2024
|
Metal complexes in cells: from design of catalytic antioxidants to imaging metal ions and designing metal-based probes in X-ray fluorescence and IR-imaging, a multidisciplinary collaborative journey in bioinorganic chemistry and inorganic chemical biology Journal Article Clotilde Policar; Nicolas Delsuc; Hél`ene Charlotte Bertrand Comptes Rendus. Chimie, 2024, (Online first). @article{CRCHIM_2024__27_S2_A12_0,
title = {Metal complexes in cells: from design of catalytic antioxidants to imaging metal ions and designing metal-based probes in X-ray fluorescence and IR-imaging, a multidisciplinary collaborative journey in bioinorganic chemistry and inorganic chemical biology},
author = {Clotilde Policar and Nicolas Delsuc and H\'{e}l`ene Charlotte Bertrand},
doi = {10.5802/crchim.295},
year = {2024},
date = {2024-01-01},
journal = {Comptes Rendus. Chimie},
publisher = {Acad\'{e}mie des sciences, Paris},
note = {Online first},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
2022
|
Improvement of Peptidyl Copper Complexes Mimicking Catalase: A Subtle Balance between Thermodynamic Stability and Resistance towards H2O2 Degradation Journal Article Yaqine Ben Hadj Hammouda; Koudedja Coulibaly; Alimatou Bathily; Magdalene Teoh Sook Han; Clotilde Policar; Nicolas Delsuc Molecules, 27 (17), 2022, ISSN: 1420-3049. @article{molecules27175476,
title = {Improvement of Peptidyl Copper Complexes Mimicking Catalase: A Subtle Balance between Thermodynamic Stability and Resistance towards H2O2 Degradation},
author = {Yaqine Ben Hadj Hammouda and Koudedja Coulibaly and Alimatou Bathily and Magdalene Teoh Sook Han and Clotilde Policar and Nicolas Delsuc},
url = {https://www.mdpi.com/1420-3049/27/17/5476},
doi = {10.3390/molecules27175476},
issn = {1420-3049},
year = {2022},
date = {2022-01-01},
journal = {Molecules},
volume = {27},
number = {17},
abstract = {Catalase mimics are low molecular weight metal complexes that reproduce the activity of catalase, an antioxidant metalloprotein that participates in the cellular regulation of H2O2 concentration by catalyzing its dismutation. H2O2 is a reactive oxygen species that is vital for the normal functioning of cells. However, its overproduction contributes to oxidative stress, which damages cells. Owing to their biocompatibility, peptidyl complexes are an attractive option for clinical applications to regulate H2O2 by enzyme mimics. We report here the synthesis and characterization of four new peptidyl di-copper complexes bearing two coordinating sequences. Characterization of the complexes showed that, depending on the linker used between the two coordinating sequences, their catalytic activity for H2O2 dismutation, their thermodynamic stability and their resistance to H2O2 degradation are very different, with (CATm2)Cu2 being the most promising catalyst.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Catalase mimics are low molecular weight metal complexes that reproduce the activity of catalase, an antioxidant metalloprotein that participates in the cellular regulation of H2O2 concentration by catalyzing its dismutation. H2O2 is a reactive oxygen species that is vital for the normal functioning of cells. However, its overproduction contributes to oxidative stress, which damages cells. Owing to their biocompatibility, peptidyl complexes are an attractive option for clinical applications to regulate H2O2 by enzyme mimics. We report here the synthesis and characterization of four new peptidyl di-copper complexes bearing two coordinating sequences. Characterization of the complexes showed that, depending on the linker used between the two coordinating sequences, their catalytic activity for H2O2 dismutation, their thermodynamic stability and their resistance to H2O2 degradation are very different, with (CATm2)Cu2 being the most promising catalyst. |
Deciphering the Metal Speciation in Low-Molecular-Weight Complexes by IMS-MS: Application to the Detection of Manganese Superoxide Dismutase Mimics in Cell Lysates Journal Article Martha Zoumpoulaki; Gabrielle Schanne; Nicolas Delsuc; Hugues Preud'homme; Elodie Quévrain; Nicolas Eskenazi; Géraldine Gazzah; Regis Guillot; Philippe Seksik; Joelle Vinh; Ryszard Lobinski; Clotilde Policar Angewandte Chemie International Edition, n/a (n/a), pp. e202203066, 2022. @article{https://doi.org/10.1002/anie.202203066,
title = {Deciphering the Metal Speciation in Low-Molecular-Weight Complexes by IMS-MS: Application to the Detection of Manganese Superoxide Dismutase Mimics in Cell Lysates},
author = {Martha Zoumpoulaki and Gabrielle Schanne and Nicolas Delsuc and Hugues Preud'homme and Elodie Qu\'{e}vrain and Nicolas Eskenazi and G\'{e}raldine Gazzah and Regis Guillot and Philippe Seksik and Joelle Vinh and Ryszard Lobinski and Clotilde Policar},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202203066},
doi = {https://doi.org/10.1002/anie.202203066},
year = {2022},
date = {2022-01-01},
journal = {Angewandte Chemie International Edition},
volume = {n/a},
number = {n/a},
pages = {e202203066},
abstract = {Abstract The detection and quantification of exogenous metal complexes are crucial to understanding their activity in intricate biological media. MnII complexes are difficult to detect and quantify because of low association constants, and high lability. The superoxide dismutase (SOD) mimic (or mimetic) labelled Mn1 is based on a 1,2-di-aminoethane functionalized with imidazole and phenolate and has good intrinsic anti-superoxide, antioxidant and anti-inflammatory activities in lipopolysaccharide (LPS)-activated intestinal epithelial HT29-MD2 cells, similar to that of its propylated analogue labelled Mn1P. Ion mobility spectrometry-mass spectrometry (IMS-MS) is a powerful technique for separating low molecular weight (LMW) metal complexes and can even separate complexes with the same ligand but bound to different divalent metal cations with similar ionic radii. We demonstrated the intracellular presence of the Mn1 and Mn1P complexes, at least partly intact, in lysates of cells incubated with the complexes and estimated the intracellular Mn1P concentration using a Co-13C6 analogue.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Abstract The detection and quantification of exogenous metal complexes are crucial to understanding their activity in intricate biological media. MnII complexes are difficult to detect and quantify because of low association constants, and high lability. The superoxide dismutase (SOD) mimic (or mimetic) labelled Mn1 is based on a 1,2-di-aminoethane functionalized with imidazole and phenolate and has good intrinsic anti-superoxide, antioxidant and anti-inflammatory activities in lipopolysaccharide (LPS)-activated intestinal epithelial HT29-MD2 cells, similar to that of its propylated analogue labelled Mn1P. Ion mobility spectrometry-mass spectrometry (IMS-MS) is a powerful technique for separating low molecular weight (LMW) metal complexes and can even separate complexes with the same ligand but bound to different divalent metal cations with similar ionic radii. We demonstrated the intracellular presence of the Mn1 and Mn1P complexes, at least partly intact, in lysates of cells incubated with the complexes and estimated the intracellular Mn1P concentration using a Co-13C6 analogue. |
Cellular Detection of a Mitochondria Targeted Brominated Vinyl Triphenylamine Optical Probe (TP−Br) by X-Ray Fluorescence Microscopy Journal Article Sounderya Nagarajan; Florent Poyer; Laura Fourmois; Delphine Naud-Martin; Kadda Medjoubi; Andrea Somogyi; Gabrielle Schanne; Lucas Henry; Nicolas Delsuc; Clotilde Policar; Helene C Bertrand; Florence Mahuteau-Betzer Chemistry – A European Journal, 28 (15), pp. e202104424, 2022. @article{https://doi.org/10.1002/chem.202104424,
title = {Cellular Detection of a Mitochondria Targeted Brominated Vinyl Triphenylamine Optical Probe (TP−Br) by X-Ray Fluorescence Microscopy},
author = {Sounderya Nagarajan and Florent Poyer and Laura Fourmois and Delphine Naud-Martin and Kadda Medjoubi and Andrea Somogyi and Gabrielle Schanne and Lucas Henry and Nicolas Delsuc and Clotilde Policar and Helene C Bertrand and Florence Mahuteau-Betzer},
url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202104424},
doi = {https://doi.org/10.1002/chem.202104424},
year = {2022},
date = {2022-01-01},
journal = {Chemistry \textendash A European Journal},
volume = {28},
number = {15},
pages = {e202104424},
abstract = {Abstract Triphenylamine (TP) derivatives such as two-branch cationic vinylbenzimidazolium triphenylamine TP−2Bzim are promising turn-on fluorescent probes suitable for two-photon imaging, labelling mitochondria in live cells. Here, we designed two TP−2Bzim derivatives as bimodal probes suitable for X-ray fluorescence imaging. The conjugation of the TP core with a rhenium tricarbonyl moiety in the TP−RePyta probe altered the localisation in live cells from mitochondria to lysosomes. The introduction of bromine on the TP core generated the TP−Br probe retaining good photophysical properties and mitochondria labelling in live cells. The influence of calcium channels in the uptake of TP−Br was studied. Synchrotron Radiation X-ray Fluorescence (SXRF) imaging of bromine enabled the detection of TP−Br and suggested a negligible presence of the probe in an unbound state in the incubated cells, a crucial point in the development of these probes. This study paves the way towards the development of TP probes as specific organelle stainers suitable for SXRF imaging.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Abstract Triphenylamine (TP) derivatives such as two-branch cationic vinylbenzimidazolium triphenylamine TP−2Bzim are promising turn-on fluorescent probes suitable for two-photon imaging, labelling mitochondria in live cells. Here, we designed two TP−2Bzim derivatives as bimodal probes suitable for X-ray fluorescence imaging. The conjugation of the TP core with a rhenium tricarbonyl moiety in the TP−RePyta probe altered the localisation in live cells from mitochondria to lysosomes. The introduction of bromine on the TP core generated the TP−Br probe retaining good photophysical properties and mitochondria labelling in live cells. The influence of calcium channels in the uptake of TP−Br was studied. Synchrotron Radiation X-ray Fluorescence (SXRF) imaging of bromine enabled the detection of TP−Br and suggested a negligible presence of the probe in an unbound state in the incubated cells, a crucial point in the development of these probes. This study paves the way towards the development of TP probes as specific organelle stainers suitable for SXRF imaging. |
SOD mimics: From the tool box of the chemists to cellular studies Journal Article Clotilde Policar; Jean Bouvet; Hélène C Bertrand; Nicolas Delsuc Current Opinion in Chemical Biology, 67 , pp. 102109, 2022, ISSN: 1367-5931. @article{POLICAR2022102109,
