8. Functional PU

were, as a result, more accessible to the reducing agent. Therefore, the amorphous copolymers PU [(ArBn80-DiT20)-HMDI] and PU[(ArMe80-DiT20)-HMDI] were those with enhanced degradation

Figure 17. Copolyurethanes derived from 1,4-di-S-benzyl-D,L-dithiothreitol.

Figure 18. Copolyurethanes degradable by glutathione under physiological conditions.

trends.

182 Aspects of Polyurethanes

The chemical modification of polymers is an important task for further applications. In this sense, click chemistry (CC) is the most popular approach to achieve chemical transformations; for instance, the thiol-ene coupling reaction of a thiol and an alkene/alkyne and the alkyne-azide cycloaddition reaction.

Galbis et al. described the preparation of new polymerizable diols based on di- and tri-O-allyland tri-O-propargyl-L-arabinitol derivatives prepared from L-arabinitol (36, 40, 49) as versatile materials for the preparation of tailor-made polyurethanes with varied degrees of functionalization, such as NHBoc, carboxylic or 1,2-dihydroxyethyl side groups (Figures 19–21) [22, 24]. This strategy provides a simple and versatile platform for the design of new materials whose functionality can be easily modified to anchor diverse biologically active molecules. From

Figure 19. Functionalization of O-allyl polyurethanes by the click thiol-ene reaction.

Figure 20. Synthesis of allyl homopolyurethanes.

Figure 21. Functional polyurethanes prepared by click reactions on O-allyl polyurethanes.

monomer 49, a series of new biodegradable comb-like copolyurethanes was achieved by the combination of step-growth polymerization and click chemistry [30]. Stiffness, hydrophilic/lipophilic character, and degradability could be adjusted by the appropriate selection of the comonomers and their feed ratios.

The preparation of novel reduction-sensitive biodegradable multiallyl- and multiamine-based copolyurethanes was also accomplished. The two functional allyl diol monomers 36 and 40 and the commercial 2,2'-dithiodiethanol (DiT) were made to react with HDI (3) and MDI (23) to give novel linear multiallyl-based copolyurethanes, useful as carriers of anionic drugs or gene materials [25]. Thus, reduction-sensitive multiamine copolymers were obtained [25] from sugar-based diol monomer Ar(NHBoc)3(41), with the amine groups conveniently protected to prevent undesirable side reactions (Figure 22). Subsequent N-deprotection led to the target materials in high yields. The copolymers functionalized with amino groups (protected or free) exhibited lower thermal stability than those bearing allyloxy pendant groups. Functionalization of the sugar moieties greatly affected the T<sup>g</sup> of the polymer precursors. At the same time, the DiT diol content controlled the T<sup>m</sup> values of the random copolymers. The best degradation rates in reductive environments were obtained for the aliphatic amino-based copolymer, with an associated weight loss close to 90% after 10 days. This polymer was used in the preparation of colon-targeted drug delivery systems. An in vitro study of tablets containing the anticancer drug methotrexate demonstrated its impressive ability to control the drug's release, despite its low concentration in the tablet.

Figure 22. Synthesis of reduction-sensitive multiamine copolyurethanes.

Figure 20. Synthesis of allyl homopolyurethanes.

184 Aspects of Polyurethanes

Figure 21. Functional polyurethanes prepared by click reactions on O-allyl polyurethanes.

Similarly, the preparation of PU with well-defined "tunable" macromolecular comb-like architectures was successfully accomplished [30] by means of a two-step procedure: preparation of multipropargyl copolyurethanes based on the tri-O-propargyl-L-arabinitol derivative 49 and DiT and their subsequent derivatization via alkyne-azide click reaction with chemically diverse azides—dodecyl azide, triethylene glycol azide, and polyethylene glycol azide. This methodology allowed the generation of PU with an extensive chemical diversity that has been unapproachable until now. It is remarkable that a wide variation in degradability under reductive environment could be attained simply by adjusting the chemical structure of the polymer to synthesize.
