SINGLE-CHAIN POLYMER NANOPARTICLES VIA PHOTO DIMERIZATION OF ANTHRACENE

IntroductionInspired 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 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 should demonstrate unique characteristics that SCPNs have yet to achieve to date.

Figure 1: Simulated Single Chain folding

Figure 2: Reaction of Anthracene

Figure 3: Mechanism of RAFT Polymerization 11

HO

O

Scheme 1

O HO

NaBH4

THF

Synthesis of Polymers

O

O

DCC, dry CH3CN

S SS

O

O

Dry Toluene and AIBNHeated to 80 o C 24-48hrs

O

O +

1

2MMA

AMMAPAMMA-r-PMMA

10

CNOH

O

OO

OO

x/y

Synthesis of Anthracene Monomer

Method and ExperimentThe selected polymerizations method was Reversible Addition Fragmentation chain Transfer or RAFT. This method was developed at the Commonwealth Scientific and Industrial Research Organization (CSIRO). The mechanism behind the robustness of the process is shown in Figure 3.11 Using this methodology, the reactions used to synthesize the anthracene containing polymers is shown in Scheme 1.

Results and AnalysisThe polymers obtained using RAFT are shown in the table below. To form nanoparticles, solutions of these polymers at 0.1 mg/mL in tetrahydrafuran (THF) were then irradiated with ultraviolet light at 350 nm. The reverse reaction was done after dimerization with 254 nm UV light. Reaction was monitored by UV-Vis Spectroscopy

UV-Vis absorption spectrum was obtained every 30 seconds along the dimerizing path way and every 15 seconds for the photo cleavage as shown in figure 4. The degree of crosslinking was calculation from the change of λmax . Furthermore, samples distributed along both path ways were analyzed by size exclusion chromatography. The data obtained are illustrated in figure 5 and table 2. Compared to the parent polymer, the nanoparticles shifted to longer retention times, lower intrinsic viscosities and smaller hydrodynamic radii. These results are consistent with the our previous work and has literature precedence for nanoparticle formation.1,2, 4, and 14 The data also shows photo cleavage occurs in a way that does not disturb the structural integrity of nanoparticle. TEM images also confirmed the formation well defined nano structures formed (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. This effect gets more pronounced with higher anthracene incorporation , but still remains insignificant as these coupled particles are absent from the SEC UV traces.

Conclusions

Future Work

Literature Cited(1) 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) Moad, G.; Chong, Y. K.; Postma, A.; Rizzardo, E.; Thang, S. H. 2005, 46, 8458–8468.

(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

• A set of polymers were made and analyzed which provided strong evidence for the formation of architecturally defined sub 20 nm nanoparticles. (Figure 7)

• The degree to which these particles are formed as well as their size is dependent on the amount of anthracene moieties incorporated along the polymer backbone.

• RAFT Polymerization provided a robust means to synthesize polymeric nanoparticles

•Complete Series 25,000 g/mol and 100,000 g/mol

•Perform additional photochemical and thermal studies to better understand the system

•Nanoparticle Functionalization using orthogonal transformations: Diels alder, Acid Base, and Thiol

Peter G. Frank, and Erik B. BerdaChemistry Department, University of New Hampshire

Acknowledgements Further Information Dr. Erik Berda

Dr. Richard Johnson

Dr. Pat. Wilkinson

Berda Group Members

Center for High-Rate Nanomanufacturing

UNH Chemistry Department

Single Chain Polymer Nanoparticle 15 RAFT Polymerization 16 Size exclusion Chromatography 17

Contact Information:Peter FrankPeter.Frank@unh.eduChemistry Dept. University of New Hampshire

Figure 4

Figure 6

Figure 7

Ultraviolet Light >300 nm

Ultraviolet Light < 300 nmor heat

2 Anthracene Molecules Anthracene Dimer

MW (g/m)* PDI* Percent of anthracene**P1 30.8 x 103 1.17 10 P2 30.6 x 103 1.14 20P3 42.9 x 103 1.16 46*Determined via GPC ** Determined via NMR

Polymer

Irradiation time (min)

Peak retention time (min)a

Rh

(nm)c[h]c

P1 0 24.85 4.0 13.31 24.93 4.1 12.5

2.5 25.03 4.2 10.36.5 25.23 4.4 9.211.5 25.37 3.4 7.5

P2 0 25.64 3.6 9.51 25.83 3.3 7.0

2.5 26 3.2 7.47.5 26.31 3.0 6.7

22.5 26.46 2.9 5.1P3 0 25.68 3.5 6.6

15 26.09 3.1 6.130 26.33 2.9 3.960 26.39 2.3 2.4

Figure 5

Figure 6Table 2

S

OO

OOx/yS

S

10

CNOH

O

Aminolysis to thiolfor thiol chemistry such Click or Nucleophiic

Acid Base Chemistry

Diels Alder

Figure 7