Publications by authors named "Serge Thorimbert"

36 Publications

A Solvent-free, Catalyst-free Formal [3+3] Cycloaddition Dearomatization Strategy: Towards New Fluorophores for Biomolecules Labelling.

ChemSusChem 2021 Apr 15;14(8):1821-1824. Epub 2021 Mar 15.

Sorbonne Université, CNRS, Institut Parisien de Chimie Moleculaire, IPCM, 75005, Paris, France.

A general, sustainable dearomatization reaction for nitrogen-containing heterocycles was developed. Under solvent free conditions and without catalyst, the biorenewable methyl coumalate (MC) reacted as an efficient C partner to convert nine types of basic aromatic rings into their pyrido[1,2-a] fused derivatives in good to excellent yields. The fluorescence properties of some of the products were harnessed to conjugate fluorescent tags to bovine serum albumin (BSA) and immunoglobulin G.
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http://dx.doi.org/10.1002/cssc.202100301DOI Listing
April 2021

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

The bio-based methyl coumalate involved Morita-Baylis-Hillman reaction.

Org Biomol Chem 2019 03;17(10):2784-2791

Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, IPCM, F-75005 Paris, France.

We report the first use of renewable, bio-based, non-hazardous feedstock methyl coumalate (MC) in organocatalyzed Morita-Baylis-Hillman (MBH) reactions. This atom-economical pathway employs inexpensive Et3N as a catalyst in ethanol. Synthon MC efficiently constructs C-C bonds with various imines and aldehydes in moderate to good yields. This catalytic process is triggered via an unprecedented 1,6-conjugated addition, as opposed to the classical MBH reaction. Moreover, this methodology expands Morita-Baylis-Hillman donor capabilities to a 2-pyrone derivative for the first time. MBH adducts described herein could be applied to the synthesis of fine chemicals with biologically active structural cores, such as diphenylmethanol, hydroisobenzofurans, and hydroisoindoles.
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http://dx.doi.org/10.1039/c9ob00328bDOI Listing
March 2019

Electrochemical primer extension based on polyoxometalate electroactive labels for multiplexed detection of single nucleotide polymorphisms.

Biosens Bioelectron 2018 Oct 7;117:201-206. Epub 2018 Jun 7.

Departament d'Enginyeria Quıímica, Universitat Rovira i Virgili, Avinguda Països Catalans 26, 43007 Tarragona, Spain; ICREA, Passeig Lluis Companys 23, 08010 Barcelona, Spain. Electronic address:

Polyoxymetalates (POMs) ([SiWO{Sn(CH)CO)}] and [PWO{Sn(CH)CO)}]) were used to modify dideoxynucleotides (ddNTPs) through amide bond formation, and applied to the multiplexed detection of single nucleotide polymorphisms (SNPs) in an electrochemical primer extension reaction. Each gold electrode of an array was functionalised with a short single stranded thiolated DNA probe, specifically designed to extend with the POM-ddNTP at the SNP site to be interrogated. The system was applied to the simultaneous detection of 4 SNPs within a single stranded 103-mer model target generated using asymmetric PCR, highlighting the potential of POM-ddNTPs for targeted, multiplexed SNP detection. The four DNA bases were successfully labelled with both ([SiWO{Sn(CH)CO)}] and [PWO{Sn(CH)CO)}]), and [SiWO{Sn(CH)CO)}] demonstrated to be the more suitable due to its single oxidation peak, which provides an unequivocal signal. The POM-ddNTP enzymatically incorporated to the DNA anchored to the surface was visualised by AFM using gold coated mica. The developed assay has been demonstrated to be highly reproducible, simple to carry out and with very low non-specific background signals. Future work will focus on applying the developed platform to the detection of SNPs associated with rifampicin resistance in real samples from patients suffering from tuberculosis.
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http://dx.doi.org/10.1016/j.bios.2018.06.014DOI Listing
October 2018

Stable Carboxylate-Terminated Gold Surfaces Produced by Spontaneous Grafting of an Alkyltin Compound.

