Synthesis, Functionalization and Reductive Degradation of Multibrominated Disulfide-containing Hyperbranched Polymers

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1 CSI PUBLISHIG Aust. J. Chem. 2012, 65, ESEACH FT Full Paper Synthesis, Functionalization and eductive Degradation of Multibrominated Disulfide-containing Hyperbranched Polymers Delia-Laura Popescu A and icolay V. Tsarevsky A,B,C A Department of Chemistry, Southern Methodist University, 3215 Daniel Avenue, Dallas, TX 75275, USA. B Center for Drug Discovery, Design, and Delivery in Dedman College, Southern Methodist University, Dallas, TX 75275, USA. C Corresponding author. nvt@smu.edu eductively degradable hyperbranched polymethacrylates with multiple peripheral alkyl bromide groups were synthesized by the azobis(2-isobutyronitrile)-initiated copolymerization of diethylene glycol methyl ether methacrylate or oligo (ethylene oxide) methyl ether methacrylate with the disulfide-containing crosslinker bis(2-methacryloyloxyethyl) disulfide (2.5.0 mol-% relative to the monomer) in the presence of carbon tetrabromide ( 40-fold excess relative to the radical initiator) as efficient chain transfer agent. The alkyl bromide groups initiated the atom-transfer radical polymerization of methyl methacrylate, and star copolymers with hyperbranched disulfide-containing cores were formed. Both the macroinitiators and the star copolymers derived from them were degraded in reducing environment. Manuscript received 22 September Manuscript accepted 14 ovember Published online: 12 December Introduction Hyperbranched polymers [1 11] are characterized by a smaller hydrodynamic diameter than their linear analogues of the same molecular weight, leading to lower melt and solution viscosity, and easier processability. Many other properties of hyperbranched polymers and their linear counterparts differ, for instance density, Young s modulus and tensile strength. Further, owing to the presence of a large number of chain ends, each of which can have an attached functional group, hyperbranched macromolecules have found numerous applications in which a large density of functionalities is desirable, including reactive adhesives and coatings, imaging and drug delivery. [12] Several synthetic approaches to hyperbranched polymers derived from vinyl monomers have been developed, including the copolymerization of monovinyl with di- or multivinyl monomers in the presence of (i) efficient chain transfer agents; [13,14] (ii) a large amount of radical initiator, comparable with the amount of the monomer; [15 17] or (iii) compounds capable of reversibly deactivating the propagating radicals. Another popular method for the preparation of hyperbranched polymers is (iv) selfcondensing vinyl polymerization (SCVP), [18 20] where compounds, referred to as inimers, that contain both a polymerizable and an initiating group are homo- or copolymerized. The SCVP route allows the synthesis of highly branched macromolecules but unlike the other mentioned strategies, it uses inimers, the synthesis of which may be cumbersome and costly. The first three approaches to hyperbranched polymers rely on the fact that the additives (chain transfer agents in (i); radicals produced from the large amounts of initiators in (ii); or radical deactivators in (iii)) are able to limit the molecular weights of the Journal compilation Ó CSI 2012 produced macromolecules as well as the average number of incorporated pendant vinyl groups per chain, thus delaying crosslinking until moderate to high monomer conversions are reached. The first mentioned strategy that employs chain transfer agents has been known for a relatively long time, [13,14] but its utility has become more widely recognized and appreciated since the work of Sherrington and his collaborators. [21 24] The second protocol, dubbed initiator-fragment incorporation radical copolymerization, has been used more rarely, perhaps mostly owing to safety issues emerging in polymerizations in the presence of large concentrations of radical sources. The third approach, namely the controlled/ living radical polymerization (CP) of monovinyl monomers in the presence of small amounts of di- or polyvinyl crosslinkers leads to the formation of hyperbranched polymers due to the much more uniform incorporation of the crosslinker in each growing chain compared with conventional radical polymerization. [25,26] Gelation is eventually observed in CP in the presence of crosslinkers, but at markedly higher conversion than in the conventional process. [27] wing to the large number of readily available or easy to synthesize multivinyl crosslinkers containing functional groups, the synthesis of backbone- or core-functionalized hyperbranched polymers by synthetic routes (i) (iii) is relatively easy. Additionally, in method (i), the chain transfer agent may be able to transfer another functional group of interest to the polymer chain ends, enabling the synthesis of hyperbranched polymers with outer-edge functionalities. This work reports the copolymerization of methacrylate monomers with a crosslinker containing the reductively degradable disulfide group, namely bis(2-methacryloyloxyethyl)disulfide,

