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1.
Chem Rev ; 119(12): 6906-6955, 2019 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-30964644

RESUMEN

Organocobalt(III) complexes (R-CoIII), defined as cobalt complexes featuring a carbon-cobalt bond, are largely used to produce carbon-centered radicals by homolytic cleavage of their C-Co bond under mild conditions. They are key compounds in cutting-edge developments in the fields of organic chemistry, biochemistry, medical research, radical reactions, and organometallic chemistry. This is the first Review of the use of R-CoIII in both organic and polymer chemistries. Although pioneering works in organic synthesis have largely contributed to the implementation of R-CoIII in polymer design, the two fields have evolved independently, with many breakthroughs on both sides. The main motivation of this Review is to confront both fields to stimulate cross-fertilization. It notably describes the most important synthetic pathways for R-CoIII, the influence of the ligand structure and the environment of the complex on the C-Co bond strength, the modes of formation of the radicals, and the most relevant R-CoIII-promoted radical reactions, with a focus on the main reaction mechanisms.

2.
Angew Chem Int Ed Engl ; 57(11): 2934-2937, 2018 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-29329495

RESUMEN

An unprecedented level of control for the radical polymerization of vinylidene fluoride (VDF), yielding well-defined PVDF (at least up to 14 500 g mol-1 ) with low dispersity (≤1.32), was achieved using organometallic-mediated radical polymerization (OMRP) with an organocobalt compound as initiator. The high chain-end fidelity was demonstrated by the synthesis of PVDF- and PVAc-containing di-and triblock copolymers. DFT calculations rationalize the efficient reactivation of both head and tail chain end dormant species.

3.
Biomacromolecules ; 18(2): 440-451, 2017 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-28036161

RESUMEN

Gene transfection with polymeric carrier remains a challenge; particularly, high transfection levels combined with low toxicity are hard to achieve. We herein revisit polyvinylamines, an old and neglected family of cationic polymers. They can be readily obtained by controlled hydrolysis of polyvinylamides prepared through (controlled) radical polymerization. A series of tailor-made and well-defined polyvinylamines bearing primary amino groups, and poly(N-methylvinylamine) bearing secondary amines, were evaluated for the transfection of cells with pDNA as a function of their molar mass, molar mass distribution, and degree of deacetylation. Unexpected high transfection levels, in combination with low cytotoxicity were recorded for both series. Surprisingly, a great impact of the molar mass was observed for the primary amine polyvinylamine series, whereas the results were mostly independent of molar mass or dispersity for the polymer bearing secondary amine. It was further established that a certain percentage of acetamide groups increased the transfection level, while maintaining low cytotoxicity. These results highlight for the first time the real potential of polyvinylamines as gene carriers, and make these polymers very attractive for further development in gene therapy.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Portadores de Fármacos/química , Terapia Genética , Plásmidos/administración & dosificación , Polímeros/química , Polivinilos/química , Células HeLa , Humanos , Plásmidos/genética , Polimerizacion
4.
Macromol Rapid Commun ; 38(15)2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28564367

RESUMEN

Organometallic-mediated radical polymerization (OMRP) has given access to well-defined poly(vinyl acetate-alt-tert-butyl-2-trifluoromethacrylate)-b-poly(vinyl acetate) and poly(VAc-alt-MAF-TBE) copolymers composed of two electronically distinct monomers: vinyl acetate (VAc, donor, D) and tert-butyl-2-trifluoromethacrylate (MAF-TBE, acceptor, A), with low dispersity (≤1.24) and molar masses up to 57 000 g mol-1 . These copolymers have a precise 1:1 alternating structure over a wide range of comonomer feed compositions. The reactivity ratios are determined as rVAc = 0.01 ± 0.01 and rMAF-TBE = 0 at 40 °C. Remarkably, from a feed containing >50% molar VAc content, poly(VAc-alt-MAF-TBE)-b-PVAc block copolymers are produced via a one-pot synthesis. Such diblock copolymers exhibit two glass transition temperatures attributed to the alternating and homopolymer sequences. The OMRP of this fluorine-containing alternating monomer system may provide access to a wide range of new polymer materials.