title = {SOD mimics: From the tool box of the chemists to cellular studies},
author = {Clotilde Policar and Jean Bouvet and H\'{e}l\`{e}ne C Bertrand and Nicolas Delsuc},
url = {https://www.sciencedirect.com/science/article/pii/S136759312100154X},
doi = {https://doi.org/10.1016/j.cbpa.2021.102109},
issn = {1367-5931},
year = {2022},
date = {2022-01-01},
journal = {Current Opinion in Chemical Biology},
volume = {67},
pages = {102109},
abstract = {Superoxide dismutases (SODs) are metalloproteins that protect cells against oxidative stress by controlling the concentration of superoxide (O2−) through catalysis of its dismutation. The activity of superoxide dismutases can be mimicked by low-molecular-weight complexes having potential therapeutic applications. This review presents recent strategies for designing efficient SOD mimics, from molecular metal complexes to nanomaterials. Studies of these systems in cells reveal that some SOD mimics, designed to react directly with superoxide, may also indirectly enhance the cellular antioxidant arsenal. Finally, a good understanding of the bioactivity requires information on the cell-penetration, speciation, and subcellular location of the SOD mimics: we will describe recent studies and new techniques that open opportunities for characterizing SOD mimics in biological environments.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Superoxide dismutases (SODs) are metalloproteins that protect cells against oxidative stress by controlling the concentration of superoxide (O2−) through catalysis of its dismutation. The activity of superoxide dismutases can be mimicked by low-molecular-weight complexes having potential therapeutic applications. This review presents recent strategies for designing efficient SOD mimics, from molecular metal complexes to nanomaterials. Studies of these systems in cells reveal that some SOD mimics, designed to react directly with superoxide, may also indirectly enhance the cellular antioxidant arsenal. Finally, a good understanding of the bioactivity requires information on the cell-penetration, speciation, and subcellular location of the SOD mimics: we will describe recent studies and new techniques that open opportunities for characterizing SOD mimics in biological environments. |
Inertness of Superoxide Dismutase Mimics Mn(II) Complexes Based on an Open-Chain Ligand, Bioactivity, and Detection in Intestinal Epithelial Cells Journal Article Gabrielle Schanne; Martha Zoumpoulaki; Géraldine Gazzah; Amandine Vincent; Hugues Preud’homme; Ryszard Lobinski; Sylvie Demignot; Philippe Seksik; Nicolas Delsuc; Clotilde Policar Oxidative Medicine and Cellular Longevity, 2022 , pp. e3858122, 2022, ISSN: 1942-0900, (Publisher: Hindawi). @article{schanne_inertness_2022,
title = {Inertness of Superoxide Dismutase Mimics Mn(II) Complexes Based on an Open-Chain Ligand, Bioactivity, and Detection in Intestinal Epithelial Cells},
author = {Gabrielle Schanne and Martha Zoumpoulaki and G\'{e}raldine Gazzah and Amandine Vincent and Hugues Preud’homme and Ryszard Lobinski and Sylvie Demignot and Philippe Seksik and Nicolas Delsuc and Clotilde Policar},
url = {https://www.hindawi.com/journals/omcl/2022/3858122/},
doi = {10.1155/2022/3858122},
issn = {1942-0900},
year = {2022},
date = {2022-01-01},
urldate = {2022-04-03},
journal = {Oxidative Medicine and Cellular Longevity},
volume = {2022},
pages = {e3858122},
abstract = {Oxidative stress is known to play a major role in the pathogenesis of inflammatory bowel diseases (IBDs), and, in particular, superoxide dismutase (SODs) defenses were shown to be weakened in patients suffering from IBDs. SOD mimics, also called SOD mimetics, as low-molecular-weight complexes reproducing the activity of SOD, constitute promising antioxidant catalytic metallodrugs in the context of IBDs. A Mn(II) complex SOD mimic (Mn1) based on an open-chain diaminoethane ligand exerting antioxidant and anti-inflammatory effects on an intestinal epithelial cellular model was shown to experience metal exchanges between the manganese center and metal ions present in the biological environment (such as Zn(II)) to some degrees. As the resulting complexes (mainly Zn(II)) were shown to be inactive, improving the kinetic inertness of Mn(II) complexes based on open-chain ligands is key to improve their bioactivity in a cellular context. We report here the study of three new Mn(II) complexes resulting from Mn1 functionalization with a cyclohexyl and/or a propyl group meant to limit, respectively, (a) metal exchanges and (b) deprotonation of an amine from the 1,2-diaminoethane central scaffold. The new manganese-based SOD mimics display a higher intrinsic SOD activity and also improved kinetic inertness in metal ion exchange processes (with Zn(II), Cu(II), Ni(II), and Co(II)). They were shown to provide anti-inflammatory and antioxidant effects in cells at lower doses than Mn1 (down to 10 μM). This improvement was due to their higher inertness against metal-assisted dissociation and not to different cellular overall accumulations. Based on its higher inertness, the SOD mimic containing both the propyl and the cyclohexyl moieties was suitable for intracellular detection and quantification by mass spectrometry, quantification, that was achieved by using a 13C-labeled Co-based analog of the SOD mimics as an external heavy standard.},
note = {Publisher: Hindawi},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Oxidative stress is known to play a major role in the pathogenesis of inflammatory bowel diseases (IBDs), and, in particular, superoxide dismutase (SODs) defenses were shown to be weakened in patients suffering from IBDs. SOD mimics, also called SOD mimetics, as low-molecular-weight complexes reproducing the activity of SOD, constitute promising antioxidant catalytic metallodrugs in the context of IBDs. A Mn(II) complex SOD mimic (Mn1) based on an open-chain diaminoethane ligand exerting antioxidant and anti-inflammatory effects on an intestinal epithelial cellular model was shown to experience metal exchanges between the manganese center and metal ions present in the biological environment (such as Zn(II)) to some degrees. As the resulting complexes (mainly Zn(II)) were shown to be inactive, improving the kinetic inertness of Mn(II) complexes based on open-chain ligands is key to improve their bioactivity in a cellular context. We report here the study of three new Mn(II) complexes resulting from Mn1 functionalization with a cyclohexyl and/or a propyl group meant to limit, respectively, (a) metal exchanges and (b) deprotonation of an amine from the 1,2-diaminoethane central scaffold. The new manganese-based SOD mimics display a higher intrinsic SOD activity and also improved kinetic inertness in metal ion exchange processes (with Zn(II), Cu(II), Ni(II), and Co(II)). They were shown to provide anti-inflammatory and antioxidant effects in cells at lower doses than Mn1 (down to 10 μM). This improvement was due to their higher inertness against metal-assisted dissociation and not to different cellular overall accumulations. Based on its higher inertness, the SOD mimic containing both the propyl and the cyclohexyl moieties was suitable for intracellular detection and quantification by mass spectrometry, quantification, that was achieved by using a 13C-labeled Co-based analog of the SOD mimics as an external heavy standard. |
2021
|
Evaluation of the compounds commonly known as superoxide dismutase and catalase mimics in cellular models Journal Article Amandine Vincent; Marion Thauvin; Elodie Quévrain; Emilie Mathieu; Sarah Layani; Philippe Seksik; Ines Batinic-Haberle; Sophie Vriz; Clotilde Policar; Nicolas Delsuc Journal of Inorganic Biochemistry, pp. 111431, 2021, ISSN: 0162-0134. @article{VINCENT2021111431,
title = {Evaluation of the compounds commonly known as superoxide dismutase and catalase mimics in cellular models},
author = {Amandine Vincent and Marion Thauvin and Elodie Qu\'{e}vrain and Emilie Mathieu and Sarah Layani and Philippe Seksik and Ines Batinic-Haberle and Sophie Vriz and Clotilde Policar and Nicolas Delsuc},
url = {https://www.sciencedirect.com/science/article/pii/S0162013421000787},
doi = {https://doi.org/10.1016/j.jinorgbio.2021.111431},
issn = {0162-0134},
year = {2021},
date = {2021-01-01},
journal = {Journal of Inorganic Biochemistry},
pages = {111431},
abstract = {Oxidative stress that results from an imbalance between the concentrations of reactive species (RS) and antioxidant defenses is associated with many pathologies. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase are among the key enzymes that maintain the low nanomolar physiological concentrations of superoxide and hydrogen peroxide. The increase in the levels of these species and their progeny could have deleterious effects. In this context, chemists have developed SOD and CAT mimics to supplement them when cells are overwhelmed with oxidative stress. However, the beneficial activity of such molecules in cells depends not only on their intrinsic catalytic activities but also on their stability in biological context, their cell penetration and their cellular localization. We have employed cellular assays to characterize several compounds that possess SOD and CAT activities and have been frequently used in cellular and animal models. We used cellular assays that address SOD and CAT activities of the compounds. Finally, we determined the effect of compounds on the suppression of the inflammation in HT29-MD2 cells challenged by lipopolysaccharide. When the assay requires penetration inside cells, the SOD mimics Mn(III) meso-tetrakis(N-(2′-nbutoxyethyl)pyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP5+) and Mn(II) dichloro[(4aR,13aR,17aR,21aR)-1,2,3,4,4a,5, 6,12,13,13a,14,15,16,17,17a,18,19,20,21,21a-eicosahydro-11,7-nitrilo-7Hdibenzo[b,h] [1, 4, 7, 10] tetra--azacycloheptadecine-κN5,κN13,κN18,κN21,κN22] (Imisopasem manganese, M40403, CG4419) were found efficacious at 10 μM, while Mn(II) chloro N-(phenolato)-N,N′-bis[2-(N-methyl-imidazolyl)methyl]-ethane-1,2-diamine (Mn1) requires an incubation at 100 μM. This study thus demonstrates that MnTnBuOE-2-PyP5+, M40403 and Mn1 were efficacious in suppressing inflammatory response in HT29-MD2 cells and such action appears to be related to their ability to enter the cells and modulate reactive oxygen species (ROS) levels.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Oxidative stress that results from an imbalance between the concentrations of reactive species (RS) and antioxidant defenses is associated with many pathologies. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase are among the key enzymes that maintain the low nanomolar physiological concentrations of superoxide and hydrogen peroxide. The increase in the levels of these species and their progeny could have deleterious effects. In this context, chemists have developed SOD and CAT mimics to supplement them when cells are overwhelmed with oxidative stress. However, the beneficial activity of such molecules in cells depends not only on their intrinsic catalytic activities but also on their stability in biological context, their cell penetration and their cellular localization. We have employed cellular assays to characterize several compounds that possess SOD and CAT activities and have been frequently used in cellular and animal models. We used cellular assays that address SOD and CAT activities of the compounds. Finally, we determined the effect of compounds on the suppression of the inflammation in HT29-MD2 cells challenged by lipopolysaccharide. When the assay requires penetration inside cells, the SOD mimics Mn(III) meso-tetrakis(N-(2′-nbutoxyethyl)pyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP5+) and Mn(II) dichloro[(4aR,13aR,17aR,21aR)-1,2,3,4,4a,5, 6,12,13,13a,14,15,16,17,17a,18,19,20,21,21a-eicosahydro-11,7-nitrilo-7Hdibenzo[b,h] [1, 4, 7, 10] tetra--azacycloheptadecine-κN5,κN13,κN18,κN21,κN22] (Imisopasem manganese, M40403, CG4419) were found efficacious at 10 μM, while Mn(II) chloro N-(phenolato)-N,N′-bis[2-(N-methyl-imidazolyl)methyl]-ethane-1,2-diamine (Mn1) requires an incubation at 100 μM. This study thus demonstrates that MnTnBuOE-2-PyP5+, M40403 and Mn1 were efficacious in suppressing inflammatory response in HT29-MD2 cells and such action appears to be related to their ability to enter the cells and modulate reactive oxygen species (ROS) levels. |