2 Multibrominated Hyperbranched Polymers 29 (MAE) 2 S 2, in conjunction with C 4 as the chain-transfer agent, yielding degradable hyperbranched polymers with alkyl bromide groups at the periphery. Experimental Materials The monomers diethylene glycol methyl ether methacrylate (DEGMEMA, 95 %, Aldrich), oligo(ethylene oxide) methyl ether methacrylate with average molecular weight of 475 g mol 1 (EGMEMA475, from Aldrich) and methyl methacrylate (MMA, 99 %, Aldrich) were purified from the polymerization inhibitor before the experiments by passing the neat liquid through a column filled with basic alumina. The crosslinker, bis(2-methacryloyloxyehtyl) disulfide ((MAE) 2 S 2 ), which was synthesized as described below, was purified in a similar manner. Tris(2-pyridylmethyl)amine (TPMA) was a product of ATP Solutions, Inc. All other reagents (bis(2-hydroxyethyl)disulfide, methacryloyl chloride, pyridine, 2,2 0 -azobisisobutyronitrile (AIB), C 4, Cu 2, tributylphosphine (Bu 3 P) and triethyleneglycol dimethyl ether (TEGDME), and the other solvents) were purchased from Aldrich and were used as received. Analyses Molecular weights and molecular weight distribution dispersities (Œ ¼ M w /M n, [28] formerly referred to as polydispersity indices, PDIs) were determined by size exclusion chromatography (SEC) on a Tosoh EcoSEC system equipped with a series of four columns (TSK gel guard Super HZ-L, Super HZM-M, Super HZM- and Super HZ20) and using a refractive index and UV detectors. Tetrahydrofuran (THF) was used as the eluent at a flow rate of 0.35 ml min 1 (408C). The SEC calibration was based on linear polystyrene standards. Monomer conversions were determined by M spectroscopy using a uker Avance DX 4 spectrometer with CDCl 3 as the solvent and tetramethylsilane as the chemical shift reference. Synthesis of Disulfide Monomer (MAE) 2 S 2 The crosslinker was prepared using a modified literature procedure. [29] In a 1-L round-bottomed flask equipped with a stir bar, methacryloyl chloride (29 ml, 0.3 mol) was added. Bis(2-hydroxyethyl)disulfide (19.25 g, mol) was weighed in a beaker and was transferred to the reaction flask with methylene chloride (2 ml) dried over a 2 S 4. The alcohol is not very soluble in methylene chloride and an emulsion was formed. Hydroquinone (0.05 g) was then added, the flask was capped with a rubber septum, and the mixture was stirred in an ice bath. Then, pyridine (25 ml, dried over a 2 S 4 ) was injected over a 30-min period. After the addition of the first ml of pyridine (in, min), a homogeneous mixture was formed, and less than min after all the pyridine had been added, the mixture became turbid. After the addition of pyridine, the reaction mixture was stirred for an additional 30 min in the cooling bath and then at room temperature for 18 h. At the end of that period, water (250 ml) was added and the mixture was stirred well for 2 h. The organic layer was separated and collected. Another extraction with water (250 ml) was performed, followed by two extractions with aqueous ahc 3 (each extraction with 250 ml of solution containing 50 g of the salt in 5 ml of water) and one additional extraction with water (250 ml). The organic layer was separated, mixed with hydroquinone (0.025 g), and dried over anhydrous a 2 S 4. The solvent was then removed by rotary evaporation. The crude yield was g. The product, which contained a small amount of methacryloyl chloride or methacrylic acid, was dissolved in ether (2 ml) and the solution was passed through a column containing basic alumina (20 g) as the bottom layer and ahc 3 ( g) as the top layer. The sorbent was then washed with ether (1 ml), hydroquinone (0.0 g) was added to the combined ether solutions, and the solvent was removed on a rotary evaporator. M analysis revealed that the product contained no methacryloyl chloride or methacrylic acid. Yield: g (40 %). The density of the crosslinker (MAE) 2 S 2 is g ml 1. The product was analyzed by 1 H M spectroscopy. d H (CDCl 3 ) 6.14 (d, 1H, ¼CH), 5.60 (d, 1H, ¼CH), 4.42 (t, 2H, CH 2 C), 2.98 (t, 2H, CH 2 S), 1.96 (s, 3H, CH 3 C¼). Synthesis of Multibrominated Hyperbranched Degradable Polymers AIB (0.82 g, 5 5 mol) and C 4 ( g, 5 5 mol, i.e. -fold