Tugce Gevrek - Academia.edu (original) (raw)

Papers by Tugce Gevrek

RSC Adv., 2014

Fabrication of well-defined chemically cross-linked poly(ethylene glycol) (PEG)-based hydrogels u... more Fabrication of well-defined chemically cross-linked poly(ethylene glycol) (PEG)-based hydrogels using the thiol–maleimide addition reaction is reported.

Bioconjugate Chemistry, 2014

Poly(ethylene glycol)-based hydrogels containing thiol-reactive maleimide functional groups is pr... more Poly(ethylene glycol)-based hydrogels containing thiol-reactive maleimide functional groups is prepared via a Diels-Alder/retro Diels-Alder reaction sequence using a masked maleimide monomer. Bulk and micropatterned hydrogels containing varying amounts of the thiol-reactive maleimide functional group are fabricated at ambient temperature. During the fabrication, the reactive maleimide functional group in the monomer is masked with a furan moiety and then unmasked to its reactive form via the retro-Diels-Alder reaction. The reactive maleimide groups embedded within the hydrogel are amenable to facile and efficient functionalization with thiol-containing molecules such as fluorescent dyes. Furthermore, these hydrogels are readily biotinylated using the nucleophilic thiol-ene conjugation to enable immobilization of streptavidin onto the hydrogel patterns to achieve facile bioimmobilization. Notably, the extent of functionalization of these hydrogels can be easily tailored by varying the amount of reactive handles incorporated during their fabrication.

ACS applied materials & interfaces, Jan 22, 2016

Development of efficient and rapid protocols for diversification of functional magnetic nanoparti... more Development of efficient and rapid protocols for diversification of functional magnetic nanoparticles (MNPs) would enable identification of promising candidates using high-throughput protocols for applications such as diagnostics and cure through early detection and localized delivery. Polymer brush coated magnetic nanoparticles find use in many such applications. A protocol that allows modular diversification of a pool of parent polymer coated nanoparticles will lead to a library of functional materials with improved uniformity. In the present study, polymer brush coated parent magnetic nanoparticles obtained using reversible addition-fragmentation chain transfer (RAFT) polymerization are modified to obtain nanoparticles with different "clickable" groups. In this design, trithiocarbonate group terminated polymer brushes are "grafted from" MNPs using a catechol group bearing initiator. A postpolymerization radical exchange reaction allows installation of "cl...

Encyclopedia of Biomedical Polymers and Polymeric Biomaterials, 2016

Journal of Polymer Science Part A: Polymer Chemistry, 2015

ACS Applied Materials & Interfaces, 2015

We demonstrate a new approach to grafting thiol-reactive nanopatterned copolymer-brush structures... more We demonstrate a new approach to grafting thiol-reactive nanopatterned copolymer-brush structures on polymeric substrates by means of extreme ultraviolet (EUV) interference lithography. The copolymer brushes were designed to contain maleimide functional groups as thiol-reactive centers. Fluoropolymer films were exposed to EUV radiation at the X-ray interference lithography beamline (XIL-II) at the Swiss Light Source, in order to create radical patterns on their surfaces. The radicals served as initiators for the copolymerization of thiol−ene "clickable" brushes, composed of a furan-protected maleimide monomer (FuMaMA) and different methacrylates, namely, methyl methacrylate (MMA), ethylene glycol methyl ether methacrylate (EGMA), or poly(ethylene glycol) methyl ether methacrylate (PEGMA). Copolymerization with ethylene-glycolcontaining monomers provides antibiofouling properties to these surfaces. The number of reactive centers on the grafted brush structures can be tailored by varying the monomer ratios in the feed. Grafted copolymers were characterized by using attenuated total reflection infrared (ATR-IR) spectroscopy. The reactive maleimide methacrylate (MaMA) units were utilized to conjugate thiol-containing moieties using the nucleophilic Michael-addition reaction, which proceeds at room temperature without the need for any metal-based catalyst. Using this approach, a variety of functionalities was introduced to yield polyelectrolytes, as well as fluorescent and light-responsive polymer-brush structures. Functionalization of the brush structures was demonstrated via ATR-IR and UV−vis spectroscopy and fluorescence microscopy, and was also indicated by a color switch. Furthermore, grafted surfaces were generated via plasma activation, showing a strongly increased wettability for polyelectrolytes and a reversible switch in static water contact angle (CA) of up to 18°for P(EGMA-co-MaMA-SP) brushes, upon exposure to alternating visible and UV-light irradiation.