Rhenium carbonyl complexes bearing methylated triphenylphosphonium cations as antibody-free mitochondria trackers for X-ray fluorescence imaging Journal Article Gabrielle Schanne; Lucas Henry; How Chee Ong; Andrea Somogyi; Kadda Medjoubi; Nicolas Delsuc; Clotilde Policar; Felipe García; Helene C Bertrand Inorg. Chem. Front., 8 , pp. 3905-3915, 2021. @article{D1QI00542A,
title = {Rhenium carbonyl complexes bearing methylated triphenylphosphonium cations as antibody-free mitochondria trackers for X-ray fluorescence imaging},
author = {Gabrielle Schanne and Lucas Henry and How Chee Ong and Andrea Somogyi and Kadda Medjoubi and Nicolas Delsuc and Clotilde Policar and Felipe Garc\'{i}a and Helene C Bertrand},
url = {http://dx.doi.org/10.1039/D1QI00542A},
doi = {10.1039/D1QI00542A},
year = {2021},
date = {2021-01-01},
journal = {Inorg. Chem. Front.},
volume = {8},
pages = {3905-3915},
publisher = {The Royal Society of Chemistry},
abstract = {Synchrotron Radiation X-ray Fluorescence (SXRF) imaging is a powerful technique for the visualization of metal complexes in biological systems. However, due to the lack of an endogenous elemental signature for mitochondria, probes for the localization of this organelle are required for colocalization studies. In this work, we designed and synthesized rhenium pyta tricarbonyl complexes conjugated to methylated triphenylphosphonium TP*P+ cations as multimodal probes for the visualization of mitochondria, suitable for fluorescence and SXRF imaging and quantification. Accumulation of the methylated triphenylphosphonium TP*P+-based conjugates in cells was observed in fixed A549 cells, and the amount of mitochondrial uptake was linked to the lipophilicity of the TPP+ vector. Our work highlights a convenient rhenium-based multimodal mitochondrial-targeted probe compatible with SXRF nano-imaging.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Synchrotron Radiation X-ray Fluorescence (SXRF) imaging is a powerful technique for the visualization of metal complexes in biological systems. However, due to the lack of an endogenous elemental signature for mitochondria, probes for the localization of this organelle are required for colocalization studies. In this work, we designed and synthesized rhenium pyta tricarbonyl complexes conjugated to methylated triphenylphosphonium TP*P+ cations as multimodal probes for the visualization of mitochondria, suitable for fluorescence and SXRF imaging and quantification. Accumulation of the methylated triphenylphosphonium TP*P+-based conjugates in cells was observed in fixed A549 cells, and the amount of mitochondrial uptake was linked to the lipophilicity of the TPP+ vector. Our work highlights a convenient rhenium-based multimodal mitochondrial-targeted probe compatible with SXRF nano-imaging. |
A di-Copper Peptidyl Complex Mimics the Activity of Catalase, a Key Antioxidant Metalloenzyme Journal Article Koudedja Coulibaly; Marion Thauvin; Adyn Melenbacher; Clara Testard; Evangelina Trigoni; Amandine Vincent; Martin J Stillman; Sophie Vriz; Clotilde Policar; Nicolas Delsuc Inorganic Chemistry, 60 (13), pp. 9309-9319, 2021. @article{doi:10.1021/acs.inorgchem.0c03718b,
title = {A di-Copper Peptidyl Complex Mimics the Activity of Catalase, a Key Antioxidant Metalloenzyme},
author = {Koudedja Coulibaly and Marion Thauvin and Adyn Melenbacher and Clara Testard and Evangelina Trigoni and Amandine Vincent and Martin J Stillman and Sophie Vriz and Clotilde Policar and Nicolas Delsuc},
url = {https://doi.org/10.1021/acs.inorgchem.0c03718},
doi = {10.1021/acs.inorgchem.0c03718},
year = {2021},
date = {2021-01-01},
journal = {Inorganic Chemistry},
volume = {60},
number = {13},
pages = {9309-9319},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
2020
|
Anti-inflammatory activity of superoxide dismutase mimics functionalized with cell-penetrating peptides Journal Article Emilie Mathieu; Anne-Sophie Bernard; Vincent H Y Ching; Andrea Somogyi; Kadda Medjoubi; Jennifer Rodon Fores; Hélène C Bertrand; Amandine Vincent; Sylvain Trépout; Jean-Luc Guerquin-Kern; Andreas Scheitler; Ivana Ivanović-Burmazović; Philippe Seksik; Nicolas Delsuc; Clotilde Policar Dalton Trans., 49 , pp. 2323-2330, 2020. @article{C9DT04619Db,
title = {Anti-inflammatory activity of superoxide dismutase mimics functionalized with cell-penetrating peptides},
author = {Emilie Mathieu and Anne-Sophie Bernard and Vincent H Y Ching and Andrea Somogyi and Kadda Medjoubi and Jennifer Rodon Fores and H\'{e}l\`{e}ne C Bertrand and Amandine Vincent and Sylvain Tr\'{e}pout and Jean-Luc Guerquin-Kern and Andreas Scheitler and Ivana Ivanovi\'{c}-Burmazovi\'{c} and Philippe Seksik and Nicolas Delsuc and Clotilde Policar},
url = {http://dx.doi.org/10.1039/C9DT04619D},
doi = {10.1039/C9DT04619D},
year = {2020},
date = {2020-01-01},
journal = {Dalton Trans.},
volume = {49},
pages = {2323-2330},
publisher = {The Royal Society of Chemistry},
abstract = {A superoxide dismutase mimic (Mn1) was functionalized with three positively charged-peptides: RRRRRRRRR (Mn1-R9), RRWWWRRWRR (Mn1-RW9) or Fx-r-Fx-K (Mn1-MPP). Characterization of the physico-chemical properties of the complexes show that they share similar binding affinity for Mn2+, apparent reduction potential and intrinsic superoxide dismutase activity. However, their accumulation in cells is different (Mn1-R9 < Mn1-MPP < Mn1-RW9 < Mn1), as well as their subcellular distribution. In addition, the three functionalized-complexes display a better anti-inflammatory activity than Mn1 when assayed at 10 μM. This improvement is due to a combination of an anti-inflammatory effect of the peptidyl moiety itself, and of the SOD mimic for Mn1-RW9 and Mn1-MPP. In contrast, the enhanced anti-inflammatory activity of Mn1-R9 is solely due to the SOD mimic.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A superoxide dismutase mimic (Mn1) was functionalized with three positively charged-peptides: RRRRRRRRR (Mn1-R9), RRWWWRRWRR (Mn1-RW9) or Fx-r-Fx-K (Mn1-MPP). Characterization of the physico-chemical properties of the complexes show that they share similar binding affinity for Mn2+, apparent reduction potential and intrinsic superoxide dismutase activity. However, their accumulation in cells is different (Mn1-R9 < Mn1-MPP < Mn1-RW9 < Mn1), as well as their subcellular distribution. In addition, the three functionalized-complexes display a better anti-inflammatory activity than Mn1 when assayed at 10 μM. This improvement is due to a combination of an anti-inflammatory effect of the peptidyl moiety itself, and of the SOD mimic for Mn1-RW9 and Mn1-MPP. In contrast, the enhanced anti-inflammatory activity of Mn1-R9 is solely due to the SOD mimic. |
An easy-to-implement combinatorial approach involving an activity-based assay for the discovery of a peptidyl copper complex mimicking superoxide dismutase Journal Article Amandine Vincent; Jennifer Rodon Fores; Elodie Tauziet; Elodie Quévrain; Ágnes Dancs; Amandine Conte-Daban; Anne-Sophie Bernard; Philippe Pelupessy; Koudedja Coulibaly; Philippe Seksik; Christelle Hureau; Katalin Selmeczi; Clotilde Policar; Nicolas Delsuc Chem. Commun., 56 , pp. 399-402, 2020. @article{C9CC07920C,
title = {An easy-to-implement combinatorial approach involving an activity-based assay for the discovery of a peptidyl copper complex mimicking superoxide dismutase},
author = {Amandine Vincent and Jennifer Rodon Fores and Elodie Tauziet and Elodie Qu\'{e}vrain and \'{A}gnes Dancs and Amandine Conte-Daban and Anne-Sophie Bernard and Philippe Pelupessy and Koudedja Coulibaly and Philippe Seksik and Christelle Hureau and Katalin Selmeczi and Clotilde Policar and Nicolas Delsuc},
url = {http://dx.doi.org/10.1039/C9CC07920C},
doi = {10.1039/C9CC07920C},
year = {2020},
date = {2020-01-01},
journal = {Chem. Commun.},
volume = {56},
pages = {399-402},
publisher = {The Royal Society of Chemistry},
abstract = {A combinatorial approach using a one-bead-one-compound method and a screening based on a SOD-activity assay was set up for the discovery of an efficient peptidyl copper complex. The complex exhibited good stability constants, suitable redox potentials and excellent intrinsic activity. This complex was further assayed in cells for its antioxidant properties and showed beneficial effects when cells were subjected to oxidative stress.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A combinatorial approach using a one-bead-one-compound method and a screening based on a SOD-activity assay was set up for the discovery of an efficient peptidyl copper complex. The complex exhibited good stability constants, suitable redox potentials and excellent intrinsic activity. This complex was further assayed in cells for its antioxidant properties and showed beneficial effects when cells were subjected to oxidative stress. |
Intracellular location matters: rationalization of the anti-inflammatory activity of a manganese(ii) superoxide dismutase mimic complex Journal Article Emilie Mathieu; Anne-Sophie Bernard; Elodie Quévrain; Martha Zoumpoulaki; Sébastien Iriart; Caroline Lung-Soong; Barry Lai; Kadda Medjoubi; Lucas Henry; Sounderya Nagarajan; Florent Poyer; Andreas Scheitler; Ivana Ivanović-Burmazović; Sergio Marco; Andrea Somogyi; Philippe Seksik; Nicolas Delsuc; Clotilde Policar Chem. Commun., pp. -, 2020. @article{D0CC03398G,
