Publications by authors named "Muriel Albalat"

14 Publications

  • Page 1 of 1

Enzymatic activity monitoring through dynamic nuclear polarization in Earth magnetic field.

J Magn Reson 2021 Dec 27;333:107095. Epub 2021 Oct 27.

Magnetic Resonance of Biological Systems, UMR5536 University of Bordeaux-CNRS, Bordeaux, France.

Cost-effective and portable MRI systems operating at Earth-field would be helpful in poorly accessible areas or in developing nations. Furthermore Earth-field MRI can provide new contrasts opening the way to the observation of pathologies at the biochemical level. However low-field MRI suffers from a dramatic lack in detection sensitivity even worsened for molecular imaging purposes where biochemical specificity requires detection of dilute compounds. In a preliminary spectroscopic approach, it is proposed here to detect protease-driven hydrolysis of a nitroxide probe thanks to electron-nucleus Overhauser enhancement in a home-made double resonance system in Earth-field. The combination of the Overhauser effect and the specific enzymatic modification of the probe provides a smart contrast reporting the enzymatic activity. The nitroxide probe is a six-line nitroxide which lines are shifted according to its substrate/product state, which requires quantum mechanical calculations to predict EPR line frequencies and Overhauser enhancements at Earth field. The NMR system is equipped with a 13-mT prepolarization coil, a 153-MHz EPR coil and a 2-kHz NMR coil. Either prepolarized NMR or DNP-NMR without prepolarization provide NMR spectra within 3 min. The frequency dependence of Overhauser enhancement was in agreement with theoretical calculations. Protease-mediated catalysis of the nitroxide probe could only be measured through the Overhauser effect with 5 min time resolution. Future developments shall open the way for the design of new low-field DNP-MRI systems.
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http://dx.doi.org/10.1016/j.jmr.2021.107095DOI Listing
December 2021

Transition metal complexes bearing atropisomeric saturated NHC ligands.

Chirality 2021 Nov 5. Epub 2021 Nov 5.

Aix Marseille Univ, CNRS, Centrale Marseille, iSm2, Marseille, France.

From achiral imidazolinium salts, chiral transition metal complexes containing an N-heterocyclic carbene (NHC) ligand were prepared (metal = palladium, copper, silver, gold, rhodium). Axial chirality in these complexes results from the formation of the metal-carbene bond leading to the restriction of rotation of dissymmetric N-aryl substituents about the C-N bond. When these complexes exhibited a sufficient configurational stability, a resolution by chiral high-performance liquid chromatography (HPLC) on preparative scale enabled isolation of enantiomers with excellent enantiopurities (>99% ee) and good yields. A study of the enantiomerization barriers revealed the effect of the backbone nature as well as the type of transition metal on its values. Nevertheless, the evaluation of palladium-based complexes in asymmetric intramolecular α-arylation of amides demonstrated that the ability to induce an enantioselectivity cannot be correlated to the configurational stability of the precatalysts.
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http://dx.doi.org/10.1002/chir.23378DOI Listing
November 2021

Hemicryptophane Cages with a -Symmetric Cyclotriveratrylene Unit.

J Org Chem 2021 Nov 1;86(21):15055-15062. Epub 2021 Oct 1.

Aix Marseille Univ, CNRS, Centrale Marseille iSm2, 13284 Marseille, France.

Two new hemicryptophanes combining a cyclotriveratrylene unit with either an aminotrisamide or a tris(2-aminoethyl)amine (tren) moiety have been synthesized. Although a conventional synthesis approach was used, the molecular cages obtained are devoid of the expected symmetry. NMR analyses and X-ray crystal structure determination showed that these hemicryptophanes exhibited symmetry due to the unusual arrangement of the substituents of the cyclotriveratrylene unit. This unprecedented arrangement is related to a change in the regioselectivity of the Friedel-Crafts reactions that led to the CTV cap. This constitutes an original approach to access enantiopure chiral molecular cages with low symmetry.
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http://dx.doi.org/10.1021/acs.joc.1c01731DOI Listing
November 2021

Two-Photon Absorbing AIEgens: Influence of Stereoconfiguration on Their Crystallinity and Spectroscopic Properties and Applications in Bioimaging.

