University of Birmingham Predicting monomers for use in polymerization- induced self-assembly

We report an in silico method to predict monomers suitable for use in polymerization-induced self-assembly (PISA). By calculating the dependence of LogPoct/surface area (SA) on the length of the growing polymer chain, the change in hydrophobicity during polymerization was determined. This allowed for evaluation of the capability of a monomer to polymerize to form self-assembled structures during chain extension. Using this method, we identified five new monomers for use in aqueous PISA via reversible additionfragmentation chain transfer (RAFT) polymerization, and confirmed that these all successfully underwent PISA to produce nanostructures of various morphologies. The results obtained using this method correlated well with and predicted the differences in morphology obtained from the PISA of block copolymers of similar molecular weight but different chemical structures. Thus, we propose this method can be utilized for the discovery of new monomers for PISA and also the prediction of their self-assembly behavior. Polymerization-induced self-assembly (PISA) has revolutionized the preparation of soft nanoparticles. Unlike traditional selfassembly strategies, in which a block copolymer is synthesized separately and transitioned into aqueous milieu, PISA occurs in situ as the polymerization progresses. During aqueous PISA, a water-soluble homopolymer is chain-extended with a second, water-miscible monomer. As the polymerization proceeds, the second block becomes gradually insoluble in the reaction media, driving self-assembly. A variety of self-assembled morphologies can be readily accessed by tuning polymerization conditions. In addition to its simplicity, PISA is advantageous as it can be conducted at high solids content (typically 10-30 w/w%) to quantitative or near quantitative conversion of monomer. Figure 1. Schematic illustration of the aqueous RAFT PISA process, A) Coreforming monomers identified in the literature for use in RAFT PISA in aqueous milieu and B) predicted core-forming monomers. Polymer nanoparticles obtained from PISA have applications in nanomedicine and drug delivery, especially in the case of worm or vesicle morphologies, which have specific advantages over [a] Dr. J. C. Foster, S. Varlas, Dr. B. Couturaud, Dr. J. R. Jones, Prof. R. K. O’Reilly School of Chemistry, University of Birmingham Edgbaston, Birmingham, B15 2TT (UK) E-mail: r.oreilly@bham.ac.uk [b] R. Keogh Department of Chemistry, University of Warwick Gibbet Hill Road, Coventry, CV4 7AL (UK) [c] Prof. R. T. Mathers Department of Chemistry, Pennsylvania State University New Kensington, PA 15068 (USA) E-mail: rtm11@psu.edu Supporting information for this article is given via a link at the end of the document. †These authors contributed equally to this work.