title = {Intracellular location matters: rationalization of the anti-inflammatory activity of a manganese(ii) superoxide dismutase mimic complex},
author = {Emilie Mathieu and Anne-Sophie Bernard and Elodie Qu\'{e}vrain and Martha Zoumpoulaki and S\'{e}bastien Iriart and Caroline Lung-Soong and Barry Lai and Kadda Medjoubi and Lucas Henry and Sounderya Nagarajan and Florent Poyer and Andreas Scheitler and Ivana Ivanovi\'{c}-Burmazovi\'{c} and Sergio Marco and Andrea Somogyi and Philippe Seksik and Nicolas Delsuc and Clotilde Policar},
url = {http://dx.doi.org/10.1039/D0CC03398G},
doi = {10.1039/D0CC03398G},
year = {2020},
date = {2020-01-01},
journal = {Chem. Commun.},
pages = {-},
publisher = {The Royal Society of Chemistry},
abstract = {A conjugate of a Mn-based superoxide dismutase mimic with a Re-based multimodal probe ̲ was studied in a cellular model of oxidative stress. Its speciation was investigated using Re and Mn X-fluorescence. Interestingly, ̲ shows a distribution different from its unconjugated analogue but a similar concentration in mitochondria and a similar bioactivity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A conjugate of a Mn-based superoxide dismutase mimic with a Re-based multimodal probe ̲ was studied in a cellular model of oxidative stress. Its speciation was investigated using Re and Mn X-fluorescence. Interestingly, ̲ shows a distribution different from its unconjugated analogue but a similar concentration in mitochondria and a similar bioactivity. |
2019
|
Oxaliplatin-induced neuropathy: the preventive effect of a new super-oxide dismutase modulator Journal Article Marie-Anne Guillaumot; Olivier Cerles; Hélène C Bertrand; Evelyne Benoit; Carole Nicco; Sandrine Chouzenoux; Alain Schmitt; Frédéric Batteux; Clotilde Policar; Romain Coriat Oncotarget, 10 (60), pp. 6418-6431, 2019, ISSN: 1949-2553. @article{OT27248,
title = {Oxaliplatin-induced neuropathy: the preventive effect of a new super-oxide dismutase modulator},
author = {Marie-Anne Guillaumot and Olivier Cerles and H\'{e}l\`{e}ne C Bertrand and Evelyne Benoit and Carole Nicco and Sandrine Chouzenoux and Alain Schmitt and Fr\'{e}d\'{e}ric Batteux and Clotilde Policar and Romain Coriat},
url = {https://www.oncotarget.com/article/27248/},
doi = {https://doi.org/10.18632/oncotarget.27248},
issn = {1949-2553},
year = {2019},
date = {2019-01-01},
journal = {Oncotarget},
volume = {10},
number = {60},
pages = {6418-6431},
publisher = {Impact Journals, LLC},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
2018
|
A Metallo Pro-Drug to Target CuII in the Context of Alzheimer's Disease Journal Article A Conte-Daban; V Ambike; R Guillot; N Delsuc; C Policar; C Hureau Chemistry - A European Journal, 24 (20), pp. 5095–5099, 2018. @article{Conte-Daban:2018,
title = {A Metallo Pro-Drug to Target CuII in the Context of Alzheimer's Disease},
author = {A Conte-Daban and V Ambike and R Guillot and N Delsuc and C Policar and C Hureau},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045131927&doi=10.1002%2fchem.201706049&partnerID=40&md5=5dc310a9e12535e296ba5429250159d3},
doi = {10.1002/chem.201706049},
year = {2018},
date = {2018-01-01},
journal = {Chemistry - A European Journal},
volume = {24},
number = {20},
pages = {5095--5099},
abstract = {Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a MnII-based superoxide dismutase (SOD) mimic ([MnII(L)]+, 1+) as a pro-drug candidate to target CuII-associated events, namely, CuII-induced formation of reactive oxygen species (ROS) and modulation of the amyloid-β (Aβ) peptide aggregation. Complex 1+ is able to remove CuII from Aβ, stop ROS and prevent alteration of Aβ aggregation as would do the corresponding free ligand LH. Using 1+ instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a MnII-based superoxide dismutase (SOD) mimic ([MnII(L)]+, 1+) as a pro-drug candidate to target CuII-associated events, namely, CuII-induced formation of reactive oxygen species (ROS) and modulation of the amyloid-β (Aβ) peptide aggregation. Complex 1+ is able to remove CuII from Aβ, stop ROS and prevent alteration of Aβ aggregation as would do the corresponding free ligand LH. Using 1+ instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim |
Rhenium tricarbonyl complexes with arenethiolate axial ligands Journal Article M He; H Y V Ching; C Policar; H C Bertrand New Journal of Chemistry, 42 (14), pp. 11312–11323, 2018. @article{He:2018,
title = {Rhenium tricarbonyl complexes with arenethiolate axial ligands},
author = {M He and H Y V Ching and C Policar and H C Bertrand},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85049750977&doi=10.1039%2fc8nj01960f&partnerID=40&md5=eac4613cb3f849f5a149c72a46384912},
doi = {10.1039/c8nj01960f},
year = {2018},
date = {2018-01-01},
journal = {New Journal of Chemistry},
volume = {42},
number = {14},
pages = {11312--11323},
abstract = {Due to their unique electronic and photophysical properties, rhenium(i) fac-tricarbonyl complexes of general formula [Re(NtextasciicircumN)(CO)3X]n+ have been arousing constant interest in many diverse fields and applications, such as CO2 (photo)electroreduction, organic light emitting diodes and materials, sensors, biological applications and bio-imaging. The photophysical properties of [Re(NtextasciicircumN)(CO)3X]n+ complexes can be modulated by structural variations of the ligands. Modifications of the NtextasciicircumN diimine ligand and of the axial X ligand have been deeply investigated. However, thiolate ligands have scarcely been used in the synthesis of rhenium tricarbonyl complexes. We describe the synthesis of a series of Pyta and Tapy-based Re(i) fac-tricarbonyl complexes with diversely para-substituted arenethiolates in the coordination sphere and report on the electrochemical, photophysical properties and DFT studies of such complexes. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Due to their unique electronic and photophysical properties, rhenium(i) fac-tricarbonyl complexes of general formula [Re(NtextasciicircumN)(CO)3X]n+ have been arousing constant interest in many diverse fields and applications, such as CO2 (photo)electroreduction, organic light emitting diodes and materials, sensors, biological applications and bio-imaging. The photophysical properties of [Re(NtextasciicircumN)(CO)3X]n+ complexes can be modulated by structural variations of the ligands. Modifications of the NtextasciicircumN diimine ligand and of the axial X ligand have been deeply investigated. However, thiolate ligands have scarcely been used in the synthesis of rhenium tricarbonyl complexes. We describe the synthesis of a series of Pyta and Tapy-based Re(i) fac-tricarbonyl complexes with diversely para-substituted arenethiolates in the coordination sphere and report on the electrochemical, photophysical properties and DFT studies of such complexes. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique. |
Labeling of Hyaluronic Acids with a Rhenium-tricarbonyl Tag and Percutaneous Penetration Studied by Multimodal Imaging Journal Article L Henry; N Delsuc; C Laugel; F Lambert; C Sandt; S Hostachy; A -S Bernard; H C Bertrand; L Grimaud; A Baillet-Guffroy; C Policar Bioconjugate Chemistry, 29 (4), pp. 987–991, 2018. @article{Henry:2018,
title = {Labeling of Hyaluronic Acids with a Rhenium-tricarbonyl Tag and Percutaneous Penetration Studied by Multimodal Imaging},
author = {L Henry and N Delsuc and C Laugel and F Lambert and C Sandt and S Hostachy and A -S Bernard and H C Bertrand and L Grimaud and A Baillet-Guffroy and C Policar},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045549363&doi=10.1021%2facs.bioconjchem.7b00825&partnerID=40&md5=87140714a264358836c5f4c7734e49a3},
doi = {10.1021/acs.bioconjchem.7b00825},
year = {2018},
date = {2018-01-01},
journal = {Bioconjugate Chemistry},
volume = {29},
number = {4},
pages = {987--991},
abstract = {Hyaluronic acids were labeled with a rhenium-tricarbonyl used as single core multimodal probe for imaging and their penetration into human skin biopsies was studied using IR microscopy and fluorescence imaging (labeled SCoMPI). The penetration was shown to be dependent on the molecular weight of the molecule and limited to the upper layer of the skin. © 2018 American Chemical Society.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hyaluronic acids were labeled with a rhenium-tricarbonyl used as single core multimodal probe for imaging and their penetration into human skin biopsies was studied using IR microscopy and fluorescence imaging (labeled SCoMPI). The penetration was shown to be dependent on the molecular weight of the molecule and limited to the upper layer of the skin. © 2018 American Chemical Society. |
Clarifying the Copper Coordination Environment in a de Novo Designed Red Copper Protein Journal Article K J Koebke; L Ruckthong; J L Meagher; E Mathieu; J Harland; A Deb; N Lehnert; C Policar; C Tard; J E Penner-Hahn; J A Stuckey; V L Pecoraro Inorganic Chemistry, 57 (19), pp. 12291–12302, 2018. @article{Koebke:2018,
title = {Clarifying the Copper Coordination Environment in a de Novo Designed Red Copper Protein},
author = {K J Koebke and L Ruckthong and J L Meagher and E Mathieu and J Harland and A Deb and N Lehnert and C Policar and C Tard and J E Penner-Hahn and J A Stuckey and V L Pecoraro},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85053716026&doi=10.1021%2facs.inorgchem.8b01989&partnerID=40&md5=1ff4fcf88039da93326134a5ecf32822},
doi = {10.1021/acs.inorgchem.8b01989},
year = {2018},
date = {2018-01-01},
journal = {Inorganic Chemistry},
volume = {57},
number = {19},
pages = {12291--12302},