Asunto(s)
Acrilatos/química , Técnicas de Química Analítica , Polímeros/síntesis química , Compuestos de Vinilo/química , Peso Molecular , Polimerizacion
5.
Macromol Rapid Commun ; 37(14): 1181-7, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26991998

RESUMEN

Amphiphilic double poly(ionic liquid) (PIL) block copolymers are directly prepared by cobalt-mediated radical polymerization induced self-assembly (CMR-PISA) in water of N-vinyl imidazolium monomers carrying distinct alkyl chains. The cobalt-mediated radical polymerization of N-vinyl-3-ethyl imidazolium bromide (VEtImBr) is first carried out until high conversion in water at 30 °C, using an alkyl bis(acetylacetonate)cobalt(III) adduct as initiator and controlling agent. The as-obtained hydrophilic poly(N-vinyl-3-ethyl imidazolium bromide) (PVEtImBr) is then used as a macroinitiator for the CMR-PISA of N-vinyl-3-octyl imidazolium bromide (VOcImBr). Self-assembly of the amphiphilic PVEtImBr-b-PVOcImBr block copolymer, i.e., of PIL-b-PIL-type, rapidly takes place in water, forming polymer nanoparticles consisting of a hydrophilic PVEtImBr corona and a hydrophobic PVOcImBr core. Preliminary investigation into the effect of the size of the hydrophobic block on the dimension of the nanoparticles is also described.


Asunto(s)
Cobalto/química , Líquidos Iónicos/síntesis química , Polímeros/síntesis química , Agua/química , Radicales Libres/química , Líquidos Iónicos/química , Estructura Molecular , Polimerizacion , Polímeros/química
6.
Macromol Rapid Commun ; 37(6): 539-44, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26787365

RESUMEN

Cobalt-mediated radical polymerization (CMRP) of vinyl acetate (VAc) is successfully achieved in supercritical carbon dioxide (scCO2). CMRP of VAc is conducted using an alkyl-cobalt(III) adduct that is soluble in scCO2. Kinetics studies coupled to visual observations of the polymerization medium highlight that the melt viscosity and PVAc molar mass (Mn) are key parameters that affect the CMRP in scCO2. It is noticed that CMRP is controlled for Mn up to 10 000 g mol(-1), but loss of control is progressively observed for higher molar masses when PVAc precipitates in the polymerization medium. Low molar mass PVAc macroinitiator, prepared by CMRP in scCO2, is then successfully used to initiate the acrylonitrile polymerization. PVAc-b-PAN block copolymer is collected as a free flowing powder at the end of the process although the dispersity of the copolymer increases with the reaction time. Although optimization is required to decrease the dispersity of the polymer formed, this CMRP process opens new perspectives for macromolecular engineering in scCO2 without the utilization of fluorinated comonomers or organic solvents.


Asunto(s)
Acrilonitrilo/química , Dióxido de Carbono/química , Cobalto/química , Compuestos de Vinilo/química , Catálisis , Cinética , Peso Molecular , Polimerizacion
7.
Macromol Rapid Commun ; 35(4): 422-30, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24338859

RESUMEN

A poly(ionic liquid)-based block copolymer (PIL BCP), namely, poly(vinyl acetate)-b-poly(N-vinyl-3-butylimidazolium bromide), PVAc-b-PVBuImBr, is synthesized by sequential cobalt-mediated radical polymerization (CMRP). A PVAc precursor is first prepared at 30 °C in bulk by CMRP of VAc, using bis(acetylacetonato)cobalt(II), Co(acac)2, and a radical source (V-70). Growth of PVBuImBr from PVAc-Co(acac)2 is accomplished by CMRP in DMF/MeOH (2:1, v/v). This PIL BCP self-assembles in the sub-micron size range into aggregated core-shell micelles in THF, whereas polymeric vesicles are observed in water, as evidenced by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Thin-solid sample cut from raw materials analyzed by TEM shows an ordered lamellar organization by temperature-dependent synchrotron small-angle X-ray scattering (SAXS). Anion exchange can be accomplished to achieve the corresponding PIL BCP with bis(trifluorosulfonyl)imide (Tf2 N(-)) anions, which also gives rise to an ordered lamellar phase in bulk samples. A complete suppression of SAXS second-order reflection suggests that this compound has a symmetric volume fraction (f ≈ 0.5). SAXS characterization of both di- and triblock PIL BCP analogues previously reported also shows a lamellar phase of very similar behavior, with only an increase of the period by about 8% at 60 °C.


