Cellular uptake of tailored copolymer synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization

The tailored copolymer poly(methoxy-PEG acrylate-co-N-hydroxysuccinimide-co-fluorescein diacetate 5-maleimide) (P1) and block copolymer poly(N-isopropylacrylamide)-b-poly(methoxy-PEG acrylate-co-N-hydroxysuccinimide-co-fluorescein diacetate 5-maleimide) (P2) were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, which were both water-soluble, fluorescent and containing active group N-hydroxysuccinimide (NHS). Due to the temperature-sensitive poly(N-isopropylacrylamide) unit, the latter copolymer P2 formed nanoparticles at 37 °C in aqueous medium. Both P1 and P2 were taken up by cultured human umbilical vein endothelial cells (HUVECs) and localized mainly in the cytoplasm, which could subsequently be detected by confocal laser scanning microscopy (CLSM).     

苯乙烯可逆加成-断裂链转移聚合动力学

为了实现可逆加成-断裂链转移(RAFT)聚合过程中,苯乙烯均聚、高分子量聚苯乙烯的合成及苯乙烯与其他单体共聚时,对苯乙烯转化率、共聚时组成和分子量大小的控制,进行了二硫代苯乙酸-1-苯基乙酯(PEPDTA)调控苯乙烯本体和细乳液聚合动力学分析。在本体聚合中,反应速率慢,链增长自由基与中间态自由基的终止反应对聚合速率影响较小,很难合成窄分布、高转化率、高分子量的聚苯乙烯;在细乳液聚合中,反应速率快、转化率高,随着PEPDTA含量增加,乳胶粒数量减少、粒径分布变宽,诱导期和缓聚现象明显;聚合物的数均分子量随转化率线性增长,RAFT试剂浓度越高,分子量分布越窄,反应时间越长,分布越宽。以Smith-Ewart方程为基础,建立了苯乙烯RAFT细乳液聚合动力学模型,模型动力学曲线与实验数据相符合,能较好地预测实验过程。     

The direct polymerization of 2-methacryloxyethyl glucoside via aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization

A preliminary study on the direct controlled radical polymerization of a glycomonomer, namely 2-methacryloxyethyl glucoside (MAGlu), under reversible addition-fragmentation chain transfer (RAFT) polymerization conditions in aqueous media has been conducted. This represents the first example detailing the direct polymerization of a sugar monomer via RAFT and, significantly, has been conducted without protecting group chemistry. 4-Cyano-4-methyl-4-thiobenzoylsulfanyl butyric acid (CTP) was employed as the RAFT chain transfer agent (CTA) due to its inherent water-solubility and its applicability for methacrylic monomers. The homopolymerization displays all the characteristics of a controlled/‘living’ polymerization—linear increase in M_n with conversion, pseudo-first order kinetics, the final polymers have narrow molecular distributions and novel block copolymers can be prepared.     

Thermal polymerization of methyl (meth)acrylate via reversible addition-fragmentation chain transfer (RAFT) process

Thermal polymerization of methyl (meth)acrylate (MMA) was carried out using 2-cyanoprop-2-yl-1-dithionaphthalate (CPDN) and cumyl dithionaphthalenoate (CDN) as chain transfer agents. The kinetic study showed the existence of induction period and rate retardation, especially in the CDN mediated systems. The molecular weights of the polymers increased linearly with the monomer conversion, and the molecular weight distributions (M_w/M_ns) of the polymers were relatively narrow up to high conversions. The maximum number-average molecular weights (M_ns) reached to 351?900 g/mol (M_w/M_n = 1.47) and 442?400 g/mol (M_w/M_n = 1.29) in the systems mediated by CPDN and CDN, respectively. Chain-extension reactions were also successfully carried out to obtain higher molecular weight PMMA and PMMA-block-polystyrene (PMMA-b-PSt) copolymer with controlled structure and narrow M_w/M_n. Thermal polymerization of methyl acrylate (MA) in the presence of CPDN, or benzyl (2-phenyl)-1-imidazolecarbodithioate (BPIC) also demonstrated “living”/controlled features with the experimented maximum molecular weight 312?500 g/mol (M_w/M_n = 1.57). The possible initiation mechanism of the thermal polymerization was discussed.     