abstract = {Cupredoxins are copper-dependent electron-transfer proteins that can be categorized as blue, purple, green, and red depending on the spectroscopic properties of the Cu(II) bound forms. Interestingly, despite significantly different first coordination spheres and nuclearity, all cupredoxins share a common Greek Key β-sheet fold. We have previously reported the design of a red copper protein within a completely distinct three-helical bundle protein, α3DChC2.(1)While this design demonstrated that a β-barrel fold was not requisite to recapitulate the properties of a native cupredoxin center, the parent peptide α3D was not sufficiently stable to allow further study through additional mutations. Here we present the design of an elongated protein GRANDα3D (GRα3D) with ΔGu = -11.4 kcal/mol compared to the original design's -5.1 kcal/mol. Diffraction quality crystals were grown of GRα3D (a first for an α3D peptide) and solved to a resolution of 1.34 r{A}. Examination of this structure suggested that Glu41 might interact with the Cu in our previously reported red copper protein. The previous bis(histidine)(cysteine) site (GRα3DChC2) was designed into this new scaffold and a series of variant constructs were made to explore this hypothesis. Mutation studies around Glu41 not only prove the proposed interaction, but also enabled tuning of the constructs' hyperfine coupling constant from 160 to 127 × 10-4 cm-1. X-ray absorption spectroscopy analysis is consistent with these hyperfine coupling differences being the result of variant 4p mixing related to coordination geometry changes. These studies not only prove that an Glu41-Cu interaction leads to the α3DChC2 construct's red copper protein like spectral properties, but also exemplify the exact control one can have in a de novo construct to tune the properties of an electron-transfer Cu site. Copyright © 2018 American Chemical Society.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cupredoxins are copper-dependent electron-transfer proteins that can be categorized as blue, purple, green, and red depending on the spectroscopic properties of the Cu(II) bound forms. Interestingly, despite significantly different first coordination spheres and nuclearity, all cupredoxins share a common Greek Key β-sheet fold. We have previously reported the design of a red copper protein within a completely distinct three-helical bundle protein, α3DChC2.(1)While this design demonstrated that a β-barrel fold was not requisite to recapitulate the properties of a native cupredoxin center, the parent peptide α3D was not sufficiently stable to allow further study through additional mutations. Here we present the design of an elongated protein GRANDα3D (GRα3D) with ΔGu = -11.4 kcal/mol compared to the original design's -5.1 kcal/mol. Diffraction quality crystals were grown of GRα3D (a first for an α3D peptide) and solved to a resolution of 1.34 Å. Examination of this structure suggested that Glu41 might interact with the Cu in our previously reported red copper protein. The previous bis(histidine)(cysteine) site (GRα3DChC2) was designed into this new scaffold and a series of variant constructs were made to explore this hypothesis. Mutation studies around Glu41 not only prove the proposed interaction, but also enabled tuning of the constructs' hyperfine coupling constant from 160 to 127 × 10-4 cm-1. X-ray absorption spectroscopy analysis is consistent with these hyperfine coupling differences being the result of variant 4p mixing related to coordination geometry changes. These studies not only prove that an Glu41-Cu interaction leads to the α3DChC2 construct's red copper protein like spectral properties, but also exemplify the exact control one can have in a de novo construct to tune the properties of an electron-transfer Cu site. Copyright © 2018 American Chemical Society. |
Macrophage-derived superoxide production and antioxidant response following skeletal muscle injury Journal Article E Le Moal; G Juban; A S Bernard; T Varga; C Policar; B Chazaud; R Mounier Free Radical Biology and Medicine, 120 , pp. 33–40, 2018. @article{LeMoal:2018,
title = {Macrophage-derived superoxide production and antioxidant response following skeletal muscle injury},
author = {E Le Moal and G Juban and A S Bernard and T Varga and C Policar and B Chazaud and R Mounier},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85044047057&doi=10.1016%2fj.freeradbiomed.2018.02.024&partnerID=40&md5=3d7a016c57bd52dfee180ac22ee70ae8},
doi = {10.1016/j.freeradbiomed.2018.02.024},
year = {2018},
date = {2018-01-01},
journal = {Free Radical Biology and Medicine},
volume = {120},
pages = {33--40},
abstract = {Macrophages are key players of immunity that display different functions according to their activation states. In a regenerative context, pro-inflammatory macrophages (Ly6Cpos) are involved in the mounting of the inflammatory response whereas anti-inflammatory macrophages (Ly6Cneg) dampen the inflammation and promote tissue repair. Reactive oxygen species (ROS) production is a hallmark of tissue injury and of subsequent inflammation as described in a bacterial challenge context. However, whether macrophages produce ROS following a sterile tissue injury is uncertain. In this study, we used complementary in vitro, ex vivo and in vivo experiments in mouse to show that macrophages do not release ROS following a sterile injury in skeletal muscle. Furthermore, expression profiles of genes involved in the response to oxidative stress in Ly6Cpos and Ly6Cneg macrophage subsets did not indicate any antioxidant response in this context. Finally, in vivo, pharmacological antioxidant supplementation with N-Acetyl-cysteine (NAC) following skeletal muscle injury did not alter macrophage phenotype during skeletal muscle regeneration. Overall, these results indicate that following a sterile injury, macrophage-derived ROS release is not involved in the regulation of the inflammatory response in the regenerating skeletal muscle. © 2018 Elsevier Inc.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Macrophages are key players of immunity that display different functions according to their activation states. In a regenerative context, pro-inflammatory macrophages (Ly6Cpos) are involved in the mounting of the inflammatory response whereas anti-inflammatory macrophages (Ly6Cneg) dampen the inflammation and promote tissue repair. Reactive oxygen species (ROS) production is a hallmark of tissue injury and of subsequent inflammation as described in a bacterial challenge context. However, whether macrophages produce ROS following a sterile tissue injury is uncertain. In this study, we used complementary in vitro, ex vivo and in vivo experiments in mouse to show that macrophages do not release ROS following a sterile injury in skeletal muscle. Furthermore, expression profiles of genes involved in the response to oxidative stress in Ly6Cpos and Ly6Cneg macrophage subsets did not indicate any antioxidant response in this context. Finally, in vivo, pharmacological antioxidant supplementation with N-Acetyl-cysteine (NAC) following skeletal muscle injury did not alter macrophage phenotype during skeletal muscle regeneration. Overall, these results indicate that following a sterile injury, macrophage-derived ROS release is not involved in the regulation of the inflammatory response in the regenerating skeletal muscle. © 2018 Elsevier Inc. |
Ferrocifens labelled with an infrared rhenium tricarbonyl tag: Synthesis, antiproliferative activity, quantification and nano IR mapping in cancer cells Journal Article Y Wang; F Heinemann; S Top; A Dazzi; C Policar; L Henry; F Lambert; G Jaouen; M Salmain; A Vessieres Dalton Transactions, 47 (29), pp. 9824–9833, 2018. @article{Wang:2018c,
title = {Ferrocifens labelled with an infrared rhenium tricarbonyl tag: Synthesis, antiproliferative activity, quantification and nano IR mapping in cancer cells},
author = {Y Wang and F Heinemann and S Top and A Dazzi and C Policar and L Henry and F Lambert and G Jaouen and M Salmain and A Vessieres},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85050854664&doi=10.1039%2fc8dt01582a&partnerID=40&md5=1eb695f8b77ceadad719c5ab75b11480},
doi = {10.1039/c8dt01582a},
year = {2018},
date = {2018-01-01},
journal = {Dalton Transactions},
volume = {47},
number = {29},
pages = {9824--9833},
abstract = {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 nucleus. © 2018 The Royal Society of Chemistry.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
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 nucleus. © 2018 The Royal Society of Chemistry. |
Graftable SCoMPIs enable the labeling and X-ray fluorescence imaging of proteins Journal Article S Hostachy; M Masuda; T Miki; I Hamachi; S Sagan; O Lequin; K Medjoubi; A Somogyi; N Delsuc; C Policar Chemical Science, 9 (19), pp. 4483–4487, 2018. @article{Hostachy:2018,
title = {Graftable SCoMPIs enable the labeling and X-ray fluorescence imaging of proteins},
author = {S Hostachy and M Masuda and T Miki and I Hamachi and S Sagan and O Lequin and K Medjoubi and A Somogyi and N Delsuc and C Policar},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047244059&doi=10.1039%2fc8sc00886h&partnerID=40&md5=4625eaa891ccc665a2357b73e20e3541},
doi = {10.1039/c8sc00886h},
year = {2018},
date = {2018-01-01},
journal = {Chemical Science},
volume = {9},
number = {19},
pages = {4483--4487},
abstract = {Bio-imaging techniques alternative to fluorescence microscopy are gaining increasing interest as complementary tools to visualize and analyze biological systems. Among them, X-ray fluorescence microspectroscopy provides information on the local content and distribution of heavy elements (Z ≥ 14) in cells or biological samples. In this context, similar tools to those developed for fluorescence microscopy are desired, including chemical probes or tags. In this work, we study rhenium complexes as a convenient and sensitive probe for X-ray fluorescence microspectroscopy. We demonstrate their ability to label and sense exogenously incubated or endogenous proteins inside cells. © The Royal Society of Chemistry 2018.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bio-imaging techniques alternative to fluorescence microscopy are gaining increasing interest as complementary tools to visualize and analyze biological systems. Among them, X-ray fluorescence microspectroscopy provides information on the local content and distribution of heavy elements (Z ≥ 14) in cells or biological samples. In this context, similar tools to those developed for fluorescence microscopy are desired, including chemical probes or tags. In this work, we study rhenium complexes as a convenient and sensitive probe for X-ray fluorescence microspectroscopy. We demonstrate their ability to label and sense exogenously incubated or endogenous proteins inside cells. © The Royal Society of Chemistry 2018. |
2017
|
Rhenium Complexes Based on 2-Pyridyl-1,2,3-triazole Ligands: A New Class of CO2 Reduction Catalysts Journal Article H Y V Ching; X Wang; M He; N Perujo Holland; R Guillot; C Slim; S Griveau; H C Bertrand; C Policar; F Bedioui; M Fontecave Inorganic Chemistry, 56 (5), pp. 2966–2976, 2017. @article{Ching:2017,
title = {Rhenium Complexes Based on 2-Pyridyl-1,2,3-triazole Ligands: A New Class of CO2 Reduction Catalysts},
author = {H Y V Ching and X Wang and M He and N Perujo Holland and R Guillot and C Slim and S Griveau and H C Bertrand and C Policar and F Bedioui and M Fontecave},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85014526293&doi=10.1021%2facs.inorgchem.6b03078&partnerID=40&md5=5aa6a6db21554e7bca56e0f1e1de9856},
doi = {10.1021/acs.inorgchem.6b03078},
year = {2017},
date = {2017-01-01},
journal = {Inorganic Chemistry},
volume = {56},
number = {5},
pages = {2966--2976},