Asunto(s)
Cobalto/química , Radicales Libres/química , Líquidos Iónicos/química , Polímeros/química , Micelas , Polímeros/síntesis química , Agua/química
8.
Colloids Surf B Biointerfaces ; 235: 113788, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38335770

RESUMEN

Surface modification of lipid nanocapsules (LNC) is necessary to impart stealth properties to these drug carriers and enhance their accumulation into the tumor microenvironment. While pegylation is commonly used to prolong the circulation time of LNC, the increased presence of anti-PEG antibodies in the human population and the internalization issues associated to the PEG shell are strong incentives to search alternatives. This work describes the development of amphiphilic poly(N-vinyl amide)-based (co)polymers, including pH-responsive ones, and their use as LNC modifiers towards improved drug delivery systems. RAFT polymerization gave access to a series of LNC modifiers composed of poly(N-methyl-N-vinyl acetamide), poly(N-vinyl pyrrolidone) or pH-responsive vinylimidazole-based sequence bearing a variety of lipophilic end-groups, namely octadecyl, dioctadecyl or phospholipid groups, for anchoring to the LNC. Decoration of the LNC with these families of poly(N-vinyl amide) derivatives was achieved via both post-insertion and per-formulation methods. This offered valuable and non-toxic LNC protection from opsonization by complement activation, emphasized the benefit of dioctadecyl in the per-formulation approach and highlighted the great potential of poly(N-methyl-N-vinyl acetamide) as PEG alternative. Moreover, incorporation of imidazole moieties in the shell of the carrier imparted pH-responsiveness to the LNC likely to increase the cellular uptake in the acidic tumor microenvironment, opening up new possibilities in the field of active targeting.


Asunto(s)
Nanocápsulas , Humanos , Portadores de Fármacos , Fosfolípidos , Concentración de Iones de Hidrógeno , Acetamidas , Amidas
9.
Adv Healthc Mater ; 13(8): e2302712, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37994483

RESUMEN

Lipid-based nanocarriers have demonstrated high interest in delivering genetic material, exemplified by the success of Onpattro and COVID-19 vaccines. While PEGylation imparts stealth properties, it hampers cellular uptake and endosomal escape, and may trigger adverse reactions like accelerated blood clearance (ABC) and hypersensitivity reactions (HSR). This work highlights the great potential of amphiphilic poly(N-methyl-N-vinylacetamide) (PNMVA) derivatives as alternatives to lipid-PEG for siRNA delivery. PNMVA compounds with different degrees of polymerization and hydrophobic segments, are synthesized. Among them, DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine)-PNMVA efficiently integrates into lipoplexes and LNP membranes and prevents protein corona formation around these lipid carriers, exhibiting stealth properties comparable to DSPE-PEG. However, unlike DSPE-PEG, DSPE-PNMVA24 shows no adverse impact on lipoplexes cell uptake and endosomal escape. In in vivo study with mice, DSPE-PNMVA24 lipoplexes demonstrate no liver accumulation, indicating good stealth properties, extended circulation time after a second dose, reduced immunological reaction, and no systemic pro-inflammatory response. Safety of DSPE-PNMVA24 is confirmed at the cellular level and in animal models of zebrafish and mice. Overall, DSPE-PNMVA is an advantageous substitute to DSPE-PEG for siRNA delivery, offering comparable stealth and toxicity properties while improving efficacy of the lipid-based carriers by minimizing the dilemma effect and reducing immunological reactions, meaning no ABC or HSR effects.


