Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers
Conventional synthesis of polymers by ATRP is relatively low throughput, involving iterative optimization of conditions in an inert atmosphere. Automated, high-throughput controlled radical polymerization was developed to accelerate catalyst optimization and production of disulfide-functionalized po...
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| Format: | Article |
| Language: | en_US |
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American Chemical Society
2013
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| Online Access: | http://hdl.handle.net/1721.1/79833 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0003-4255-0492 |
| _version_ | 1826201480037662720 |
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| author | Siegwart, Daniel J. Leiendecker, Matthias Anderson, Daniel Griffith Langer, Robert S |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Siegwart, Daniel J. Leiendecker, Matthias Anderson, Daniel Griffith Langer, Robert S |
| author_sort | Siegwart, Daniel J. |
| collection | MIT |
| description | Conventional synthesis of polymers by ATRP is relatively low throughput, involving iterative optimization of conditions in an inert atmosphere. Automated, high-throughput controlled radical polymerization was developed to accelerate catalyst optimization and production of disulfide-functionalized polymers without the need of an inert gas. Using ARGET ATRP, polymerization conditions were rapidly identified for eight different monomers, including the first ARGET ATRP of 2-(diethylamino)ethyl methacrylate and di(ethylene glycol) methyl ether methacrylate. In addition, butyl acrylate, oligo(ethylene glycol) methacrylate 300 and 475, 2-(dimethylamino)ethyl methacrylate, styrene, and methyl methacrylate were polymerized using bis(2-hydroxyethyl) disulfide bis(2-bromo-2-methylpropionate) as the initiator, tris(2-pyridylmethyl)amine as the ligand, and tin(II) 2-ethylhexanoate as the reducing agent. The catalyst and reducing agent concentration was optimized specifically for each monomer, and then a library of polymers was synthesized systematically using the optimized conditions. The disulfide-functionalized chains could be cleaved to two thiol-terminated chains upon exposure to dithiothreitol, which may have utility for the synthesis of polymer bioconjugates. Finally, we demonstrated that these new conditions translated perfectly to conventional batch polymerization. We believe the methods developed here may prove generally useful to accelerate the systematic optimization of a variety of chemical reactions and polymerizations. |
| first_indexed | 2024-09-23T11:52:27Z |
| format | Article |
| id | mit-1721.1/79833 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:52:27Z |
| publishDate | 2013 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | mit-1721.1/798332022-10-01T06:36:10Z Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers Siegwart, Daniel J. Leiendecker, Matthias Anderson, Daniel Griffith Langer, Robert S Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Anderson, Daniel Griffith Siegwart, Daniel J. Leiendecker, Matthias Langer, Robert Conventional synthesis of polymers by ATRP is relatively low throughput, involving iterative optimization of conditions in an inert atmosphere. Automated, high-throughput controlled radical polymerization was developed to accelerate catalyst optimization and production of disulfide-functionalized polymers without the need of an inert gas. Using ARGET ATRP, polymerization conditions were rapidly identified for eight different monomers, including the first ARGET ATRP of 2-(diethylamino)ethyl methacrylate and di(ethylene glycol) methyl ether methacrylate. In addition, butyl acrylate, oligo(ethylene glycol) methacrylate 300 and 475, 2-(dimethylamino)ethyl methacrylate, styrene, and methyl methacrylate were polymerized using bis(2-hydroxyethyl) disulfide bis(2-bromo-2-methylpropionate) as the initiator, tris(2-pyridylmethyl)amine as the ligand, and tin(II) 2-ethylhexanoate as the reducing agent. The catalyst and reducing agent concentration was optimized specifically for each monomer, and then a library of polymers was synthesized systematically using the optimized conditions. The disulfide-functionalized chains could be cleaved to two thiol-terminated chains upon exposure to dithiothreitol, which may have utility for the synthesis of polymer bioconjugates. Finally, we demonstrated that these new conditions translated perfectly to conventional batch polymerization. We believe the methods developed here may prove generally useful to accelerate the systematic optimization of a variety of chemical reactions and polymerizations. National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award (Individual Postdoctoral Fellows) National Institutes of Health (U.S.) (Award F32EB011867) Alnylam Pharmaceuticals (Firm) Johannes Gutenberg-Universität (Graduate School of Excellence Materials Science in Mainz (MAINZ)) Studienstiftung des Deutschen Volkes 2013-08-12T19:18:52Z 2013-08-12T19:18:52Z 2012-02 2012-01 Article http://purl.org/eprint/type/JournalArticle 0024-9297 1520-5835 http://hdl.handle.net/1721.1/79833 Siegwart, Daniel J., Matthias Leiendecker, Robert Langer, and Daniel G. Anderson. Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers. Macromolecules 45, no. 3 (February 14, 2012): 1254-1261. https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1021/ma3000219 Macromolecules Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society PMC |
| spellingShingle | Siegwart, Daniel J. Leiendecker, Matthias Anderson, Daniel Griffith Langer, Robert S Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers |
| title | Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers |
| title_full | Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers |
| title_fullStr | Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers |
| title_full_unstemmed | Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers |
| title_short | Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers |
| title_sort | automated arget atrp accelerates catalyst optimization for the synthesis of thiol functionalized polymers |
| url | http://hdl.handle.net/1721.1/79833 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0003-4255-0492 |
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