Bioconjugate Chemistry, 2015

Design and synthesis of novel water-soluble polymers bearing reactive side chains are actively pu... more Design and synthesis of novel water-soluble polymers bearing reactive side chains are actively pursued due to their increasing demand in areas such as bioconjugation and drug delivery. This study reports the fabrication of poly(ethylene glycol) methacrylate based thiol-reactive water-soluble polymeric supports that can serve as targeted drug delivery vehicles. Thiol-reactive maleimide units were incorporated into polymers as side chains by use of a furan-protected maleimide containing monomer. Atom transfer radical polymerization (ATRP) was employed to obtain a family of well-defined copolymers with narrow molecular weight distributions. After the polymerization, the maleimide groups were activated to their reactive form, ready for conjugation with thiol-containing molecules. Efficient functionalization of the maleimide moieties was demonstrated by conjugation of a tripeptide glutathione under mild and reagent-free aqueous conditions. Additionally, hydrophobic thiol-containing dye (Bodipy-SH) and a cyclic peptide-based targeting group (cRGDfC) were sequentially appended onto the maleimide bearing polymers to demonstrate their efficient multifunctionalization. The conjugates were utilized for in vitro experiments over both cancerous and healthy breast cell lines. Obtained results demonstrate that the conjugates were nontoxic, and displayed efficient cellular uptake. The presence of the peptide based targeting group had a clear effect on increasing the uptake of the dye-conjugated polymers into cells when compared to the construct devoid of the peptide. Overall, the facile synthesis and highly efficient multifunctionalization of maleimide-containing thiol-reactive copolymers offer a novel and attractive class of polyethylene glycol-based water-soluble supports for drug delivery.

RSC Adv., 2014

ABSTRACT Fabrication of well-defined chemically cross-linked poly(ethylene glycol) (PEG) based hy... more ABSTRACT Fabrication of well-defined chemically cross-linked poly(ethylene glycol) (PEG) based hydrogels using the thiol-maleimide addition reaction is reported. Maleimide containing homobifunctional PEGs with different molecular weights were synthesized and reacted with thiol functionalized β-cyclodextrin (β-CD(SH)7) to yield hydrogels with high efficiency under mild conditions. The resulting hydrogels were characterized by their water uptake properties, surface morphologies and rheological behaviours. In order to introduce reactive functional groups into the hydrogels, the stoichiometry of the thiol and maleimide groups was varied to obtain either thiol or maleimide functionalized hydrogels. Efficient functionalization of these reactive hydrogels in a tailored fashion was demonstrated through conjugation of appropriately functionalized fluorescent dye molecules.

Macromolecules, 2014

ABSTRACT In this study, we report on the synthesis of novel thiol-reactive polymers containing a ... more ABSTRACT In this study, we report on the synthesis of novel thiol-reactive polymers containing a catechol moiety at their chain ends and demonstrate their application toward surface modification of magnetic nanoparticles. Poly(ethylene glycol) methyl ether acrylate (PEGMEA) based hydrophilic polymers incorporating maleimide group containing side-chains were synthesized using reversible addition fragmentation chain transfer (RAFT) polymerization. A novel furan-protected maleimide-containing acrylate monomer was synthesized and copolymerized with hydrophilic monomers in the presence of a catechol moiety containing chain transfer unit. Removal of the furan protecting group after polymerization yields thiol-reactive polymers possessing an intact catechol unit at their chain-end for anchoring onto various surfaces. Polymers with varying composition of the masked maleimide monomer were obtained with narrow molecular weight distributions as inferred from size exclusion chromatography. Obtained polymers were characterized using proton nuclear magnetic resonance ((HNMR)-H-1), infrared (IR) spectroscopy, and electrochemistry to establish their chemical composition. Oleic acid coated organo-dispersible magnetic nanoparticles were modified with the hydrophilic catechol terminated polymers to obtain water dispersible polymer-coated magnetic nanoparticles. The reactive maleimide units on the polymer-coated nanoparticles were utilized to conjugate thiol-containing hydrophobic dye using the nucleophilic Michael addition reaction to obtain water dispersible magnetic and fluorescent nanoparticles. Alternatively, it was demonstrated that radical thiol-ene reaction can also be utilized to functionalize nanoparticles coated with polymers where the maleimide group is in masked as a furan-cycloadduct. Efficient anchoring of the polymer onto nanoparticle surfaces and their subsequent functionalization was verified using various techniques such as infrared spectroscopy (IR), thermogravimetric analysis (TGA), and phase transfer studies, whereas the subsequent functionalization was evident from the organic to aqueous phase transfer of the hydrophobic fluorescent dye.

