C. da Silva, M. Salmain, A. Vessieres, P. Cloetens, G. Jaouen, et S. Bohic, « Synchrotron Radiation X-Ray Fluorescence Nanoimaging Reveal the Intracellular Localization of Potent Anticancer Drug Osmocenyl-Tamoxifen Derivative », Microscopy and Microanalysis, vol. 24, nᵒ S2, p. 348-349, 2018.


  • R. Karim, E. Lepeltier, L. Esnault, P. Pigeon, L. Lemaire, C. Lépinoux-Chambaud, N. Clere, G. Jaouen, J. Eyer, G. Piel, et C. Passirani, « Enhanced and preferential internalization of lipid nanocapsules into human glioblastoma cells: effect of a surface-functionalizing NFL peptide », Nanoscale, vol. 10, nᵒ 28, p. 13485-13501, 2018.
    Résumé : Increasing intracellular drug concentration using nanocarriers can be a potential strategy to improve efficacy against glioblastoma (GBM). Here, the fluorescent-labelled NFL-TBS·40-63 peptide (fluoNFL) concentration on a lipid nanocapsule (LNC) was studied to enhance nanovector internalization into human GBM cells. LNC surface-functionalization with various fluoNFL concentrations was performed by adsorption. LNC size and surface charge altered gradually with increasing peptide concentration, but their complement protein consumption remained low. Desorption of fluoNFL from the LNC surface was found to be slow. Furthermore, it was observed that the rate and extent of LNC internalization in the U87MG human glioblastoma cells were dependent on the surface-functionalizing fluoNFL concentration. In addition, we showed that the uptake of fluoNFL-functionalized LNCs was preferential towards U87MG cells compared to healthy human astrocytes. The fluoNFL-functionalized LNC internalization into the U87MG cells was energy-dependent and occurred possibly by macropinocytosis and clathrin-mediated and caveolin-mediated endocytosis. A new ferrocifen-type molecule (FcTriOH), as a potent anticancer candidate, was then encapsulated in the LNCs and the functionalization improved its in vitro efficacy compared to other tested formulations against U87MG cells. In the preliminary study, on subcutaneous human GBM tumor model in nude mice, a significant reduction of relative tumor volume was observed at one week after the second intravenous injection with FcTriOH-loaded LNCs. These results showed that enhancing NFL peptide concentration on the LNC surface is a promising approach for increased and preferential nanocarrier internalization into human GBM cells, and the FcTriOH-loaded LNCs are a promising therapy approach for GBM. ER
    Mots-clés : CHEMBIO, POLE3.


  • F. Najlaoui, P. Pigeon, S. Aroui, M. Pezet, L. Sancey, N. Marrakchi, A. Rhouma, G. Jaouen, M. Waard, B. Busser, et S. Gibaud, « Anticancer properties of lipid and poly(ε-caprolactone) nanocapsules loaded with ferrocenyl-tamoxifen derivatives », Journal of Pharmacy and Pharmacology, vol. 70, nᵒ 11, p. 1474-1484, 2018.
    Résumé : Abstract Objective We synthesized new tamoxifen derivatives as anticancer drug candidates and elaborated on convection-enhanced delivery (CED) as a strategy for delivery. Methods To overcome the issue of their poor solubility, these ferrocenyl-tamoxifen derivatives were esterified and encapsulated into different nanocarriers, that is lipid (LNC) and polymeric nanocapsules (PNL-NC). We describe the chemistry, the encapsulation and the physicochemical characterization of these formulations. Key findings Starting compounds [phthalimido-ferrocidiphenol and succinimido-ferrocidiphenol], esterified prodrugs and their nanocapsules formulations were characterized. These drug candidates displayed a strong in vitro activity against breast and glioblastoma cancer cells. The ester prodrugs were toxic for glioblastoma cells (IC50 = 9.2 ? 10?2 ?m and 6.7 ? 10?2 ?m, respectively). The IC50 values for breast cancer cells were higher for these compounds. The encapsulation of the esterified compounds in LNCs (≈50 nm) or PCL-NCs (≈300 nm) did not prevent their efficacy on glioblastoma cells. These anticancer effects were due to both blockade in the S-phase of the cell cycle and apoptosis. Moreover, the tamoxifen derivatives-loaded nanocapsules induced no toxicity for healthy astrocytes and showed no haemolytic properties. Loaded Lipid Nanocapsules (LNCs) presented interesting profiles for the optimal delivery of active compounds. Conclusions Phthalimido- and Succinimido-esters represent an innovative approach to treat cancers with cerebral localizations such as glioblastoma or brain metastases from breast cancers.
    Mots-clés : breast cancer, CHEMBIO, ferrocenyl-tamoxifen derivatives, glioblastoma, Lipid nanocapsules, POLE 3, polymer nanocapsules.
    Note Note
    <p>doi: 10.1111/jphp.12998</p>


