Synlett 2018; 29(19): 2582-2587
DOI: 10.1055/s-0037-1611340
cluster
© Georg Thieme Verlag Stuttgart · New York

Mixing End Groups in Thiol-Ene/Yne Reactions as a Simple Approach toward Multienzyme-Responsive Polymeric Amphiphiles

Assaf J. Harnoy
a  Department of Organic Chemistry, School of Chemistry, Faculty of Exact Sciences, Tel-Aviv University, Tel-Aviv 6997801, Israel   Email: amirroey@tauex.tau.ac.il
b  Tel Aviv University Center for Nanoscience and Nanotechnology, Tel-Aviv University, Tel-Aviv 6997801, Israel
,
Nitsan Papo
a  Department of Organic Chemistry, School of Chemistry, Faculty of Exact Sciences, Tel-Aviv University, Tel-Aviv 6997801, Israel   Email: amirroey@tauex.tau.ac.il
b  Tel Aviv University Center for Nanoscience and Nanotechnology, Tel-Aviv University, Tel-Aviv 6997801, Israel
,
Gadi Slor
a  Department of Organic Chemistry, School of Chemistry, Faculty of Exact Sciences, Tel-Aviv University, Tel-Aviv 6997801, Israel   Email: amirroey@tauex.tau.ac.il
b  Tel Aviv University Center for Nanoscience and Nanotechnology, Tel-Aviv University, Tel-Aviv 6997801, Israel
,
Roey J. Amir*
a  Department of Organic Chemistry, School of Chemistry, Faculty of Exact Sciences, Tel-Aviv University, Tel-Aviv 6997801, Israel   Email: amirroey@tauex.tau.ac.il
b  Tel Aviv University Center for Nanoscience and Nanotechnology, Tel-Aviv University, Tel-Aviv 6997801, Israel
c  BLAVATNIK CENTER for Drug Discovery, Tel-Aviv University, Tel-Aviv 6997801, Israel
› Author Affiliations
This research was funded by the ISRAEL SCIENCE FOUNDATION (grant No. 1553/18).
Further Information

Publication History

Received: 03 October 2018

Accepted after revision: 09 November 2018

Publication Date:
16 November 2018 (online)


Published as part of the Cluster Synthesis of Materials

Abstract

Taking advantage of the high fidelity of thiol-ene and thiol-yne chemistries, we used mixtures of thiols to prepare degradable PEG-dendron amphiphiles functionalized with two different types of enzymatically cleavable end groups. By tuning the feed ratios of the two thiols, we achieved mixtures of hybrids with statistically different ratios of end groups. Studies of the disassembly of statistically mixed hybrids showed that these amphiphiles have higher degrees of response when incubated with each of the activating enzymes, whereas a greater degree of selectivity was observed for a control mixture of two distinct amphiphiles, which required the presence of both types of enzyme to undergo complete disassembly. The potential to introduce different end groups by using a mixture of thiols in an efficient single thiol-ene or thiol-yne step opens the way for simple modification of various ene- or yne-containing polymers and tailoring of their structural and functional properties.

Supporting Information

 
  • References

  • 1 Shi Y, Lammers T, Storm G, Hennink WE. Macromol. Biosci. 2017; 17: 1600160
  • 2 Zhao S, Wang D, Zhang K, Zhang H. Int. J. Polym. Mater. Polym. Biomater. 2015; 64: 792
  • 3 Mickler FM, Vachutinsky Y, Oba M, Miyata K, Nishiyama N, Kataoka K, Bräuchle C, Ruthardt N. J. Controlled Release 2011; 156: 364
  • 4 Gillies ER, Jonsson TB, Fréchet JM. J. J. Am. Chem. Soc. 2004; 126: 11936
  • 5 Gitsov I. J. Polym. Sci., Part A: Polym. Chem. 2008; 46: 5295
  • 6 Kabanov AV, Lemieux P, Vinogradov S, Alakhov V. Adv. Drug Delivery Rev. 2002; 54: 223
  • 7 Miyata K, Christie RJ, Kataoka K. React. Funct. Polym. 2011; 71: 227
  • 8 Grossen P, Witzigmann D, Sieber S, Huwyler J. J. Controlled Release 2017; 260: 46
  • 9 Vancoillie G, Brooks WL. A, Mees MA, Sumerlin BS, Hoogenboom R. Polym. Chem. 2016; 7: 6725
  • 10 Kumari M, Gupta S, Achazi K, Böttcher C, Khandare J, Sharma SK, Haag R. Macromol. Rapid Commun. 2015; 36: 254
  • 11 Owen SC, Chan DP. Y, Shoichet MS. Nano Today 2012; 7: 53
  • 12 Torchilin VP. J. Controlled Release 2001; 73: 137
  • 13 Kataoka K, Harada A, Nagasaki Y. Adv. Drug Delivery Rev. 2012; 64: 37
  • 14 Movassaghian S, Merkel OM, Torchilin VP. Wiley Interdiscip. Rev.: Nanomed. Nanobiotechnol. 2015; 7: 691
  • 15 Hu Q, Katti PS, Gu Z. Nanoscale 2014; 6: 12273
  • 16 Shim MS, Kwon YJ. Adv. Drug Delivery Rev. 2012; 64: 1046
  • 17 Lowe AB. Polym. Chem. 2014; 5: 4820
  • 18 Massi A, Nanni D. Org. Biomol. Chem. 2012; 10: 3791
  • 19 Walter MV, Malkoch M. Chem. Soc. Rev. 2012; 41: 4593
  • 20 Killops KL, Campos LM, Hawker CJ. J. Am. Chem. Soc. 2008; 130: 5062
  • 21 Kang T, Amir RJ, Khan A, Ohshimizu K, Hunt JN, Sivanandan K, Montañez MI, Malkoch M, Ueda M, Hawker CJ. Chem. Commun. 2010; 46: 1556
  • 22 Amir RJ, Albertazzi L, Willis J, Khan A, Kang T, Hawker CJ. Angew. Chem. Int. Ed. 2011; 50: 3425
  • 23 Antoni P, Robb MJ, Campos L, Montanez M, Hult A, Malmström E, Malkoch M, Hawker CJ. Macromolecules 2010; 43: 6625
  • 24 Granskog V, Andrén OC. J, Cai Y, González-Granillo M, Felländer-Tsai L, von Holst H, Haldosen L.-A, Malkoch M. Adv. Funct. Mater. 2015; 25: 6596
  • 25 Ghirardello M, Öberg K, Staderini S, Renaudet O, Berthet N, Dumy P, Hed Y, Marra A, Malkoch M, Dondoni A. J. Polym. Sci., Part A: Polym. Chem. 2014; 52: 2422
  • 26 Sharma R, Naresh K, Chabre YM, Rej R, Saadeh NK, Roy R. Polym. Chem. 2014; 5: 4321
  • 27 Harnoy AJ, Buzhor M, Tirosh E, Shaharabani R, Beck R, Amir RJ. Biomacromolecules 2017; 18: 1218
  • 28 Harnoy AJ, Rosenbaum I, Tirosh E, Ebenstein Y, Shaharabani R, Beck R, Amir RJ. J. Am. Chem. Soc. 2014; 136: 7531
  • 29 Segal M, Avinery R, Buzhor M, Shaharabani R, Harnoy AJ, Tirosh E, Beck R, Amir RJ. J. Am. Chem. Soc. 2017; 139: 803
  • 30 Azagarsamy MA, Sokkalingam P, Thayumanavan S. J. Am. Chem. Soc. 2009; 131: 14184