Concepts, Guidelines, and Applications, 2012

ABSTRACT This chapter contains sections titled: Introduction Maleimide Functional Group Containin... more ABSTRACT This chapter contains sections titled: Introduction Maleimide Functional Group Containing Polymeric Materials The Diels-Alder/Retro Diels-Alder Cycloaddition-Cycloreversion Reactions Application of Diels-Alder/Retro Diels-Alder Reaction to Synthesize Maleimide-Containing Polymers Conclusions References

Bioconjugate Chemistry, 2014

Poly(ethylene glycol)-based hydrogels containing thiol-reactive maleimide functional groups is pr... more Poly(ethylene glycol)-based hydrogels containing thiol-reactive maleimide functional groups is prepared via a Diels-Alder/retro Diels-Alder reaction sequence using a masked maleimide monomer. Bulk and micropatterned hydrogels containing varying amounts of the thiol-reactive maleimide functional group are fabricated at ambient temperature. During the fabrication, the reactive maleimide functional group in the monomer is masked with a furan moiety and then unmasked to its reactive form via the retro-Diels-Alder reaction. The reactive maleimide groups embedded within the hydrogel are amenable to facile and efficient functionalization with thiol-containing molecules such as fluorescent dyes. Furthermore, these hydrogels are readily biotinylated using the nucleophilic thiol-ene conjugation to enable immobilization of streptavidin onto the hydrogel patterns to achieve facile bioimmobilization. Notably, the extent of functionalization of these hydrogels can be easily tailored by varying the amount of reactive handles incorporated during their fabrication.

Macromolecules, 2014

ABSTRACT Polymer brushes that present side chain functional reactive groups are attractive platfo... more ABSTRACT Polymer brushes that present side chain functional reactive groups are attractive platforms for the development of functional surface coatings. From the wide spectrum of possible postpolymerization modification reactions, thiol-based conjugation chemistries are particularly appealing as they can be performed reagent-less under mild conditions and can allow the site-selective conjugation of biomolecules. This manuscript reports a direct approach for the preparation of maleimide-functionalized polymer brushes. These brushes were obtained by surface-initiated atom transfer radical copolymerization of poly(ethylene glycol) methacrylate and a furan-protected, maleimide containing monomer, followed by a thermally induced retro Diels–Alder reaction to unmask the maleimide groups. The feasibility of these brushes to serve as a platform for postpolymerization functionalization was explored in a series of model experiments using a variety of low molecular weight thiols, including a fluorescent dye and a thiol-modified biotin-derivative. The biotinylated brushes were subsequently used for the immobilization of streptavidin-coated quantum-dots. The copolymer brushes presented in this manuscript are attractive since they combine the nonbiofouling properties of the poly(ethylene glycol) methacrylate monomer with the chemoselective reactivity of the maleimide containing monomer, which makes them an attractive platform, e.g., for the immobilization of biomolecules.

Biomaterials Science, 2013

ABSTRACT In this study, we report a facile fabrication of poly(ethylene glycol) (PEG) based bulk ... more ABSTRACT In this study, we report a facile fabrication of poly(ethylene glycol) (PEG) based bulk and micro-patterned hydrogels that are amenable to functionalization with thiol-bearing molecules using the metal-free radical 'thiol-ene' click reaction. The hydrogels were synthesized using photopolymerization of commercially available monomers, namely allyl methacrylate and PEG-methacrylate in the presence of a PEG-dimethacrylate based crosslinker. Swelling behaviour of these hydrogels could be tailored by varying the amount of the hydrophilic monomer in the feed as well as varying the length of the PEG-chain in the methacrylate monomer. Importantly, the extent of functionalization of these hydrogels could be readily tuned by varying the amount of the reactive allyl methacrylate monomer. Analysis of nitrogen content in the hydrogels after conjugation of cysteamine demonstrated that the amount of cysteamine incorporation was in correlation with the amount of allyl groups in the hydrogels. Three-dimensional hydrogel patterns were fabricated using micromolding in capillaries. Tuneable conjugation of a thiol-containing dye molecule and a ligand-mediated immobilization of streptavidin onto these hydrogel patterns were realized. It was found that the swellability of the hydrogel patterns control the diffusion of streptavidin into the interior of the hydrogel matrix. These bio-inert hydrogels could be appended with peptides to promote cellular adhesion. Furthermore, it was demonstrated that the photochemical thiol-ene based method of conjugation enables localized attachment of thiol-containing molecules within these reactive hydrogels.