Chemistry 2018 Aug 2;24(43):11177-11184. Epub 2018 Jul 2.

Departament d'Enginyeria Química, Universitat Rovira i Virgili, Avinguda Països Catalans 26, 43007, Tarragona, Spain.

Self-assembled monolayers formed by chemisorption of thiolated molecules on gold surfaces are widely applied for biosensing. Moreover, and due to the low stability of thiol-gold chemistry, contributions to the functionalisation of gold substrates with linkers that provide a more stable platform for the immobilisation of electroactive or biological molecules are highly appreciated. Herein, it is demonstrated that a carboxylated organotin compound can be successfully grafted onto gold substrates to form a highly stable organic layer with reactivity for subsequent binding to an aminated molecule. A battery of techniques were used to characterise the surface chemistry. The grafted layer was used to anchor aminoferrocene and subjected to both thermostability tests and long-term stability studies over a period of one year, demonstrating thermostability up to 90 °C and storage stability for at least 12 months at 4 °C protected from light. The stable surface tethering of molecules on gold substrates can be exploited in a plethora of applications, including molecular techniques, such as solid-phase amplification and solid-phase melting curve analysis, that require elevated temperature stability, as well as biosensors, which require long-term storage stability.
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http://dx.doi.org/10.1002/chem.201801854DOI Listing
August 2018

PCR Incorporation of Polyoxometalate Modified Deoxynucleotide Triphosphates and Their Application in Molecular Electrochemical Sensing of Yersinia pestis.

Chemistry 2017 Aug 18;23(44):10597-10603. Epub 2017 Jul 18.

Department d'Enginyeria Química, Universitat Rovira i Virgili, Avinguda Països Catalans 26, 43007, Tarragona, Spain.

Redox-labeled nucleotides are of increasing interest for the fabrication of next generation molecular tools and should meet requirements of being thermally stable, sensitive, and compatible with polymerase-mediated incorporation while also being electrochemically discriminable. The synthesis and characterization of Keggin and Dawson polyoxometalate-deoxynucleotide (POM-dNTP) bioconjugates linked through 7-deaza-modified purines is described. The modified POM-dNTPs were used for polymerase-based amplification of a DNA sequence specific for Yersinia pestis and the amplified DNA detected using an electrochemical DNA sensor. This highlights the potential of polyoxometalates as thermally stable, sensitive and polymerase-compatible redox labels for exploitation in bioanalytical applications.
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http://dx.doi.org/10.1002/chem.201701295DOI Listing
August 2017

Preparation of Substituted 2H-Pyrans via a Cascade Reaction from Methyl Coumalate and Activated Methylene Nucleophiles.

J Org Chem 2017 05 9;82(10):5499-5505. Epub 2017 May 9.

Sorbonne Universités , UPMC Univ Paris 06, Institut Parisien de Chimie Moléculaire, UMR CNRS 8232, 4 place Jussieu, F-75005 Paris, France.

The reaction of methyl coumalate with a wide range of methylene active compounds, such as keto-esters or keto-sulfones and cyclic or acyclic diketones, afforded more than 30 2,3,5,6-tetrasubstituted 2H-pyrans. The reaction proceeds via a cascade reaction involving a Michael addition-6π-electrocyclic ring opening-proton transfer and 6π electrocyclization, in which a variety of functional groups were tolerated.
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http://dx.doi.org/10.1021/acs.joc.7b00761DOI Listing
May 2017

Design, synthesis and biological evaluation of gentiopicroside derivatives as potential antiviral inhibitors.

Eur J Med Chem 2017 Apr 21;130:308-319. Epub 2017 Feb 21.

Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Biomedicine Key Laboratory of Shaanxi Province, Northwest University, Xi'an 710069, China; Sorbonne Universités, UPMC Univ Paris 06, Institut Parisien de Chimie Moléculaire, CNRS UMR 8232, 4 place Jussieu, 75005 Paris, France; Institute for Interdisciplinary Research, Jianghan University, Wuhan Economic and Technological Development Zone, Wuhan 430056, China. Electronic address:

Based on classical drug design theory, a novel series of gentiopicroside derivatives was designed and synthesized. All synthesized compounds were then biologically evaluated for their inhibition of influenza virus and anti-HCV activity in vitro. Some of the gentiopicroside derivatives, such as 11a, 13d and 16 showed interesting anti-influenza virus activity with IC at 39.5 μM, 45.2 μM and 44.0 μM, respectively. However, no significant anti-HCV activity was found for all of gentiopicroside derivatives. The preliminary results indicate that modification of the sugar moiety on gentiopicroside was helpful for enhancing the anti-influenza activities. Our works demonstrate the importance of secoiridoid natural products as new leads in the development of potential antiviral inhibitors.
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http://dx.doi.org/10.1016/j.ejmech.2017.02.028DOI Listing
April 2017

Research Progress of Natural Product Gentiopicroside - a Secoiridoid Compound.

Mini Rev Med Chem 2017 ;17(1):62-77

Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 8232, 4 place Jussieu, 75005 Paris, France.

Gentiopicroside is a secoiridoid compound isolated from Gentiana lutea which is called Qin Jiao in Chinese. It is one of the most common herbal medicines used in China. In this article, we review the pharmacological and biological activity (antiviral, anti-inflammatory, analgesia, antihepatotoxic and choleretic), as well as biotransformation of the gentiopicroside. In addition, attempt towards the total synthesis of gentiopicroside is also presented.
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http://dx.doi.org/10.2174/1389557516666160624124127DOI Listing
March 2017

Biofunctionalization of Polyoxometalates with DNA Primers, Their Use in the Polymerase Chain Reaction (PCR) and Electrochemical Detection of PCR Products.

Chemistry 2015 Dec 22;21(49):17721-7. Epub 2015 Oct 22.

Sorbonne Universités, UPMC Univ Paris 06, CNRS, Institut Parisien de Chimie Moléculaire (UMR 8232), 4 place Jussieu, 75005 Paris (France).

The bioconjugation of polyoxometalates (POMs), which are inorganic metal oxido clusters, to DNA strands to obtain functional labeled DNA primers and their potential use in electrochemical detection have been investigated. Activated monooxoacylated polyoxotungstates [SiW11 O39 {Sn(CH2 )2 CO}](8-) and [P2 W17 O61 {Sn(CH2 )2 CO}](6-) have been used to link to a 5'-NH2 terminated 21-mer DNA forward primer through amide coupling. The functionalized primer was characterized by using a battery of techniques, including electrophoresis, mass spectrometry, as well as IR and Raman spectroscopy. The functionality of the POM-labeled primers was demonstrated through hybridization with a surface-immobilized probe. Finally, the labeled primers were successfully used in the polymerase chain reaction (PCR) and the PCR products were characterized by using electrophoresis.
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http://dx.doi.org/10.1002/chem.201502247DOI Listing
December 2015

Chiral Dawson-Type Hybrid Polyoxometalate Catalyzes Enantioselective Diels-Alder Reactions.

Chemistry 2015 Nov 25;21(46):16512-6. Epub 2015 Sep 25.

Sorbonne Universités, Université Pierre et Marie Curie Paris 06, UMR 8232, Institut Parisien de Chimie Moléculaire (IPCM), 75005 Paris (France).

Can achiral organocatalysts linked to chiral polyanionic metal oxide clusters provide good selectivity in enantioselective C-C bond formations? The answer to this question is investigated by developing a new active hybrid polyoxometalate-based catalyst for asymmetric Diels-Alder reaction. Chirality transfer from the chiral anionic polyoxometalate to the covalently linked achiral imidazolidinone allows Diels-Alder cycloaddition products to be obtained with good yields and high enantioselectivities when using cyclopentadiene and acrylaldehydes as partners.
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http://dx.doi.org/10.1002/chem.201502839DOI Listing
November 2015

Exploring the utility of organo-polyoxometalate hybrids to inhibit SOX transcription factors.

Cell Regen 2014 19;3:10. Epub 2014 Jul 19.

