There are no acknowledgments.

1. Drying of toluene
NOTE: If you have access to dry solvent towers, collect the toluene and degas by five freeze-pump-thaw cycles.
<ol>
	<li>Dry 3 &#197; molecular sieves in a 250 mL Schlenk flask at 250-300 &#176;C under vacuum for 48 h and transfer into a glovebox.</li>
	<li>Dry two ampoules in the oven at 150 &#176;C overnight and transfer them into the glovebox.</li>
	<li>Transfer the activated molecular sieves into the two ampoules and remove from the glovebox.</li>
	<li>Dry a two-neck...

<ol>
	<li>Geng, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Shape+effects+of+filaments+versus+spherical+particles+in+flow+and+drug+delivery.">Shape effects of filaments versus spherical particles in flow and drug delivery.</a> Nature Nanotechnology. 2, 249 (2007).</li><li>Won, Y. -. Y., Davis, H. T., Bates, F. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Giant+Wormlike+Rubber+Micelles.">Giant Wormlike Rubber Micelles.</a> Science. 283 (5404), 960-963 (1999).</li><li>Mai, Y., Eisenberg, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-assembly+of+block+copolymers.">Self-assembly of block copolymers.</a> Chemical Society Reviews. 41 (18), 5969-5985 (2012).</li><li>Charleux, B., Delaittre, G., Rieger, J., D&#8217;Agosto, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Polymerization-Induced+Self-Assembly:+From+Soluble+Macromolecules+to+Block+Copolymer+Nano-Objects+in+One+Step.">Polymerization-Induced Self-Assembly: From Soluble Macromolecules to Block Copolymer Nano-Objects in One Step.</a> Macromolecules. 45 (17), 6753-6765 (2012).</li><li>Gilroy, J. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Monodisperse+cylindrical+micelles+by+crystallization-driven+living+self-assembly.">Monodisperse cylindrical micelles by crystallization-driven living self-assembly.</a> Nature Chemistry. 2, 566 (2010).</li><li>Boott, C. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Probing+the+Growth+Kinetics+for+the+Formation+of+Uniform+1D+Block+Copolymer+Nanoparticles+by+Living+Crystallization-Driven+Self-Assembly.">Probing the Growth Kinetics for the Formation of Uniform 1D Block Copolymer Nanoparticles by Living Crystallization-Driven Self-Assembly.</a> ACS Nano. 12 (9), 8920-8933 (2018).</li><li>G&#228;dt, T., Ieong, N. S., Cambridge, G., Winnik, M. A., Manners, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Complex+and+hierarchical+micelle+architectures+from+diblock+copolymers+using+living,+crystallization-driven+polymerizations.">Complex and hierarchical micelle architectures from diblock copolymers using living, crystallization-driven polymerizations.</a> Nature Materials. 8, 144 (2009).</li><li>Wang, X., Guerin, G., Wang, H., Wang, Y., Manners, I., Winnik, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cylindrical+Block+Copolymer+Micelles+and+Co-Micelles+of+Controlled+Length+and+Architecture.">Cylindrical Block Copolymer Micelles and Co-Micelles of Controlled Length and Architecture.</a> Science. 317 (5838), (2007).</li><li>Sch&#246;bel, J., Karg, M., Rosenbach, D., Krauss, G., Greiner, A., Schmalz, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patchy+Wormlike+Micelles+with+Tailored+Functionality+by+Crystallization-Driven+Self-Assembly:+A+Versatile+Platform+for+Mesostructured+Hybrid+Materials.">Patchy Wormlike Micelles with Tailored Functionality by Crystallization-Driven Self-Assembly: A Versatile Platform for Mesostructured Hybrid Materials.</a> Macromolecules. 49 (7), 2761-2771 (2016).</li><li>Arno, M. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Precision+Epitaxy+for+Aqueous+1D+and+2D+Poly(&#949;-caprolactone)+Assemblies.">Precision Epitaxy for Aqueous 1D and 2D Poly(&#949;-caprolactone) Assemblies.</a> Journal of the American Chemical Society. 139 (46), 16980-16985 (2017).</li><li>Sun, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tuning+the+Size+of+Cylindrical+Micelles+from+Poly(l-lactide)-b-poly(acrylic+acid)+Diblock+Copolymers+Based+on+Crystallization-Driven+Self-Assembly.">Tuning the Size of Cylindrical Micelles from Poly(l-lactide)-b-poly(acrylic acid) Diblock Copolymers Based on Crystallization-Driven Self-Assembly.