excess relative to AIB) were added to a glass tube equipped with a magnetic stir bar. DEGMEMA (2 ml, mol) and TEGDME (1 ml) were then added followed by (MAE) 2 S 2 (68 ml, 2.5 mol-% v. DEGMEMA) and the tube was capped with a rubber septum. The reaction tube was placed in an ice bath and the homogeneous reaction mixture was purged with 2 for 30 min. The reaction was carried out at 608C. Samples were periodically withdrawn with a nitrogen-purged syringe. Part of each sample was diluted with CDCl 3 for determination of the monomer conversion by M, while another fraction was diluted with THF and was used for SEC analysis. A gel was formed in 3.5 h. This reaction is designated as hb-polydegmema(2.5 S 2 )( C 4 ) x in the following text, where 2.5 S 2 refers to the molar percentage of the disulfide crosslinker v. the monomer, and C 4 is the molar ratio of transfer agent C 4 to the initiator AIB. The reactions with the other monomers were carried out under similar conditions. The volumes of monomer and solvent (TEGDME) and the amount of AIB were kept constant in all experiments. The amount of (MAE) 2 S 2 was varied and was 2.5, 5.0, 7.5, or.0 mol-% relative to the monomer. The amount of C 4 was also varied in order to prevent early gelation. It was found that 40-fold excess v. AIB was sufficient to prevent crosslinking up to at least 80 % monomer conversion, and that was the amount of transfer agent used in most experiments. Chain Extension of the Multibrominated Hyperbranched Polymers by Initiators for Continuous Activator egeneration (ICA) ATP Polymer hb-polydegmema( S 2 )(40 C 4 ) x obtained after 3 h of polymerization and purified (0.1 g) was dissolved in DMF (1.8 ml) in a flask to which a magnetic stir bar was added. Then, MMA (3 ml, g) was added. Separately, a catalyst stock solution was prepared by dissolving Cu 2 (0.56 g, mol), TPMA (0.73 g, mol) and AIB (0.26 g, mol) in DMF (2 ml). Then, 0.2 ml of the stock solution was added to the solution of hyperbranched macroinitiator in DMF and MMA, the reaction flask was tightly capped with a rubber septum, and the reaction mixture was purged with 2 for 1 h, while cooling in ice. The reaction was carried out at 708C. Samples were periodically withdrawn and analyzed by both M in CDCl 3 (conversion) and SEC in THF. In 4 h, gel was formed.

3 30 D.-L. Popescu and. V. Tsarevsky eductive Degradation of Disulfide-containing Hyperbranched Macroinitiators and Star Polymers with Hyperbranched Cores To each vial containing THF solution of the polymer (,0.01 g in 1 ml), Bu 3 P (0.01 ml) was added and the reaction mixture was left to react for 2 5 h under ambient conditions. SEC analysis was then performed to verify the cleavage of the disulfide bridges, which was accompanied by a decrease in the apparent molecular weight (i.e., longer elution time). esults and Discussion Synthesis of Multibrominated Hyperbranched Polymers The radical copolymerization of MMA and divinylbenzene or ethylene glycol dimethacrylate in the presence of C 4 has been shown to yield multibrominated hyperbranched polymers. [13,14,30] In the early reports, no crosslinkers bearing functional groups were employed as a means for the synthesis of functional macromolecules, neither was advantage taken of the presence of the large number of peripheral alkyl bromide groups for further functionalization (e.g. via nucleophilic substitution reactions). Polymeric alkyl bromides are useful for the synthesis of segmented copolymers, either via transformation of the alkyl bromide group into a cation, followed by cationic polymerization, [31] or via direct chain extension under atom transfer radical polymerization (ATP) conditions. [32 34] In a recent example, the synthesis of crosslinked particles with surfaces decorated with alkyl bromide groups was accomplished by the copolymerization of MMA and divinylbenzene in the presence of C 4 ; the accessible alkyl bromide groups were further used to initiate the ATP of MMA. [35] This work describes the synthesis of reductively degradable hyperbranched polymers with internal disulfide groups and multiple peripheral alkyl bromide groups, which were used to initiate polymerization under ATP conditions at very low concentrations of copper-based catalyst. The prepared (bio)degradable hyperbranched structures are of interest in biomedical applications such as controlled delivery. The monomers used in this study included methacrylates with di- or oligo (ethylene oxide) methyl ether as the pendant groups. Multibrominated hyperbranched polymers were synthesized by using C 4 as the chain transfer agent, as shown in Scheme 1. The chain transfer constant for C 4 in the radical polymerization of MMA at 608C is 0.27 