Genome Institute of Singapore, 60 Biopolis Street, Buona Vista 138672, Singapore ; Genome Regulation Laboratory, Drug Development Pipeline, Guangzhou Institutes of Biomedicine, 190 Kai Yuan Avenue, Science Park, 510530 Guangzhou, China.

Background: SOX transcription factors constitute an attractive target class for intervention with small molecules as they play a prominent role in the field of regenerative biomedicine and cancer biology. However, rationally engineering specific inhibitors that interfere with transcription factor DNA interfaces continues to be a monumental challenge in the field of transcription factor chemical biology. Polyoxometalates (POMs) are inorganic compounds that were previously shown to target the high-mobility group (HMG) of SOX proteins at nanomolar concentrations. In continuation of this work, we carried out an assessment of the selectivity of a panel of newly synthesized organo-polyoxometalate hybrids in targeting different transcription factor families to enable the usage of polyoxometalates as specific SOX transcription factor drugs.

Results: The residual DNA-binding activities of 15 different transcription factors were measured after treatment with a panel of diverse polyoxometalates. Polyoxometalates belonging to the Dawson structural class were found to be more potent inhibitors than the Keggin class. Further, organically modified Dawson polyoxometalates were found to be the most potent in inhibiting transcription factor DNA binding activity. The size of the polyoxometalates and its derivitization were found to be the key determinants of their potency.

Conclusion: Polyoxometalates are highly potent, nanomolar range inhibitors of the DNA binding activity of the Sox-HMG family. However, binding assays involving a limited subset of structurally diverse polyoxometalates revealed a low selectivity profile against different transcription factor families. Further progress in achieving selectivity and deciphering structure-activity relationship of POMs require the identification of POM binding sites on transcription factors using elaborate approaches like X-ray crystallography and multidimensional NMR. In summary, our report reaffirms that transcription factors are challenging molecular architectures and that future polyoxometalate chemistry must consider further modification strategies, to address the substantial challenges involved in achieving target selectivity.
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http://dx.doi.org/10.1186/2045-9769-3-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306199PMC
February 2015

Intramolecular anion effect in polyoxometalate-based organocatalysts: reactivity enhancement and chirality transfer by a metal oxide-organic cation interaction.

Chemistry 2014 Dec 24;20(49):16074-7. Epub 2014 Oct 24.

Institut Parisien de Chimie Moléculaire (UMR CNRS 7201), UPMC Univ Paris 06, 4 Place Jussieu, 75005 Paris (France).

An α1 -Dawson polyanion bearing a lateral side chain with a 4-aminopyridine end group was synthesized. This organopolyoxometalate catalyzes the addition of indenyl allyl silanes to cinnamoyl fluorides. The polyanionic framework influences the organocatalyst activity and selectivity. A moderate but nonzero chirality transfer from the chiral inorganic framework to the organic substrate was observed.
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http://dx.doi.org/10.1002/chem.201403989DOI Listing
December 2014

Pd-containing organopolyoxometalates derived from Dawson polyoxometalate [P₂W₁₅V₃O₆₂]⁹⁻: Lewis acidity and dual site catalysis.

Org Lett 2014 Aug 16;16(15):3860-3. Epub 2014 Jul 16.

Sorbonne Universités, UPMC Univ Paris 06 , Institut Parisien de Chimie Moléculaire, 4 place Jussieu, 75005 Paris, France.

Grafting of a palladium complex to the Dawson vanadotungstate polyanion [P2W15V3O62](9-) via an organic ligand generates a large family of pincer-type hybrid polyoxometalates. The palladium-POM derivatives have dual catalytic properties. Unlike their parent inorganic polyanions, they catalyze allylations while retaining their oxidant character, which leads to single-pot dual site catalysis. This opens a new route for multicatalytic reactions.
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http://dx.doi.org/10.1021/ol501644cDOI Listing
August 2014

Access to pyridyl-substituted 1,3,5-triazines from 4H-pyrido[1,3]oxazin-4-ones via a cyclocondensation process.

J Org Chem 2014 Jul 1;79(14):6579-89. Epub 2014 Jul 1.

