Publications by authors named "Jérémy M Zimbron"

4 Publications

  • Page 1 of 1

Insights into the antiproliferative mechanism of (C^N)-chelated half-sandwich iridium complexes.

Dalton Trans 2020 Dec;49(48):17635-17641

Institut Parisien de Chimie Moléculaire (IPCM), Sorbonne Université, CNRS, 4 place Jussieu, F-75005 Paris, France.

Transition metal-based anticancer compounds, as an 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.
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http://dx.doi.org/10.1039/d0dt03414bDOI Listing
December 2020

Real-Time Control of the Enantioselectivity of a Supramolecular Catalyst Allows Selecting the Configuration of Consecutively Formed Stereogenic Centers.

Angew Chem Int Ed Engl 2017 11 4;56(45):14016-14019. Epub 2017 Oct 4.

Sorbonne Universités, UPMC Univ Paris 06, CNRS, Institut Parisien de Chimie Moléculaire, Equipe Chimie des Polymères, 4 Place Jussieu, 75005, Paris, France.

The enantiomeric state of a supramolecular copper catalyst can be switched in situ in ca. five seconds. The dynamic property of the catalyst is provided by the non-covalent nature of the helical assemblies supporting the copper centers. These assemblies are formed by mixing an achiral benzene-1,3,5-tricarboxamide (BTA) phosphine ligand (for copper coordination) and both enantiomers of a chiral phosphine-free BTA co-monomer (for chirality amplification). The enantioselectivity of the hydrosilylation reaction is fixed by the BTA enantiomer in excess, which can be altered by simple BTA addition. As a result of the complete and fast stereochemical switch, any combination of the enantiomers was obtained during the conversion of a mixture of two substrates.
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http://dx.doi.org/10.1002/anie.201706757DOI Listing
November 2017

A dual anchoring strategy for the localization and activation of artificial metalloenzymes based on the biotin-streptavidin technology.

J Am Chem Soc 2013 Apr 2;135(14):5384-8. Epub 2013 Apr 2.

Biozentrum and Department of Chemistry, University of Basel, CH-4056 Basel, Switzerland.

Artificial metalloenzymes result from anchoring an active catalyst within a protein environment. Toward this goal, various localization strategies have been pursued: covalent, supramolecular, or dative anchoring. Herein we show that introduction of a suitably positioned histidine residue contributes to firmly anchor, via a dative bond, a biotinylated rhodium piano stool complex within streptavidin. The in silico design of the artificial metalloenzyme was confirmed by X-ray crystallography. The resulting artificial metalloenzyme displays significantly improved catalytic performance, both in terms of activity and selectivity in the transfer hydrogenation of imines. Depending on the position of the histidine residue, both enantiomers of the salsolidine product can be obtained.
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http://dx.doi.org/10.1021/ja309974sDOI Listing
April 2013

Chemo-genetic optimization of DNA recognition by metallodrugs using a presenter-protein strategy.

Chemistry 2010 Nov;16(43):12883-9

University of Basel, Department of Chemistry, Spitalstrasse 51, 4056 Basel, Switzerland.

The mode of action of precious metal anticancer metallodrugs is generally believed to involve DNA as a target. However, the poor specificity of such drugs often requires high doses and leads to undesirable side-effects. With the aim of improving the specificity of a ruthenium piano-stool complex towards DNA, we employed a presenter protein strategy based on the biotin-avidin technology. Guided by the X-ray structure of the assembly of streptavidin and a biotinylated piano-stool, we explored the formation of metallodrug-mediated ternary complexes with the presenter protein and DNA. The assemblies bound more strongly to telomere G-quadruplexes than to double-stranded DNA; chemo-genetic modifications (varying the complex or mutating the protein) modulated binding to these targets. We suggest that rational targeting of small molecules by presenter proteins could be exploited to bind metallodrugs to preferred macromolecular targets.
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http://dx.doi.org/10.1002/chem.201001573DOI Listing
November 2010