abstract = {A series of [Re(NtextasciicircumN)(CO)3(X)] (NtextasciicircumN = diimine and X = halide) complexes based on 4-(2-pyridyl)-1,2,3-triazole (pyta) and 1-(2-pyridyl)-1,2,3-triazole (tapy) diimine ligands have been prepared and electrochemically characterized. The first ligand-based reduction process is shown to be highly sensitive to the nature of the isomer as well as to the substituents on the pyridyl ring, with the peak potential changing by up to 700 mV. The abilities of this class of complexes to catalyze the electroreduction and photoreduction of CO2 were assessed for the first time. It is found that only Re pyta complexes that have a first reduction wave with a peak potential at ca. −1.7 V vs SCE are active, producing CO as the major product, together with small amounts of H2 and formic acid. The catalytic wave that is observed in the CVs is enhanced by the addition of water or trifluoroethanol as a proton source. Long-term controlled potential electrolysis experiments gave total Faradaic yield close to 100%. In particular, functionalization of the triazolyl ring with a 2,4,6-tri-tert-butylphenyl group provided the catalyst with a remarkable stability. © 2017 American Chemical Society.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A series of [Re(NtextasciicircumN)(CO)3(X)] (NtextasciicircumN = diimine and X = halide) complexes based on 4-(2-pyridyl)-1,2,3-triazole (pyta) and 1-(2-pyridyl)-1,2,3-triazole (tapy) diimine ligands have been prepared and electrochemically characterized. The first ligand-based reduction process is shown to be highly sensitive to the nature of the isomer as well as to the substituents on the pyridyl ring, with the peak potential changing by up to 700 mV. The abilities of this class of complexes to catalyze the electroreduction and photoreduction of CO2 were assessed for the first time. It is found that only Re pyta complexes that have a first reduction wave with a peak potential at ca. −1.7 V vs SCE are active, producing CO as the major product, together with small amounts of H2 and formic acid. The catalytic wave that is observed in the CVs is enhanced by the addition of water or trifluoroethanol as a proton source. Long-term controlled potential electrolysis experiments gave total Faradaic yield close to 100%. In particular, functionalization of the triazolyl ring with a 2,4,6-tri-tert-butylphenyl group provided the catalyst with a remarkable stability. © 2017 American Chemical Society. |
A Cell-Penetrant Manganese Superoxide Dismutase (MnSOD) Mimic Is Able to Complement MnSOD and Exerts an Antiinflammatory Effect on Cellular and Animal Models of Inflammatory Bowel Diseases Journal Article E Mathieu; A -S Bernard; N Delsuc; E Quévrain; G Gazzah; B Lai; F Chain; P Langella; M Bachelet; J Masliah; P Seksik; C Policar Inorganic Chemistry, 56 (5), pp. 2545–2555, 2017. @article{Mathieu:2017,
title = {A Cell-Penetrant Manganese Superoxide Dismutase (MnSOD) Mimic Is Able to Complement MnSOD and Exerts an Antiinflammatory Effect on Cellular and Animal Models of Inflammatory Bowel Diseases},
author = {E Mathieu and A -S Bernard and N Delsuc and E Qu\'{e}vrain and G Gazzah and B Lai and F Chain and P Langella and M Bachelet and J Masliah and P Seksik and C Policar},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85014763334&doi=10.1021%2facs.inorgchem.6b02695&partnerID=40&md5=acd51065ea36d5da707ec8c1915634a0},
doi = {10.1021/acs.inorgchem.6b02695},
year = {2017},
date = {2017-01-01},
journal = {Inorganic Chemistry},
volume = {56},
number = {5},
pages = {2545--2555},
abstract = {Inorganic complexes are increasingly used for biological and medicinal applications, and the question of the cell penetration and distribution of metallodrugs is key to understanding their biological activity. Oxidative stress is known to be involved in inflammation and in inflammatory bowel diseases for which antioxidative defenses are weakened. We report here the study of the manganese complex Mn1 mimicking superoxide dismutase (SOD), a protein involved in cell protection against oxidative stress, using an approach in inorganic cellular chemistry combining the investigation of Mn1 intracellular speciation using mass spectrometry and of its quantification and distribution using electron paramagnetic resonance and spatially resolved X-ray fluorescence with evaluation of its biological activity. More precisely, we have looked for and found the MS signature of Mn1 in cell lysates and quantified the overall manganese content. Intestinal epithelial cells activated by bacterial lipopolysaccharide were taken as a cellular model of oxidative stress and inflammation. DNBS-induced colitis in mice was used to investigate Mn1 activity in vivo. Mn1 exerts an intracellular antiinflammatory activity, remains at least partially coordinated, with diffuse distribution over the whole cell, and functionally complements mitochondrial MnSOD. © 2017 American Chemical Society.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Inorganic complexes are increasingly used for biological and medicinal applications, and the question of the cell penetration and distribution of metallodrugs is key to understanding their biological activity. Oxidative stress is known to be involved in inflammation and in inflammatory bowel diseases for which antioxidative defenses are weakened. We report here the study of the manganese complex Mn1 mimicking superoxide dismutase (SOD), a protein involved in cell protection against oxidative stress, using an approach in inorganic cellular chemistry combining the investigation of Mn1 intracellular speciation using mass spectrometry and of its quantification and distribution using electron paramagnetic resonance and spatially resolved X-ray fluorescence with evaluation of its biological activity. More precisely, we have looked for and found the MS signature of Mn1 in cell lysates and quantified the overall manganese content. Intestinal epithelial cells activated by bacterial lipopolysaccharide were taken as a cellular model of oxidative stress and inflammation. DNBS-induced colitis in mice was used to investigate Mn1 activity in vivo. Mn1 exerts an intracellular antiinflammatory activity, remains at least partially coordinated, with diffuse distribution over the whole cell, and functionally complements mitochondrial MnSOD. © 2017 American Chemical Society. |
Synthesis of Homoditopic Ligands with an Incrementable Rodlike Backbone Journal Article P Demay-Drouhard; L -M Chamoreau; R Guillot; C Policar; H C Bertrand European Journal of Organic Chemistry, 2017 (1), pp. 131–137, 2017. @article{Demay-Drouhard:2017,
title = {Synthesis of Homoditopic Ligands with an Incrementable Rodlike Backbone},
author = {P Demay-Drouhard and L -M Chamoreau and R Guillot and C Policar and H C Bertrand},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85007178925&doi=10.1002%2fejoc.201601081&partnerID=40&md5=4e3e60591df3842d6c169cf43161de0f},
doi = {10.1002/ejoc.201601081},
year = {2017},
date = {2017-01-01},
journal = {European Journal of Organic Chemistry},
volume = {2017},
number = {1},
pages = {131--137},
abstract = {We describe the synthesis of architectures that consist of a symmetrical rodlike oligo(phenylene-ethynylene) (OPE) backbone of incrementable length connected to a pair of classical ligands for metal coordination. OPE spacers decorated with various end groups and incorporating up to seven phenylene-acetylene repeat units were quickly obtained through a bidirectional approach. Efficient further functionalization with useful coordinating groups were achieved. The resulting homoditopic platforms are of interest in numerous fields ranging from supramolecular chemistry to materials science. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We describe the synthesis of architectures that consist of a symmetrical rodlike oligo(phenylene-ethynylene) (OPE) backbone of incrementable length connected to a pair of classical ligands for metal coordination. OPE spacers decorated with various end groups and incorporating up to seven phenylene-acetylene repeat units were quickly obtained through a bidirectional approach. Efficient further functionalization with useful coordinating groups were achieved. The resulting homoditopic platforms are of interest in numerous fields ranging from supramolecular chemistry to materials science. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim |
Re(I) carbonyl complexes: Multimodal platforms for inorganic chemical biology Journal Article S Hostachy; C Policar; N Delsuc Coordination Chemistry Reviews, 351 , pp. 172–188, 2017. @article{Hostachy:2017,
title = {Re(I) carbonyl complexes: Multimodal platforms for inorganic chemical biology},
author = {S Hostachy and C Policar and N Delsuc},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85020033654&doi=10.1016%2fj.ccr.2017.05.004&partnerID=40&md5=ea1241c6f9199448b3fbb2bfc259b363},
doi = {10.1016/j.ccr.2017.05.004},
year = {2017},
date = {2017-01-01},
journal = {Coordination Chemistry Reviews},
volume = {351},
pages = {172--188},
abstract = {Bio-imaging, by enabling the visualization of biomolecules of interest, has proved to be highly informative in the study of biological processes. Although fluorescence microscopy is probably one of the most used techniques, alternative methods of imaging, providing complementary information, are emerging. In this context, metal complexes represent valuable platforms for multimodal imaging, since they may combine interesting spectroscopic features and biologically relevant functionalization on a single molecular core. In particular, d6 low-spin rhenium tri-carbonyl complexes display unique luminescence and vibrational properties, and can be readily functionalized. Here we review their applications and potential as probes or drugs relying on their photophysical properties, before focusing on their use as multimodal probes for the labelling and imaging of peptides and proteins. © 2017 Elsevier B.V.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bio-imaging, by enabling the visualization of biomolecules of interest, has proved to be highly informative in the study of biological processes. Although fluorescence microscopy is probably one of the most used techniques, alternative methods of imaging, providing complementary information, are emerging. In this context, metal complexes represent valuable platforms for multimodal imaging, since they may combine interesting spectroscopic features and biologically relevant functionalization on a single molecular core. In particular, d6 low-spin rhenium tri-carbonyl complexes display unique luminescence and vibrational properties, and can be readily functionalized. Here we review their applications and potential as probes or drugs relying on their photophysical properties, before focusing on their use as multimodal probes for the labelling and imaging of peptides and proteins. © 2017 Elsevier B.V. |
2016
|
A Bis-Manganese(II)–DOTA Complex for Pulsed Dipolar Spectroscopy Journal Article P Demay-Drouhard; H Y V Ching; D Akhmetzyanov; R Guillot; L C Tabares; H C Bertrand; C Policar ChemPhysChem, pp. 2066–2078, 2016. @article{Demay-Drouhard:2016,
title = {A Bis-Manganese(II)\textendashDOTA Complex for Pulsed Dipolar Spectroscopy},