Exploratory Unit, Sanofi R&D , 1 Avenue Pierre Brossolette, 91385 Chilly Mazarin Cedex, France.

Pyridyl-substituted 1,3,5-triazines were synthesized in good to excellent yields via an unprecedented one-step cyclocondensation of 4H-pyrido[1,3]oxazin-4-ones with amidines at room temperature or under microwave irradiations. The broad applicability was demonstrated by 33 examples with a variety of amidines and three different 4H-pyrido[1,3]oxazin-4-one chemical series. In addition, a one-pot process from 4H-pyrido[1,3]oxazin-4-one precursors (imide sodium salts) was developed and led to the desired triazines compounds, thus allowing a one-step economy in their global synthetic preparation. This approach provides rapid access to pyridyl (or pyridone)-substituted 1,3,5-triazines with high potential in various fields of application.
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http://dx.doi.org/10.1021/jo5010668DOI Listing
July 2014

Expeditive access to 2-substituted 4H-pyrido[1,3]oxazin-4-ones via an intramolecular O-arylation.

Org Lett 2013 Jul 5;15(14):3494-7. Epub 2013 Jul 5.

Sanofi R&D, Exploratory Unit, 1 Avenue Pierre Brossolette, 91385 Chilly Mazarin Cedex, France.

Unreported 2-substituted 4H-pyrido[e][1,3]oxazin-4-ones are synthesized via an unprecedented intramolecular O-arylation of N-aroyl- and N-heteroaroyl-(iso)nicotinamides under microwave irradiations, in good to excellent yields. The broad applicability was demonstrated by 24 examples with a variety of substituents at the 2-position of the final compounds and 3 possible positions for the nitrogen atom of the pyridine ring. In addition, transformation of one of these compounds into 2-hydroxypyridyl-substituted 1,2,4-triazole and 1,2,4-oxazinone was realized. This approach opens a rapid access to a new bicyclic heteroaromatic chemical series with high potential in medicinal chemistry.
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http://dx.doi.org/10.1021/ol401516eDOI Listing
July 2013

Self-buffering hybrid gold-polyoxometalate catalysts for the catalytic cyclization of acid-sensitive substrates.

Chemistry 2012 Oct 3;18(41):12962-5. Epub 2012 Sep 3.

UPMC Sorbonne universités, Institut Parisien de Chimie Moléculaire (UMR CNRS 7201), 4 place Jussieu, C. 229, 75005 Paris, France.

Grafting of a gold complex to an organo-polyoxometalate delivers catalytically active bitopic hybrids. The gold end activates allenes, while the metal-oxide surface can capture protons (see scheme). The scope of the gold-catalyzed oxacyclization of allenols is expanded to highly sensitive tertiary benzylic alcohols.
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http://dx.doi.org/10.1002/chem.201201007DOI Listing
October 2012

Lanthanide polyoxocationic complexes: experimental and theoretical stability studies and Lewis acid catalysis.

Chemistry 2011 Dec 10;17(50):14129-38. Epub 2011 Nov 10.

Institut Lavoisier de Versailles, UMR 8180, Université de Versailles Saint-Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles Cedex, France.

The [ε-PMo(V)(8)Mo(VI)(4)O(36)(OH)(4){Ln(III)(H(2)O)}(4)](5+) (Ln=La, Ce, Nd, Sm) polyoxocations, called εLn(4), have been synthesized at room temperature as chloride salts soluble in water, MeOH, EtOH, and DMF. Rare-earth metals can be exchanged, and (31)P NMR spectroscopic studies have allowed a comparison of the affinity of the reduced {ε-PMo(12)} core, thus showing that the La(III) ions have the highest affinity and that rare earths heavier than Eu(III) do not react with the ε-Keggin polyoxometalate. DFT calculations provide a deeper insight into the geometries of the systems studied, thereby giving more accurate information on those compounds that suffer from disorder in crystalline form. It has also been confirmed by the hypothetical La→Gd substitution reaction energy that Ln ions beyond Eu cannot compete with La in coordinating the surface of the ε-Keggin molybdate. Two of these clusters (Ln=La, Ce) have been tested to evidence that such systems are representative of a new efficient Lewis acid catalyst family. This is the first time that the catalytic activity of polyoxocations has been evaluated.
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http://dx.doi.org/10.1002/chem.201101754DOI Listing
December 2011

Carbonyl-inserted organo-hybrids of a Dawson-type phosphovanadotungstate: scope and chemoselective oxidation catalysis.