</a> Macromolecules. 46 (22), 9074-9082 (2013).</li><li>Fan, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Crystallization-driven+one-dimensional+self-assembly+of+polyethylene-b-poly(tert-butylacrylate)+diblock+copolymers+in+DMF:+effects+of+crystallization+temperature+and+the+corona-forming+block.">Crystallization-driven one-dimensional self-assembly of polyethylene-b-poly(tert-butylacrylate) diblock copolymers in DMF: effects of crystallization temperature and the corona-forming block.</a> Soft Matter. 12 (1), 67-76 (2016).</li><li>He, W. -. N., Zhou, B., Xu, J. -. T., Du, B. -. Y., Fan, Z. -. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Two+Growth+Modes+of+Semicrystalline+Cylindrical+Poly(&#949;-caprolactone)-b-poly(ethylene+oxide)+Micelles.">Two Growth Modes of Semicrystalline Cylindrical Poly(&#949;-caprolactone)-b-poly(ethylene oxide) Micelles.</a> Macromolecules. 45 (24), 9768-9778 (2012).</li><li>Patra, S. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cylindrical+Micelles+of+Controlled+Length+with+a+&#960;-Conjugated+Polythiophene+Core+via+Crystallization-Driven+Self-Assembly.">Cylindrical Micelles of Controlled Length with a &#960;-Conjugated Polythiophene Core via Crystallization-Driven Self-Assembly.</a> Journal of the American Chemical Society. 133 (23), 8842-8845 (2011).</li><li>Kynaston, E. L., Nazemi, A., MacFarlane, L. R., Whittell, G. R., Faul, C. F. J., Manners, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Uniform+Polyselenophene+Block+Copolymer+Fiberlike+Micelles+and+Block+Co-micelles+via+Living+Crystallization-Driven+Self-Assembly.">Uniform Polyselenophene Block Copolymer Fiberlike Micelles and Block Co-micelles via Living Crystallization-Driven Self-Assembly.</a> Macromolecules. 51 (3), 1002-1010 (2018).</li><li>Rizis, G., Mvan de Ven, T. G., Eisenberg, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Crystallinity-driven+morphological+ripening+processes+for+poly(ethylene+oxide)-block-polycaprolactone+micelles+in+water.">Crystallinity-driven morphological ripening processes for poly(ethylene oxide)-block-polycaprolactone micelles in water.</a> Soft Matter. 10 (16), 2825-2835 (2014).</li><li>Jin, X. -. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-range+exciton+transport+in+conjugated+polymer+nanofibers+prepared+by+seeded+growth.">Long-range exciton transport in conjugated polymer nanofibers prepared by seeded growth.</a> Science. 360 (6391), (2018).</li><li>Rizis, G., van&#8197;de&#8197;Ven, T. G. M., Eisenberg, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=&#8220;Raft&#8221;+Formation+by+Two-Dimensional+Self-Assembly+of+Block+Copolymer+Rod+Micelles+in+Aqueous+Solution.">&#8220;Raft&#8221; Formation by Two-Dimensional Self-Assembly of Block Copolymer Rod Micelles in Aqueous Solution.</a> Angewandte Chemie International Edition. 53 (34), 9000-9003 (2014).</li><li>Qiu, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Uniform+patchy+and+hollow+rectangular+platelet+micelles+from+crystallizable+polymer+blends.">Uniform patchy and hollow rectangular platelet micelles from crystallizable polymer blends.</a> Science. 352 (6286), 701 (2016).</li><li>Zhou, H., Lu, Y., Yu, Q., Manners, I., Winnik, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Monitoring+Collapse+of+Uniform+Cylindrical+Brushes+with+a+Thermoresponsive+Corona+in+Water.">Monitoring Collapse of Uniform Cylindrical Brushes with a Thermoresponsive Corona in Water.</a> ACS Macro Letters. 7 (2), 166-171 (2018).</li></ol>

The synthesis and living CDSA of the triblock copolymer PCL50-PMMA10-PDMA200 has been outlined. Although stringent conditions are required, the ring-opening polymerization of &#949;-caprolactone gave polymers with excellent properties that enabled the successful chain extensions of MMA and DMA. These polymers were successful in their self-seeding, obtaining a pure phase of cylindrical micelles, which were sonicated into seed particles of LN 98 nm. Through simple additi...