Asunto(s)
Liposomas , Polietilenglicoles , Polivinilos , Ratones , Humanos , Animales , Liposomas/química , Polietilenglicoles/química , Vacunas contra la COVID-19 , Pez Cebra/genética , Pez Cebra/metabolismo , ARN Interferente Pequeño/genética , Fosfatidiletanolaminas/química
10.
J Control Release ; 361: 87-101, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37482343

RESUMEN

The recent approval of Onpattro® and COVID-19 vaccines has highlighted the value of lipid nanoparticles (LNPs) for the delivery of genetic material. If it is known that PEGylation is crucial to confer stealth properties to LNPs, it is also known that PEGylation is responsible for the decrease of the cellular uptake and endosomal escape and for the production of anti-PEG antibodies inducing accelerated blood clearance (ABC) and hypersensitivity reactions. Today, the development of PEG alternatives is crucial. Poly(N-vinyl pyrrolidone) (PNVP) has shown promising results for liposome decoration but has never been tested for the delivery of nucleic acids. Our aim is to develop a series of amphiphilic PNVP compounds to replace lipids-PEG for the post-insertion of lipoplexes dedicated to siRNA delivery. PNVP compounds with different degrees of polymerization and hydrophobic segments, such as octadecyl, dioctadecyl and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), were generated. Based on the physicochemical properties and the efficiency to reduce protein corona formation, we showed that the DSPE segment is essential for the integration into the lipoplexes. Lipoplexes post-grafted with 15% DSPE-PNVP30 resulted in gene silencing efficiency close to that of lipoplexes grafted with 15% DSPE-PEG. Finally, an in vivo study in mice confirmed the stealth properties of DSPE-PNVP30 lipoplexes as well as a lower immune response ABC effect compared to DSPE-PEG lipoplexes. Furthermore, we showed a lower immune response after the second injection with DSPE-PNVP30 lipoplexes compared to DSPE-PEG lipoplexes. All these observations suggest that DSPE-PNVP30 appears to be a promising alternative to PEG, with no toxicity, good stealth properties and lower immunological response.


Asunto(s)
COVID-19 , Polietilenglicoles , Ratones , Humanos , Animales , Polietilenglicoles/química , Vacunas contra la COVID-19 , Liposomas/química , ARN Interferente Pequeño , Silenciador del Gen
11.
Chemistry ; 18(40): 12834-44, 2012 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-22907863

RESUMEN

This work reveals the preponderance of an intramolecular metal chelation phenomenon in a controlled radical polymerization system involving the reversible trapping of the radical chains by a cobalt complex bis(acetylacetonato)cobalt(II). The cobalt-mediated radical polymerization (CMRP) of a series of N-vinyl amides was considered with the aim of studying the effect of the cobalt chelation by the amide moiety of the last monomer unit of the chain. The latter reinforces the cobalt-polymer bond in the order N-vinylpyrrolidone

12.
ACS Macro Lett ; 10(3): 313-320, 2021 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-35549068

RESUMEN

Partly or fully renewable (co)polymers are gaining interest in both academia and industry. Polyethylene is a widely used polymer, classically derived from fossil fuels, with a high versatility stemming from the introduction of comonomers altering the mechanical properties. The introduction of renewable functionalities into this polymer is highly attractive to obtain functional, tunable, and at least partially renewable polyethylenes. We herein report the introduction of biosourced cyclic carbonates into polyethylene using organometallic-mediated radical polymerization under mild conditions. Molecular weights of up to 14 600 g mol-1 with dispersities as low as 1.19 were obtained, and the cyclic carbonate content could be easily tuned by the ethylene pressure during the polymerization. As a proof of concept, the hydrolysis of the cyclic carbonates of a representative copolymer was explored, and it provided polyethylene-bearing vicinal diols, with a hydrolysis degree of 71%. Given the multitude of chemoselective modifications possible on cyclic carbonates as well as the fact that many allylic- and alkylidene-type cyclic carbonates are accessible from renewable resources, this work opens up an avenue for the design of functional and more sustainable polyethylenes.