  • Ortiz Mayreli, Debela Ahmed M., Méthivier Christophe, Thorimbert Serge, Hasenknopf Bernold, et O'Sullivan Ciara K., « Stable Carboxylate-Terminated Gold Surfaces Produced by Spontaneous Grafting of an Alkyltin Compound », Chemistry – A European Journal, vol. 24, nᵒ 43, p. 11177-11184, 2018.
    Résumé : Abstract Self-assembled monolayers formed by chemisorption of thiolated molecules on gold surfaces are widely applied for biosensing. Moreover, and due to the low stability of thiol?gold chemistry, contributions to the functionalisation of gold substrates with linkers that provide a more stable platform for the immobilisation of electroactive or biological molecules are highly appreciated. Herein, it is demonstrated that a carboxylated organotin compound can be successfully grafted onto gold substrates to form a highly stable organic layer with reactivity for subsequent binding to an aminated molecule. A battery of techniques were used to characterise the surface chemistry. The grafted layer was used to anchor aminoferrocene and subjected to both thermostability tests and long-term stability studies over a period of one year, demonstrating thermostability up to 90?°C and storage stability for at least 12?months at 4?°C protected from light. The stable surface tethering of molecules on gold substrates can be exploited in a plethora of applications, including molecular techniques, such as solid-phase amplification and solid-phase melting curve analysis, that require elevated temperature stability, as well as biosensors, which require long-term storage stability.
    Mots-clés : biosensors, CHEMBIO, electrochemistry, GOBS, gold, POLE 3, surface chemistry, tin.
    Note Note
    <p>doi: 10.1002/chem.201801854</p>


  • K. Passador, S. Thorimbert, et C. Botuha, « Heteroaromatic Rings of the Future’: Exploration of Unconquered Chemical Space », Synthesis, vol. 51, nᵒ 02, p. 384-398, nov. 2018.
    Résumé : William Pitt and co-workers have created a virtual exploratory heterocyclic library ‘VEHICLe’ containing over 200 unconquered bicyclic heteroaromatic rings, synthetically feasible with potential medicinal interest. Since the publication of the 22 ‘heteroaromatic rings of the future’ by Pitt in 2009, 15 of them have been successfully synthesized as bicyclic or polycyclic forms and evaluated for applications in both biology and material science. This short review presents the critical synthesis associated with innovative synthetic methodologies of the synthetically conquered ring scaffolds from the list of 22 with a spotlight on the scientific contribution of this fascinating article for the expansion of the chemical diversity.
    Mots-clés : CHEMBIO, POLE 3.


  • Y. Wang, P. M. Dansette, P. Pigeon, S. Top, M. J. McGlinchey, D. Mansuy, et G. Jaouen, « A new generation of ferrociphenols leads to a great diversity of reactive metabolites, and exhibits remarkable antiproliferative properties », Chemical Science, vol. 9, p. 70-78, 2018.


