RAFT dispersion polymerisation of lauryl methacrylate in ethanol–water binary mixtures: synthesis of diblock copolymer vesicles with deformable membranes

Polymerisation-induced self-assembly (PISA) is widely recognised to be a powerful platform technology for the rational synthesis of diblock copolymer nano-objects. RAFT alcoholic dispersion polymerisation is an important PISA formulation that has been used to prepare block copolymer spheres, worms and vesicles. In this study, we have utilised the RAFT dispersion polymerisation of lauryl methacrylate (LMA) using a poly(N-(2-methacryloyloxy)ethyl pyrrolidone) (PNMEP) stabiliser in order to prepare vesicles with highly deformable membranes. More specifically, a PNMEP28 precursor was chain-extended with LMA in an 80 : 20 w/w ethanol–water mixture to produce a series of PNMEP28-PLMAx diblock copolymer nano-objects (Mw/Mn ≤ 1.40; LMA conversions ≥98% in all cases, as indicated by 1H NMR spectroscopy). Differential scanning calorimetry studies confirmed that the membrane-forming PLMA block had a relatively low glass transition temperature. Transmission electron microscopy and small angle X-ray scattering were used to identify copolymer morphologies for these highly asymmetric diblock copolymers. A mixed sphere and vesicle morphology was observed when targeting x = 43, while polydisperse vesicles were obtained for x = 65–151. Slightly smaller vesicles with lower mean aggregation numbers and thicker membranes were obtained when targeting higher PLMA DPs. A minor population of sheet-like lamellae was observed for each target copolymer composition, with lamellar stacking leading to a structure peak in the scattering patterns recorded for PNMEP28-PLMA129 and PNMEP28-PLMA151. Bearing in mind potential industrial applications, RAFT chain-end removal strategies were briefly explored for such PNMEP28-PLMAx vesicles. Thus, 96% of dithiobenzoate chain-ends could be removed within 3 h at 50 °C via LED irradiation of a 7.5% aqueous dispersion of PNMEP28-PLMA87 vesicles at a wavelength of 405 nm. This appears to be an attractive method for RAFT chain-end removal from diblock copolymer nano-objects, particularly those comprising highly hydrophobic cores

In Situ Spectroscopic Studies of Highly Transparent Nanoparticle Dispersions Enable Assessment of Trithiocarbonate Chain-End Fidelity during RAFT Dispersion Polymerization in Nonpolar Media

We report the synthesis of highly transparent poly(stearyl methacrylate)-poly(2,2,2-trifluoroethyl methacrylate) (PSMA-PTFEMA) diblock copolymer nanoparticles via polymerization-induced self-assembly (PISA) in nonpolar media at 70 °C. This was achieved by chain-extending a PSMA precursor block via reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of TFEMA in n-tetradecane. This n-alkane has the same refractive index as the PTFEMA core-forming block at 70 °C, which ensures high light transmittance when targeting 33 nm spherical nanoparticles. Such isorefractivity enables visible absorption spectra to be recorded with minimal light scattering even at 30% w/w solids. However, in situ monitoring of the trithiocarbonate RAFT end-groups during PISA requires selection of a weak n → π* band at 446 nm. Conversion of TFEMA into PTFEMA causes a contraction in the reaction solution volume, leading to an initial increase in absorbance that enables the kinetics of polymerization to be monitored via dilatometry. At ∼98% TFEMA conversion, this 446 nm band remains constant for 2 h at 70 °C, indicating surprisingly high RAFT chain-end fidelity (and hence pseudoliving character) under monomer-starved conditions. In situ 19F NMR spectroscopy studies provide evidence for (i) the onset of micellar nucleation, (ii) solvation of the nanoparticle cores by TFEMA monomer, and (iii) surface plasticization of the nanoparticle cores by n-tetradecane at 70 °C. Finally, the kinetics of RAFT chain-end removal can be conveniently monitored by in situ visible absorption spectroscopy: addition of excess initiator at 70 °C causes complete discoloration of the dispersion, with small-angle X-ray scattering studies confirming no change in nanoparticle morphology under these conditions

