A Facile Amino-Functionalization of Poly(2-oxazoline)s’ Distal End Through Sequential Azido End-Capping and Staudinger Reactions

Significance Statement

Different poly(2-susbstituted 2-oxazoline)s POxs polymers have been successfully implemented in biomedical applications due to their favorable structural capabilities under certain physical conditions coupled with their ability to produce several functional groups when reacted with their applicable monomers.

The facile introduction of amino groups at the distal chain ends of POxs has not been established despite their attractive features in initiating polymerization of N-carboxy anhydride NCA monomers. The few studies performed additionally takes a longer time for completion of this reaction.

A group of researchers from Japan developed a method of introducing a primary amino group at the distal chain end of POxs through the serial procedure of azido end-capping and Staudinger reactions. The research work is now published in peer-reviewed journal, European Polymer Journal.

They performed a cationic ring-opening polymerization of 2-ethyl-2-oxazoline EtOx, followed by the end-capping reaction with sodium azide, Results from the matrix assisted laser desorption/ionization time-of-flight mass spectroscopy MALDI-TOF-MS measurements confirmed successful polymerization of EtOx and the quantitative introduction of azido group at the distal chain end of the poly(2-ethyl-2-oxazoline) PEtOx. Furthermore, using MALDI-TOF-MS the authors showed successful progress of azide–amine conversion via Staudinger reaction using triphenylphosphine. Introduction of a primary amino group was highly efficient indicative of an amino-functionalization ratio of 96%, determined from gel permeation chromatography GPC with ion exchange column.

Another advantage of this method was the optimized reaction time for the conversion process to amino-functionalized PEtOx, achieving the shortening of time to 1h for the introduction of the azido group and only 3h for the conversion of the azido group to the primary amino group. It should be emphasized that this reaction can proceed in one-pot system, without changing the reactor.

They performed a ring-opening polymerization of L-Lysine (TFA)-NCA from the primary amino group of the synthesized PEtOx-NH2 to obtain PEtOx-b-PLys(TFA). Analysis on the obtained PEtOx-b-PLys(TFA) by size exclusion chromatography SEC and 1H NMR spectroscopy showed a successful block copolymerization of L-Lysine (TFA)-NCA. This end result proves that the amino-functionalized PEtOx can initiate polymerization of NCA monomers.

Apart from the versatility of the procedure in developing functional POx derivatives, the successfully derived block polymer PEtOx-b-PLys(TFA) might have various biomedical applications such as in drug delivery, hydrogel formulation and biological surface coatings.

A Facile Amino-Functionalization of Poly(2-oxazoline)s’ Distal End Through Sequential Azido End-Capping and Staudinger Reactions - Advances in Engineering

About The Author

Dr. Kazunori Kataoka is a Director General of Innovation Center of NanoMedicine (iCONM), Kawasaki Institute of Industry Promotion. He is also a Professor at Policy Alternatives Research Institute, The University of Tokyo.

He received his B.Eng. (1974) in Organic Chemistry, M.Eng. (1976) and Ph.D. (1979) in Polymer Chemistry from The University of Tokyo. He started his academic career at Institute of Biomedical Engineering, Tokyo Women’s Medical College as Assistant Professor (1979) and was promoted to Associate Professor in 1988. He moved to Department of Materials Engineering, Tokyo University of Science in 1989 as Associate Professor and was promoted to full Professor in 1994. He joined Department of Materials Engineering, The University of Tokyo in 1998 as full Professor. He was appointed joint-position of full Professor at Center for Disease Biology and Integrative Medicine, The University of Toyo Medical School in 2004. In 2016, he took mandatory retirement from Graduate School of Engineering/Graduate School of Medicine, The University of Tokyo, and moved to the current position. He has been appointed as Adjunct Professor at Eshelman School of Pharmacy, University of North Carolina Chapel Hill since 2015.

He has received several scientific awards, including the Clemson Award from the Society for Biomaterials, USA (2005), the Founder’s Award from the Controlled Release Society (2008), Humboldt Research Award from Alexander von Humboldt Foundation (2012), and Leo Esaki Prize (2012).

He has been elected as a Foreign Member of the US National Academy of Engineering (NAE) since 2017. His current major research interests include supramolecular materials for nanobiotechnology, focusing on drug and gene delivery systems.

About The Author

Shigehito OSAWA received a bachelor degree in 2011 from Department of Material Engineering, The University of Tokyo, a master degree in 2013 from Department of Material Engineering, Graduate School of Engineering, the University of Tokyo, and received a PhD degree in 2016 from Department of Material Engineering, Graduate School of Engineering, the University of Tokyo with a study on thermoresponsive poly(2-oxazoline)-based polymeric micelle loading nucleic acid, under the supervision of Professor Kazunori Kataoka. After receiving his PhD, he has been involved in the laboratory of Professor Kazunori Kataoka at Innovation Center of NanoMedicine (iCONM), Institute of Industry Promotion-Kawasaki as a research scientist.

His research interest involves design and synthesis of stimuli-responsive polymers and development of drug and nucleic acid delivery system based on the stimuli-responsive polymers.

About The Author

Kensuke OSADA received a bachelor degree at 1997 and a master degree at 1999 from the Department of Organic and Polymeric Materials, Tokyo Institute Technology, and received a PhD degree at 2002 with a study on morphology of polyester chain in liquid crystalline phase, under the supervision of Professor Junji Watanabe. He received JSPS DC1 fellowship during the PhD course from 1999 to 2002. After finishing his PhD, he worked in the laboratory of Professor Kazunori Kataoka at the Department of Materials Engineering, The University of Tokyo as a JSPS postdoctoral researcher. He promoted his position to Assistant Professor in 2004 and to Associate Professor in 2006.

From 2012, he was selected as JST-PRESTO Researcher. During his job history, he committed to education programs of the Nano-Bioengineering Education Program, Center for Medical System Innovation, and Graduate Program for Leaders in Life Innovation. His research interest involves development of drug and nucleic acid delivery system based on polymer assembly.

Journal Reference

Shigehito Osawa1, 2, Takehiko Ishii3, Hiroyasu Takemoto4, Kensuke Osada5, 6 , Kazunori Kataoka1, 2, 6 7. A Facile Amino-Functionalization of Poly(2-oxazoline)s’ Distal End Through Sequential Azido End-Capping and Staudinger Reactions, European Polymer Journal (2017) 88, 553-561.

 

Show Affiliations

1 Innovation Center of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion, 3-25-14, Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan

2 Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656, Japan

3 Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656, Japan

4 Laboratory for Chemistry and Life Science, Institute of Innovation Research, Tokyo Institute of Technology, R1-11, 4259 Nagatsuka, Midori-ku, Yokohama 226-8503, Japan

5 Japan Science and Technology Agency, PRESTO, 4-1-8 Motomachi, Kawaguchi, Saitama 332-0012, Japan

6 Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan

7 Policy Alternatives Research Institute, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan

 

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