Org Lett 2011 Nov 26;13(22):5990-3. Epub 2011 Oct 26.

UPMC Univ Paris 06, Institut Parisien de Chimie Moléculaire (UMR CNRS 7201), C. 229, 4 place Jussieu, 75005 Paris, France.

The Dawson-type polyoxometalate (POM) [P(2)V(3)W(15)O(62)](9-) is a prototype for inclusion of carbonyls of amides, ureas, carbamates, and thiocarbamates into polyoxometallic structures. The carbonyl-inserted POMs catalyze the oxidation of sulfides. Chemoselectivity depends primarily on the proton content of the POM, but it is also influenced by the organic substituent.
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http://dx.doi.org/10.1021/ol202430eDOI Listing
November 2011

Chemoselective catalysis with organosoluble Lewis acidic polyoxotungstates.

Chemistry 2010 Jun;16(24):7256-64

UPMC Univ Paris 06, Institut Parisien de Chimie Moléculaire (UMR 7201), C. 229, 4 place Jussieu, 75005 Paris, France.

The preparation of new organosoluble Lewis acidic polyoxometalates (POMs) is reported. These complexes were prepared by the incorporation of Zr, Sc, and Y atoms into the corresponding monolacunary Dawson [P(2)W(17)O(61)](10-) and Keggin [PW(11)O(39)](7-) polyoxotungstates. The catalytic activity of these compounds was evaluated for C-C bond formation in the Diels-Alder, Mannich, and Mukaiyama-type reactions. Comparisons with previously described Lewis acidic POMs are reported. Competitive reactions between imines and aldehydes or between various imines demonstrated that fine tuning of the reactivity could be reached by varying the metal atom incorporated into the polyanionic framework. A series of experiments that employed pyridine derivatives allowed us to distinguish between the Lewis and induced Brønsted acidity of the POMs. These catalysts activate imines in a Lewis acidic way, whereas aldehydes are activated by indirect Brønsted catalysis.
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http://dx.doi.org/10.1002/chem.201000411DOI Listing
June 2010

Chiral recognition of hybrid metal oxide by peptides.

Angew Chem Int Ed Engl 2009 ;48(19):3466-8

UPMC Univ Paris 06, Institut Parisien de Chimie Moléculaire (UMR CNRS 7201), C. 229, 4 place Jussieu, 75005 Paris, France.

Resolution of gram quantities of a subtly chiral polyoxometalate (POM; the chirality originates from substitution of one metal in the nanosized framework) is possible by reaction with small peptides. Functionalizable acyl polyoxotungstate (TBA)(6)[alpha(1)-P(2)W(17)O(61){SnCH(2)CH(2)C(=O)}] (see picture) can be resolved by kinetic resolution. This approach paves the way for applications of chiral POMs ranging from asymmetric catalysis to their bioactivity.
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http://dx.doi.org/10.1002/anie.200806247DOI Listing
June 2009

Insertion of amides into a polyoxometalate.

Angew Chem Int Ed Engl 2009 ;48(11):2035-8

UPMC Univ Paris 06, CNRS UMR 7201, Institut Parisien de Chimie Moléculaire, 4 place Jussieu, 75005 Paris, France.

POM alert: The incorporation of an amide oxygen atom into the framework of the Dawson-type polyoxometalate (POM) cluster [P(2)V(3)W(15)O(62)](9-) (see picture) allows the communication of electronic effects between the organic and the inorganic parts of the molecule, including fine-tuning of the redox properties of the entire hybrid POM by the organic components, and transmission of the POM's electron-attracting properties to the organic moiety.
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http://dx.doi.org/10.1002/anie.200805964DOI Listing
April 2009

Identification of polyoxometalates as nanomolar noncompetitive inhibitors of protein kinase CK2.