One-dimensional (1D) nanostructures, such as cylinders, fibers and tubes, have garnered increasing attention in a variety of fields. Amongst these, their popularity in polymer science is owed to their rich variety of properties. For example, Geng et al. demonstrated that filomicelles exhibit a tenfold increase in residence time in the bloodstream of a rodent model compared to their spherical counterparts, and Won et al. revealed that polybutadiene-b-poly(ethylene oxide) fiber dispersions display an increase in storage modulus by two orders of magnitude upon crosslinking of the core during rheological measurements1,2. Interestingly, many of these systems are synthesized via the self-assembly of block copolymers, whether this be through more traditional methods of solvent switching and thin-film rehydration3, or more advanced methods such as polymerization-induced self-assembly and crystallization-driven self-assembly (CDSA)4,5. Each technique holds their own advantages, however, only CDSA can produce rigid particles with a uniform and controllable length distribution.
Pioneering work by Gilroy et al. formed long polyferrocenylsilane-b-polydimethylsiloxane (PFS-PDMS) cylinders in hexanes and, when using mild sonication, very short cylinders with a low contour length dispersity (Ln). Upon the addition of a predetermined mass of diblock copolymer chains in a common solvent, cylinders of varying lengths with an Ln as low as 1.03 were synthesised5,6. Further work by the Manners group highlighted the high degree of control possible with the PFS system, which may be used to form remarkably complex and hierarchal structures: block-co-micelles, scarf shaped and dumbbell micelles to name a few7,8. Following these demonstrations, researchers investigated other, more functional systems for CDSA including: semi-crystalline commodity polymers (polyethylene, poly(&#949;-caprolactone), polylactide)9,10,11,12,13 and conducting polymers (poly(3-hexylthiophene), polyselenophene)14,15. Armed with this toolbox of diblock copolymer systems that can be assembled quickly and efficiently, researchers have carried out more application-driven research in recent years16.&#160; Jin et al. have demonstrated exciton diffusion lengths in the hundreds of nanometers in polythiophene block copolymers and our group demonstrated the formation of gels from poly(&#949;-caprolactone) (PCL) containing cylindrical constructs10,17.
Although it is a powerful technique, CDSA does have its limitations. The block copolymers must have a semi-crystalline component, as well as low dispersity values and high end group fidelities; lower order block contaminants may cause particle aggregation or induce morphology changes18,19. Due to these restrictions, living polymerizations are used. However, significant reagent purification, drying procedures and water/oxygen free environments are required in order to achieve polymers with the aforementioned properties. Attempts have been made to design systems that overcome this. For example, PFS block copolymers have been formed using click chemistry to couple polymer chains together20. Although the resulting cylindrical nanoparticles have demonstrated exemplary properties, the block copolymers are typically purified by preparative size exclusion chromatography and the synthesis of PFS still requires the use of living anionic polymerizations. Our group recently realized the living CDSA of PCL, the success of which revolved around using both living organobase-catalyzed ring-opening polymerizations (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerizations10. Although this method is simpler, living polymerizations are still required.
As the field is moving towards more application-driven research, and due to the problems associated with living polymerizations, it is believed that an outline of the polymer synthesis and self-assembly protocols will be advantageous to future scientific work. Thus, in this manuscript, the complete synthesis and self-assembly of a PCL-b-PMMA-b-PDMA copolymer is outlined. Drying techniques will be highlighted in the context of an organocatalyzed ROP of &#949;-caprolactone and the subsequent RAFT polymerizations of MMA and DMA will be outlined. Finally, a living CDSA protocol for this polymer in ethanol will be presented and common errors in characterization data due to poor experimental technique will be critiqued.

