Solid-state Mechanochemical ω-functionalization of Poly(ethylene Glycol)

Overview

Journal Beilstein J Org Chem

Specialty Chemistry

Date 2017 Oct 25

PMID 29062415

Citations 6

Authors

Michael Y Malca

Pierre-Olivier Ferko

Tomislav Friscic

Audrey Moores

Affiliations

Soon will be listed here.

Abstract

Poly(ethylene glycol) (PEG) is a linear polymer with a wide range of applications in chemical manufacturing, drug development and nanotechnology. PEG derivatives are being increasingly used to covalently modify small molecule and peptide drugs, as well as bioactive nanomaterials in order to improve solubility in biological serum, reduce immunogenicity, and enhance pharmacokinetic profiles. Herein we present the development of mechanochemical procedures for PEG functionalization without the need for bulk solvents, offering a cleaner and more sustainable alternative to existing solution-based PEG procedures. The herein presented mechanochemical procedures enable rapid and solvent-free derivatization of PEG with tosyl, bromide, thiol, carboxylic acid or amine functionalities in good to quantitative yields and with no polymer chain oligomerization, proving the versatility of the method.

Citing Articles

Mechanochemically Synthesized PEG-OTs as a Green Corrosion Inhibitor.

Wang Q, Sang Y, Yang J, Liu H Polymers (Basel). 2025; 17(3).

PMID: 39940624 PMC: 11820882. DOI: 10.3390/polym17030422.

Liquid-assisted grinding enables a direct mechanochemical functionalization of polystyrene waste.

Skala M, Zeitler S, Golder M Chem Sci. 2024; 15(28):10900-10907.

PMID: 39027266 PMC: 11253180. DOI: 10.1039/d4sc03362k.

Semi-Telechelic Polymers from Mechanochemical C─C Bond Activation.

Schwarz R, Diesendruck C Adv Sci (Weinh). 2023; 10(34):e2304571.

PMID: 37870199 PMC: 10700232. DOI: 10.1002/advs.202304571.

TM-Free and TM-Catalyzed Mechanosynthesis of Functional Polymers.

Al-Ithawi W, Khasanov A, Kovalev I, Nikonov I, Platonov V, Kopchuk D Polymers (Basel). 2023; 15(8).

PMID: 37112002 PMC: 10142995. DOI: 10.3390/polym15081853.

The mechanochemical synthesis of polymers.

Krusenbaum A, Gratz S, Tigineh G, Borchardt L, Kim J Chem Soc Rev. 2022; 51(7):2873-2905.

PMID: 35302564 PMC: 8978534. DOI: 10.1039/d1cs01093j.

References

Dunn P . The importance of green chemistry in process research and development. Chem Soc Rev. 2011; 41(4):1452-61. DOI: 10.1039/c1cs15041c. View

Abuchowski A, McCoy J, Palczuk N, van Es T, DAVIS F . Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. J Biol Chem. 1977; 252(11):3582-6. View

Ohn N, Shin J, Kim S, Kim J . Mechanochemical Ring-Opening Polymerization of Lactide: Liquid-Assisted Grinding for the Green Synthesis of Poly(lactic acid) with High Molecular Weight. ChemSusChem. 2017; 10(18):3529-3533. DOI: 10.1002/cssc.201700873. View

Klibanov A, Maruyama K, Beckerleg A, Torchilin V, Huang L . Activity of amphipathic poly(ethylene glycol) 5000 to prolong the circulation time of liposomes depends on the liposome size and is unfavorable for immunoliposome binding to target. Biochim Biophys Acta. 1991; 1062(2):142-8. DOI: 10.1016/0005-2736(91)90385-l. View

Karki S, Friscic T, Jones W, Motherwell W . Screening for pharmaceutical cocrystal hydrates via neat and liquid-assisted grinding. Mol Pharm. 2007; 4(3):347-54. DOI: 10.1021/mp0700054. View