  • Y. Wang, F. Heinemann, S. Top, A. Dazzi, C. Policar, L. Henry, F. Lambert, G. Jaouen, M. Salmain, et A. Vessieres, « Ferrocifens labelled with an infrared rhenium tricarbonyl tag: synthesis, antiproliferative activity, quantification and nano IR mapping in cancer cells », Dalton Transactions, vol. 47, p. 9824-9833, 2018.
    Résumé : Antiproliferative activities of several members of the ferrocifen family, both in vitro and in vivo, are well documented although their precise location in cancer cells has not yet been elucidated. However, two different infrared imaging techniques have been used to map the non-cytotoxic cyrhetrenyl analogue of ferrociphenol in a single cell. This observation prompted us to tag two ferrocifens with a cyrhetrenyl unit [CpRe(CO)3; Cp = η5-cyclopentadienyl] by grafting it, via an ester bond, either to one of the phenols (4, 5) or to the hydroxypropyl chain (6). Complexes 4–6 retained a high cytotoxicity on breast cancer cells (MDA-MB-231) with IC50 values in the range 0.32–2.5 μM. Transmission IR spectroscopy was used to quantify the amount of cyrhetrenyl tag present in cells incubated with 5 or 6. The results show that after a 1-hour incubation of cells at 37 °C, complexes 5 and 6 are mainly present within cells while only a limited percentage, quantified by ICP-OES, remained in the incubation medium. AFM-IR spectroscopy, a technique coupling infrared irradiation with near-field AFM detection, was used to map the cyrhetrenyl unit in a single MDA-MB-231 cell, incubated at 37 °C for 1 hour with 10 μM of 6. The results show that signal distribution of the characteristic band of the Re(CO)3 entity at 1950 cm−1 matched those of amide and phosphate, thus indicating a location of the complex mainly in the cell nucl
    Mots-clés : CHEMBIO, POLE 3.


  • K. Wu, J. Y. Park, R. Al-Saadon, H. Nam, Y. Lee, S. Top, G. Jaouen, M. - H. Baik, et W. E. Geiger, « Oxidation of Cymantrene Analogues of Ferrocifen: Electrochemical, Spectroscopic, and Computational Studies of the Parent Complex 1,1′-Diphenyl-2-cymantrenylbutene », Organometallics, vol. 37, nᵒ 12, p. 1910-1918, 2018.
    Résumé : The oxidative electrochemical behavior of 1,1′-diphenyl-2-cymantrenylbutene (1), a cymantrene analogue of the breast cancer drug ferrocifen, was shown to involve the sequential electron-transfer series 1/1+/12+ in dichloromethane/0.05 M [NBu4][B(C6F5)4] (E1/2 values 0.78 and 1.18 V vs ferrocene). By a combination of spectroscopic and computational techniques, it was shown that the cymantrene functionality plays an important role in dissipating the positive charges in the oxidized compounds and is therefore an active participant in the redox events. The redox-active orbital goes from roughly equal degrees of organometallic and π-organic (diphenylolefin) makeup in 1 to increasingly organic based fractions in 1+ and 12+. Structural changes mimicking those of oxidized tetrakis(aryl)ethylenes accompany the one-electron oxidations. There is sufficient unpaired electron density on the manganese center in 1+ to allow for oxidatively induced ligand exchange of one or more of the carbonyl ligands with donor ligands, including phosphites and pyridine. The complex Mn(CO)2P(OPh)3(η5-C5H4(Et)C═C(C6H5)2) was prepared by the “electrochemical switch” method, wherein [Mn(CO)2P(OPh)3(η5-C5H4(Et)C═C(C6H5)2)]+, produced by the oxidation of 1 in the presence of P(OPh)3, was reduced back to the neutral CO-substituted complex.
    Mots-clés : CHEMBIO, POLE 3.
    Note Note
    <p>doi: 10.1021/acs.organomet.8b00186</p>

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