Asunto(s)
Carbonatos , Polietileno , Peso Molecular , Polimerizacion , Polímeros
13.
Cancers (Basel) ; 13(9)2021 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-33922267

RESUMEN

Despite significant advances in melanoma therapy, low response rates and multidrug resistance (MDR) have been described, reducing the anticancer efficacy of the administered molecules. Among the causes to explain these resistances, the decreased intratumoral pH is known to potentiate MDR and to reduce the sensitivity to anticancer molecules. Nanomedicines have been widely exploited as the carriers of MDR reversing molecules. Lipid nanocapsules (LNC) are nanoparticles that have already demonstrated their ability to improve cancer treatment. Here, LNC were modified with novel copolymers that combine N-vinylpyrrolidone (NVP) to impart stealth properties and vinyl imidazole (Vim), providing pH-responsive ability to address classical chemoresistance by improving tumor cell entry. These copolymers could be post-inserted at the LNC surface, leading to the property of going from neutral charge under physiological pH to positive charge under acidic conditions. LNC modified with polymer P5 (C18H37-P(NVP21-co-Vim15)) showed in vitro pH-responsive properties characterized by an enhanced cellular uptake under acidic conditions. Moreover, P5 surface modification led to an increased biological effect by protecting the nanocarrier from opsonization by complement activation. These data suggest that pH-sensitive LNC responds to what is expected from a promising nanocarrier to target metastatic melanoma.

14.
Chemistry ; 16(6): 1799-811, 2010 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-20039349

RESUMEN

Cobalt-mediated radical coupling (CMRC) is a straightforward approach to the synthesis of symmetrical macromolecules that relies on the addition of 1,3-diene compounds onto polymer precursors preformed by cobalt-mediated radical polymerization (CMRP). Mechanistic features that make this process so efficient for radical polymer coupling are reported here. The mechanism was established on the basis of NMR spectroscopy and MALDI-MS analyses of the coupling product and corroborated by DFT calculations. A key feature of CMRC is the preferential insertion of two diene units in the middle of the chain of the coupling product mainly according to a trans-1,4-addition pathway. The large tolerance of CMRC towards the diene structure is demonstrated and the impact of this new coupling method on macromolecular engineering is discussed, especially for midchain functionalization of polymers. It is worth noting that the interest in CMRC goes beyond the field of polymer chemistry, since it constitutes a novel carbon-carbon bond formation method that could be applied to small organic molecules.

15.
ACS Macro Lett ; 9(1): 134-139, 2020 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-35638665

RESUMEN

Interconnected macroporous imidazolium-based monoliths are produced via the modified Radziszewski multicomponent reaction (MCR) applied to triamines under high internal phase emulsion (HIPE) conditions. This straightforward one-pot synthesis combines the efficiency and versatility of MCRs with the ease of implementation of the emulsion templating polymerization process. The characterization of the chemical structure and morphology of the resulting materials confirms the formation of the expected macroporous poly(ionic liquid)s (PILs) networks. The promising catalytic activity and recyclability of these porous PIL monoliths are illustrated for the transesterification reaction and the decarboxylation of caffeic acid. In these cases, almost complete conversion is reached while benefiting from the advantages associated with a heterogeneous catalyst.

16.
Angew Chem Int Ed Engl ; 48(8): 1422-4, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19142919

RESUMEN

Tackling blocks: The isoprene-assisted radical coupling (I-ARC) of polymers prepared by cobalt-mediated radical polymerization (see picture) is the first efficient radical coupling method that is not restricted to short chains. When applied to AB diblock copolymers, I-ARC constitutes a straightforward approach to the preparation of novel symmetrical ABA triblock copolymers.

