Facile Syntese af ormelignende Miceller af synligt lys Mediated Dispersion polymerisering Brug Photoredox Catalyst
Summary
This article describes a process for producing polymeric self-assembled nanoparticles using visible light mediated dispersion polymerization. Using low energy visible light to control the polymerization allows for the reproducible formation of self-assembled worm-like micelles at high solids content.
Abstract
Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins with the synthesis of a hydrophilic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) homopolymer using reversible addition-fragmentation chain-transfer (RAFT) polymerization. Under mild visible light irradiation (λ = 460 nm, 0.7 mW/cm2), this macro-chain transfer agent (macro-CTA) in the presence of a ruthenium based photoredox catalyst, Ru(bpy)3Cl2 can be chain extended with a second monomer to form a well-defined block copolymer in a process known as Photoinduced Electron Transfer RAFT (PET-RAFT). When PET-RAFT is used to chain extend POEGMA with benzyl methacrylate (BzMA) in ethanol (EtOH), polymeric nanoparticles with different morphologies are formed in situ according to a polymerization-induced self-assembly (PISA) mechanism. Self-assembly into nanoparticles presenting POEGMA chains at the corona and poly(benzyl methacrylate) (PBzMA) chains in the core occurs in situ due to the growing insolubility of the PBzMA block in ethanol. Interestingly, the formation of highly pure worm-like micelles can be readily monitored by observing the onset of a highly viscous gel in situ due to nanoparticle entanglements occurring during the polymerization. This process thereby allows for a more reproducible synthesis of worm-like micelles simply by monitoring the solution viscosity during the course of the polymerization. In addition, the light stimulus can be intermittently applied in an ON/OFF manner demonstrating temporal control over the nanoparticle morphology.
Introduction
Syntesen af ikke-sfæriske (og andre) nanopartikel morfologier er traditionelt blevet udført ved anvendelse af en flertrinsproces selvsamlende procedure startende med syntesen og oprensningen af veldefinerede amfifil diblok (eller multiblok) copolymerer. En af de mest almindelige selvsamlende teknikker blev udbredt af Eisenberg i 1990'erne og involverer opløsningen af den amfifile blok-copolymer i et fælles opløsningsmiddel for både polymerblokke efterfulgt af langsom tilsætning af et opløsningsmiddel selektive for en af blokkene 1-3 . Som tilføjes selektivt opløsningsmiddel (typisk vand), blokcopolymeren undergår selv-samling til dannelse af polymere nanopartikler. Den endelige morfologi (eller blandinger af morfologier) af nanopartiklerne er bestemt af en lang række faktorer såsom de relative længder af hver polymer-blok, hastighed for vand tilsætning og arten af den fælles opløsningsmiddel. Men denne tilgang generelt kun muliggør fremstillingen af nanopartikler ved relativt lavt faststofindhold (mindre end 1 vægt-%) og så begrænser dens praktiske skalerbarhed 4. Desuden kan den reproducerbare dannelse af "mellemliggende" faser såsom ormelignende miceller være vanskelig på grund af smal vifte af parametre, der kræves for at stabilisere denne ikke-sfærisk morfologi 5.
Polymerisationen-induceret selvsamlende (Pisa) tilgang delvist løser ulemperne ved den Eisenberg fremgangsmåde ved anvendelse polymerisationsprocessen selv at drive selvsamling in situ muliggør nanopartikel syntese ved meget højere faststofindhold (typisk 10-30 vægt-%) 6 -8. I en typisk PISA tilgang, er en levende polymerisation, der anvendes til kæde udvide et opløsningsmiddel opløselig makroinitiator (eller makro-CTA) med en monomer, der indledningsvis er opløselige i reaktionsmediet, men udgør en uopløselig polymer. PISA fremgangsmåde er blevet anvendt til at syntetisere ormelignende miceller ved systematisk at teste en række ex telle parametre og bruge detaljerede diagrammer fase som et syntetisk "køreplan" 5,9.
Trods deres udfordrende syntese, er der stor interesse for ormelignende nanopartikler på grund af deres interessante egenskaber i forhold til deres sfæriske modstykker. For eksempel har vi vist, at narkotika indlæst korte og lange ormelignende miceller syntetiseret under anvendelse af en PISA tilgang har signifikant højere in vitro cytotoksicitet sammenlignet med sfæriske miceller eller vesikler 10. Andre har vist en sammenhæng mellem nanopartikel billedformat og blodcirkulation tid i in vivo modeller 11. Andre har vist, at syntesen af ormelignende nanopartikler anvendelse af en passende PISA metode giver en makroskopisk gel grundet nanoskala sammenfiltring af nanopartikel filamenter. Disse geler har vist potentiale som steriliserbare geler på grund af deres termoreversibel sol-gel adfærd 12.