author = {P Demay-Drouhard and H Y V Ching and D Akhmetzyanov and R Guillot and L C Tabares and H C Bertrand and C Policar},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84977597209&doi=10.1002%2fcphc.201600234&partnerID=40&md5=38a2466ad0f00d0edb158d200429986c},
doi = {10.1002/cphc.201600234},
year = {2016},
date = {2016-01-01},
journal = {ChemPhysChem},
pages = {2066--2078},
abstract = {High-spin gadolinium(III) and manganese(II) complexes have emerged as alternatives to standard nitroxide radical spin labels for measuring nanometric distances by using pulsed electron\textendashelectron double resonance (PELDOR or DEER) at high fields/frequencies. For certain complexes, particularly those with relatively small zero-field splitting (ZFS) and short distances between the two metal centers, the pseudosecular term of the dipolar coupling Hamiltonian is non-negligible. However, in general, the contribution from this term during conventional data analysis is masked by the flexibility of the molecule of interest and/or the long tethers connecting them to the spin labels. The efficient synthesis of a model system consisting of two [Mn(dota)]2− (MnDOTA; DOTA4−=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) directly connected to the ends of a central rodlike oligo(phenylene\textendashethynylene) (OPE) spacer is reported. The rigidity of the OPE is confirmed by Q-band PELDOR measurements on a bis-nitroxide analogue. The MnII−MnII distance distribution profile determined by W-band PELDOR is in reasonable agreement with one simulated by using a simple rotamer analysis. The small degree of flexibility arising from the linking MnDOTA arm appears to outweigh the contribution from the pseudosecular term at this interspin distance. This study illustrates the potential of MnDOTA-based spin labels for measuring fairly short nanometer distances, and also presents an interesting candidate for in-depth studies of pulsed dipolar spectroscopy methods on MnII−MnII systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
High-spin gadolinium(III) and manganese(II) complexes have emerged as alternatives to standard nitroxide radical spin labels for measuring nanometric distances by using pulsed electron–electron double resonance (PELDOR or DEER) at high fields/frequencies. For certain complexes, particularly those with relatively small zero-field splitting (ZFS) and short distances between the two metal centers, the pseudosecular term of the dipolar coupling Hamiltonian is non-negligible. However, in general, the contribution from this term during conventional data analysis is masked by the flexibility of the molecule of interest and/or the long tethers connecting them to the spin labels. The efficient synthesis of a model system consisting of two [Mn(dota)]2− (MnDOTA; DOTA4−=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) directly connected to the ends of a central rodlike oligo(phenylene–ethynylene) (OPE) spacer is reported. The rigidity of the OPE is confirmed by Q-band PELDOR measurements on a bis-nitroxide analogue. The MnII−MnII distance distribution profile determined by W-band PELDOR is in reasonable agreement with one simulated by using a simple rotamer analysis. The small degree of flexibility arising from the linking MnDOTA arm appears to outweigh the contribution from the pseudosecular term at this interspin distance. This study illustrates the potential of MnDOTA-based spin labels for measuring fairly short nanometer distances, and also presents an interesting candidate for in-depth studies of pulsed dipolar spectroscopy methods on MnII−MnII systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim |
Bimodal X-ray and Infrared Imaging of an Organometallic Derivative of Praziquantel in Schistosoma mansoni Journal Article S Clède; N Cowan; F Lambert; H C Bertrand; R Rubbiani; M Patra; J Hess; C Sandt; N Trcera; G Gasser; J Keiser; C Policar ChemBioChem, 17 (11), pp. 1004–1007, 2016. @article{Clede:2016,
title = {Bimodal X-ray and Infrared Imaging of an Organometallic Derivative of Praziquantel in Schistosoma mansoni},
author = {S Cl\`{e}de and N Cowan and F Lambert and H C Bertrand and R Rubbiani and M Patra and J Hess and C Sandt and N Trcera and G Gasser and J Keiser and C Policar},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84973124415&doi=10.1002%2fcbic.201500688&partnerID=40&md5=608b1bb28a5237e0717a29ee815e73bc},
doi = {10.1002/cbic.201500688},
year = {2016},
date = {2016-01-01},
journal = {ChemBioChem},
volume = {17},
number = {11},
pages = {1004--1007},
abstract = {An organometallic derivative of praziquantel was studied directly in worms by using inductively coupled plasma-mass spectrometry (ICP-MS) for quantification and synchrotron-based imaging. X-ray fluorescence (XRF) and IR absorption spectromicroscopy were used for the first time in combination to directly locate this organometallic drug candidate in schistosomes. The detection of both CO (IR) and Cr (XRF) signatures proved that the Cr(CO)3 core remained intact in the worms. Images showed a preferential accumulation at the worm's tegument, consistent with a possible targeting of the calcium channel but not excluding other biological targets inside the worm. Imaginative imaging: Two synchrotron-based techniques - X-ray fluorescence and IR absorption spectroscopy - were used in combination for the first time to directly locate an organometallic drug candidate in schistosomes. This represents a novel approach to examine mechanisms of actions for organometallic compounds and might lead to the discovery of new drug candidates. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
An organometallic derivative of praziquantel was studied directly in worms by using inductively coupled plasma-mass spectrometry (ICP-MS) for quantification and synchrotron-based imaging. X-ray fluorescence (XRF) and IR absorption spectromicroscopy were used for the first time in combination to directly locate this organometallic drug candidate in schistosomes. The detection of both CO (IR) and Cr (XRF) signatures proved that the Cr(CO)3 core remained intact in the worms. Images showed a preferential accumulation at the worm's tegument, consistent with a possible targeting of the calcium channel but not excluding other biological targets inside the worm. Imaginative imaging: Two synchrotron-based techniques - X-ray fluorescence and IR absorption spectroscopy - were used in combination for the first time to directly locate an organometallic drug candidate in schistosomes. This represents a novel approach to examine mechanisms of actions for organometallic compounds and might lead to the discovery of new drug candidates. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Bioinspired superoxide-dismutase mimics: The effects of functionalization with cationic polyarginine peptides Journal Article H Y V Ching; I Kenkel; N Delsuc; E Mathieu; I Ivanović-Burmazović; C Policar Journal of Inorganic Biochemistry, 160 , pp. 172–179, 2016. @article{Ching:2016a,
title = {Bioinspired superoxide-dismutase mimics: The effects of functionalization with cationic polyarginine peptides},
author = {H Y V Ching and I Kenkel and N Delsuc and E Mathieu and I Ivanovi\'{c}-Burmazovi\'{c} and C Policar},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84964372716&doi=10.1016%2fj.jinorgbio.2016.01.025&partnerID=40&md5=035d0c2b5ffd4ee0b6fb74df285838da},
doi = {10.1016/j.jinorgbio.2016.01.025},
year = {2016},
date = {2016-01-01},
journal = {Journal of Inorganic Biochemistry},
volume = {160},
pages = {172--179},
abstract = {Continuing a bio-mimetic approach, we have prepared peptide conjugates of a superoxide dismutase (SOD) mimic [MnL]+ (where HL = N-(2-hydroxybenzyl)-N,N'-bis[2-(N-methylimidazolyl)methyl]ethane-1,2-diamine), namely [MnL'-Arg(n-1)]n+ (where n = 2, 4, 7 and 10) and [MnL'-Gly1]+. [MnL'-Arg(n-1)]n+ contained cationic residue(s) that emulate the electrostatic channel of the enzyme. Physicochemical methods showed that functionalization at the secondary amine of HL did not impair coordination to MnII with association constants (Kassoc) between 1.6 and 3.3 × 106 M- 1. The MnIII/MnII redox potential of the conjugates was between 0.27 and 0.30 V vs SCE, slightly higher than [MnL]+ under the same conditions, but remain at a value that facilitates O2•- dismutation. The catalytic rate constant (kcat) of the dismutation for the series was studied using a direct stopped-flow method, which showed that for compounds with the same overall charge, the alkylation of the secondary amine of [MnL]+ (kcat = 5.0 ± 0.1 × 106 M- 1 s- 1) led to a lower value (i.e. for [MnL'Gly]+},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Continuing a bio-mimetic approach, we have prepared peptide conjugates of a superoxide dismutase (SOD) mimic [MnL]+ (where HL = N-(2-hydroxybenzyl)-N,N'-bis[2-(N-methylimidazolyl)methyl]ethane-1,2-diamine), namely [MnL'-Arg(n-1)]n+ (where n = 2, 4, 7 and 10) and [MnL'-Gly1]+. [MnL'-Arg(n-1)]n+ contained cationic residue(s) that emulate the electrostatic channel of the enzyme. Physicochemical methods showed that functionalization at the secondary amine of HL did not impair coordination to MnII with association constants (Kassoc) between 1.6 and 3.3 × 106 M- 1. The MnIII/MnII redox potential of the conjugates was between 0.27 and 0.30 V vs SCE, slightly higher than [MnL]+ under the same conditions, but remain at a value that facilitates O2•- dismutation. The catalytic rate constant (kcat) of the dismutation for the series was studied using a direct stopped-flow method, which showed that for compounds with the same overall charge, the alkylation of the secondary amine of [MnL]+ (kcat = 5.0 ± 0.1 × 106 M- 1 s- 1) led to a lower value (i.e. for [MnL'Gly]+ |
Human TTR conformation altered by rhenium tris-carbonyl derivatives Journal Article L Ciccone; C Policar; E A Stura; W Shepard Journal of Structural Biology, 195 (3), pp. 353–364, 2016. @article{Ciccone:2016,
title = {Human TTR conformation altered by rhenium tris-carbonyl derivatives},
author = {L Ciccone and C Policar and E A Stura and W Shepard},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84991363542&doi=10.1016%2fj.jsb.2016.07.002&partnerID=40&md5=86e7e8d956bfdb39ae832e52b01a9dea},
doi = {10.1016/j.jsb.2016.07.002},
year = {2016},
date = {2016-01-01},
journal = {Journal of Structural Biology},
volume = {195},
number = {3},
pages = {353--364},