Chem Biol 2008 Jul;15(7):683-92

Laboratoire de Transduction du Signal, Institut de Recherche en Technologies et Sciences pour le Vivant, CEA, 17 Rue des Martyrs 38054 Grenoble, France.

Protein kinase CK2 is a multifunctional kinase of medical importance that is dysregulated in many cancers. In this study, polyoxometalates were identified as original CK2 inhibitors. [P2Mo18O62](6-) has the most potent activity. It inhibits the kinase in the nanomolar range by targeting key structural elements located outside the ATP- and peptide substrate-binding sites. Several polyoxometalate derivatives exhibit strong inhibitory efficiency, with IC50 values < or = 10 nM. Furthermore, these inorganic compounds show a striking specificity for CK2 when tested in a panel of 29 kinases. Therefore, polyoxometalates are effective CK2 inhibitors in terms of both efficiency and selectivity and represent nonclassical kinase inhibitors that interact with CK2 in a unique way. This binding mode may provide an exploitable mechanism for developing potent drugs with desirable properties, such as enhanced selectivity relative to ATP-mimetic inhibitors.
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http://dx.doi.org/10.1016/j.chembiol.2008.05.018DOI Listing
July 2008

Water dissociation on alpha1-hafnium and ytterbium substituted Dawson polyoxotungstates: a density functional theory study.

J Phys Chem A 2008 Dec;112(50):13002-5

UPMC Univ Paris 06, Laboratoire de chimie organique (UMR CNRS 7611), Institut de chimie moléculaire (FR 2769), C. 229, 4 place Jussieu, 75005 Paris, France.

Density functional theory (DFT) calculations were devised to get insight into Lewis acidic catalysis by POMs, especially on the intriguing activation of complexed water molecules that was observed in some experimental cases. Computationally, it appears that deprotonation is feasible with [alpha(1)-Hf(H(2)O)P(2)W(17)O(61)](6-), but not with [alpha(1)-Yb(H(2)O)P(2)W(17)O(61)](7-). This reflects the difference of the electronic structures (diamagnetic for hafnium POM, paramagnetic for ytterbium POM). From a mechanistical point of view, indirect Brønsted catalysis cannot be excluded in the hafnium case, especially for Mannich reactions. But our calculations show that catalysis by [alpha(1)-Yb(H(2)O)P(2)W(17)O(61)](7-) (and presumably all the lanthanide series) proceeds through direct complexation of the substrates to the POM.
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http://dx.doi.org/10.1021/jp8038362DOI Listing
December 2008

Regioselective activation of oxo ligands in functionalized dawson polyoxotungstates.

J Am Chem Soc 2008 Apr 11;130(13):4553-61. Epub 2008 Mar 11.

UPMC Univ Paris 06, Laboratoire de chimie organique (UMR CNRS 7611), Institut de chimie moléculaire (FR 2769), C. 229, 4 place Jussieu, 75005 Paris, France.

The organic side chain of tin-substituted Dawson polyoxotungstates alpha1- and alpha2-[P2W17O61{SnCH2CH2COOH}]7- can be used to direct regioselective acylations of oxo ligands in the inorganic backbone, which was examined both experimentally and computationally. Acylation of the oxo ligand gave exalted electrophilicity to the acyl moiety, and the compounds that were obtained led to direct ligation of POMs to complex organic molecules.
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http://dx.doi.org/10.1021/ja800072qDOI Listing
April 2008

Sensing the chirality of Dawson lanthanide polyoxometalates [alpha1-LnP2W17O61]7- by multinuclear NMR spectroscopy.

Chemistry 2008 ;14(5):1532-40

Laboratoire de chimie inorganique et matériaux moléculaires (UMR CNRS 7071), Institut de chimie moléculaire (FR 2769), Université Pierre et Marie Curie-Paris 6, Case courrier 42, 4 place Jussieu, Paris cedex 05, France.