Synthesis of carboxylic acid functionalized nanoparticles by reversible addition-fragmentation chain transfer (RAFT) miniemulsion polymerization of styrene

In this study, an addition-fragmentation chain transfer agent bearing carboxylic acid, 4-toluic acid dithiobenzoate (TADB), was used to synthesize carboxylic acid functionalized PS nanospheres via the miniemulsion polymerization. In addition, non-functionalized RAFT agent, benzyl dithiobenzoate (BDB), was also used to compare the surface properties of the PS nanoparticles. For the TADB system, the rate of polymerization was approximately two-fold faster than the BDB system, while the molecular weights and PDI of PS remain intact.With increasing the molar ratio of [TADB]/[AIBN] from 0 to 3.0, the average particle diameter is substantially increased from 90 to 126 nm. The absolute value of zeta potential and conductivity also correspondingly increase from 49.1 mV and 3.47 mS/cm to 53.9 mV and 4.21 mS/cm, respectively. The results indicate that the surface of PS nanospheres could be functionalized by means of a carboxylic acid group on the RAFT agent and the stability of the PS miniemulsion latex could be significantly improved.     

Dispersion of calcite by poly(sodium acrylate) prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization

Calcite is dispersed into nanoparticles with the use of polysodium acrylate, PAANa. The molecular weight distribution of PAANa greatly influences the characteristics of the dispersion. Near-monodisperse PAANa adsorbs irreversibly and totally onto the CaCO₃ surface, but for polydisperse PAANa, a mass segregation occurs, where only chains with a selected molecular weight are adsorbed. With polydisperse samples, small spherical CaCO₃ particles are generated in addition to calcite crystals. This bimodal dispersion is less viscous than the dispersion containing only calcite crystals.     

Kinetic modeling of pseudoliving free-radical styrene polymerization occurring via reversible addition-fragmentation chain transfer

A kinetic model has been constructed for 2,2′-azobisisobutyronitrile-initiated pseudoliving free-radical styrene polymerization occurring via reversible addition-fragmentation chain transfer in the presence of dibenzyl trithiocarbonate. The inverse problem of determining the unknown temperature-dependent rate constants of the elementary reactions of the kinetic scheme has been solved. The model has been validated by comparing the theoretical and experimental molecular weight characteristics of polystyrene. The model has been employed to investigate the effects of control factors of the process on the molecular weight characteristics of polystyrene.     

Reversible addition-fragmentation chain transfer (RAFT) polymerization of styrene in the presence of oxygen

Reversible addition-fragmentation chain transfer polymerization (RAFT) of styrene (St) was carried out in the presence of oxygen using 2-cyanoprop-2-yl 1-dithionaphthalate (CPDN) or benzyl (2-phenyl)-1-imidazolecarbodithioate (BPIC) as the RAFT agent. The characteristics of the “living”/controlled radical polymerization were observed at high concentration of RAFT agent and low polymerization temperature. A slight increase in the rate of polymerization was found when oxygen was added at high concentration to the polymerization system; however, the presence of oxygen incurred greater polydispersities of the polymer at the same monomer conversion compared to that obtained in the absence of oxygen. The possible mechanism of the RAFT polymerization of St in the presence of oxygen was discussed.     

Polymer-layered silicate nanocomposites prepared through in situ reversible addition-fragmentation chain transfer (RAFT) polymerization

Reversible addition-fragmentation chain transfer (RAFT) polymerizations were performed in the presence of organically modified clays and successfully prepared polystyrene-, poly(methyl methacrylate)-, and poly(n-butyl acrylate)-layered silicate nanocomposites. The polymers had well-defined molecular weights and low polydispersities, as expected from RAFT polymerizations. The morphology of polystyrene-, and poly(n-butyl acrylate)-nanocomposites were found to be exfoliated using montmorillonite modified with N,N-dimethyl-n-hexadecyl-(4-vinylbenzyl) ammonium (MMT-VB16). In the case of PMMA nanocomposite, the structure was a mixture of intercalated and exfoliated when MMT-VB16 was used, while the use of montmorillonite modified with 2-methacryloyloxyethyl-hexadecyldimethyl ammonium (MMT-MA16) resulted in exfoliation.     

Living radical dispersion photopolymerization of styrene by a reversible addition-fragmentation chain transfer (RAFT) agent

In this study, an addition-fragmentation chain transfer agent bearing dithioester group is synthesized and applied to conventional dispersion photopolymerization of styrene in ethanol medium in the presence of poly(N-vinylpyrrolidone) stabilizer with varying amounts of the RAFT agent and optionally with conventional initiator, azobisisobutyronitril (AIBN) at various temperatures. Monomer conversion, molecular weight evolution, polydispersity index (PDI), and final particle sizes are measured. The PDI of the formed polymer is between 1.5 and 2.5 in the presence of RAFT agent. Higher concentration of RAFT agent or elevated temperature leads to the acceleration of the polymerization rate resulting in fast conversion, and reducing molecular weight and PDI. Stable polystyrene beads above 1 μm in diameter are successfully prepared by means of RAFT method applied in dispersion polymerization. The weight average particle sizes are between 1.08 and 2.04 μm, and the uniformity (D_w/D_n) is ranged from 1.26 to 2.51.     