17.
ACS Macro Lett ; 8(4): 427-434, 2019 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-35651127

RESUMEN

Due to their great modularity, ease of implementation, and atom economy, multicomponent reactions (MCRs) are becoming increasingly popular macromolecular engineering tools. In this context, MCRs suitable in polymer synthesis are eagerly searched for. This work demonstrates the potential of the Ugi-three component reaction (Ugi-3CR) for the design of polymers and, in particular, of poly(α-amino amide)s. A series of polymers containing amino and amido groups within their backbone were obtained through a one-pot process by reacting aliphatic or aromatic diamines, diisocyanides, and aldehydes. The impact of temperature, concentration, catalyst loading, and substrates on polymerization efficiency is discussed. A preliminary study on the thermal properties and the solution behavior of these poly(α-amino amide)s was carried out. An aliphatic-rich derivative notably showed some pH-responsiveness in water via protonation-deprotonation of its amino groups.

18.
Macromol Biosci ; 18(4): e1700353, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29392880

RESUMEN

Poly(N-methylvinylamines) with secondary amines can form complexes with plasmid DNA (pDNA) and provide transfection efficiency in HeLa cells in the same order as linear polyethyleneimine but with higher cell viability. Chemical modifications of poly(N-methylvinylamine) backbones are performed to further improve transfection efficiency while maintaining low degree of cytotoxicity. In a first type of polymer, primary amino groups are incorporated via a copolymerization strategy. In a second one, primary amino and imidazole groups are incorporated also via a copolymerization strategy. In a third one, secondary amino groups are substituted with methylguanidine functions through a postpolymerization reaction. Thus, novel polymers of various molecular masses are synthesized, characterized, and their interaction with pDNA studied. Then, their transfection efficiency and cytotoxicity are tested in HeLa cells. Two polymethylvinylamine-based copolymers, one containing 20% of imidazole moieties and another one composed of 12% of guanidinyl units allow remarkable transfection efficiency of HeLa, pulmonary (16HBE), skeletal muscle (C2C12), and dendritic (DC2.4) cells. Overall, this work thus identifies new promising DNA carriers and chemical modifications that improve the transfection efficiency while maintaining low degree of cytotoxicity.


Asunto(s)
ADN/efectos de los fármacos , Técnicas de Transferencia de Gen , Polímeros/química , Compuestos de Vinilo/química , Supervivencia Celular/efectos de los fármacos , Células HeLa , Humanos , Plásmidos/efectos de los fármacos , Polímeros/farmacología , Transfección , Compuestos de Vinilo/farmacología
19.
Polymers (Basel) ; 9(12)2017 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-30966002

RESUMEN

The organometallic-mediated radical polymerization (OMRP) of vinyl acetate (VAc) and its OMR copolymerization (OMRcoP) with tert-butyl 2-trifluoromethylacrylate (MAF-TBE) mediated by Co(SAL)2 (SAL = 2-formylphenolato or deprotonated salicylaldehyde) produced relatively well-defined PVAc and poly(VAc-alt-MAF-TBE) copolymers at moderate temperature (<40 °C) in bulk. The resulting alternating copolymer was characterized by ¹H-, 13C- and 19F-nuclear magnetic resonance (NMR) spectroscopies, and by size exclusion chromatography. The linear first-order kinetic plot, the linear evolutions of the molar mass with total monomer conversion, and the relatively low dispersity (D~1.55) of the resulting copolymers suggest that this cobalt complex provides some degree of control over the copolymerization of VAc and MAF-TBE. Compared to the previously investigated cobalt complex OMRP mediators having a fully oxygen-based first coordination sphere, this study emphasizes a few peculiarities of Co(SAL)2: a lower ability to trap radical chains as compared to Co(acac)2 and the absence of catalytic chain transfer reactions, which dominates polymerizations carried in the presence of 9-oxyphenalenone cobalt derivative.

20.
Chem Commun (Camb) ; (40): 4180-2, 2006 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-17031424

RESUMEN

Cobalt complexes supported on silica and Merrifield resin are effective mediators for the controlled radical polymerization of vinyl acetate.

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