Hydrolases Part I: Enzyme Mechanism, Selectivity and Control in the Synthesis of Well-Defined Polymers - Enzymatic Polymerisation - page 61

3.1.2 Control Over Polydispersity and Molecular Weight

in ROP of Lactones

Numerous comparative studies on the ROP of CL in organic solvents have been
conducted to enhance the mechanistic and kinetic understanding of lipase-catalyzed
ROP. Investigated reaction parameters are, for example, the enzyme origin [ 62 , 97 -
100 ] , concentration of monomer [ 70 ] , temperature [ 68 , 69 ], organic solvent [ 61 ,
101 ] , and water content [ 72 , 73 ] . Enzymatic ROP reactions have also been investi-
gated in alternative solvents such as supercritical media [ 102 - 104 ] and ionic liquids
[ 105 , 106 ] .
CL is a particularly interesting monomer because it has a high ring strain,
making it reactive in (chemical) ROP [ 107 ]. Its corresponding polymer, poly( -

caprolactone) (pCL), has been evaluated in a number of biomedical applications.
A key factor in the lipase-catalyzed ROP of CL is the ability to control the poly-
dispersity and molecular weight during the polymerization reaction. Gross and
coworkers proposed that the ROP of CL is pseudo-living, based on linearity of the
ln(1-conversion) versus time plots and the linear increase of molecular weight with
conversion [ 60 ] . However, the polydispersities (polydispersity index, PDI, was typ-
ically between 1.5 and 2.0) suggested a limited control during the polymerization.
Moreover, at high substrate conversions (

ε

80%), deviations from linearity appeared
that were attributed to concomitant condensation reactions [ 64 ]. In fact, most papers
dealing with lipase-catalyzed ROP report a PDI in the range of 2.0 for unprecipi-
tated samples, showing that side reactions also occur during the ROP. The fact that a
lipase can activate every ester bond, and preferably accepts transoid ester bonds as
substrates, implies that transacylation reactions will always compete with monomer
activation during the polymerization. In other words, competing transacylation re-
actions and chain transfer cannot be avoided during lipase-catalyzed polymerization
reactions. A PDI of 2.0 is expected as a result of the statistically randomized chain
length distribution.
Control over the molecular weight, on the other hand, has been achieved reason-
ably well. In the absence of water, high molecular weight polyesters are typically
obtained [ 74 , 75 , 108 ] , whereas increasing the water content (which acts as an ini-
tiator) leads to a higher number of polymer chains and thus lower molecular weight
polyesters [ 64 , 101 ] . Also, the use of initiators containing an alcohol allows the
preparation polymers of predictable molecular weight [ 72 , 76 , 109 , 110 ] .

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3.1.3 Endgroup Fidelity in Lipase-Catalyzed ROP of Lactones

A second key factor in the lipase-catalyzed ROP of CL is the ability to control
the nature of the endgroups. This has important consequences in preparation of
α , ω -functionalized polyesters, which are currently being explored in a variety of

applications [ 111 , 112 ] . A systematic study by Heise and coworkers on the initiating
efficiency of different initiators ( 1-3 in Fig. 5 ) in the CALB-catalyzed ROP of CL
showed that three polymeric products were formed: cyclic species, water-initiated