High-Throughput Process for the Discovery of Antimicrobial Polymers and Their Upscaled Production via Flow Polymerization

Abstract

The combination of high-throughput (HTP) processes and flow-mediated synthesis allows large data sets to be generated quickly while also permitting large quantities of materials to be prepared in a continuous fashion. In this work, the benefits of wellplate-based HTP polymerization and flow-mediated chemistry are used to streamline the screening and upscaling of value-added biomedical materials through a robust photopolymerization strategy, namely, photoinduced electron/energy transfer-reversible addition− fragmentation chain transfer (PET-RAFT) polymerization. A library of potential antimicrobial polymers was generated from an initial pool of monomers and tested for their activity against Pseudomonas aeruginosa (PA). The antimicrobial activity of the most promising candidates was then elucidated through structure−property analyses performed via both plate and flow polymerization processes; interestingly, terpolymerization of mixtures of acrylate and acrylamide monomers produced terpolymers with gradient architectures due to their reactivity ratios, which ultimately dictated the resulting antimicrobial activity. Finally, the polymers found to have the highest antimicrobial activity were upscaled in a flow reactor. This workflow provides a general and highly accessible methodology for the discovery and synthetic scaling of optimized polymer structures for biomedical applications such as new antimicrobial agents.

Progress and Perspectives Beyond Traditional RAFT Polymerization

“…[152][153][154][155] In recent years, the ability to conduct RAFT without traditional deoxygenation protocols has facilitated a growing number of benchtop combinatorial and high-throughput studies, which are particularly advantageous for generating polymers with specific biological interactions. Enzymatic degassing [84,156] and photochemical oxygen sequestration [155,[157][158][159][160][161][162][163][164][165][166] have afforded access to (ultra)low reaction volumes and finely controlled reagent conditions that are common prerequisites for high-throughput translation.…”

New Light in Polymer Science: Photoinduced Reversible Addition-Fragmentation Chain Transfer Polymerization (PET-RAFT) as Innovative Strategy for the Synthesis of Advanced Materials

“…These studies highlight the possibility of test multiblock copolymers made via a highly efficient polymerization technique against a range of bacteria in short time and systematically manner. Finally, in a very recent work [ 123 ] high throughput process and flow polymerization were merged for upscaled production of antimicrobial polymers. In this work the authors highlight the possibility to build up a library of antimicrobial polymers, testing their antimicrobial activity through structure-properties analysis via both plate and flow polymerization.…”

Initiation of RAFT Polymerization: Electrochemically Initiated RAFT Polymerization in Emulsion (Emulsion eRAFT), and Direct PhotoRAFT Polymerization of Liquid Crystalline Monomers

“…[10][11][12][13] The recent upsurge in interest in direct photoinitiated RAFT and photoinduced energy or electron transfer (PET)-RAFT [14,15] can largely be linked to the desire to obtain polymers free from initiator-derived by-products (a particular concern in RAFT single-unit monomer insertion (RAFT-SUMI)) [16,17] and in the synthesis of sequence-defined polymers [18,19] and the need for spatial and temporal control over the RAFT process, which is critically important in flow and high-throughput polymer synthesis. [20,21] Electrochemically initiated RAFT polymerization, dubbed eRAFT, has recently attracted attention for similar reasons. [22][23][24][25][26] Electrochemically Initiated RAFT Polymerization (eRAFT) in Emulsion…”