<table>
	<tbody>
		<tr>
			<td>2,2&#39;-azobisisobutyrnitrile</td>
			<td>Sigma Aldrich</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>250 mL ampoule</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>250 mL two neck RBF</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Ampoule (25 mL)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>B19 tap</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>B24 stopper</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Basic Alumina</td>
			<td>Fluka</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Buchner Flask</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Buchner Funnel</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Caclium Hydride</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Cannulae</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>caprolactone</td>
			<td>Arcos Organics</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Chain Transfer Agent</td>
			<td>Made in House</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Conical Flask (multiple sizes)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Dessicator</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Diethyl Ether</td>
			<td>Merck</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Dioxane</td>
			<td>Fisher</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>diphenylphosphate</td>
			<td>Sigma Aldrich</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Distillation Condenser</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Ethanol</td>
			<td>Fisher</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Filter Paper (multiple sizes)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Gel Permeation Chrmoatography Instrument</td>
			<td>Agilent Technologies Infinity 1260 II</td>
			<td></td>
			<td>Running DMF at 50 &#176;C</td>
		</tr>
		<tr>
			<td>Glovebox</td>
			<td>Mbraun, Unilab</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Hotplate</td>
			<td>IKA, RCT basic</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Mercury Thermometer</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Methyl Methacrylate</td>
			<td>Sigma Aldrich</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Molecular seives</td>
			<td>Fisher</td>
			<td>MS/1030/53</td>
			<td></td>
		</tr>
		<tr>
			<td>N,N-dimethyl acrylamide</td>
			<td>Sigma Aldrich</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>NMR spectrometer</td>
			<td>Bruker 400 MHz</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Phosphorus pentoxide</td>
			<td>Sigma Aldrich</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>RBF (multiple sizes)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Schlenk Cap (B24)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Schlenk Flask (250 mL)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Schlenk Line</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Sonication Probe</td>
			<td>Bandelin Sonoplus</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Suba Seal (multiple sizes)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>TEM grids</td>
			<td>EmResolutions, Formvar/carbon film 300 mesh copper</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>THF</td>
			<td>Merck</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>three neck adaptor</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Toluene</td>
			<td>Fisher</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Transmission Electron Microscope</td>
			<td>Jeol 2100</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

synthesis of monodisperse cylindrical nanoparticles via crystallization-driven self-assembly of biodegradable block copolymers

The production of monodisperse cylindrical micelles is a significant challenge in polymer chemistry. Most cylindrical constructs formed from diblock copolymers are produced by one of three techniques: thin film rehydration, solvent switching or polymerization-induced self-assembly, and produce only flexible, polydisperse cylinders. Crystallization-driven self-assembly (CDSA) is a method which can produce cylinders with these properties, by stabilizing structures of a lower curvature due to the formation of a crystalline core. However, the living polymerization techniques by which most core-forming blocks are formed are not trivial processes and the CDSA process may yield unsatisfactory results if carried out incorrectly. Here, the synthesis of cylindrical nanoparticles from simple reagents is shown. The drying and purification of reagents prior to a ring-opening polymerization of &#949;-caprolactone catalyzed by diphenyl phosphate is described. This polymer is then chain extended by methyl methacrylate (MMA) followed by N,N-dimethyl acrylamide (DMA) using reversible addition&#8722;fragmentation chain-transfer (RAFT) polymerization, affording a triblock copolymer that can undergo CDSA in ethanol. The living CDSA process is outlined, the results of which yield cylindrical nanoparticles up to 500 nm in length and a length dispersity as low as 1.05. It is anticipated that these protocols will allow others to produce cylindrical nanostructures and elevate the field of CDSA in the future.

PCL was analyzed by 1H NMR spectroscopy and gel permeation chromatography (GPC). The 1H NMR spectrum yielded a degree of polymerization (DP) of 50, by comparison of resonances at 3.36 ppm and 4.08 ppm, which correspond to the end group ethyl protons and the in-chain ester &#945;-protons respectively (Figure 1b). This provided validation of the molecular weight values obtained by GPC where a single peak, with a dispersity value of 1.07, w...

Watch this Scientific Journal Video about Synthesis of Monodisperse Cylindrical Nanoparticles via Crystallization-driven Self-assembly of Biodegradable Block Copolymers at JoVE.com

Synthesis of Monodisperse Cylindrical Nanoparticles via Crystallization-driven Self-assembly of Biodegradable Block Copolymers

Crystallization-driven self-assembly (CDSA) displays the unique ability to fabricate cylindrical nanostructures of narrow length distributions. The organocatalyzed ring-opening polymerization of &#949;-caprolactone and subsequent chain extensions of methyl methacrylate and N,N-dimethyl acrylamide are demonstrated. A living CDSA protocol that produces monodisperse cylinders up to 500 nm in length is outlined.

The production of monodisperse cylindrical micelles is a significant challenge in polymer chemistry. Most cylindrical constructs formed from diblock ...