Macromolecular Chemistry and Physics, 2012

The fabrication of polymeric thin fi lms amenable to facile functionalization by reactive μ CP vi... more The fabrication of polymeric thin fi lms amenable to facile functionalization by reactive μ CP via a Diels-Alder reaction is described. Precursor copolymers containing FuMA, PEGMA, and TMSMA are prepared using ATRP. Surface-tethered thin fi lms of these polymers are obtained on oxidized silicon and glass substrates and patterned with maleimide-appended dye molecules by simple μ CP to demonstrate effi cient functionalization via Diels-Alder reaction. Printing of biotin-based ligands is carried out to demonstrate directed immobilization of the enzyme streptavidin. Due to the thermoreversible nature of the Diels-Alder reaction, these surfaces can be used as rewritable platforms. This is demonstrated by sequential write-erase-rewrite protocols via μ CP of a maleimide-containing fl uorescent dye.

European Polymer Journal, 2015

ABSTRACT A simple and efficient methodology for the fabrication of poly(ethylene glycol) (PEG) ba... more ABSTRACT A simple and efficient methodology for the fabrication of poly(ethylene glycol) (PEG) based chemically cross-linked hydrogels containing discrete β-cyclodextrin (β-CD) units is outlined. Hydrogels were synthesized using homo-bifunctional linear PEGs containing allyl groups and heptavalent thiol-functionalized β-CD as crosslinkers via the radical-induced thiol-ene click chemistry. Various hydrogels comprising of different molecular weight PEGs and varying crosslinker feed were investigated in terms of their physical properties such as water uptake capacity, surface morphology and rheological behaviors. Uptake and controlled release of a poorly water-soluble drug, namely, puerarin was demonstrated using these hydrogels. The drug uptake and release was found to be depended on the hydrogels composition. Benefiting from the photochemically induced gel formation, the methodology was extended to fabricate hydrogel micro-structures on solid substrates.

RSC Adv., 2014

Fabrication of well-defined chemically cross-linked poly(ethylene glycol) (PEG)-based hydrogels u... more Fabrication of well-defined chemically cross-linked poly(ethylene glycol) (PEG)-based hydrogels using the thiol–maleimide addition reaction is reported.

Bioconjugate Chemistry, 2014

Poly(ethylene glycol)-based hydrogels containing thiol-reactive maleimide functional groups is pr... more Poly(ethylene glycol)-based hydrogels containing thiol-reactive maleimide functional groups is prepared via a Diels-Alder/retro Diels-Alder reaction sequence using a masked maleimide monomer. Bulk and micropatterned hydrogels containing varying amounts of the thiol-reactive maleimide functional group are fabricated at ambient temperature. During the fabrication, the reactive maleimide functional group in the monomer is masked with a furan moiety and then unmasked to its reactive form via the retro-Diels-Alder reaction. The reactive maleimide groups embedded within the hydrogel are amenable to facile and efficient functionalization with thiol-containing molecules such as fluorescent dyes. Furthermore, these hydrogels are readily biotinylated using the nucleophilic thiol-ene conjugation to enable immobilization of streptavidin onto the hydrogel patterns to achieve facile bioimmobilization. Notably, the extent of functionalization of these hydrogels can be easily tailored by varying the amount of reactive handles incorporated during their fabrication.

ACS applied materials & interfaces, Jan 22, 2016

Development of efficient and rapid protocols for diversification of functional magnetic nanoparti... more Development of efficient and rapid protocols for diversification of functional magnetic nanoparticles (MNPs) would enable identification of promising candidates using high-throughput protocols for applications such as diagnostics and cure through early detection and localized delivery. Polymer brush coated magnetic nanoparticles find use in many such applications. A protocol that allows modular diversification of a pool of parent polymer coated nanoparticles will lead to a library of functional materials with improved uniformity. In the present study, polymer brush coated parent magnetic nanoparticles obtained using reversible addition-fragmentation chain transfer (RAFT) polymerization are modified to obtain nanoparticles with different "clickable" groups. In this design, trithiocarbonate group terminated polymer brushes are "grafted from" MNPs using a catechol group bearing initiator. A postpolymerization radical exchange reaction allows installation of "cl...

