Block copolymers chemoenzymatic synthesis

Initial reports on chemoenzymatic block copolymer synthesis focus on the enzymatic macroinitiation from chemically obtained hydroxy-functional polymers (route A in Fig. 4). The first report on enzymatic macroinitiation was published by Kumar et ah, who used anionically synthesized hydroxy-functional polybutadiene of various molecular weights ranging from 2600 to 19,000Da (Fig. 5) [16]. In a systematic study, the authors investigated the efficiency of the macroinitiation of CL and PDF by Novozym 435 as a function of the polybutadiene macroinitiator. The reaction profile showed that polybutadiene consumption steadily increased with the reaction... 

Fig. 4 Chemoenzymatic strategies (a—c) for the synthesis of block copolymers employing enzymatic ROP and radical polymerization techniques...

Fig. 6 Left Strategy for consecutive chemoenzymatic and simultaneous one-pot block copolymer synthesis combining enzymatic ROP and ATRP. Right Influence of ATRP-catalyst system on the conversion of CL in the enzymatic ROP of MMA at 60 °C using ATRP-3 as initiator filled squares reaction in absence of ATRP-catalyst open circles CuBr/PMDETA (1 1 1 ratio with respect to initiator) jiWed triangles CuBr/dNbpy (1 2.1 1 ratio with respect to initiator) open inverted triangles CuBr (1 1 ratio with respect to initiator) yiHed diamonds CuBr2 (1 1 ratio to initiator). CL conversion was determined with H-NMR [26]...

Scheme 2 Chemoenzymatic synthesis of block copolymers consisting of a semifluorinated block of poly(l//, IH, 2H, 2//-perfluorooctyl metharylate) and PCL [29]...

Sha et al. applied the commercially available dual initiator ATRP-4 for the chemoenzymatic synthesis of block copolymers. In a first series of publications, the group reported the successful synthesis of a block copolymer comprising PCL and polystyrene (PS) blocks [31, 32]. This concept was then further applied for the chemoenzymatic synthesis of amphiphilic block copolymers by macroinitiation of glycidyl methacrylate (GMA) from the ATRP functional PCL [33]. This procedure yielded well-defined block copolymers, which formed micelles in aqueous solution. Sha et al. were also the first to apply the dual enzyme/ATRP initiator concept to an enzymatic polycondensation of 10-hydroxydecanoic acid [34]. This concept was then extended to the ATRP of GMA and the formation of vesicles from the corresponding block copolymer [35]. 

The second strategy for the chemoenzymatic synthesis of block copolymers from enzymatic macroinitiators employs an individual modification step of the enzymatic block with an initiator for the chemical polymerization (route B in Fig. 4). This strategy has the advantage that it does not depend on a high incorporation rate of the dual initiator. On the other hand, quantitative end-functionalization becomes more... 

Scheme 4 One-pot chemoenzymatic cascade polymerization combining enzymatic ROP and NMP for the synthesis of (chiral) block copolymer [43]...

Apart from ATRP, the concept of dual initiation was also applied to other (controlled) polymerization techniques. Nitroxide-mediated living free radical polymerization (LFRP) is one example reported by van As et al. and has the advantage that no further metal catalyst is required [43], Employing initiator NMP-1, a PCL macroinitiator was obtained and subsequent polymerization of styrene produced a block copolymer (Scheme 4). With this system, it was for the first time possible to successfully conduct a one-pot chemoenzymatic cascade polymerization from a mixture containing NMP-1, CL, and styrene. Since the activation temperature of NMP is around 100 °C, no radical polymerization will occur at the reaction temperature of the enzymatic ROP. The two reactions could thus be thermally separated by first carrying out the enzymatic polymerization at low temperature and then raising the temperature to around 100 °C to initiate the NMP. Moreover, it was shown that this approach is compatible with the stereoselective polymerization of 4-MeCL for the synthesis of chiral block copolymers. 

The second strategy for the chemoenzymatic synthesis of block copolymers from enzymatic macroinitiators employs an individual modification step of the... 

Heise, Palmans, de Geus, Villarroya and their collaborators (17,41,42) have been working on a chemoenzymatic cascade synthesis to prepare block copolymers. They combine enzymatic ring-opening polymerization (eROP) and atom transfer radical polymerization (ATRP). The synthesis of block copolymers was successful in two consecutive steps, i.e., eROP followed by ATRP. In the one-pot approach, block copolymers could be obtained by sequential addition of the ATRP catalyst, but side reactions were observed when all components were present from at the onset of reactions. A successful one-pot synthesis was achieved by conducting the reaction in supercritical carbon dioxide. 

Compartmentalization by sequential monomer addition was also successfully demonstrated in the chemoenzymatic synthesis of block copolymers in SCCO2 using lH,lH,2H,2H-perfluorooctyl methacrylate (FOMA) as an ATRP monomer. Detailed analysis of the obtained polymer P(FOMA-i>-PCL) confirmed the presence of predominantly block copolymer structures (16). The clear advantage of the SCCO2 in this approach is that unlike conventional solvents it solubilises the fluorinated monomer. 

We investigated the chemoenzymatic synthesis of block copolymers combining eROP and ATRP using a bifunctional initiator. A detailed analysis of the reaction conditions revealed that a high block copolymer yield can be realized under optimized reaction conditions. Side reactions, such as the formation of PCL homopolymer, in the enzymatic polymerization of CL could be minimized to < 5 % by an optimized enzyme (hying procedure. Moreover, the structure of the bifunctional initiator was foimd to play a major role in the initiation behavior and hence, the yield of PCL macroinitiator. Block copolymers were obtained in a consecutive ATRP. Detailed analysis of the obtained polymer confirmed the presence of predominantly block copolymer structures. Optimization of the one-pot procedure proved more difficult. While the eROP was compatible with the ATRP catalyst, incompatibility with MMA as an ATRP monomer led to side-reactions. A successfiil one-pot synthesis could only be achieved by sequential addition of the ATRP components or partly with inert monomers such as /-butyl methacrylate. One-pot block copolymer synthesis was successful, however, in supercritical carbon dioxide. Side reactions such as those observed in organic solvents were not apparent. 

The mechanism of catalysis of green biocatalysts and metal catalysts is quite different, but if booth are mutually compatible, then it allows the application concurrently in the same reaction system. The combination of these different types of catalysts is also addressed as chemoenzymatic method. Utilizing the advantages of enzymes, the chemoenzymatic method has been developed for the synthesis of various block copolymers, which are otherwise difficult to prepare. 

Chapter 4 shows that the range of polymeric structures from enzymatic polymerization can be further increased by combination with chemical methods. The developments in chemoenzymatic strategies towards polymeric materials in the synthesis of polymer architectures such as block and graft copolymers and polymer networks are highlighted. Moreover, the combination of chemical and enzymatic catalysis for the synthesis of unique chiral polymers is discussed. 

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