Preparation of molecularly imprinted polymer microspheres via reversible addition-fragmentation chain transfer precipitation polymerization

The first combined use of reversible addition-fragmentation chain transfer (RAFT) polymerization and precipitation polymerization in the molecular imprinting field is described. The new polymerization technique, namely RAFT precipitation polymerization (RAFTPP), provides MIP microspheres with obvious molecular imprinting effects towards the template, fast template binding process and an appreciable selectivity over structurally related compounds, while only irregular MIP aggregates were obtained via traditional radical precipitation polymerization (TRPP) under similar reaction conditions. The MIP microspheres prepared via RAFTPP have proven to show improved binding capacity, larger binding constant and apparent maximum number for high-affinity sites, and significantly higher high-affinity binding site density in comparison with the MIP prepared via TRPP.     

Radical copolymerization of maleic anhydride and substituted styrenes by reversible addition-fragmentation chain transfer (RAFT) polymerization

Reversible addition fragmentation transfer (RAFT) copolymerization with benzyl dithiobenzoate (BDTB) as chain transfer agent was used to copolymerize maleic anhydride (MA) with styrene (St) and with the substituted styrenes p-chlorostyrene (pClSt), p-methoxystyrene (pMeOSt) and p-methylstyrene (pMeSt). Kinetic studies indicated that radical copolymerizations proceeded with apparent ‘living’ character, deduced from experiments demonstrating an increase in molar mass with monomer conversion, narrow molar mass distribution and chain extension to form block copolymer. All copolymers were alternating in chain structure as confirmed by determinations of monomer reactivity ratios. The degree of control in the RAFT mechanism and the establishment of the fragmentation equilibrium incorporating MA are discussed for styrene and for p-substituted styrenes, in relation to experimental copolymerizations producing molar masses somewhat higher than expected. For copolymerizations of MA with α-methylstyrene (αMeSt), conventional rather than controlled behaviour was observed, suggesting that the fragmentation equilibrium could be shifted towards the αMeSt propagating radical.     

三嵌段共聚物PS-b-PI-b-PVBC的RAFT合成与表征

采用可逆加成-断裂链转移自由基聚合法,以S-正十二烷基-S'-(α,α'-二甲基-α″-乙酸基)三硫代碳酸酯为链转移剂,偶氮二异丁腈为引发剂,合成窄分子量分布的聚苯乙烯大分子链转移剂(PS-CTA),在PS-CTA存在下,由引发剂依次引发异戊二烯(Ip)和对氯甲基苯乙烯(VBC)聚合,得到三嵌段聚合物PS-b-PI-b-PVBC。运用凝胶色谱、IR、原子力显微镜、1H NMR等技术对产物的结构进行表征。结果表明,所得嵌段共聚物分子量分布较窄(PDI=1.93),聚合过程具有活性/可控特征,聚合物薄膜在热退火后形成微观相分离,平均相区尺寸约为100 nm。     

三嵌段共聚物PS-b-PI-b-PVBC的RAFT合成与表征

采用可逆加成-断裂链转移自由基聚合法,以S-正十二烷基-S'-(α,α'-二甲基-α″-乙酸基)三硫代碳酸酯为链转移剂,偶氮二异丁腈为引发剂,合成窄分子量分布的聚苯乙烯大分子链转移剂(PS-CTA),在PS-CTA存在下,由引发剂依次引发异戊二烯(Ip)和对氯甲基苯乙烯(VBC)聚合,得到三嵌段聚合物PS-b-PI-b-PVBC。运用凝胶色谱、IR、原子力显微镜、1H NMR等技术对产物的结构进行表征。结果表明,所得嵌段共聚物分子量分布较窄(PDI=1.93),聚合过程具有活性/可控特征,聚合物薄膜在热退火后形成微观相分离,平均相区尺寸约为100 nm。     

Grafting of poly(acrylic acid) onto poly(amidoamine)-functionalized graphene oxide via surface-mediated reversible addition-fragmentation chain transfer polymerization

Graphene oxide was modified with third-generation poly(amidoamine) (PAMAM) to obtain dendrimer-grafted GO (DGO) with high content of functional groups. DGO's amine groups were conjugated with S-(thiobenzoyl)thioglycolic acid as proved by XPS and poly(acrylic acid) was grafted onto surface via RAFT polymerization (DGO@PAA). FT-IR results approved the synthesis of samples whereas TGA revealed 40.3% grafting of PAA. XRD patterns showed that with further modification, d-spacing increased. According to Raman spectra, modification resulted in more disordered structure whereas DGO@PAA showed a high value of I_D/I_G. Morphological studies were performed by SEM and TEM that showed a polymeric layer covered the surface of nanosheets.     