Encyclopedia of Biomedical Polymers and Polymeric Biomaterials, 2016

Journal of Polymer Science Part A: Polymer Chemistry, 2015

ACS Applied Materials & Interfaces, 2015

We demonstrate a new approach to grafting thiol-reactive nanopatterned copolymer-brush structures... more We demonstrate a new approach to grafting thiol-reactive nanopatterned copolymer-brush structures on polymeric substrates by means of extreme ultraviolet (EUV) interference lithography. The copolymer brushes were designed to contain maleimide functional groups as thiol-reactive centers. Fluoropolymer films were exposed to EUV radiation at the X-ray interference lithography beamline (XIL-II) at the Swiss Light Source, in order to create radical patterns on their surfaces. The radicals served as initiators for the copolymerization of thiol−ene "clickable" brushes, composed of a furan-protected maleimide monomer (FuMaMA) and different methacrylates, namely, methyl methacrylate (MMA), ethylene glycol methyl ether methacrylate (EGMA), or poly(ethylene glycol) methyl ether methacrylate (PEGMA). Copolymerization with ethylene-glycolcontaining monomers provides antibiofouling properties to these surfaces. The number of reactive centers on the grafted brush structures can be tailored by varying the monomer ratios in the feed. Grafted copolymers were characterized by using attenuated total reflection infrared (ATR-IR) spectroscopy. The reactive maleimide methacrylate (MaMA) units were utilized to conjugate thiol-containing moieties using the nucleophilic Michael-addition reaction, which proceeds at room temperature without the need for any metal-based catalyst. Using this approach, a variety of functionalities was introduced to yield polyelectrolytes, as well as fluorescent and light-responsive polymer-brush structures. Functionalization of the brush structures was demonstrated via ATR-IR and UV−vis spectroscopy and fluorescence microscopy, and was also indicated by a color switch. Furthermore, grafted surfaces were generated via plasma activation, showing a strongly increased wettability for polyelectrolytes and a reversible switch in static water contact angle (CA) of up to 18°for P(EGMA-co-MaMA-SP) brushes, upon exposure to alternating visible and UV-light irradiation.

Bioconjugate Chemistry, 2015

Design and synthesis of novel water-soluble polymers bearing reactive side chains are actively pu... more Design and synthesis of novel water-soluble polymers bearing reactive side chains are actively pursued due to their increasing demand in areas such as bioconjugation and drug delivery. This study reports the fabrication of poly(ethylene glycol) methacrylate based thiol-reactive water-soluble polymeric supports that can serve as targeted drug delivery vehicles. Thiol-reactive maleimide units were incorporated into polymers as side chains by use of a furan-protected maleimide containing monomer. Atom transfer radical polymerization (ATRP) was employed to obtain a family of well-defined copolymers with narrow molecular weight distributions. After the polymerization, the maleimide groups were activated to their reactive form, ready for conjugation with thiol-containing molecules. Efficient functionalization of the maleimide moieties was demonstrated by conjugation of a tripeptide glutathione under mild and reagent-free aqueous conditions. Additionally, hydrophobic thiol-containing dye (Bodipy-SH) and a cyclic peptide-based targeting group (cRGDfC) were sequentially appended onto the maleimide bearing polymers to demonstrate their efficient multifunctionalization. The conjugates were utilized for in vitro experiments over both cancerous and healthy breast cell lines. Obtained results demonstrate that the conjugates were nontoxic, and displayed efficient cellular uptake. The presence of the peptide based targeting group had a clear effect on increasing the uptake of the dye-conjugated polymers into cells when compared to the construct devoid of the peptide. Overall, the facile synthesis and highly efficient multifunctionalization of maleimide-containing thiol-reactive copolymers offer a novel and attractive class of polyethylene glycol-based water-soluble supports for drug delivery.

RSC Adv., 2014

ABSTRACT Fabrication of well-defined chemically cross-linked poly(ethylene glycol) (PEG) based hy... more ABSTRACT Fabrication of well-defined chemically cross-linked poly(ethylene glycol) (PEG) based hydrogels using the thiol-maleimide addition reaction is reported. Maleimide containing homobifunctional PEGs with different molecular weights were synthesized and reacted with thiol functionalized β-cyclodextrin (β-CD(SH)7) to yield hydrogels with high efficiency under mild conditions. The resulting hydrogels were characterized by their water uptake properties, surface morphologies and rheological behaviours. In order to introduce reactive functional groups into the hydrogels, the stoichiometry of the thiol and maleimide groups was varied to obtain either thiol or maleimide functionalized hydrogels. Efficient functionalization of these reactive hydrogels in a tailored fashion was demonstrated through conjugation of appropriately functionalized fluorescent dye molecules.

