Reactive copolymers based on N-vinyl lactams with pyridyl disulfide side groups via RAFT polymerization and postmodification via thiol-disulfide exchange reaction

Huan Peng, Kristin Rübsam, Xiaobin Huang, Felix Jakob, Marcel Karperien, Ulrich Schwaneberg, Andrij Pich

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)

Abstract

Herein, we report the synthesis of a series of novel pyridyl disulfide (PDS)-functionalized statistical reactive copolymers that enable facile access to complex polymeric architectures through highly selective thiol-disulfide exchange reaction with thiol-containing ligands or proteins. Functional reactive poly(N-vinyl lactam)-based copolymers including poly(N-vinylpyrrolidone-co-pyridyl disulfide ethyl methacrylate) (PVPD), poly(N-vinylpiperidone-co-pyridyl disulfide ethyl methacrylate) (PVPID), and poly(N-vinylcaprolactam-co-pyridyl disulfide ethyl methacrylate) (PVD) with PDS side groups were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization at 60 °C in anisole with methyl 2-(ethoxycarbonothioylthio)propanoate as chain transfer agent. The PDS contents in the synthesized copolymers were varied from 2 to 10 mol % (as confirmed by systematical characterization with FTIR/Raman and 1H NMR spectroscopy) using well-controlled continuous feeding method. The kinetics study suggested that copolymerizations were less favored with the enlargement of the lactam rings, indicated by lower conversions and larger dispersity indexes. The PDS-functionalized reactive polymers were amenable to functionalization with a variety of thiol-containing molecules, including 3-mercaptopropionic acid (3M), 2-phenylethanethiol (2P), methyl 3-mercaptopropionate (M3), 2-mercaptoethanol (2M), 2-aminoethanethiol (2A), poly(ethylene glycol) methyl ether thiol (PEG-SH), and enhanced green fluorescent protein (EGFP) via thiol-disulfide exchange reaction under mild conditions, confirmed by 1H NMR and SDS-PAGE. The conversions in all cases were higher than 95%, displaying that the thiol-disulfide exchange reaction to PDS groups with thiol-containing molecules is highly selective and tolerant to different ligands including amine, carboxyl, hydroxyl, phenyl, PEG and even polypeptides, providing a versatile scaffold for facile conjugation of various biological components. The contact angle measurement results and fluorescence microscopy study indicated that the reactive films based on the PDS-functionalized copolymers allowed facile, direct, and environmental-friendly surface engineering of surfaces from aqueous solution suggesting potential application in surface decoration of tissue-engineering scaffolds and medical implants. The initial cell culture experiments with HeLa cells displayed that the unmodified PVPD film was nontoxic and biocompatible while the film modified with PEG (a type of antifouling polymer) showed diminished cell attachment and growth, indicating that elegant engineering of the film surface can meet demands of particular applications.

Original languageEnglish
Pages (from-to)7141-7154
Number of pages14
JournalMacromolecules
Volume49
Issue number19
DOIs
Publication statusPublished - 11 Oct 2016

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Lactams
Sulfhydryl Compounds
Disulfides
Polyethylene glycols
Ion exchange
Copolymers
Polymerization
Ligands
Proteins
Functional polymers
Molecules
Fluorescence microscopy
Polypeptides
Bioelectric potentials
Physical vapor deposition
Scaffolds (biology)
Angle measurement
Tissue engineering
Cell culture
Scaffolds

