Voorter Pieter-Jan, Dev Gayathri, Buckinx Axel-Laurenz, Dai Jinhuo, Subramanian Priya, Kumar Anil, Cameron Neil R, Junkers Tanja
Polymer Reaction Design Group, School of Chemistry, Monash University 19 Rainforest Walk, Building 23 Clayton VIC 3800 Australia
Department of Materials Science and Engineering, Monash University 14 Alliance Lane Clayton Victoria 3800 Australia.
Chem Sci. 2023 Jun 6;14(32):8466-8473. doi: 10.1039/d3sc01819a. eCollection 2023 Aug 16.
A one-pass continuous flow strategy to form block copolymer nanoaggregates directly from monomers is presented. A key development towards such a sophisticated continuous flow setup is a significant improvement in continuous flow dialysis. Often impurities or solvent residues from polymerizations must be removed before block extensions or nanoaggregate formation can be carried out, typically disrupting the workflow. Hence, inline purification systems are required for fully continuous operation and eventual high throughput operation. An inline dialysis purification system is developed and exemplified for amphiphilic block copolymer synthesis from thermal and photoiniferter reversible addition fragmentation chain transfer (RAFT) polymerization. The inline dialysis system is found to be significantly faster than conventional batch dialysis and the kinetics are found to be very predictable with a diffusion velocity coefficient of 4.1 × 10 s. This is at least 4-5 times faster than conventional dialysis. Moreover, the newly developed setup uses only 57 mL of solvent for purification per gram of polymer, again reducing the required amount by almost an order of magnitude compared to conventional methods. Methyl methacrylate (MMA) or butyl acrylate (BA) was polymerized in a traditional flow reactor as the first block RAFT polymerization, followed by a 'dialysis loop', which contains a custom-built inline dialysis device. Clearance of residual monomers is monitored in-line NMR. The purified reaction mixture can then be chain extended in a second reactor stage to obtain block copolymers using poly(ethylene glycol) methyl ether acrylate (PEGMEA) as the second monomer. In the last step, nano-objects are created, again from flow processes. The process is highly tuneable, showing for the chosen model system a variation in nanoaggregate size from 34 nm to 188 nm.
本文提出了一种直接从单体形成嵌段共聚物纳米聚集体的单程连续流动策略。实现这种复杂连续流动装置的一个关键进展是连续流动透析的显著改进。通常，在进行嵌段扩展或纳米聚集体形成之前，必须去除聚合反应中产生的杂质或溶剂残留，这通常会打乱工作流程。因此，为了实现完全连续操作和最终的高通量操作，需要在线纯化系统。本文开发了一种在线透析纯化系统，并以通过热引发和光引发的可逆加成-断裂链转移（RAFT）聚合合成两亲性嵌段共聚物为例进行了说明。结果发现，在线透析系统比传统的间歇透析快得多，其动力学表现出非常可预测的扩散速度系数为4.1×10⁻⁵ s⁻¹。这至少比传统透析快4-5倍。此外，新开发的装置每克聚合物仅使用57 mL溶剂进行纯化，与传统方法相比，所需量再次减少了近一个数量级。甲基丙烯酸甲酯（MMA）或丙烯酸丁酯（BA）在传统流动反应器中作为第一嵌段进行RAFT聚合，随后进入一个“透析回路”，其中包含一个定制的在线透析装置。通过在线核磁共振监测残留单体的清除情况。然后，纯化后的反应混合物可以在第二个反应器阶段进行链扩展，以使用聚（乙二醇）甲基醚丙烯酸酯（PEGMEA）作为第二单体获得嵌段共聚物。在最后一步中，同样通过流动过程制备纳米物体。该过程具有高度可调性，对于所选的模型系统，纳米聚集体尺寸在34 nm至188 nm之间变化。