Macromolecules, 2014

ABSTRACT In this study, we report on the synthesis of novel thiol-reactive polymers containing a ... more ABSTRACT In this study, we report on the synthesis of novel thiol-reactive polymers containing a catechol moiety at their chain ends and demonstrate their application toward surface modification of magnetic nanoparticles. Poly(ethylene glycol) methyl ether acrylate (PEGMEA) based hydrophilic polymers incorporating maleimide group containing side-chains were synthesized using reversible addition fragmentation chain transfer (RAFT) polymerization. A novel furan-protected maleimide-containing acrylate monomer was synthesized and copolymerized with hydrophilic monomers in the presence of a catechol moiety containing chain transfer unit. Removal of the furan protecting group after polymerization yields thiol-reactive polymers possessing an intact catechol unit at their chain-end for anchoring onto various surfaces. Polymers with varying composition of the masked maleimide monomer were obtained with narrow molecular weight distributions as inferred from size exclusion chromatography. Obtained polymers were characterized using proton nuclear magnetic resonance ((HNMR)-H-1), infrared (IR) spectroscopy, and electrochemistry to establish their chemical composition. Oleic acid coated organo-dispersible magnetic nanoparticles were modified with the hydrophilic catechol terminated polymers to obtain water dispersible polymer-coated magnetic nanoparticles. The reactive maleimide units on the polymer-coated nanoparticles were utilized to conjugate thiol-containing hydrophobic dye using the nucleophilic Michael addition reaction to obtain water dispersible magnetic and fluorescent nanoparticles. Alternatively, it was demonstrated that radical thiol-ene reaction can also be utilized to functionalize nanoparticles coated with polymers where the maleimide group is in masked as a furan-cycloadduct. Efficient anchoring of the polymer onto nanoparticle surfaces and their subsequent functionalization was verified using various techniques such as infrared spectroscopy (IR), thermogravimetric analysis (TGA), and phase transfer studies, whereas the subsequent functionalization was evident from the organic to aqueous phase transfer of the hydrophobic fluorescent dye.

Concepts, Guidelines, and Applications, 2012

ABSTRACT This chapter contains sections titled: Introduction Maleimide Functional Group Containin... more ABSTRACT This chapter contains sections titled: Introduction Maleimide Functional Group Containing Polymeric Materials The Diels-Alder/Retro Diels-Alder Cycloaddition-Cycloreversion Reactions Application of Diels-Alder/Retro Diels-Alder Reaction to Synthesize Maleimide-Containing Polymers Conclusions References

Bioconjugate Chemistry, 2014

Poly(ethylene glycol)-based hydrogels containing thiol-reactive maleimide functional groups is pr... more Poly(ethylene glycol)-based hydrogels containing thiol-reactive maleimide functional groups is prepared via a Diels-Alder/retro Diels-Alder reaction sequence using a masked maleimide monomer. Bulk and micropatterned hydrogels containing varying amounts of the thiol-reactive maleimide functional group are fabricated at ambient temperature. During the fabrication, the reactive maleimide functional group in the monomer is masked with a furan moiety and then unmasked to its reactive form via the retro-Diels-Alder reaction. The reactive maleimide groups embedded within the hydrogel are amenable to facile and efficient functionalization with thiol-containing molecules such as fluorescent dyes. Furthermore, these hydrogels are readily biotinylated using the nucleophilic thiol-ene conjugation to enable immobilization of streptavidin onto the hydrogel patterns to achieve facile bioimmobilization. Notably, the extent of functionalization of these hydrogels can be easily tailored by varying the amount of reactive handles incorporated during their fabrication.

