No abstract

Monodisperse sequence-defined oligomers have been synthesized in solution in the absence of protecting groups. These structures have been prepared stepwise using two consecutive chemoselective reactions: 1,3-dipolar cycloaddition of terminal alkynes and azides and amidification of carboxylic acids with primary amines. These oligomers were efficiently constructed on either a conventional solid support (commercial Wang resin) or tailor-made soluble polystyrene supports synthesized by atom-transfer radical polymerization. The latter approach was found to be very versatile. Indeed, well-defined soluble macromolecular supports allowed not only the synthesis and cleavage of defined oligomers (i.e., sacrificial support) but also the preparation of noncleavable block copolymers containing sequence-defined segments.

Thermoresponsive oligo(ethylene glycol)-based copolymers were investigated for trypsin conjugation. These copolymers have been synthesized by atom transfer radical polymerization of 2-(2-methoxyethoxy)ethyl methacrylate (MEO(2)MA) with oligo(ethylene glycol) methyl ether methacrylate (OEGMA(475), M(n) = 475 g.mol(-1)) at 60 degrees C in the presence of copper(I) chloride and 2,2'-bipyridyl. Two different ATRP initiators, containing succinimidyl ester moieties, were tested, namely, N-succinimidyl-2-bromopropionate and N-succinimidyl-2-bromoisobutyrate. In both cases, ATRP afforded well-defined polymers with a narrow molecular weight distribution and controlled chain-ends. However, the efficiency of initiation of the two initiators was lower than 1 and therefore the formed polymers exhibited a higher than expected mean degree of polymerization. Nevertheless, all types of polymers could be conjugated to trypsin. The conjugation reaction was performed in borax-HCl buffer. Sodium dodecyl sulfate poly(acrylamide) gel electrophoresis (SDS-PAGE) indicated that polymer/enzyme conjugates were obtained in all cases. However, (co)polymers initiated by N-succinimidyl-2-bromopropionate led to the best conjugation results. The formed P(MEO(2)MA-co-OEGMA(475))-trypsin conjugates were found to be thermoresponsive and moreover exhibited a higher enzymatic activity than unmodified trypsin.

A step-growth strategy was investigated for preparing functional periodic copolymers. Functional heterotelechelic R-alkyne, ω-azido poly(styrene-co-N-substituted maleimide) precursors (M n ≈ 2500 g 3 mol -1 ) have been prepared and subsequently polymerized by copper-catalyzed azide-alkyne cycloaddition (CuAAC). These precursors have been first synthesized by sequential atom transfer radical copolymerization of styrene and a N-substituted maleimide (i.e., benzyl maleimide, N-(2-(amino-tBOC)ethylen)-maleimide, or benzyl N,N-maleoylglycinate) initiated by 3-(1,1,1-trimethylsilyl)-2-propynyl 2-bromo-2-methylpropanoate. In this approach, styrene homopolymerization was first started, and a discrete amount of the maleimide comonomer (e.g., 1 equiv as compared to initiator) was added when styrene half-conversion was reached. This controlled maleimide addition resulted in the formation of well-defined polystyrene segments containing a functional maleimide in the middle of their chains (i.e., in average 1 unit per chain). Subsequently, the sequence-controlled copolymers poly(styrene-co-N-substituted maleimide) have been transformed into reactive heterotelechelic polymers. Various synthetic pathways have been compared for preparing these reactive intermediates. Ultimately, these heterotelechelic precursors were polymerized by CuAAC. 1 H NMR and SEC evidenced the formation of high-molecular-weight periodic copolymers.