Application of anthracene towards the synthesis and manipulation of single-chain polymer nanoparticles Peter G Frank a, Mark Cashman a, Alka Prasher a , Bryan T Tuten b , Danming Chao c, and  Erik B Berda a,b a Chemistry Department, b Material Science Program, University of New Hampshire , c Alan G. MacDiarmid Institute, College of Chemistry, Jilin University, Changchun, P. R. China Introduction Inspired by biopolymers, the concept of single-chain polymer nanoparticles (SCPNs) was recently developed as a means to reliably build well defined functional macromolecular structures in the sub-20 nm size regime. Such materials are promising to applications in drug delivery and diagnosis, as well as recyclable catalysis.1-9 The key to creating these nanoparticles from polymers is intramolecular cross-linking, whereby different parts of a single chain are connected as shown in Figure 1. These connections can be induced by utilizing a variety of interactions namely, covalent bonds,3 supramolecular cross-linkages,4 pi-pi stacking,5 and metal coordination.5 Dilute conditions are therefore required to promote intra-chain reactions rather than inter-chain coupling reactions. Our approach to creating SCPNs uses light to facilitate polymer folding. Photosensitive polymer chains do not require cross-linking agents but still offers controlled particle formation, in addition to tunability of the light required to form the particle and functional group tolerance.10 This work utilizes the homo-coupling of two anthracene molecules to form a dimer as shown in Figure 2. This dynamic system has been shown to be reversibly dimerized by light of different wavelengths and can also be uncoupled using heat.11 Incorporating a multitude of anthracene along a polymer chain allows the utilization of light as a non-invasive means to create and manipulate nanoparticles per application. Furthermore, with heat as an additional stimulus, as well as the fluorescence and rigid properties of anthracene, the resulting polymer may demonstrate unique characteristics that SCPNs have yet to achieve to date. Compared to the parent polymer, the nanoparticles shifted to longer retention times, lower intrinsic viscosities and smaller hydrodynamic radii (Table 2 below). These results are consistent with our previous work and has literature precedence for nanoparticle formation.1,2, 4, and 14 TEM images also confirmed the formation well defined nano structures formed (Figure 6). Figure 6 As expected, higher incorporation of anthracene led to the formation of smaller particles (Table 2). It was also observed that minute amounts of chain–chain coupling is possible as shown by the shoulders of the SEC MALS and the absence of shoulders on the SEC UV traces of Figure 4. This effect gets more pronounced with higher anthracene incorporation , but still remains insignificant as these coupled particles are absent from the SEC UV traces. It was also observed that larger and more flexible polymers often experience a greater decrease in Rh and [ƞ]. This suggests that particle properties can be further tuned with polymerizations techniques and monomers species. Figure 1: Simulated Single Chain folding Conclusions Results and Analysis Photo-responsive polymers made demonstrated strong evidence for the formation of architecturally defined sub 20 nm nanoparticles. Particle formation is dependent on the polymer backbone, the amount of anthracene moieties incorporated and the irradiation time. The statistical copolymers obtained are shown in the table below. P1 to 3 are methyl methacrylate based, BMP1 to 2 are butyl methacrylate based and RP1 to 3 are ROMP made polymers. To form nanoparticles, solutions of these polymers at 0.1 mg/mL in tetrahydrafuran (THF) were then irradiated with ultraviolet light at 350 nm. Reaction was monitored by UV-Vis Spectroscopy A selection of