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

被引:60
作者
Judzewitsch, Peter R. [1 ]
Corrigan, Nathaniel [1 ]
Trujillo, Francisco [1 ]
Xu, Jiangtao [1 ]
Moad, Graeme [2 ]
Hawker, Craig J. [3 ,4 ,5 ,6 ]
Wong, Edgar H. H. [1 ]
Boyer, Cyrille [1 ]
机构
[1] UNSW, Sydney, NSW, Australia
[2] CSIRO, Mfg Bag 10, Clayton, Vic 3169, Australia
[3] Univ Calif Santa Barbara, Mat Res Lab, Santa Barbara, CA 93106 USA
[4] Univ Calif Santa Barbara, Dept Mat, Santa Barbara, CA 93106 USA
[5] Univ Calif Santa Barbara, Dept Chem, Santa Barbara, CA 93106 USA
[6] Univ Calif Santa Barbara, Dept Biochem, Santa Barbara, CA 93106 USA
基金
澳大利亚研究理事会; 美国国家科学基金会;
关键词
LIVING RADICAL POLYMERIZATION; PET-RAFT POLYMERIZATION; DE-NOVO DESIGN; COMBINATORIAL; COPOLYMERS; CHEMISTRY; PHARMACEUTICALS; PURIFICATION; MECHANISM; LIBRARIES;
D O I
10.1021/acs.macromol.9b02207
中图分类号
O63 [高分子化学(高聚物)];
学科分类号
070305 ; 080501 ; 081704 ;
摘要
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, terpolyrnerization 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.
引用
收藏
页码:631 / 639
页数:9
相关论文
共 83 条
  • [1] On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system
    Adamo, Andrea
    Beingessner, Rachel L.
    Behnam, Mohsen
    Chen, Jie
    Jamison, Timothy F.
    Jensen, Klavs F.
    Monbaliu, Jean-Christophe M.
    Myerson, Allan S.
    Revalor, Eve M.
    Snead, David R.
    Stelzer, Torsten
    Weeranoppanant, Nopphon
    Wong, Shin Yee
    Zhang, Ping
    [J]. SCIENCE, 2016, 352 (6281) : 61 - 67
  • [2] Antibiotic resistance: a rundown of a global crisis
    Aslam, Bilal
    Wang, Wei
    Arshad, Muhammad Imran
    Khurshid, Mohsin
    Muzammil, Saima
    Rasool, Muhammad Hidayat
    Nisar, Muhammad Atif
    Alvi, Ruman Farooq
    Aslam, Muhammad Aamir
    Qamar, Muhammad Usman
    Salamat, Muhammad Khalid Farooq
    Baloch, Zulqarnain
    [J]. INFECTION AND DRUG RESISTANCE, 2018, 11 : 1645 - 1658
  • [3] REACTIVITY RATIOS IN THE REDOX COPOLYMERIZATION OF ACRYLAMIDE AND N-BUTYL ACRYLATE IN DIMETHYLFORMAMIDE
    BALASUBRAMANIAM, TR
    MAHADEVAN, V
    [J]. JOURNAL OF MACROMOLECULAR SCIENCE-CHEMISTRY, 1984, A21 (02): : 245 - 251
  • [4] Elucidating the effect of sequence and degree of polymerization on antimicrobial properties for block copolymers
    Barbon, Stephanie M.
    Truong, Nghia P.
    Elliott, Alysha G.
    Cooper, Matthew A.
    Davis, Thomas P.
    Whittaker, Michael R.
    Hawker, Craig J.
    Anastasaki, Athina
    [J]. POLYMER CHEMISTRY, 2020, 11 (01) : 84 - 90
  • [5] The Right Light: De Novo Design of a Robust Modular Photochemical Reactor for Optimum Batch and Flow Chemistry
    Bonfield, Holly E.
    Mercer, Kayleigh
    Diaz-Rodriguez, Alba
    Cook, Gemma C.
    McKay, Blandine S. J.
    Slade, Pawel
    Taylor, George M.
    Ooi, Wei Xiang
    Williams, Jason D.
    Roberts, Jack P. M.
    Murphy, John A.
    Schmermund, Luca
    Kroutil, Wolfgang
    Mielke, Tamara
    Cartwright, Jared
    Grogan, Gideon
    Edwards, Lee J.
    [J]. CHEMPHOTOCHEM, 2020, 4 (01): : 45 - 51
  • [6] Photoinduced Controlled Radical Polymerizations Performed in Flow: Methods, Products, and Opportunities
    Buss, Bonnie L.
    Miyake, Garret M.
    [J]. CHEMISTRY OF MATERIALS, 2018, 30 (12) : 3931 - 3942
  • [7] Combining batch and continuous flow setups in the end-to-end synthesis of naturally occurring curcuminoids
    Carmona-Vargas, Christian C.
    Alves, Leandro de C.
    Brocksom, Timothy J.
    de Oliveira, Kleber T.
    [J]. REACTION CHEMISTRY & ENGINEERING, 2017, 2 (03): : 366 - 374
  • [8] Role of peptide hydrophobicity in the mechanism of action of α-helical antimicrobial peptides
    Chen, Yuxin
    Guarnieri, Michael T.
    Vasil, Adriana I.
    Vasil, Michael L.
    Mant, Colin T.
    Hodges, Robert S.
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2007, 51 (04) : 1398 - 1406
  • [9] De novo design and in vivo activity of conformationally restrained antimicrobial arylamide foldamers
    Choi, Sungwook
    Isaacs, Andre
    Clements, Dylan
    Liu, Dahui
    Kim, Hyemin
    Scott, Richard W.
    Winkler, Jeffrey D.
    DeGrado, William F.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (17) : 6968 - 6973
  • [10] Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow CGMP conditions
    Cole, Kevin P.
    Groh, Jennifer McClary
    Johnson, Martin D.
    Burcham, Christopher L.
    Campbell, Bradley M.
    Diseroad, William D.
    Heller, Michael R.
    Howell, John R.
    Kallman, Neil J.
    Koenig, Thomas M.
    May, Scott A.
    Miller, Richard D.
    Mitchell, David
    Myers, David P.
    Myers, Steven S.
    Phillips, Joseph L.
    Polster, Christopher S.
    White, Timothy D.
    Cashman, Jim
    Hurley, Declan
    Moylan, Robert
    Sheehan, Paul
    Spencer, Richard D.
    Desmond, Kenneth
    Desmond, Paul
    Gowran, Olivia
    [J]. SCIENCE, 2017, 356 (6343) : 1144 - 1150