ACS Appl Mater Interfaces 2020 Dec 20;12(49):55157-55168. Epub 2020 Nov 20.

Univ. Lyon, ENS Lyon, CNRS, Université Lyon 1, Laboratoire de Chimie, UMR 5182, 46 Allée d'Italie, 69364 Lyon, France.

This paper aims at designing chromophores with efficient aggregation-induced emission (AIE) properties for two-photon fluorescence microscopy (2PFM), which is one of the best-suited types of microscopy for the imaging of living organisms or thick biological tissues. Tetraphenylethylene (TPE) derivatives are common building blocks in the design of chromophores with efficient AIE properties. Therefore, in this study, extended TPE AIEgens specifically optimized for two-photon absorption (2PA) are synthesized and the resulting (/) isomers are separated using chromatography on chiral supports. Comparative characterization of the AIE properties is performed on the pure () and () isomers and the mixture, allowing us, in combination with powder X-ray diffraction and solid-state NMR, to document a profound impact of crystallinity on solid-state fluorescence properties. In particular, we show that stereopure AIEgens form aggregates of superior crystallinity, which in turn exhibit a higher fluorescence quantum yield compared to diastereoisomers mixtures. Preparation of stereopure organic nanoparticles affords very bright fluorescent contrast agents, which are then used for cellular and intravital two-photon microscopy on human breast cancer cells and on zebrafish embryos.
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http://dx.doi.org/10.1021/acsami.0c15810DOI Listing
December 2020

Enantiopure encaged Verkade's superbases: Synthesis, chiroptical properties, and use as chiral derivatizing agent.

Chirality 2020 02 17;32(2):139-146. Epub 2019 Dec 17.

Aix Marseille Univ, CNRS, Centrale Marseille, iSm2, Marseille, France.

Verkade's superbases, entrapped in the cavity of enantiopure hemicryptophane cages, have been synthesized with enantiomeric excess (ee) superior to 98%. Their absolute configuration has been determined by using electronic circular dichroism (ECD) spectroscopy. These enantiopure encaged superbases turned out to be efficient chiral derivatizing agents for chiral azides, underlining that the chirality of the cycloveratrylene (CTV) macrocycle induces different magnetic and chemical environments around the phosphazide functions.
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http://dx.doi.org/10.1002/chir.23156DOI Listing
February 2020

From Prochiral N-Heterocyclic Carbenes to Optically Pure Metal Complexes: New Opportunities in Asymmetric Catalysis.

J Am Chem Soc 2020 01 23;142(1):93-98. Epub 2019 Dec 23.

Aix Marseille Univ , CNRS, Centrale Marseille, iSm2 , Marseille , France.

Well-defined optically pure transition metal (TM) complexes bearing - and -symmetric N-heterocyclic carbene (NHC) ligands were prepared from prochiral NHC precursors. As predicted by DFT calculations, our strategy capitalizes on the formation of a metal-carbene bond which induces an axis of chirality. Configurationally stable atropisomers of various NHC-containing TM complexes were isolated by preparative HPLC on a chiral stationary phase in good yields and excellent optical purities (up to 99.5% ee). The carbene transfer from an optically pure Cu complex to a gold or palladium center reveals, for the first time, a full stereoretentivity, supporting the hypothesis of an associative mechanism for the transmetalation. The potential of these new chiral TM complexes was illustrated in asymmetric catalysis with up to 98% ee.
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http://dx.doi.org/10.1021/jacs.9b12698DOI Listing
January 2020

Synthesis, resolution, and chiroptical properties of hemicryptophane cage controlling the chirality of propeller arrangement of a C triamide unit.