samples were isolated along the crosslinking pathway and analyzed via multi-detection gel permeation chromatography. The degree of crosslinking was calculation from the change of λmax and was found to be 85% on average This method was previously shown to be an effective approach to characterizing these systems.11 Figure 4 and 5 illustrates the incremental crosslinking by sequential shifting to longer retention on the size exclusion chromatograms. Figure 2: Reaction of Anthracene Future Work Polymers ^ RAFT ~ ROMP MW (kDA)* PDI* Percent of anthracene** ^P1 30.8 1.17 10 ^P2 30.6 1.14 20 ^P3 42.9 1.16 46 ^BMP1 126.7 1.07 ^BMP2 450.3 1.3 ~RP1 14 1.01 ~RP2 49.9 1.04 ~RP3 276.3 Explore additional polymeric backbone to study their intra-crosslinking ability Explore applications of these photo responsive polymer systems Experiment Literature Cited The selected polymerization methods were Reversible Addition-Fragmentation chain Transfer( RAFT) and Ring Opening Metathesis Polymerization (ROMP). Both techniques facilitate the synthesis of well defined polymeric architectures i.e. target molecular weight, narrow molecular weight distributions, and statistical incorporation of the desired monomers. The synthetic methods are shown in Scheme 1 and 2. Aiertza, M. K.; Odriozola, I.; Cabañero, G.; Grande, H.-J.; Loinaz, I. Cell Mol. Life Sci . 2012, 69, 337–46. (2) Altintas, O.; Barner-Kowollik, C. Macromol. Rapid. Commun. 2012, 33, 958–71. (3) Jackson, A. W.; Fulton, D. a. Polym. Chem.. 2013, 4, 31. (4) Foster, E. J.; Berda, E. B.; Meijer, E. W. J. Polym. Sci., Part A: Polym.. Chem.. 2011, 49, 118–126. (5) Brunsveld, L.; Folmer, B. J.; Meijer, E. W.; Sijbesma, R. P. Chem . Rev. 2001, 101, 4071–98. (6) Kost, J.; Langer, R. Adv . Drug Deliv . Rev . 2001, 46, 125–48. (7) Lattuada, M.; Hatton, T. A. Nano Today 2011, 6, 286–308. (8) Helms, B.; Guillaudeu, M.; Hawker, C. J.; Fréchet, J. M. J. Angew. Chem. Int. Ed. Engl. 2005, 44, 6384–7. (9) Stuart, M. a C.; Huck, W. T. S.; Genzer, J.; Müller, M.; Ober, C.; Stamm, M.; Sukhorukov, G. B.; Szleifer, I.; Tsukruk, V. V; Urban, M.; Winnik, F.; Zauscher, S.; Luzinov, I.; Minko, S. Nat. Mater. 2010, 9, 101–113. (10) Breton, G. W.; Vang, X. J. Chem. Edu. 1998, 75, 81–82. (11) Frank, P. G.; Tuten, B. T.; Prasher, A.; Chao, D.; Berda, E. B. Macromol. Rapid Commun. 2014, 35, 249–253. (12) He, J.; Tremblay, L.; Lacelle, S.; Zhao, Y. Soft Matter 2011, 7, 2380. (13) Gillissen, M. a. J.; Voets, I. K.; Meijer, E. W.; Palmans, A. R. a. Polym. Chem. 2012, 3, 3166. (14) Tuten, T.B.; Chao, .D; Lyon, C.; Berda, E. Polym. Chem. 2012, 3, 3068-3071. (15) Mes, Tristan, and Anja Palmans. "Single-chain Polymeric Nanoparticles by Stepwise Folding." YouTube. YouTube, 23 Dec. 2011. Web. 12 Apr. 2013 (16) CSIRO. "RAFT - Reversible Addition-Fragmentation Chain Transfer." YouTube. YouTube, 23 June 2009. Web. 12 Apr. 2013 (17) GE Life Sciences. "Principles of Gel Filtration Chromatography." YouTube. YouTube, 13 Sept. 2012. Web. 12 Apr. 2013 *Determined via GPC ** Determined via NMR Figure 5 Polymer Irradiation time (min) Mn( kDA) PDI Rh (nm) [ƞ] (mg/L) P1 30.8 1.17 4 13.3 11.5 33.50 1.16 3.40 7.50 P2 30.6 1.14 3.6 9.5 22.5 29.90 2.90 5.10 P3 42.9 3.5 6.6 60 36.70 2.30 1.67 BMP1 126.70 1.07 5.90 11.50 72 125.80 1.04 5.20 7.10 BMP2 450.3 1.30 10.30 19.28 96 449.90 1.22 7.70 6.87 RP1 14.00 1.01 10.89 15 2.70 9.61 RP2 49.9 6 27.86 45 49.10 1.03 5.40 20.35 RP3 276.60 59.65 54 276.20 1.02 11.70 35.70 Figure 4 Acknowledgement Further Information Chem. Dept. and Grad. School of The University of New Hampshire Thank you sponsors: Henry Hill Trust and NESACS Single -Chain Polymer Nanoparticle 15 RAFT Polymerization 16 Size exclusion Chromatography 17 Contact Information: Peter Frank Peter.Frank@unh.edu Chemistry Dept. University of New Hampshire Dr. Erik Berda Dr. Patricia Wilkinson Dr. Richard Johnson Berda Group Members