degradation. The flow rate was lowered to 2 mL min-1 in order to reduce the pressure in the system. There was also a possibility that radical species, which may react with and alter the column material, were still present in the solution after injection. Therefore, an inhibitor, 2,6-di-tert-butyl-4-methylphenol (BHT) was added to the eluent to quench any lingering radical species.
2.4.1.3 GPC Protocol for PtBuAm Synthesis
For the RAFT polymerisations of tert-butyl acrylamide (tBuAm), THF GPC was employed with a flow rate of 2 mL min-1(6 minutes chromatograms) to minimise column degradation. To assess the consistency of THF GPC, chromatograms for the RAFT polymerisation of tBuAm were collected at steady state over 160 minutes (Figure 2.22a). Consistent overlapping chro-matograms were obtained, however calculated molecular weight data (Figure 2.22b) showed a slight variation in both Mn and Đ, likely due to noisy baseline data. The small variation was not expected to significantly affect any self-optimisation processes.
Figure 2.22: a) GPC chromatograms and b) molecular weight data obtained continuously over 160 minutes for PtBuAm200 on online platform. As more samples are taken (black to red) no chromatogram broadening is observed. 3 µL of sample was injected per measurement.
2.5 Conclusion
In this chapter a series of flow reactors, with gradually increasing capabilities, and associated methodologies developed throughout this thesis were described. Reactor A was used perform RAFT polymerisations in chapter 3. Furthermore a transient kinetic profiling method was developed using this reactor. Reactor B was used to characterise the reactor coils (5 or 20 mL) used in chapter 3. The 20 mL reactor coil was found to have a narrower residence time distribution than the 5 mL coil due to the reduced impact of dead zones. The number of
2.5. Conclusion
reactor volumes required to reach steady state (3 reactor volumes) was also determined using Reactor B. Reactor C was developed in order to perform and kinetically profile, via online NMR, ultrafast RAFT-PISA polymerisations during chapter 4. The number of scans, pulse method and flow cell geometry were all optimised to generate an NMR protocol with a fast spectra acquisition time that maintained high spectra quality. Reactor D was developed to perform the automated multi-objective screening and self-optimisation of RAFT polymerisations using NMR and GPC analysis in chapter 5. DMF GPC protocols for the RAFT polymerisation of dimethylacrylamide allowed for the collection of chromatograms in three minutes. However constant use of this protocol led to broadening of chromatograms due to degradation of the column material. THF GPC protocols for the RAFT polymerisation of tert-butylacrylamide allowed for collection of chromatograms in six minutes. Continuous collection of chromatograms over 160 minutes indicated consistent chromatograms with no broadening observed.
Chapter 3
Synthesis and Kinetic Profiling of Block Copolymer Nano-objects via RAFT Polymerisation using a Flow Platform
3.1 Introduction
Flow chemistry is an alternative to batch chemistry, it offers improvements in reaction pa-rameters such as: heat transfer, scale up, reproducibility and safety.187,188 These benefits have seen uptake of flow chemistry into many areas of chemical synthesis.4 Given that block copoly-mers are already present in a vast number of advanced materials,189 precise control of their structure over a variety of scales is of paramount importance. This can be achieved in batch by using reversible deactivation radical polymerisation (RDRP) technologies such as ATRP,90 NMP89 and RAFT polymerisation.92 Controlled radical polymer syntheses are seeing an in-creased uptake in the use of flow chemistry.190 Polymerisations are exothermic reactions and as a result, large temperature increases can be observed when performed in batch reactors.109,111 Effective dissipation of heat is then dependent on reactor geometry. More severely, the quality of the polymer becomes dependent on the type of reactor chosen, as changing temperature profiles result in altered kinetics which govern chain growth reactions. This reactor
depen-3.1. Introduction
dence and need to dissipate large amounts of heat hinders the scalability of batch polymeri-sations.109 The better heat transfer, reproducibility and scalability afforded by flow reactors make them an ideal alternative to batch reactors, which will ultimately allow for the greater control over polymer quality and architecture required for the generation of new advanced polymeric materials. The improved heat transfer and the ability to conduct the reaction at temperatures above the solvent boiling point, by operating at high pressure, has also enabled acceleration of the process.153 Flow platforms have more recently been combined with new gen-eration RAFT technologies such as photo RAFT191–193 and oxygen tolerant PET-RAFT,164 while novel reactor configurations such as looped flow reactors and the ability to telescope processes has also enabled the preparation of multi-block copolymers by sequential polymeri-sation.30 Heterogeneous RAFT polymerisation technologies have been widely reported over the last 15 years or so and are popular since they allow rational production of a variety of block copolymer nanoparticles via polymerisation-induced self-assembly (PISA).13,194,195 Fur-thermore, the precise nature of the polymerisation enables control not just over the morphology, but the specific dimensions of the resulting nanoparticles.196,197 This precision could provide additional complementary control over polymer nanoparticles within flow systems. Of the rel-atively few reports where PISA has been conducted in tubular reactors, surfactant-free RAFT emulsion polymerisation of methyl methacrylate (MMA),178 and RAFT dispersion polymeri-sation of MMA using a poly(poly(ethylene glycol)methyl ether methacrylate) macro-CTA in a water/ethanol solvent mixture have both produced well-defined spherical particles.179 Non-spherical morphologies have also been synthesised via visible light-mediated PISA in a tubular reactor using a poly(ethylene glycol) macro-CTA.32,167 This chapter focuses on the synthesis and kinetic monitoring of poly(dimethylacrylamide)-based block co-polymers by RAFT aque-ous dispersion polymerisation using a flow platform (Figure 3.1). Initially, batch kinetics for all RAFT polymerisations were obtained. Then using Reactor A and the transient profiling method described in chapter 2, kinetic data obtained for the RAFT polymerisation of dimethy-lacrylamide was compared to traditional sampling methods. Further kinetic profiling of the chain extension of poly(dimethylacrylamide) via RAFT aqueous dispersion polymerisation with both N -isopropylacrylamide (NIPAm) and diacetone acrylamide (DAAm) was performed and the subsequent polymer nanoparticles produced were characterised by DLS and TEM.