Chemistry Reference
In-Depth Information
Scheme 8.4
Grafting procedures on the glucuronic COOH group performed in water. Water-
soluble condensing agents are employed to make pH-controlled coupling reactions with amino-
terminated polymers [
30
,
31
](R
ΒΌ
polymeric chain)
reactions, are employed to activate the COOH functionality for coupling amino-
terminated water-soluble polymers (Scheme
8.4
). The water-soluble condensing
agent 1-ethyl-3-[3-(dimethy-lamino)-propyl]-carbodiimide (EDC) is more efficient
at pH comprised between 3 and 5 even if amine is more reactive at basic pH [
29
,
30
]. However, at higher pH, the activated O-acyl ureic intermediate can easily
rearrange in the stable intermediate
N
-acyl urea, and then the amidation reaction
can be impeded [
31
]. Better reactivity at lower pH can be obtained using Hydrazide-
terminated polymers reducing the possibility of EDC rearrangement. Bulpitt and
Aelschiman proposed to couple to the EDC a second activating agent such as
1-hydroxybenzotriazole (HOBt) or
N
-hydroxysulfosuccinimide (NHSS) obtaining
in such way the formation of more stable intermediate O-NHS or O-benzotriazole
that avoids the possible rearrangement into
N
-acyl urea and make more efficient
coupling with amine at pH 6-8 (see Scheme
8.4
)[
32
].
The same reaction can be performed also in dimethylsulfoxide (DMSO)
employing HA-TBA; in this case, the rearrangement of the O-acyl adducts is not
possible, and the activation reaction is more efficient. Both strategies employing
