Hydrolases Part I: Enzyme Mechanism, Selectivity and Control in the Synthesis of Well-Defined Polymers - Enzymatic Polymerisation - page 71

melting points and refractive indices than the corresponding polyesters [ 166 , 167 ] .
Moreover, some microorganisms are known to form (co)polymers based on

β -

mercapto propionic acid and -hydroxy propionic acid, which has renewed interest

in this class of polymers [ 168 - 171 ].
Some examples of lipase-catalyzed polythioester synthesis have been mentioned
in the literature, although thioesters and thiol groups generally possess a lower reac-
tivity than the corresponding carboxylic esters and hydroxy nucleophiles in lipase-
catalyzed reactions. The lower reactivity has been demonstrated by the O-selective
acylation of

β

-mercapto alkanols [ 172 ] and the possibility to selectively end-cap
polymers with thiol groups with a high degree of efficiency, as discussed before
[ 80 ]. The lower reactivity of thiol nucleophiles in CALB-catalyzed reactions neces-
sitates the use of relatively large amounts of enzyme, high reaction temperatures,
and long reaction times for the preparation of polythioesters. However, some exam-
ples are known in which lipases showed a high reactivity towards thiol nucleophiles
[ 31 ], thioesters [ 173 ], and thioacids [ 174 ].
CALB-catalyzed copolymerization of CL with 11-mercaptoundecanoic acid
(11MU) leads to the formation of poly(ester- co -thioester)s having a M n of 13.7 kDa
(PDI 1.6) after precipitation [ 30 ] (Fig. 11 ) . The amount of incorporated 11MU
(8.7 mol%) was slightly less than the feed ratio (10 mol%). Similar results were ob-
tained when using 3-mercaptopropionic acid (3MP) as a comonomer ( M n 14.3 kDa,
PDI 1.4). CALB-catalyzed transesterification of pCL with either 11MU or 3MP re-
sulted in similar 1 H-NMR and 13 C-NMR spectra as the direct copolymerization of
the two monomers, showing that continuous transesterification plays an important
role in the microstructure of the polymer [ 30 ] .
Later, polythioesters were prepared by the polycondensation of dicarboxylic acid
diesters with a dithiol [ 43 ](Fig. 12 ) . Initially, various lipases were screened in
the polycondensation between diethyl adipate and hexane-1,6-dithiol at 120 ◦ Cin
the presence of molecular sieves. The use of 70 wt% immobilized CALB as cata-
lyst proved to be efficient in these polycondensation reactions with dicarboxylic acid

ω

Fig. 11 Copolymerization of CL with aliphatic ω -mercapto carboxylic acids ( top ) and transester-

ification of pCL with aliphatic ω -mercapto carboxylic acids ( bottom ) to give random copolymers

with thioester linkages [ 30 ]