Hydrolases Part I: Enzyme Mechanism, Selectivity and Control in the Synthesis of Well-Defined Polymers - Enzymatic Polymerisation - page 68

their monomers in a unit cell, which facilitates tuning the degradation behavior
without compromising on the thermal and mechanical properties of the copoly-
mers [ 159 ] .
Cyclic carbonates are not commercially available and have to be synthesized
prior to use. As a result, commercially available carbonates such as diethyl carbon-
ate [ 55 - 57 ] or diphenyl carbonate [ 93 ] were evaluated in polycondensation reactions
with diols to prepare polycarbonates since they allow a broader spectrum of poly-
mers to be accessed. Unfortunately, polymerizations employing diethyl carbonate
require the use of an excess diethyl carbonate [ 55 ]. Nevertheless, polymers with
molecular weight of 40 kDa were achieved within 16 h. Also, the polymerization
of diphenyl carbonate with butane-1,4-diol or hexane-1,6-diol via the formation
of a cyclic dimer produced polymers with molecular weights ranging from 119 to
339 kDa [ 93 ] .

5 Polyamides

Polyamides are a very important class of polymers with everyday applications in
textiles, automotive materials, and plastics for electronics. Typically, polyamides
are chemically prepared by ROP of lactams or the polycondensation of diamines
and diacids. Although ester and carbonate bonds are excellent substrates for lipases,
amide bonds are not. The hydrolysis of an amide bond is usually impossible using
lipases because of the higher activation energy required for the formation of the
enzyme-bound tetrahedral transition state of amides in comparison to the more po-
lar ester substrates [ 160 ] . This is attributed to the electron delocalization present in
the amide bond, which increases resonance stabilization in the ground state. Nev-
ertheless, structural features that prevent resonance stabilization can activate amide
substrates towards electrophilic attack by water. Thus, strained amides present in
β

-lactam (four-membered) rings are readily hydrolyzed using lipases [ 23 , 161 , 162 ] .
Alternatively, the reaction of an ester and an amine (a reaction that is exploited
industrially in the kinetic resolution of racemic amines) also gives amide prod-
ucts [ 163 - 165 ] . Interestingly, amines are much poorer nucleophiles than alcohols
in a lipase-catalyzed reaction, which significantly reduces the reaction rate. For ex-
ample, in a kinetic resolution of 1-phenylethanol with methyl butyrate the rate is
approximately 130 times higher than in a kinetic resolution of 1-phenylethanamine
(Table 2 ) . Introduction of an oxygen at the -position of the ester bond resulted in

a 100-fold rate enhancement for the kinetic resolution of the amine but not for the
alcohol. A structural basis for this effect was recently given by Hult and coworkers
[ 28 ]. A molecular modeling study of the transition-state analog for the aminolysis
showed that an interaction between the

β

-oxygen atom in methoxyacetate and the
amine nitrogen atom could be a key factor in the rate enhancement. This interaction
presumably stabilizes the transition state and increases the reaction rate.
Despite the feasibility of making and breaking amide bonds using lipases in small
molecules, the use of lipases in polyamide synthesis is still very limited. The prime

β