Automated Synthesis of SequenceControlled Polymers Delphine Chan-Seng and Jean-François Lutz* Precision Macromolecular Chemistry, Institut Charles Sadron, 23 rue du Loess, B. P. 84047, 67034 Strasbourg Cedex 2, France,
[email protected] OVERVIEW Deoxyribonucleic acid (DNA) and proteins are among the most studied natural biomacromolecules and possess a sequence controlled primary structure. For decades, many researchers have looked at different approaches to mimic the degree of sequence control existing in proteins.1-2 The first technique considered was solid phase synthesis, widely used for the preparation of peptides, allowing the synthesis of sequence-controlled oligomers that has been extended to the preparation of unnatural oligomers including oligoamides, oligocarbamates and oligo(amidoamine)s.3 While this method allows a very good control of the sequences, the range of monomers used up to now is still limited to constituting units able to be added under step-growth condensation reactions. The sequence control of polymers prepared under chain-growth polymerization conditions is more challenging to realize. Polymer chemists were interested in the sequence control of the repeat units of the polymer in vinyl polymerization using various strategies. For example, Sawamoto reported an approach consisting in using a template-bearing initiator assisting the polymerization by recognizing a particular monomer in a relatively rigid framework,4 while Kamigaito designed monomers constituted of the sequence of repeat units desired that is then polymerized by metal-catalyzed step-growth radical polymerization.5 Another approach looks at the sequence control of vinyl comonomers on the polymer backbone governed by kinetics during the polymerization process.6 The first illustration of this concept concerns the synthesis of alternating copolymers prepared by radical polymerization using specific comonomer pairs such as styrene/maleic anhydride and vinylcarbazole/fumaronitrile.7-11 Recently, the group of Lutz has developed a concept based on the copolymerization characteristics of styrene and N-substituted maleimides under controlled radical polymerization conditions.12-13 In fact, N-substituted maleimides have a low tendency to homopolymerize, but a strong tendency to copolymerize with styrene leading to alternated copolymers when the comonomers are used in equimolar proportions. While performing the controlled radical polymerization of this comonomer pair in the presence of an excess of styrene, N-substituted maleimide is consumed fast and locally on the polymer backbone. This method allows the introduction of various N-substituted maleimides with a precise control of their positioning along the polystyrene chain as illustrated in Figure 1. Controlled monomer addition R2 O
t0
N
O
t1 convS ~ 0.25
t2
t3
convS ~ 0.5
convS ~ 0.75
Living chain-growth
Figure 1. General concept of the synthesis of sequence-controlled polymers prepared by controlled radical polymerization of styrene with Studied N-substituted maleimides precise local addition of N-substituted maleimides.
While this concept works well in a traditional chemistry laboratory, we are interested in investigating the performances and limitations of this polymerization system when used on an automated platform. Indeed, apart from well-established automated solid-phase synthesis, it was recently evidenced that robotic platforms may be of great interest for liquid-phase polymer chemistry.14-15 The synthesizer used (Figure 2) is equipped with various tools able to distribute solid and liquid reagents, perform reactions under inert gas upon heating, withdraw samples during the polymerization, etc. permitting the adaptation of the polymerization traditionally performed by a chemist with standard chemistry glassware to this robotic platform. The results obtained for the polymerization of styrene under controlled radical polymerization with the precise local introduction of N-substituted maleimides using the automated platform will be discussed in this presentation.
a
b
Figure 2. Description of the automated synthesizer used for the synthesis of sequence-controlled polymers: (a) General view of the robotic platform. This particular picture does not fully correspond to the configuration used in the experiments. Picture reprinted by courtesy of Chemspeed Technologies AG. (b) Configuration used in the present work including tools for automated dosage of solids and liquids into glass reactors and automated withdrawal of aliquots during the polymerization. ACKNOWLEDGEMENTS The authors thank the CNRS, the University of Strasbourg, the international Center for Frontier Research in Chemistry and the European Research Council (ERC grant agreement n°258593) for financial support. REFERENCES Badi, N.; Lutz, J.-F. Chem. Soc. Rev. 2009, 38, 3383-3390. Brudno, Y.; Liu, D. R. Chem. Biol. 2009, 16, 265-276. Hartmann, L.; Börner, H. G. Adv. Mater. 2009, 21, 3425-3431. Ida, S.; Terashima, T.; Ouchi, M.; Sawamoto, M. J. Am. Chem. Soc. 2009, 131, 10808-10809. 5. Satoh, K.; Ozawa, S.; Mizutani, M.; Nagai, K.; Kamigaito, M. Nat. Commun. 2010, 1, 6. 6. Lutz, J.-F. Polym. Chem. 2010, 1, 55-62. 7. Cowie, J. M. G., Alternating copolymers. Plenum Press: New York, 1985. 8. Benoit, D.; Hawker, C. J.; Huang, E. E.; Lin, Z.; Russell, T. P. 2000, 33, 1505-1507. StudiedMacromolecules styrenics 9. Chen, G.-Q.; Wu, Z.-Q.; Wu, J.-R.; Li, Z.-C.; Li, F.-M. 2000, 33, 232-234. (a) Macromolecules (b) 10. Chernikova, E.; Terpugova, P.; Bui, C.; Charleux, B. Polymer 2003, 44, 4101-4107. 11. Ma, J.; Cheng, C.; Sun, G.; Wooley, K. L. J. Polym. Sci. Part A: Polym. Chem. 2008, 46, 3488-3498. 12. Pfeifer, S.; Lutz, J.-F. J. Am. Chem. Soc. 2007, 129, 9542-9543. 13. Lutz, J.-F.; Schmidt, B. V. K. J.; Pfeifer, S. Macromol. Rapid Commun. 2011, 32, 127-135. 14. Becer, C. R.; Groth, A. M.; Hoogenboom, R.; Paulus, R. M.; Schubert, U. S. QSAR Comb. Sci. 2008, 27, 977-983. 15. Eggenhuisen, T. M.; Becer, C. R.; Fijten, M. W. M.; Eckardt, R.; Hoogenboom, R.; Schubert, U. S. Macromolecules 2008, 41, 5132-5140. 1. 2. 3. 4.
(21) R = -C6H4-COO-C6F5
(1)
R = -CH3
(11)
R = -C6H4-pOH
(2)
R = -CH2-CH2-CH3
(12)
R = -C6H4-pCF3
(3)
R = -(CH2)9-CH3
(13)
R = -C6H4-mCF3
(4)
R = -CH2-C6H5
(14)
(5)
R = -C6H5
(15)
(22) R = R = -C )2 6H3-m(CF3Materials: Polymeric Science & Engineering 2012 , 107, R = -CH2-C≡CH
(6)
R = -C6F5
(16)
R = -CH2-C≡C-TMS
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