Synthetic method of polyethylene-poly(methylmethacrylate) (PE-PMMA) polymer hybrid via reversible addition-fragmentation chain transfer (RAFT) polymerization with functionalized polyethylene

Summary Polyethylene-poly(methylmethacrylate) (PE-PMMA) polymer hybrid was synthesized via RAFT polymerization of MMA with PE chain transfer agent (PE-CTA) for the first time. The structure of PE-CTA produced by sequential functionalization of terminally hydroxylated PE was confirmed by ¹H NMR and FT-IR analyses. The results of GPC after MMA polymerization revealed that the molecular weight (M_w) of the resulting polymers increased compared with the one of the PE-CTA. ¹H NMR analysis of resulting polymers confirmed that the amounts of PMMA segments were in a range of 7.8 and 23 wt %. TEM images indicated the nanometer level microphase-separation morphology between the PE segment and PMMA segment.     

New chain transfer agents for reversible addition-fragmentation chain transfer (RAFT) polymerisation in aqueous solution

New chain transfer agents for free radical polymerisation via reversible addition-fragmentation chain transfer (RAFT) were synthesised that are particularly suited for aqueous solution polymerisation. The new compounds bear dithioester and trithiocarbonate moieties as well as permanently ionic groups to confer solubility in water. Their stability against hydrolysis was studied, and compared with the one of a frequently employed water-soluble RAFT agent, using UV-Vis-spectroscopy and ¹H-NMR measurements. An improved resistance to hydrolysis was found for the new RAFT agents compared to the reference one, providing good stabilities in the pH range between 1 and 8, and up to temperatures of 70 °C.     

Novel W(II) complexes for reversible addition-fragmentation chain transfer (RAFT) polymerizations

Alkylation of the phosphorus coordination of the diphenyl(dithioformato)phosphine ligand in [W(CO)₅(PPh₂CS₂)]NEt₄ (1) at the S atom results in the formation of the novel RAFT agent S═C[W(CO)₅PPh₂]S–R (2a, R = CH₂Ph; 2b, R = CH₂CH═CH₂). These compounds have been shown to be highly effective in reversible addition-fragmentation chain transfer (RAFT) polymerization to produce polymers (homopolymer and diblock copolymer) of predetermined molecular weight and narrow polydispersity (< 1.3). Electron-withdrawing organometallic substituents can increase the activity of RAFT agents. To the best of our knowledge, this is the first report of their use as RAFT agents in polymerization.     

Synthesis of polystyrene end-capped with pyrene via reversible addition-fragmentation chain transfer polymerization

A novel benzodithioate compound with a pyrene structure in the R group, pyrenylmethyl benzodithioate (PMB) was synthesized. Using PMB as the chain transfer agent (CTA), the RAFT polymerizations of styrene with AIBN as an initiator were carried out in different reaction conditions. The results indicated that PMB was an effective CTA for the RAFT polymerizations of styrene with the “living”/controlled characteristics. The structures of the obtained polymers were characterized by ¹H NMR. The results showed that majority of the polymer chains contained the pyrene moiety in the chain end. The enhanced fluorescence property in CHCl₃ solution was observed. The chain-extension experiments of the obtained polystyrene (PS) with the monomers of styrene and methyl acrylate were successfully carried out.     

Kinetic study on reversible addition-fragmentation chain transfer (RAFT) process for block and random copolymerizations of styrene and methyl methacrylate

The degenerative (exchange) chain transfer constant C_ex was determined for the dithioacetate-mediated living radical block and random copolymerizations of styrene (St) and methyl methacrylate (MMA) at 40 °C. The addition of the polystyrene (PSt) radical to a polymer-dithioacetate adduct (P-X) to form the intermediate radical (PSt-(X)-P) was (about twice) faster than that of the poly(methyl methacrylate) (PMMA) radical to form the intermediate radical PMMA-(X)-P. The fragmentation (release) of the PMMA radical from the PSt-(X)-PMMA intermediate formed at the initiating stage of block copolymerization was much (about 100 times) faster than the release of the PSt radical, explaining why the block copolymerization of MMA from a PSt-dithiocarbonate adduct is not so satisfactory as that of St from a PMMA-dithiocarbonate adduct. In the random copolymerization, there was implicit penultimate unit effect on the exchange chain transfer process, which appeared in the addition process but not in the fragmentation process.