Cite this

Peng, Huan ; Rübsam, Kristin ; Huang, Xiaobin ; Jakob, Felix ; Karperien, Marcel ; Schwaneberg, Ulrich ; Pich, Andrij. / Reactive copolymers based on N-vinyl lactams with pyridyl disulfide side groups via RAFT polymerization and postmodification via thiol-disulfide exchange reaction. In: Macromolecules. 2016 ; Vol. 49, No. 19. pp. 7141-7154.
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title = "Reactive copolymers based on N-vinyl lactams with pyridyl disulfide side groups via RAFT polymerization and postmodification via thiol-disulfide exchange reaction",
abstract = "Herein, we report the synthesis of a series of novel pyridyl disulfide (PDS)-functionalized statistical reactive copolymers that enable facile access to complex polymeric architectures through highly selective thiol-disulfide exchange reaction with thiol-containing ligands or proteins. Functional reactive poly(N-vinyl lactam)-based copolymers including poly(N-vinylpyrrolidone-co-pyridyl disulfide ethyl methacrylate) (PVPD), poly(N-vinylpiperidone-co-pyridyl disulfide ethyl methacrylate) (PVPID), and poly(N-vinylcaprolactam-co-pyridyl disulfide ethyl methacrylate) (PVD) with PDS side groups were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization at 60 °C in anisole with methyl 2-(ethoxycarbonothioylthio)propanoate as chain transfer agent. The PDS contents in the synthesized copolymers were varied from 2 to 10 mol {\%} (as confirmed by systematical characterization with FTIR/Raman and 1H NMR spectroscopy) using well-controlled continuous feeding method. The kinetics study suggested that copolymerizations were less favored with the enlargement of the lactam rings, indicated by lower conversions and larger dispersity indexes. The PDS-functionalized reactive polymers were amenable to functionalization with a variety of thiol-containing molecules, including 3-mercaptopropionic acid (3M), 2-phenylethanethiol (2P), methyl 3-mercaptopropionate (M3), 2-mercaptoethanol (2M), 2-aminoethanethiol (2A), poly(ethylene glycol) methyl ether thiol (PEG-SH), and enhanced green fluorescent protein (EGFP) via thiol-disulfide exchange reaction under mild conditions, confirmed by 1H NMR and SDS-PAGE. The conversions in all cases were higher than 95{\%}, displaying that the thiol-disulfide exchange reaction to PDS groups with thiol-containing molecules is highly selective and tolerant to different ligands including amine, carboxyl, hydroxyl, phenyl, PEG and even polypeptides, providing a versatile scaffold for facile conjugation of various biological components. The contact angle measurement results and fluorescence microscopy study indicated that the reactive films based on the PDS-functionalized copolymers allowed facile, direct, and environmental-friendly surface engineering of surfaces from aqueous solution suggesting potential application in surface decoration of tissue-engineering scaffolds and medical implants. The initial cell culture experiments with HeLa cells displayed that the unmodified PVPD film was nontoxic and biocompatible while the film modified with PEG (a type of antifouling polymer) showed diminished cell attachment and growth, indicating that elegant engineering of the film surface can meet demands of particular applications.",
author = "Huan Peng and Kristin R{\"u}bsam and Xiaobin Huang and Felix Jakob and Marcel Karperien and Ulrich Schwaneberg and Andrij Pich",
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Reactive copolymers based on N-vinyl lactams with pyridyl disulfide side groups via RAFT polymerization and postmodification via thiol-disulfide exchange reaction. / Peng, Huan; Rübsam, Kristin; Huang, Xiaobin; Jakob, Felix; Karperien, Marcel; Schwaneberg, Ulrich; Pich, Andrij.

In: Macromolecules, Vol. 49, No. 19, 11.10.2016, p. 7141-7154.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Reactive copolymers based on N-vinyl lactams with pyridyl disulfide side groups via RAFT polymerization and postmodification via thiol-disulfide exchange reaction