Our protocol focuses on both ring-opening and RAFT polymerizations to produce block copolymer cylinders of a controlled length using living crystallization-driven self-assembly. The combination of both ring-opening and RAFT polymerizations allows the production of polymers with both semi-crystalline and functional regions. This opens the field of CDSA to other potential applications.The success of the protocol resolves around the dryness of the starting reagents. Make sure the system never comes into contact with the atmosphere once the drying procedure has begun. The method requires knowledge in air-sensitive chemistry techniques.We believe that committing these practices to video form will give researchers freedom to introduce new ideas without hindrance from a lack of practical experience. To begin, transfer all glassware and stir bars, dried in a 150 degrees Celsius oven overnight, to the bench. Clamp the two-neck 250-milliliter round-bottom flask, equipped with a stir bar, on a stand over a stir plate, and secure an air-tight tap on the small neck.Add 100 milliliters of epsilon-caprolactone to the flask. Connect the round-bottom flask to a nitrogen line through the tap on one neck. Under a steady flow of nitrogen at three psi, add one gram of calcium hydride into the flask through the primary neck.Fit the second neck with a glass stopper, and stir overnight at room temperature under a nitrogen atmosphere. Attack the flask to the Schlenk line, and open to a steady flow of nitrogen. Assemble the vacuum distillation equipment on two stands, by clamping the epsilon-caprolactone round-bottom flask to one stand and another round-bottom flask to the other stand.Maintain a steady flow of nitrogen through the system to prevent water from entering the system. Insert a thermometer into the still head, and seal in place. Attach the adapter to the Schlenk line.Turn off the nitrogen flow, and open the system to vacuum through this new connection to the Schlenk line. Heat the epsilon-caprolactone in a 60-to-80-degrees heating mantle, collecting the first five milliliters in the small round-bottom flasks and the rest in the two-neck round-bottom flask. Place the flasks in liquid nitrogen to condense the caprolactone effectively.To speed up the process, wrap the distillation equipment in cotton wool and foil. Attach the Schlenk line to the two-neck round-bottom flask. Turn the line to vacuum for 120 seconds and to nitrogen for 10 seconds, a total of three times, to purge the line.Open the line and the system to nitrogen. Then add one gram of calcium hydride to the collection flask fit with a stopper, and stir under a nitrogen atmosphere overnight. Meanwhile, dispose of the excess calcium hydride by dropwise addition of 10 milliliters of isopropanol, followed by five milliliters of methanol.Once bubbling ceases, add an excess of water. Rinse the distillation equipment with acetone, and place in the oven overnight. In the morning, repeat the vacuum distillation again without adding calcium hydride to the monomer once finished.Then open the flask to nitrogen to start transferring the caprolactone, via cannula, into an ampule. Transfer the ampule to a glove box. In the glove box, prepare stock solutions.Into three separate vials, add 0.011 grams of hydroxyl chain transfer agent, as initiator, 0.01 grams of diphenyl phosphate, as catalyst, and 0.25 grams of the dried monomer, caprolactone. Add 0.5 milliliters of toluene to each of the initiator and catalyst vials, and gently agitate until the reagents are dissolved. Then mix the initiator and diphenyl phosphate stock solutions into one vial, and add a stir bar.Fix the vial on a stirrer, adjust the speed to moderate stirring, and add the monomer solution into the initiator-catalyst vial. Fit the vial with a lid, and stir for eight hours at room temperature. Then remove the vial from the glove box, and immediately use a Pasteur pipette to add the mixture, dropwise, into an excess of cold diethyl ether, to precipitate.Through a Buchner funnel, filter the white solid, dry in the ambient atmosphere, and dissolve it in one milliliter of tetrahydrofuran. Precipitate in diethyl ether twice more, and dry thoroughly. First prepare several basic alumina plugs in three-milliliter syringes.Filter the dioxane and MMA into separate vials to remove stabilizers. Weigh 0.5 grams of the previously synthesized PCL, 0.424 grams of MMA, measure two milliliters of dioxane into a vial, and allow to dissolve. Prepare a pure AIBN stock solution of 10 milligrams per milliliter, and pipette 139 microliters into the reaction mixture.Transfer the mixture into an ampule equipped with a stir bar, and seal. Next attach the ampule to the Schlenk line, and place into liquid nitrogen. Once the solution is frozen, introduce the ampule to vacuum until the vacuum gauge reads at most one times 10 to the negative one millibar.Close