Lanthanide complexes of the chiral Dawson phosphotungstate [alpha(1)-P(2)W(17)O(61)](10-) were used to study the formation of diastereomers with optically pure organic ligands. The present work started with the full assignment of the (183)W NMR spectra of [alpha(1)-Yb(H(2)O)(4)P(2)W(17)O(61)](7-) at different temperatures and concentrations, which allowed the structure of the dimerized form in aqueous solution to be established. Different enantiopure amino acids and phosphonic acids were screened as ligands. Both types allowed chiral differentiation by multinuclear NMR spectroscopy under fast-exchange conditions. Functional groups with a good affinity for the oxo framework of the polyoxometalate were identified, and maps of the interactions between L-serine and N-phosphonomethyl-L-proline with [alpha(1)-Yb(H(2)O)(4)P(2)W(17)O(61)](7-) were established. This demonstrates the power of (183)W NMR spectroscopy to elucidate the molecular recognition of inorganic molecules by organic compounds. N-Phosphonomethyl-L-proline appears to be a convenient ligand to promote separation of the diastereomers and ultimately resolution of the enantiomers of [alpha(1)-Yb(H(2)O)(4)P(2)W(17)O(61)](7-).
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http://dx.doi.org/10.1002/chem.200701429DOI Listing
May 2008

A general strategy for ligation of organic and biological molecules to Dawson and Keggin polyoxotungstates.

Org Lett 2007 Sep 8;9(20):3981-4. Epub 2007 Sep 8.

Laboratoire de chimie organique (UMR CNRS 7611), Institut de chimie moléculaire (FR 2769), Université Pierre et Marie Curie-Paris 6, 4 place Jussieu, C. 229, 75005 Paris, France.

The copper-catalyzed azide/alkyne cycloaddition (click chemistry) is used for the first time in polyoxometalate chemistry to graft any kind of organics (lipophilic, water-soluble, biologically relevant) to polyoxotungstates to generate hybrids. The method is not limited by solvent matching between the polyoxometallic platforms and the organic substrates.
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http://dx.doi.org/10.1021/ol701701fDOI Listing
September 2007

Increased Lewis acidity in hafnium-substituted polyoxotungstates.

Chemistry 2007 ;13(19):5426-32

Université Pierre et Marie Curie-Paris 6, Laboratoire de chimie organique (UMR CNRS 7611), Institut de chimie moléculaire (FR 2769), C. 229, 4 place Jussieu, 75005 Paris, France.

Monolacunary polyoxotungstates [alpha(1)-P(2)W(17)O(61)](10-) and [alpha-PW(11)O(39)](7-) react with HfCl(4) to yield [alpha(1)-HfP(2)W(17)O(61)](6-) and [alpha-Hf(OH)PW(11)O(39)](4-), isolated as organo-soluble tetrabutylammonium (TBA) salts. Subsequent analyses, including mass spectrometry, show that they are stronger Lewis acids than (TBA)(5)H(2)[alpha(1)-YbP(2)W(17)O(61)]. The new polyoxotungstates catalyze Lewis acid mediated organic reactions, such as Mukaiyama aldol and Mannich-type additions. In particular, reactions with aldehydes, which were impossible with lanthanide polyoxotungstates, are made possible. Thus these modifications of the polyoxometalate composition allowed fine tuning of the Lewis acidity. The catalysts could be easily recovered and reused.
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http://dx.doi.org/10.1002/chem.200700010DOI Listing
August 2007

Lanthanide complexes of the monovacant Dawson polyoxotungstate [alpha1-P2W17O61]10- as selective and recoverable Lewis acid catalysts.

Angew Chem Int Ed Engl 2006 May;45(20):3324-7

Université Pierre et Marie Curie-Paris 6, Institut de chimie moléculaire (FR 2769), Laboratoire de chimie inorganique et matériaux moléculaires (UMR CNRS 7071), 75252 Paris cedex 05, France.

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http://dx.doi.org/10.1002/anie.200600364DOI Listing
May 2006
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