AU - Peng, Huan

AU - Rübsam, Kristin

AU - Huang, Xiaobin

AU - Jakob, Felix

AU - Karperien, Marcel

AU - Schwaneberg, Ulrich

AU - Pich, Andrij

PY - 2016/10/11

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N2 - Herein, we report the synthesis of a series of novel pyridyl disulfide (PDS)-functionalized statistical reactive copolymers that enable facile access to complex polymeric architectures through highly selective thiol-disulfide exchange reaction with thiol-containing ligands or proteins. Functional reactive poly(N-vinyl lactam)-based copolymers including poly(N-vinylpyrrolidone-co-pyridyl disulfide ethyl methacrylate) (PVPD), poly(N-vinylpiperidone-co-pyridyl disulfide ethyl methacrylate) (PVPID), and poly(N-vinylcaprolactam-co-pyridyl disulfide ethyl methacrylate) (PVD) with PDS side groups were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization at 60 °C in anisole with methyl 2-(ethoxycarbonothioylthio)propanoate as chain transfer agent. The PDS contents in the synthesized copolymers were varied from 2 to 10 mol % (as confirmed by systematical characterization with FTIR/Raman and 1H NMR spectroscopy) using well-controlled continuous feeding method. The kinetics study suggested that copolymerizations were less favored with the enlargement of the lactam rings, indicated by lower conversions and larger dispersity indexes. The PDS-functionalized reactive polymers were amenable to functionalization with a variety of thiol-containing molecules, including 3-mercaptopropionic acid (3M), 2-phenylethanethiol (2P), methyl 3-mercaptopropionate (M3), 2-mercaptoethanol (2M), 2-aminoethanethiol (2A), poly(ethylene glycol) methyl ether thiol (PEG-SH), and enhanced green fluorescent protein (EGFP) via thiol-disulfide exchange reaction under mild conditions, confirmed by 1H NMR and SDS-PAGE. The conversions in all cases were higher than 95%, displaying that the thiol-disulfide exchange reaction to PDS groups with thiol-containing molecules is highly selective and tolerant to different ligands including amine, carboxyl, hydroxyl, phenyl, PEG and even polypeptides, providing a versatile scaffold for facile conjugation of various biological components. The contact angle measurement results and fluorescence microscopy study indicated that the reactive films based on the PDS-functionalized copolymers allowed facile, direct, and environmental-friendly surface engineering of surfaces from aqueous solution suggesting potential application in surface decoration of tissue-engineering scaffolds and medical implants. The initial cell culture experiments with HeLa cells displayed that the unmodified PVPD film was nontoxic and biocompatible while the film modified with PEG (a type of antifouling polymer) showed diminished cell attachment and growth, indicating that elegant engineering of the film surface can meet demands of particular applications.

AB - Herein, we report the synthesis of a series of novel pyridyl disulfide (PDS)-functionalized statistical reactive copolymers that enable facile access to complex polymeric architectures through highly selective thiol-disulfide exchange reaction with thiol-containing ligands or proteins. Functional reactive poly(N-vinyl lactam)-based copolymers including poly(N-vinylpyrrolidone-co-pyridyl disulfide ethyl methacrylate) (PVPD), poly(N-vinylpiperidone-co-pyridyl disulfide ethyl methacrylate) (PVPID), and poly(N-vinylcaprolactam-co-pyridyl disulfide ethyl methacrylate) (PVD) with PDS side groups were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization at 60 °C in anisole with methyl 2-(ethoxycarbonothioylthio)propanoate as chain transfer agent. The PDS contents in the synthesized copolymers were varied from 2 to 10 mol % (as confirmed by systematical characterization with FTIR/Raman and 1H NMR spectroscopy) using well-controlled continuous feeding method. The kinetics study suggested that copolymerizations were less favored with the enlargement of the lactam rings, indicated by lower conversions and larger dispersity indexes. The PDS-functionalized reactive polymers were amenable to functionalization with a variety of thiol-containing molecules, including 3-mercaptopropionic acid (3M), 2-phenylethanethiol (2P), methyl 3-mercaptopropionate (M3), 2-mercaptoethanol (2M), 2-aminoethanethiol (2A), poly(ethylene glycol) methyl ether thiol (PEG-SH), and enhanced green fluorescent protein (EGFP) via thiol-disulfide exchange reaction under mild conditions, confirmed by 1H NMR and SDS-PAGE. The conversions in all cases were higher than 95%, displaying that the thiol-disulfide exchange reaction to PDS groups with thiol-containing molecules is highly selective and tolerant to different ligands including amine, carboxyl, hydroxyl, phenyl, PEG and even polypeptides, providing a versatile scaffold for facile conjugation of various biological components. The contact angle measurement results and fluorescence microscopy study indicated that the reactive films based on the PDS-functionalized copolymers allowed facile, direct, and environmental-friendly surface engineering of surfaces from aqueous solution suggesting potential application in surface decoration of tissue-engineering scaffolds and medical implants. The initial cell culture experiments with HeLa cells displayed that the unmodified PVPD film was nontoxic and biocompatible while the film modified with PEG (a type of antifouling polymer) showed diminished cell attachment and growth, indicating that elegant engineering of the film surface can meet demands of particular applications.

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U2 - 10.1021/acs.macromol.6b01210

DO - 10.1021/acs.macromol.6b01210

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EP - 7154

JO - Macromolecules

JF - Macromolecules

SN - 0024-9297

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ER -