a relatively large value, although lower than the values for other monomers such as methyl acrylate (0.41), styrene (2.2) or vinyl acetate (.39) obtained at the same temperature. [36] The differences in the efficiency of transfer of a atom from C 4 to the propagating radicals are strongly dependent on the nature, i.e. reactivity, of the latter, and, in copolymerizations, penultimate effects have been reported. [37] Importantly, C 4 efficiently transfers a atom to macroradicals derived from a large variety of vinyl monomers. The radical 3 C formed in the transfer can itself initiate polymerization, yielding C 3 -capped polymers. The end group of these polymers may also participate in transfer reactions by transferring a atom to another propagating chain, yielding a 2 C - containing macroradical, which can in turn propagate until a termination or transfer event stops the process. Consequently, anching point Initiator in in Termination C 4 C 3 in... Termination 3 C anching point 2 C 3 C C 3 C 4 C 2 (CH 2 CH 2 ) n CH 3 S S ' Scheme 1. Copolymerization of monomethacrylates with the disulfide-containing dimethacrylate crosslinker (MAE) 2 S 2 in the presence of C 4 as chaintransfer agent, yielding multibrominated hyperbranched polymers.

4 Multibrominated Hyperbranched Polymers 31 depending on the efficiency of transfer of a atom from the C 3 -terminal group, some of the polymer chains formed may contain an internal C 2 fragment. This possibility is also presented in Scheme 1. When the amount of crosslinker (MAE) 2 S 2 was 2.5 mol-% v. DEGMEMA and the amount of transfer agent C 4 was only times higher than the initiator AIB, macroscopic gelation was observed in less than 3.5 h. A two-fold increase of the amount of transfer agent (to [C 4 ] 0 /[AIB] 0 ¼ 20:1) was sufficient to prevent crosslinking up to,90 % monomer conversion. When the concentration of disulfide crosslinker was increased to 5.0 mol-% relative to the monomer, and using the larger amount of transfer agent (20-fold excess v. AIB), crosslinking was observed in,4 h. In order to prevent crosslinking in this system employing a larger quantity of crosslinker, the amount of C 4 had to be increased to [C 4 ] 0 /[AIB] 0 ¼ 40:1. The polymerization rates were virtually unaffected by the amount of crosslinker or transfer agent (Fig. 1a). However, the amount of transfer agent impacted the width of the polymer molecular weight distribution (MWD). The evolution of the apparent molecular weights (i.e. calculated using SEC calibrated with linear polystyrene standards) and the dispersities with monomer conversion are shown in Fig. 1b. The obtained results are summarized in Table 1. At higher concentrations of transfer agent, not only was the gelation delayed but also the MWD became narrower. For instance, for the experiments with 2.5 mol-% of disulfide crosslinker relative to the monomer DEGMEMA, the values of the MWD dispersity (Œ ¼ M w /M n ) were 19.6 at 72 % monomer conversion when -fold excess of C 4 v. AIB was used, 4.9 at the same 71 % monomer conversion, when using a 20-fold excess of the transfer agent, and only 2.5 at 79 % monomer conversion when the ratio [C 4 ] 0 /[AIB] 0 was increased to 40 (entries 1 3 in Table 1). Likewise, for the experiments where the amount of crosslinker was increased to 5.0 mol-% v. DEGMEMA, the values of M w /M n were 9.6 at 67 % monomer conversion and (a) 1.0 (b) Conversion hb-polydegmema(2.5 S 2 )( C 4 ) x 0.2 hb-polydegmema(2.5 S 2 )(20 C 4 ) x hb-polydegmema(5.0 S 2 )(20 C 4 ) x hb-polydegmema(5.0 S 2 )(40 C 4 ) x Time [h] M n, app [g mol 1 ] Conversion M w /M n Fig. 1. Copolymerization of diethylene glycol methyl ether methacrylate with the disulfide-containing crosslinker bis(2-methacryloyloxyethyl)disulfide (2.5 or 5.0 mol-% relative to the monomer) initiated by AIB at 608C in TEGDME in the presence of various amounts of C 4 (the ratio of C 4 to AIB is shown in the parentheses): (a) kinetics, and (b) evolution of the apparent number-average molecular weights (solid symbols) and dispersities Œ ¼ M w /M n with monomer conversion (empty symbols with the same shape represent the same experiment). Table 1. Summary of hyperbranched multibrominated polymers obtained in this work # Monomer (MAE) 2 S 2 [mol-%] A [C 4 ] 0 :[AIB] 0 eaction time [h] Conversion (M) M n,app B [g mol 1 ] M w /M n B 1 DEGMEMA gel gel EGMEMA C 1.9 C C 2.1 C C 2.2 C C 2.0 C A Molar percentage of disulfide crosslinker relative to the monomer. B Determined by size exclusion chromatography using linear polystyrene standards for the calibration. C The peak of the unreacted monomer partially overlapped with that of the formed polymer and was included in the calculation of M n and M w /M n.