Gref , Luck , Quellec , MARCHAND , Dellacherie , HARNISCH . 'Stealth' corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surf B Biointerfaces. 2000; 18(3-4):301-313. DOI: 10.1016/s0927-7765(99)00156-3. View

Gombotz W, Wang G, Horbett T, Hoffman A . Protein adsorption to poly(ethylene oxide) surfaces. J Biomed Mater Res. 1991; 25(12):1547-62. DOI: 10.1002/jbm.820251211. View

Gentili D, Ori G, Franchini M . Double phase transfer of gold nanorods for surface functionalization and entrapment into PEG-based nanocarriers. Chem Commun (Camb). 2009; (39):5874-6. DOI: 10.1039/b911582j. View

Loiseau F, Hii K, Hill A . Multigram synthesis of well-defined extended bifunctional polyethylene glycol (PEG) chains. J Org Chem. 2004; 69(3):639-47. DOI: 10.1021/jo035042v. View

10.

Klok H, Genzer J . Expanding the Polymer Mechanochemistry Toolbox through Surface-Initiated Polymerization. ACS Macro Lett. 2022; 4(6):636-639. DOI: 10.1021/acsmacrolett.5b00295. View

11.

Tan D, Loots L, Friscic T . Towards medicinal mechanochemistry: evolution of milling from pharmaceutical solid form screening to the synthesis of active pharmaceutical ingredients (APIs). Chem Commun (Camb). 2016; 52(50):7760-81. DOI: 10.1039/c6cc02015a. View

12.

Michalchuk A, Tumanov I, Konar S, Kimber S, Pulham C, Boldyreva E . Challenges of Mechanochemistry: Is In Situ Real-Time Quantitative Phase Analysis Always Reliable? A Case Study of Organic Salt Formation. Adv Sci (Weinh). 2017; 4(9):1700132. PMC: 5604370. DOI: 10.1002/advs.201700132. View

13.

Abuchowski A, van Es T, Palczuk N, DAVIS F . Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. J Biol Chem. 1977; 252(11):3578-81. View

14.

Smolensky E, Park H, Berquo T, Pierre V . Surface functionalization of magnetic iron oxide nanoparticles for MRI applications - effect of anchoring group and ligand exchange protocol. Contrast Media Mol Imaging. 2011; 6(4):189-99. PMC: 3123420. DOI: 10.1002/cmmi.417. View

15.

Veronese F, Pasut G . PEGylation, successful approach to drug delivery. Drug Discov Today. 2005; 10(21):1451-8. DOI: 10.1016/S1359-6446(05)03575-0. View

16.

Hrkach J, Peracchia M, Domb A, Lotan N, Langer R . Nanotechnology for biomaterials engineering: structural characterization of amphiphilic polymeric nanoparticles by 1H NMR spectroscopy. Biomaterials. 1997; 18(1):27-30. DOI: 10.1016/s0142-9612(96)00077-4. View

17.

Moghimi S, Hunter A, Murray J . Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev. 2001; 53(2):283-318. View

18.

Gref R, Domb A, Quellec P, Blunk T, Muller R, Verbavatz J . The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres. Adv Drug Deliv Rev. 2014; 16(2-3):215-233. PMC: 4144462. DOI: 10.1016/0169-409X(95)00026-4. View

19.

Jakobs R, Ma S, Sijbesma R . Mechanocatalytic Polymerization and Cross-Linking in a Polymeric Matrix. ACS Macro Lett. 2022; 2(7):613-616. DOI: 10.1021/mz400201c. View

20.

Goswami L, Houston Z, Sarma S, Jalisatgi S, Hawthorne M . Efficient synthesis of diverse heterobifunctionalized clickable oligo(ethylene glycol) linkers: potential applications in bioconjugation and targeted drug delivery. Org Biomol Chem. 2013; 11(7):1116-26. PMC: 3562135. DOI: 10.1039/c2ob26968f. View