Chirality 2019 Nov 2;31(11):910-916. Epub 2019 Sep 2.

Aix Marseille Univ, CNRS, Centrale Marseille, iSm2, Marseille, France.

The five-steps synthesis of a hemicryptophane cage combining a benzene-1,3,5-tricarboxamide unit and a cyclotriveratrylene (CTV) moiety is described. Chiral high-performance liquid chromatography (HPLC) was used to resolve the racemic mixture. The absolute configuration of the isolated enantiomers was assigned by comparison of the experimental electronic circular dichroism (ECD) spectra with the calculated ones. X-ray molecular structures reveal that the capped benzene-1,3,5-tricarboxamide unit adopts a structurally chiral conformation in solid state: the chirality of CTV moiety controls the Λ or Δ orientation of the three amides.
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http://dx.doi.org/10.1002/chir.23131DOI Listing
November 2019

Effect of substituents on the configurational stability of the stereogenic nitrogen in metal(II) complexes of α-amino acid Schiff bases.

Chirality 2019 05 27;31(5):401-409. Epub 2019 Mar 27.

Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country, San Sebastián, Spain.

Herein, we report a general method for quantitative measurement of the configurational stability of the stereogenic nitrogen coordinated to M (II) in the corresponding square planar complexes. This stereochemical approach is quite sensitive to steric and electronic effects of the substituents and shown to work well for Ni(II), Pd(II), and Cu(II) complexes. Structural simplicity of the compounds used, coupled with high sensitivity and reliability of experimental procedures, bodes well for application of this approach in evaluation of chemical stability and stereochemical properties of newly designed chiral ligands for general asymmetric synthesis of tailor-made amino acids.
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http://dx.doi.org/10.1002/chir.23066DOI Listing
May 2019

Umpolung Reactivity of in Situ Generated Phosphido-Boranes: An Entry to P-Stereogenic Aminophosphine-Boranes.

J Org Chem 2019 Apr 12;84(7):4551-4557. Epub 2019 Mar 12.

Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 , Marseille 13397 , France.

The synthesis of P-stereogenic aminophosphine-boranes has been developed on the basis of umpolung reactivity of in situ generated alkylarylphosphido-boranes, which are normally configurationally unstable intermediates. In our case, their high configurational stability was due to the slow release of the hydroxyalkyl protecting group, together with the fast formation of the iodophosphanylborane in the presence of N-iodosuccinimide. The subsequent substitution reaction was found to proceed in moderate to good yields and in a very high stereospecifity (es) using a variety of amines as nucleophiles.
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http://dx.doi.org/10.1021/acs.joc.9b00333DOI Listing
April 2019

Improved synthesis, resolution, absolute configuration determination and biological evaluation of HLM006474 enantiomers.

Bioorg Med Chem Lett 2019 02 17;29(3):380-382. Epub 2018 Dec 17.

UNIV. NIMES, EA7352 CHROME, Rue du Dr G. Salan, 30021 Nîmes Cedex 1, France. Electronic address:

An improved green synthesis of the E2F inhibitor HLM0066474 is described, using solvent-free and microwave irradiation conditions. The two enantiomers are separated using semi-preparative separation on Chiralpak ID and their absolute configuration is determined by vibrational circular dichroism (VCD) analysis. Biological evaluation of both enantiomers on E2F1 transcriptional activity reveals that the (+)-R, but not the (-)-S enantiomer is biologically active in repressing E2F1 transcriptional activity.
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http://dx.doi.org/10.1016/j.bmcl.2018.12.037DOI Listing
February 2019

Enantiopure C-Cyclotriveratrylene with a Reversed Spatial Arrangement of the Substituents.

Org Lett 2019 01 14;21(1):160-165. Epub 2018 Dec 14.

Aix Marseille Univ, CNRS, Centrale Marseille , iSm2 , Marseille , France.