5 32 D.-L. Popescu and. V. Tsarevsky 3.1 at 71 % conversion at [C 4 ] 0 /[AIB] 0 ¼ 20 and 40 respectively (entries 4 and 5 in Table 1). As the amount of crosslinker was increased from 2.5 to 5.0 mol-% v. DEGMEMA, for the same amount of transfer agent C 4 and at similar monomer conversions, the degree of branching increased and the MWD became broader (see entries 2 and 4 in Table 1 for [C 4 ] 0 / [AIB] 0 ¼ 20:1 and entries 3 and 5 for [C 4 ] 0 /[AIB] 0 ¼ 40:1). The broadening of the MWDs as the amount of chain transfer agent is decreased at the same crosslinker-to-monomer feed ratio or as the amount of crosslinker is increased while keeping the amount of transfer agent constant has been reported for other polymerization systems. [24] In all studied cases, using a 40-fold excess of C 4 relative to initiator was sufficient to prevent gelation up to high conversions even when the amount of crosslinker was as high as mol-% v. the monomer. As seen from the data in Table 1 and as mentioned earlier, the polymerization kinetics or the polymer yields were not significantly influenced by either the amount of crosslinker or chain transfer agent. The polymerization of EGMEMA475 did not yield very highly branched polymers, as judged from the relatively narrow MWDs (entries 8 11 in Table 1). This was plausibly due to the less efficient addition of propagating radicals to the pendant double bond, originating from the incorporated crosslinker in the polymethacrylates with bulkier oligomeric pendant groups. efractive index response Bu 3 P, 275 min hb-polydegmema(2.5 S 2 )(40 C 4 ) x Elution time [min] Fig. 2. Size exclusion chromatography traces of polymer hb-polydegmema(2.5 S 2 )(40 C 4 ) x before (top curve), and after (bottom) reductive degradation with Bu 3 P for 275 min in THF at room temperature. Degradation of the Disulfide-containing Multibrominated Hyperbranched Polymers The obtained polymers contained multiple disulfide links, which are reductively degradable. Several very efficient reducing agents are known that cleave disulfide groups, including thiols and phosphines. [38,39] Tributylphosphine (Bu 3 P) has been shown to rapidly cleave disulfide groups in linear, [29] hyperbranched [40] or crosslinked polymers, [29,41] and was chosen as the reducing agent in this work. When Bu 3 P was added to solutions of the hyperbranched polymers in THF, degradation took place in less than 2 5 h at room temperature. For example, the degradation of the polymer derived from DEGMEMA obtained after 5-h polymerization in the presence of 2.5 mol-% of crosslinker relative to the monomer and using 40-fold excess of C 4 is presented in Fig. 2. The SEC trace of the degradation products, as expected, shifted towards longer elution time. Chain Extension of the Disulfide-containing Multibrominated Hyperbranched Polymers under ATP Conditions and eductive Degradation of the btained Star Copolymers with Hyperbranched Cores An important benefit of using C 4 as the chain transfer agent in radical polymerizations is that the produced polymers are -terminated, which allows further functionalization, e.g. via nucleophilic substitution reactions. Additionally, polymeric alkyl bromides can be used as macroinitiators for ATP. Although the former functionalization route has not been explored yet, the latter was the subject of this work. To be able to conduct ATP reactions at low catalyst concentration, a reducing agent has to be added to the reaction mixture to regenerate the Cu I -based activator, which would normally be irreversibly converted to the corresponding Cu II halide complex owing to the inevitable radical termination, i.e. owing to the persistent radical effect. [42 44] Many compounds can be used as reducing agents, but when a radical source such as AIB is employed, the process, presented in Scheme 2, is termed initiators for continuous activator regeneration (ICA) ATP. [44] The method has already been successfully used for the controlled polymerization of various monomers, including the functional and reactive monomer glycidyl methacrylate. [45] For a ligand L to be suitable for an ICA ATP reaction, it has to form very stable Cu I and Cu II complexes that do not appreciably dissociate at high dilutions. In addition, the Cu I complex should be a very active ATP catalyst, the Cu II complex should P k-x Cu I TPMA k act k deact k p P k X-Cu II TPMA TPMA I-X k t 1/2 P k -P l X-Cu II TPMA I Δ AIB Scheme 2. Mechanism of ICA ATP of MMA mediated by the Cu complexes of TPMA. P k and P l represent polymer chains with degrees of polymerization of k and l, respectively.