Indholdsproduktion "> Denne protokol beskriver en fremgangsmåde, der tillader in situ overvågning af dannelsen af ormelignende miceller ved blot at observere opløsningens viskositet under polymerisationen. Tidligere undersøgelser af lignende ormelignende micellære geler har vist, at over en kritisk temperatur, disse nanopartikler undergår en reversibel orm-sfære overgang og så danne fritflydende dispersioner ved forhøjede temperaturer. til dato har disse systemer anvendes et termisk følsomt azoforbindelse at indlede den styrede polymerisation 13,14 og så gelering kan ikke let observeret i disse systemer under den termiske polymerisation. Ud fra disse undersøgelser blev det antaget, at syntetisering PISA afledte nanopartikler ved lavere temperaturer kan muliggøre observation af denne geleringsadfærd in situ.Vi har for nylig beskrevet anvendelsen af en let stuetemperatur fotopolymerisation teknik til at mediere PISA processen til opnåelse nanopartikler afforskellige morfologier 15. Her er en visualiseret protokol præsenteret for reproducerbar syntese af ormelignende miceller ved at observere løsning viskositet opførsel under polymeriseringen. Dispersionen polymerisationen skrider let ved anvendelse af kommercielt tilgængelige lysdioder (LED) (λ = 460 nm, 0,7 mW / cm2).
Protocol
Representative Results
Discussion
Denne visualiseret protokol demonstrerer evnen til at overvåge dannelsen af ormelignende miceller simpelthen ved at observere indtræden af gel-lignende opførsel. Anvendeligheden af denne fremgangsmåde ligger i evnen til at overvåge ormen dannelse under polymeriseringen i forhold til andre metoder. Denne procedure kan udføres ved anvendelse af en to-trins polymerisation af to kommercielt tilgængelige monomerer (OEGMA og BzMA) til opnåelse selvsamlede POEGMA- b -PBzMA amfifile diblokcopo…
Divulgazioni
The authors have nothing to disclose.
Acknowledgements
CB is thankful for his Future Fellowship from Australian Research Council (ARC-FT12010096) and UNSW Australia.
Materials
| 4-Cyano-4-(phenylcarbonothioylthio)pentanoic acid (CPADB) | Sigma-Aldrich | 722995-5G | |
| Oligo(ethylene glycol) methyl ether methacrylate (OEGMA) | Sigma-Aldrich | 447935-500ML | Average Mn 300, contains 100 ppm MEHQ as inhibitor, 300 ppm BHT as inhibitor |
| 2,2′-Azobis(2-methylpropionitrile) (AIBN) | Sigma-Aldrich | ||
| Ru(bpy)3Cl2.6H2O | Sigma-Aldrich | 544981-1G | |
| Benzyl methacrylate (BzMA) | Sigma-Aldrich | 409448-1L | Contains monomethyl ether hydroquinone as inhibitor |
| Aluminium oxide (basic) | Chem-Supply Pty Ltd Australia | AL08371000 | |
| 95% Ethanol (EtOH) | Sucrogen Bio Ethanol | 80889 | |
| Acetonitrile (MeCN) | Chem-Supply Pty Ltd Australia | RP1005-G2.5L | |
| Tetrahydrofuran (THF) | Chem-Supply Pty Ltd Australia | TA011-2.5L | |
| Petroleum Spirits (40-60oC) | Chem-Supply Pty Ltd Australia | PA044-2.5L | |
| Diethyl Ether | Chem-Supply Pty Ltd Australia | EA0362.5L | |
| Dimethylacetamide (DMAc) | VWR International Australia | ALFA22916.M1 | For GPC analysis |
| Pasteur pipettes (230 mm) | Labtek | 355.050.503 | |
| Glass beakers | Labtek | 025.01.902 (2L)/ 2110654 (1L) | 2L beaker is for attaching LED strips to form the circular reactor |
| Commercial LED strip | EcoLab | n/a | λ = 460 nm, 4.8 W/m |
| 4 mL Glass Vials | Labtek | APC502214B | |
| 0.9 mL Quartz Cuvette | Starna Scientific Ltd | 21/Q/2 | |
| Needle (0.8 mm x 38 mm) | Beckton Dickson | 302017 | For deoxygenating reactions |
| Needle (0.8 mm x 120 mm) | B Braun Australia | 4665643 | For deoxygenating reactions |
| Sleeve stopper septa (rubber septum) | Sigma-Aldrich | z564680/z564702 | |
| Stirring hotplates | VWR International Australia/In Vitro Technologies | 97018-488/RADRR91200 | |
| Vortex mixer | VWR International Australia | 412-0098 | |
| Vacuum oven | In Vitro Technologies | MEMVO200 |
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