abstract = {Transthyretin (TTR) is a 54 kDa homotetrameric serum protein that transports thyroxine (T4) and retinol. TTR is potentially amyloidogenic due to homotetramer dissociation into monomeric intermediates that self-assemble as amyloid deposits and insoluble fibrils. Most crystallographic structures, including those of amyloidogenic variants show the same tetramer without major variations in the monomer-monomer interface nor in the volume of the interdimeric cavity. Soaking TTR crystals in a solution containing rhenium tris-carbonyl derivatives yields a TTR conformer never observed before. Only one of the two monomers of the crystallographic dimer is significantly altered, and the inner part of the T4 binding cavity is expanded at one end and shrunk at the other. The result redefines the mechanism of allosteric communication between the two sites, suggesting that negative cooperativity is a function of dimer asymmetry, which can be induced through internal or external binding. An aspect that remains unexplained is why the conformational changes are ubiquitous throughout the crystal although the heavy metal content of the derivatized crystals is relatively low. The conformational changes observed, which include Leu82, may represent a form of TTR better at scavenging β-Amyloid. At a resolution of 1.69 r{A}, with excellent refinement statistics and well defined electron density for all parts of the structure, it is possible to envisage answering important questions that range from protein cooperative behavior to heavy atom induced protein conformational modifications that can result in crystallographic non-isomorphism. © 2016 Elsevier Inc.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Transthyretin (TTR) is a 54 kDa homotetrameric serum protein that transports thyroxine (T4) and retinol. TTR is potentially amyloidogenic due to homotetramer dissociation into monomeric intermediates that self-assemble as amyloid deposits and insoluble fibrils. Most crystallographic structures, including those of amyloidogenic variants show the same tetramer without major variations in the monomer-monomer interface nor in the volume of the interdimeric cavity. Soaking TTR crystals in a solution containing rhenium tris-carbonyl derivatives yields a TTR conformer never observed before. Only one of the two monomers of the crystallographic dimer is significantly altered, and the inner part of the T4 binding cavity is expanded at one end and shrunk at the other. The result redefines the mechanism of allosteric communication between the two sites, suggesting that negative cooperativity is a function of dimer asymmetry, which can be induced through internal or external binding. An aspect that remains unexplained is why the conformational changes are ubiquitous throughout the crystal although the heavy metal content of the derivatized crystals is relatively low. The conformational changes observed, which include Leu82, may represent a form of TTR better at scavenging β-Amyloid. At a resolution of 1.69 Å, with excellent refinement statistics and well defined electron density for all parts of the structure, it is possible to envisage answering important questions that range from protein cooperative behavior to heavy atom induced protein conformational modifications that can result in crystallographic non-isomorphism. © 2016 Elsevier Inc. |
Monitoring bicosomes containing antioxidants in normal and irradiated skin Journal Article E Fernández; S Hostachy; C Sandt; G Rodríguez; H C Bertrand; S Clède; M Cócera; A D L Maza; F Lambert; C Policar; O López RSC Advances, 6 (76), pp. 72559–72567, 2016. @article{Fernandez:2016,
title = {Monitoring bicosomes containing antioxidants in normal and irradiated skin},
author = {E Fern\'{a}ndez and S Hostachy and C Sandt and G Rodr\'{i}guez and H C Bertrand and S Cl\`{e}de and M C\'{o}cera and A D L Maza and F Lambert and C Policar and O L\'{o}pez},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84982684419&doi=10.1039%2fc6ra11170j&partnerID=40&md5=126bef944046a09450ae86ce5985c07f},
doi = {10.1039/c6ra11170j},
year = {2016},
date = {2016-01-01},
journal = {RSC Advances},
volume = {6},
number = {76},
pages = {72559--72567},
abstract = {This study evaluates the penetration of bicosome systems incorporating two different antioxidants into normal skin and skin exposed to ultraviolet-visible radiation (UV-VIS) by Fourier-transform infrared microspectroscopy (FT-IR) using synchrotron radiation. Bicosomes are phospholipid assemblies based on mixtures of discoidal lipid structures protected by spherical lipid vesicles able to incorporate different molecules. In the current work, the antioxidants incorporated in these systems were β-carotene and a Mn complex as a superoxide dismutase (SOD) mimic. Additionally, a rhenium tri-carbonyl derivative was incorporated in the bicosome systems in order to map their penetration following the tag specific carbonyl signal by FT-IR microspectroscopy. The characterization of bicosome systems using the dynamic light scattering technique (DLS) showed a modification in the size of the systems containing β-carotene (Bcβ) or MnII complex (BcMn). After skin permeation, FT-IR results indicated a higher and deeper penetration of the BcMn system than the Bcβ system into the skin. Likely, the different physicochemical properties of both antioxidants could be responsible for this effect. Moreover, the penetration of both bicosome systems in irradiated skin was lower in comparison with the normal skin. This fact could be a consequence of the alteration of water transport in the skin during the irradiation process. In conclusion, these results indicated the effectiveness of bicosome systems as skin carriers, and provide information to protect skin under radiation using antioxidants. © The Royal Society of Chemistry 2016.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
This study evaluates the penetration of bicosome systems incorporating two different antioxidants into normal skin and skin exposed to ultraviolet-visible radiation (UV-VIS) by Fourier-transform infrared microspectroscopy (FT-IR) using synchrotron radiation. Bicosomes are phospholipid assemblies based on mixtures of discoidal lipid structures protected by spherical lipid vesicles able to incorporate different molecules. In the current work, the antioxidants incorporated in these systems were β-carotene and a Mn complex as a superoxide dismutase (SOD) mimic. Additionally, a rhenium tri-carbonyl derivative was incorporated in the bicosome systems in order to map their penetration following the tag specific carbonyl signal by FT-IR microspectroscopy. The characterization of bicosome systems using the dynamic light scattering technique (DLS) showed a modification in the size of the systems containing β-carotene (Bcβ) or MnII complex (BcMn). After skin permeation, FT-IR results indicated a higher and deeper penetration of the BcMn system than the Bcβ system into the skin. Likely, the different physicochemical properties of both antioxidants could be responsible for this effect. Moreover, the penetration of both bicosome systems in irradiated skin was lower in comparison with the normal skin. This fact could be a consequence of the alteration of water transport in the skin during the irradiation process. In conclusion, these results indicated the effectiveness of bicosome systems as skin carriers, and provide information to protect skin under radiation using antioxidants. © The Royal Society of Chemistry 2016. |
RIDME spectroscopy on high-spin Mn2+ centers Journal Article D Akhmetzyanov; H Y V Ching; V Denysenkov; P Demay-Drouhard; H C Bertrand; L C Tabares; C Policar; T F Prisner; S Un Physical Chemistry Chemical Physics, 18 (44), pp. 30857–30866, 2016. @article{Akhmetzyanov:2016,
title = {RIDME spectroscopy on high-spin Mn2+ centers},
author = {D Akhmetzyanov and H Y V Ching and V Denysenkov and P Demay-Drouhard and H C Bertrand and L C Tabares and C Policar and T F Prisner and S Un},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85025823502&doi=10.1039%2fc6cp05239h&partnerID=40&md5=d3a6cd609c88b382cf0297ed361d4003},
doi = {10.1039/c6cp05239h},
year = {2016},
date = {2016-01-01},
journal = {Physical Chemistry Chemical Physics},
volume = {18},
number = {44},
pages = {30857--30866},
abstract = {Pulsed EPR dipolar spectroscopy is a powerful tool for determining the structure and conformational dynamics of biological macromolecules, as it allows precise measurements of distances in the range of 1.5-10 nm. Utilization of high-spin Mn2+ species as spin probes for distance measurements is of significant interest, because they are biologically compatible and endogenous in numerous biological systems. However, to date dipolar spectroscopy experiments with this kind of species have been underexplored. Here we present pulsed electron electron double resonance (PELDOR also called DEER) and relaxation-induced dipolar modulation enhancement (RIDME) experiments, which have been performed at W-band (94 GHz) and J-band frequencies (263 GHz) on a bis-MnDOTA (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) model system. The distances obtained from these experiments are in good agreement with predictions. RIDME experiments reveal a significantly higher modulation depth compared to PELDOR, which is an important consideration for biological samples. These experiments also feature higher harmonics of the dipolar coupling frequency due to effective multiple-quantum relaxation of high-spin Mn2+ as well as the multiple-component background function. Harmonics of the dipolar coupling frequency were taken into account by including additional terms in the kernel function of Tikhonov regularization analysis. © The Owner Societies 2016.},
keywords = {},
pubstate = {published},
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Pulsed EPR dipolar spectroscopy is a powerful tool for determining the structure and conformational dynamics of biological macromolecules, as it allows precise measurements of distances in the range of 1.5-10 nm. Utilization of high-spin Mn2+ species as spin probes for distance measurements is of significant interest, because they are biologically compatible and endogenous in numerous biological systems. However, to date dipolar spectroscopy experiments with this kind of species have been underexplored. Here we present pulsed electron electron double resonance (PELDOR also called DEER) and relaxation-induced dipolar modulation enhancement (RIDME) experiments, which have been performed at W-band (94 GHz) and J-band frequencies (263 GHz) on a bis-MnDOTA (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) model system. The distances obtained from these experiments are in good agreement with predictions. RIDME experiments reveal a significantly higher modulation depth compared to PELDOR, which is an important consideration for biological samples. These experiments also feature higher harmonics of the dipolar coupling frequency due to effective multiple-quantum relaxation of high-spin Mn2+ as well as the multiple-component background function. Harmonics of the dipolar coupling frequency were taken into account by including additional terms in the kernel function of Tikhonov regularization analysis. © The Owner Societies 2016. |