Cyclotriveratrylene (CTV) is a macrocyclic cyclophane presenting a bowl-shaped conformation, used as building block to construct cryptophane and hemicryptophane capsules. A method to synthesize new enantiopure CTV derivatives with an unprecedented spatial arrangement of their substituents, exhibiting C symmetry, is described. The absolute configuration was assigned by ECD spectroscopy coupled with modeling. A statistical model has allowed for optimization of the proportion of C CTV, and the modularity of this approach is also highlighted.
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http://dx.doi.org/10.1021/acs.orglett.8b03621DOI Listing
January 2019

Hit optimization studies of 3-hydroxy-indolin-2-one analogs as potential anti-HIV-1 agents.

Bioorg Chem 2018 09 9;79:212-222. Epub 2018 May 9.

Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani Campus, Pilani 333031, Rajasthan, India. Electronic address:

In the current study, twenty-two compounds based upon 3-hydroxy-3-(2-oxo-2-phenylethyl)indolin-2-one nucleus were designed, synthesized and in vitro evaluated for HIV-1 RT inhibition and anti-HIV-1 activity. Compounds 3d, 5c and 5e demonstrated encouraging potency against RT enzyme as well as HIV-1 in low micromolar to nanomolar concentration with good to excellent safety index. Structure activity relationship studies revealed that halogens such as bromo or chloro at 5th the position of oxindole ring remarkably enhanced the potency against RT. Moreover, methoxy or chloro groups at the ortho position of phenyl ring also significantly favored RT inhibition activity. Seven compounds (3b, 3c, 3d, 3e, 5b, 5c and 5e) with better anti-HIV-1 potency were tested against the mutant HIV-1 strain The putative binding mode, as well as interaction patterns of the best active compound 5c with wild HIV-1 RT were studied via docking studies.
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http://dx.doi.org/10.1016/j.bioorg.2018.04.027DOI Listing
September 2018

Helical Chirality Induces a Substrate-Selectivity Switch in Carbohydrates Recognitions.

J Org Chem 2018 06 29;83(12):6301-6306. Epub 2018 May 29.

Aix Marseille Univ, CNRS , Centrale Marseille, iSm2 , Marseille F-13397 , France.

A new chiral hemicryptophane cage combining an electron-rich cyclotriveratrylene (CTV) unit and polar amine functions has been synthesized. The resolution of the racemic mixture has been performed by chiral HPLC, and the assignment of the absolute configuration of the two enantiomers has been achieved using ECD spectroscopy. In contrast with other hemicryptophane receptors, the two enantiomeric hosts display both remarkable enantioselectivities in the recognition of carbohydrates and good binding constants. Moreover, by switching the chirality of the CTV unit from M to P, a strong preference shift from glucose to mannose derivatives is observed.
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http://dx.doi.org/10.1021/acs.joc.8b00276DOI Listing
June 2018

Steric Scale of Common Substituents from Rotational Barriers of N-(o-Substituted aryl)thiazoline-2-thione Atropisomers.

J Org Chem 2017 10 25;82(19):10188-10200. Epub 2017 Sep 25.

Aix Marseille Univ , CNRS, Centrale Marseille, iSm2, Marseille, France.

A steric scale of 20 recurrent groups was established from comparison of rotational barriers on N-(o-substituted aryl)thiazoline-2-thione atropisomers. The resulting energy of activation ΔG reflects the spatial requirement of the ortho substituent borne by the aryl moiety, electronic aspects and external parameters (temperature and solvent) generating negligible contributions. Concerning divergent rankings reported in the literature, the great sensitivity of this model allowed us to show unambiguously that a methyl appears bigger than a chlorine and gave the following order in size: CN > OMe > OH. For the very bulky CF and iPr groups, constraints in the ground state decreased the expected ΔG values resulting in a minimization of their apparent sizes.
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http://dx.doi.org/10.1021/acs.joc.7b01698DOI Listing
October 2017
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