6 Multibrominated Hyperbranched Polymers 33 MMA, Cu 2 /TPMA, AIB, DMF, 70 C (CH 2 CH 2 ) n CH 3 Scheme 3. Synthesis of star copolymers with hyperbranched cores using multibrominated hyperbranched polymethacrylates as the core precursors. (a) 1.5 (b) ln([mma] 0 /[MMA]) M n, app [g mol 1 ] M w /M n Time [h] Conversion 2 Fig. 3. (a) Kinetics, and (b) evolution of molecular weights (filled symbols) and dispersities (open symbols) during the chain extension of hp-polydegmema( S 2 )(40 C 4 ) x with MMA under ICA ATP conditions. be able to strongly bind to a halide anion X (i.e. it has to be very halidophilic [46] and form a Cu II halide complex stable with respect to heterolytic dissociation), and the rate constant of radical deactivation by the Cu II halide complex should be large. The ligand TPMA meets all mentioned requirements and was used in this work. The multibrominated hyperbranched disulfide-containing polymers were employed as ATP macroinitiators in chain extension reactions with MMA, which yielded star copolymers with polymma arms and hyperbranched reductively degradable cores (Scheme 3). Fig. 3 shows the kinetics of ICA ATP of MMA as well as the evolution of molecular weights and polymer dispersities with monomer conversion for a chain extension reaction employing hp-polydegmema( S 2 )(40 C 4 ) x which was obtained after 3 h reaction time, isolated, purified and then used as the macroinitiator. The first-order kinetic plot for MMA consumption was linear and the molecular weight increased in a linear fashion with conversion, as expected for a controlled/ living polymerization. At 3 h, the monomer conversion reached 63 %, but after 4 h, the reaction mixture gelled due to radical termination. efractive index response hb-polydegmema( S 2 )(40 C 4 )(polymma) y Bu 3 P, 120 min Elution time [min] Fig. 4. Size exclusion chromatography traces of the star copolymer with reductively degradable core and polymma-based arms hb-polydeg- MEMA( S 2 )(40 C 4 )(polymma) y before (top curve), and after (bottom) reductive degradation with Bu 3 P for 120 min in THF at room temperature.

7 34 D.-L. Popescu and. V. Tsarevsky The disulfide groups in the hyperbranched cores of the star copolymers could also be reductively cleaved in the presence of Bu 3 P, yielding lower-molecular-weight segmented copolymers with polymma blocks. For instance, the degradation of a star copolymer with polymma-based arms and a core originating from the polymer hb-polydegmema( S 2 )(40 C 4 ) x is shown in Fig. 4. The reductive degradation of the hyperbranched polymers described in this work yields thiol-terminated polymers that can be further used as precursors of functional materials, e.g. by thiol-ene [47,48] or thiol-yne [49] chemistry, or oxidative coupling with other thiols. Conclusions Carbon tetrabromide, when used in sufficient excess relative to the radical initiator AIB, prevented or significantly delayed the gelation point in the copolymerization of dior oligo(ethylene oxide) methyl ether methacrylates with a disulfide-containing crosslinker, bis(2-methacryloyloxyethyl) disulfide. 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