Hydrolases Part I: Enzyme Mechanism, Selectivity and Control in the Synthesis of Well-Defined Polymers - Enzymatic Polymerisation - page 69

Tabl e 2 Initial reaction rates
and normalized reaction rates
(between brackets) of
alcohols and amines using a
normal acyl donor or a
β

Substrate

OH NH 2

Acyl
Donor

-oxygen-activated acyl
donor [ 28 ]

O

7.8 (1) 0.06 (1)

Me

O

O

8.1 (1) 13 (200)

Me O

O

Fig. 9 Polymerization of

β -lactam into poly( β -alanine)

with Novozym 435

reason is presumably the poor solubility of polyamides in the (apolar) solvents
that are typically applied in lipase-catalyzed reactions. Recently, some very ele-
gant approaches have appeared in the literature and show that the preparation of
well-defined polyamides by lipase catalysis is feasible.
The synthesis of poly( -lactam was achieved by

Loos and coworkers using Novozym 435 as the catalyst at 90 ◦ C in anhydrous
toluene [ 22 ] . The polymer formation proceeded by ring opening of the

β -alanine) from unsubstituted β

-lactam,
after which oligomers were built up by reaction of the amine chain end with an ac-
tivated monomer (Fig. 9 ) . A control reaction with deactivated enzyme resulted in
less than 5% product, showing the necessity of the lipase in the monomer activation
step. Maldi-TOF-MS showed a distribution with peaks up to 18 monomeric units,
and both cyclic and linear species were found. From 1 H-NMR, an average degree
of polymerization of eight could be derived, which was limited by the solubility of
the formed polymer in the reaction medium.
In order to keep polyamides soluble in relatively apolar solvents, the use of flex-
ible (macro)monomers such as

β

-(diaminopropyl)polydimethylsiloxane [ 52 ] or
oligoethyleneglycol-based diamines [ 53 , 54 ] has been proven to be a successful
approach (Fig. 10 ) . Polycondensations of dimethyl adipate with a variety of di-
amines were successful in bulk and at moderate temperatures between 60 and 100 ◦ C
(reaction A in Fig. 10 ) . The low temperatures

α , ω

60-100 ◦ C that suffice in these poly-

merizations also allow the use of monomers that are thermally instable, such as
diethyl fumarate [ 53 ]. Moreover, multifunctional amines could be regioselectively
polymerized up to molecular weights of 9 kDa, making lipase catalysts a valuable
tool for the preparation of well-defined polyamides that can be further functional-
ized with active groups.
For the silicon-containing polyamides, molecular weights up to 9.4 kDa
were achieved (reaction B in Fig. 10 ) . Copolymerizations of 1,8-octanediol,

( )