the ampule, and allow to thaw completely. Repeat this freeze-pump-thaw cycle two additional times. Upon completion of the last cycle, backfill the ampule with nitrogen, and place it into a preheated oil bath at 65 degrees Celsius for four hours.To monitor conversion, obtain the ampule from the oil bath, switch the cap for super seal under a flow of nitrogen, extract two drops, mix with 600 microliters of deuterated chloroform in a vial, and transfer to an NMR tube. Transfer the sample to the autosampler of an NMR instrument to run a proton spectrum. Replace the cap whilst under a steady flow of nitrogen, and place back into the oil bath.Now, place the ampule that has been heated in the oil bath into liquid nitrogen until frozen, and then in a fume hood, open the ampule to air to quench the polymerization for one minute. Next, dropwise add the mixture into a vast excess of cold diethyl ether to precipitate. Isolate by Buchner filtration, and dry.Dissolve the polymer and tetrahydrofuran, and precipitate twice more. Dry the polymer thoroughly for proton NMR spectroscopy and SEC analysis. Repeat this procedure with 0.5 grams of the generated PCL-PMMA, 1.406 grams of DMA, two milliliters of dioxane, and 111 microliters of ten milligrams per milliliter AIBN and dioxane.Heat the polymerization at 70 degrees Celsius for one hour, and precipitate the reaction mixture in cold diethyl ether three times. Place five milligrams of the generated triblock copolymer into a vial, and add one milliliter of ethanol. Seal the vial with lid and parafilm.Heat at 70 degrees Celsius and a heating mantle for three hours. After that, take the vial out to cool slowly to room temperature. Leave the solution to age at room temperature for two weeks.The solution turns cloudy and forms a distinct layer at the bottom when fully assembled. Dilute the dispersion to one milligram per milliliter with ethanol in a sonication-proof tube. Place the tube in an ice bath.Insert the tip of the sonication probe into the middle area of the dispersion. Sonicate the solution for 15 cycles of two minutes at the lowest intensity, allowing to cool for 15 minutes between cycles. Take an aliquot of the sonicated seed dispersion and dilute to 0.18 milligrams per milliliter with ethanol in a tube.Then, prepare a solution of unimer and tetrahydrofuran to the concentration of 25 milligrams per milliliter. Add 32.8 microliters of the unimer solution into the diluted seed dispersion and gently shake to allow full dissolution. Leave the dispersion to age for three days with the lid slightly ajar, so the tetrahydrofuran can evaporate.This will produce 90 nanometer starting seeds to 500 nanometer cylinders. Ring-opening polymerization of epsilon-caprolactone resulted in a degree of polymerization of 50, determined by the proton NMR spectrum with resonances of the end-group ethyl protons at 3.36 PPM, and the end-chain ester alpha protons at 4.08 PPM. GPC trace shows a typical molecular weight distribution with a single peak, having a dispersity value of 1.07 and a number average molecular weight of 10, 800 grams per mole.By comparison, polymerization that was reacted for 12 hours gave a high molecular weight shoulder at 15, 500 grams per mole. Using reagents not correctly dried yielded a product mixture with a low molecular weight tail. The successive RAFT polymerizations achieved a degree of polymerization of 10 for the PMMA block with a unimodal peak in the GPC trace.However, when deliberately taken to too high conversions greater than 70 percent, a broadening of molecular weight and a high molecular weight shoulder was observed. The degree of polymerization of the final block of PDMA was 200, upon comparison of the PCL end-chain ether protons at 4.08 PPM and the DMA side-chain methyl protons at 2.93 PPM. The GPC trace was narrow and unimodal.Upon repetition of the chain extension using impure PCL-PMMA, a low molecular weight shoulder appeared. Remember to take your time on drying the system, as any presence of water can cause the polymerization of caprolactone to fail. Make sure everything is dry.A buffer region between the core and corona of the cylinder could allow other CDSA construct to be stabilized in water, opening new avenues of research and collaboration.

synthesis-monodisperse-cylindrical-nanoparticles-via-crystallization

Research

JoVE Journal

Chemistry

7.7K visualizações.  University of Birmingham. Nosso protocolo se concentra tanto na abertura de anel quanto nas polimerizações de RAFT para produzir cilindros copolímeros de bloco de um comprimento controlado usando auto-montagem orientada para cristalização viva. A combinação de polimerizações de abertura de anel e RAFT permite a produção de polímeros com regiões semi-cristalinas e funcionais. Isso abre o campo do CDSA para outras aplicações potenciais.O sucesso do protocolo resolve em torno da secura dos reagentes...