RAFT dispersion polymerization of methyl methacrylate in mineral oil : high glass transition temperature of the core-forming block constrains the evolution of copolymer morphology

RAFT dispersion polymerization of a prototypical methacrylic monomer, methyl methacrylate (MMA), is performed in mineral oil using various poly(lauryl methacrylate) (PLMA) precursors prepared with a trithiocarbonate-based RAFT agent. GPC analysis indicated reasonably narrow molecular weight distributions (Mw/Mn ≤ 1.39) for all diblock copolymers, with 1H NMR studies indicating high MMA conversions (≥95%) for all syntheses. An efficient one-pot synthesis protocol enabled high blocking efficiencies to be achieved when targeting higher PMMA DPs. However, the relatively high glass transition temperature (Tg) of the corresponding core-forming PMMA block unexpectedly constrains the evolution in copolymer morphology during polymerization-induced self-assembly (PISA). More specifically, well-defined PLMA22–PMMAx spheres (x = 19–39) and relatively short worms (x = 69–97) can be obtained at 90 °C when using a PLMA22 precursor but targeting higher x values (x ≥ 108) invariably leads to colloidally unstable aggregates of spheres, rather than long worms or vesicles. Interestingly, similar constraints were observed when targeting higher solids, when using n-dodecane instead of mineral oil, or when employing an alternative steric stabilizer block. Raising the PISA synthesis temperature from 90 to 115 °C (i.e., from below to above the Tg of the final PMMA block) does not alleviate this unexpected problem. Moreover, only spherical nanoparticles can be obtained at 115 °C when targeting PMMA DPs between 50 and 400 with the same PLMA22 precursor. This suggests that nanoparticle formation may occur by a chain expulsion/insertion mechanism at this relatively high reaction temperature. PLMA22–PMMAx nanoparticles were characterized in terms of their particle size and morphology using dynamic light scattering (DLS), transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS). DLS and TEM studies of a 0.1% w/w dispersion of PLMA22–PMMA69 short worms indicated an irreversible worm-to-sphere transition on heating from 20 to 150 °C. Oscillatory rheology and TEM studies indicated that this thermal transition was only partially reversible for a 20% w/w dispersion of PLMA22–PMMA69 short worms

Time-resolved small-angle neutron scattering studies of the thermally-induced exchange of copolymer chains between spherical diblock copolymer nanoparticles prepared via polymerization-induced self-assembly

Sterically-stabilized diblock copolymer nanoparticles (a.k.a. micelles) are prepared directly in non-polar media via polymerization-induced self-assembly (PISA). More specifically, a poly(lauryl methacrylate) chain transfer agent is chain-extended via reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of methyl methacrylate (MMA) to form sterically-stabilized spheres at 20% w/w solids in n-dodecane at 90 °C. Both fully hydrogenous (PLMA39–PMMA55 and PLMA39–PMMA94) and core-deuterated (PLMA39–d8PMMA57 and PLMA39–d8PMMA96) spherical nanoparticles with mean core diameters of approximately 20 nm were prepared using this protocol. After diluting each dispersion in turn to 1.0% w/w with n-dodecane, small-angle X-ray scattering studies confirmed essentially no change in spherical nanoparticle diameter after thermal annealing at 150 °C. Time-resolved small angle neutron scattering was used to examine whether copolymer chain exchange occurs between such nanoparticles at elevated temperatures. Copolymer chain exchange for a binary mixture of PLMA39–PMMA55 and PLMA39–d8PMMA57 nanoparticles produced hybrid (mixed) cores containing both PMMA55 and d8PMMA57 blocks within 3 min at 150 °C. In contrast, a binary mixture of PLMA39–PMMA94 and PLMA39–d8PMMA96 nanoparticles required 8 min at this temperature before no further reduction in neutron scattering intensity could be observed. These observations suggest that the rate of copolymer chain exchange depends on the degree of polymerization of the core-forming block. Relatively slow copolymer chain exchange was also observed at 80 °C, which is below the Tg of the core-forming PMMA block as determined by DSC studies. These observations confirm rapid exchange of individual copolymer chains between sterically-stabilized nanoparticles at elevated temperature. The implications of these findings are briefly discussed in the context of PISA, which is a powerful technique for the synthesis of sterically-stabilized nanoparticles