Macromolecules, 2014

ABSTRACT Polymer brushes that present side chain functional reactive groups are attractive platfo... more ABSTRACT Polymer brushes that present side chain functional reactive groups are attractive platforms for the development of functional surface coatings. From the wide spectrum of possible postpolymerization modification reactions, thiol-based conjugation chemistries are particularly appealing as they can be performed reagent-less under mild conditions and can allow the site-selective conjugation of biomolecules. This manuscript reports a direct approach for the preparation of maleimide-functionalized polymer brushes. These brushes were obtained by surface-initiated atom transfer radical copolymerization of poly(ethylene glycol) methacrylate and a furan-protected, maleimide containing monomer, followed by a thermally induced retro Diels–Alder reaction to unmask the maleimide groups. The feasibility of these brushes to serve as a platform for postpolymerization functionalization was explored in a series of model experiments using a variety of low molecular weight thiols, including a fluorescent dye and a thiol-modified biotin-derivative. The biotinylated brushes were subsequently used for the immobilization of streptavidin-coated quantum-dots. The copolymer brushes presented in this manuscript are attractive since they combine the nonbiofouling properties of the poly(ethylene glycol) methacrylate monomer with the chemoselective reactivity of the maleimide containing monomer, which makes them an attractive platform, e.g., for the immobilization of biomolecules.

Biomaterials Science, 2013

ABSTRACT In this study, we report a facile fabrication of poly(ethylene glycol) (PEG) based bulk ... more ABSTRACT In this study, we report a facile fabrication of poly(ethylene glycol) (PEG) based bulk and micro-patterned hydrogels that are amenable to functionalization with thiol-bearing molecules using the metal-free radical 'thiol-ene' click reaction. The hydrogels were synthesized using photopolymerization of commercially available monomers, namely allyl methacrylate and PEG-methacrylate in the presence of a PEG-dimethacrylate based crosslinker. Swelling behaviour of these hydrogels could be tailored by varying the amount of the hydrophilic monomer in the feed as well as varying the length of the PEG-chain in the methacrylate monomer. Importantly, the extent of functionalization of these hydrogels could be readily tuned by varying the amount of the reactive allyl methacrylate monomer. Analysis of nitrogen content in the hydrogels after conjugation of cysteamine demonstrated that the amount of cysteamine incorporation was in correlation with the amount of allyl groups in the hydrogels. Three-dimensional hydrogel patterns were fabricated using micromolding in capillaries. Tuneable conjugation of a thiol-containing dye molecule and a ligand-mediated immobilization of streptavidin onto these hydrogel patterns were realized. It was found that the swellability of the hydrogel patterns control the diffusion of streptavidin into the interior of the hydrogel matrix. These bio-inert hydrogels could be appended with peptides to promote cellular adhesion. Furthermore, it was demonstrated that the photochemical thiol-ene based method of conjugation enables localized attachment of thiol-containing molecules within these reactive hydrogels.

Macromolecular Chemistry and Physics, 2012

The fabrication of polymeric thin fi lms amenable to facile functionalization by reactive μ CP vi... more The fabrication of polymeric thin fi lms amenable to facile functionalization by reactive μ CP via a Diels-Alder reaction is described. Precursor copolymers containing FuMA, PEGMA, and TMSMA are prepared using ATRP. Surface-tethered thin fi lms of these polymers are obtained on oxidized silicon and glass substrates and patterned with maleimide-appended dye molecules by simple μ CP to demonstrate effi cient functionalization via Diels-Alder reaction. Printing of biotin-based ligands is carried out to demonstrate directed immobilization of the enzyme streptavidin. Due to the thermoreversible nature of the Diels-Alder reaction, these surfaces can be used as rewritable platforms. This is demonstrated by sequential write-erase-rewrite protocols via μ CP of a maleimide-containing fl uorescent dye.

European Polymer Journal, 2015

ABSTRACT A simple and efficient methodology for the fabrication of poly(ethylene glycol) (PEG) ba... more ABSTRACT A simple and efficient methodology for the fabrication of poly(ethylene glycol) (PEG) based chemically cross-linked hydrogels containing discrete β-cyclodextrin (β-CD) units is outlined. Hydrogels were synthesized using homo-bifunctional linear PEGs containing allyl groups and heptavalent thiol-functionalized β-CD as crosslinkers via the radical-induced thiol-ene click chemistry. Various hydrogels comprising of different molecular weight PEGs and varying crosslinker feed were investigated in terms of their physical properties such as water uptake capacity, surface morphology and rheological behaviors. Uptake and controlled release of a poorly water-soluble drug, namely, puerarin was demonstrated using these hydrogels. The drug uptake and release was found to be depended on the hydrogels composition. Benefiting from the photochemically induced gel formation, the methodology was extended to fabricate hydrogel micro-structures on solid substrates.