Semi-groupe de Lie associé à un cône symétrique

Volcanic arcs are the surface expression of magmatic systems that result from the subduction of mostly oceanic lithosphere at convergent plate boundaries. Arcs with a submarine component include intraoceanic arcs and island arcs that span almost 22,000 km on Earth\u27s surface, the vast majority of which are located in the Pacific region. Hydrothermal systems hosted by submarine arc volcanoes commonly contain a large component of magmatic fluid. This magmatic-hydrothermal signature, coupled with the shallow water depths of arc volcanoes and their high volatile contents, strongly influences the chemistry of the fluids and resulting mineralization and likely has important consequences for the biota associated with these systems. The high metal contents and very acidic fluids in these hydrothermal systems are thought to be important analogs to numerous porphyry copper and epithermal gold deposits mined today on land

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Transurethral deroofing of midline prostatic cyst for subfertile men

We evaluated the efficacy of transurethral deroofing of a midline prostatic cyst in subfertile men with one or more of the following semen abnormalities: decreased ejaculatory volume, decreased sperm motility and oligo- or azoospermia. Results from treatment of a series of 11 subfertile men with a midline prostatic cyst by transurethral deroofing of the cyst are presented. Five patients showed an improvement of seminal volume. Only one patient demonstrated an improvement of sperm count. Sperm motility was not influenced. No relationship was found between positive outcome following operation and either size of the cyst or dilatation of the seminal vesicles. Spontaneous pregnancies did not occur after transurethral deroofing of the midline prostatic cyst. In conclusion, our study suggests a poor efficacy of transurethral deroofing of a midline prostatic cyst in subfertile men with the above mentioned semen abnormalities

Effect of salt on the formation and stability of water-in-oil Pickering nanoemulsions stabilized by diblock copolymer nanoparticles

Sterically stabilized diblock copolymer nanoparticles are prepared in n-dodecane using polymerization-induced self-assembly. Precursor Pickering macroemulsions are then prepared by the addition of water followed by high-shear homogenization. In the absence of any salt, high-pressure microfluidization of such precursor emulsions leads to the formation of relatively large aqueous droplets with DLS measurements indicating a mean diameter of more than 600 nm. However, systemically increasing the salt concentration produces significantly finer droplets after microfluidization, until a limiting diameter of around 250 nm is obtained at 0.11 M NaCl. The mean size of these aqueous droplets can also be tuned by systematically varying the nanoparticle concentration, applied pressure, and the number of passes through the microfluidizer. The mean number of nanoparticles adsorbed onto each aqueous droplet and their packing efficiency are calculated. SAXS studies conducted on a Pickering nanoemulsion prepared using 0.11 M NaCl confirms that the aqueous droplets are coated with a loosely packed monolayer of nanoparticles. The effect of varying the NaCl concentration within the droplets on their initial rate of Ostwald ripening is investigated using DLS. Finally, the long-term stability of these water-in-oil Pickering nanoemulsions is assessed using analytical centrifugation. The rate of droplet ripening can be substantially reduced by using 0.11 M NaCl instead of pure water. However, increasing the salt concentration up to 0.43 M provided no further improvement in the long-term stability of such nanoemulsions

Investigation of Alkyne Regioselectivity in the Ni-Catalyzed Benzannulation of Cyclobutenones

A Ni-catalyzed benzannulation reaction of cyclobutenones and alkynes provides a rapid synthesis of heavily substituted phenols. The regioselectivity of this reaction can be modulated by variation of substituents on the alkyne. Though the incorporation of Lewis basic donors provides modest selectivities, the use of aryl substituents can provide high levels of regiocontrol. Finally, alkynylboronates derived from alkyl-substituted acetylenes provide both high yields and regioselectivities. This study suggests that alkynes bearing one sp2- and one sp3-based substituent can undergo benzannulation with high levels of regiocontrol whereby the sp3-based group is incorporated ortho-to the phenolic OH