Maleimide based thiol reactive hydrogels and polymers from orthogonally functionalizable biodegradable dendrons

Abstract

Hydrogels and polymers with reactive side chains have gained an increased attention in recent years due to their amenability to efficient post-functionalization. Wide applications of such hydrogels and polymers in biomedical and pharmaceutical areas and materials science result in new investigations regarding design and synthesis of biofunctionalizable and biodegradable materials. This thesis consists of two different projects. In the first project, poly (ethylene glycol)-based reactive hydrogels were synthesized using a second generation poly (ester) dendron which has an orthogonal character because of the masked malemide unit at its core and alkyne moieties at its periphery. Hydrogel formation was achieved via Huisgen type [3+2] "click" cycloaddition and unmasking of maleimide functionalities to their reactive forms was achieved via retro Diels-Alder strategy. Positional control of these groups allow to investigate the efficiency of maleimide incorporation and functionalization of the hydrogel. All the functionalizations were performed under mild, reagent-free conditions via derivatization with different thiol containing molecules. Extent of functionalization was investigated through immobilization of the enzyme FITC-streptavidin onto biotinylated hydrogels. In the second project, a series of carbonate based homo- and lactide based copolymers containing thiol reactive maleimide groups as their side chains have been synthesized via utilizing organocatalytic ring-opening polymerization (ROP). A novel cyclic carbonate monomer was synthesized and polymerizations were achieved at room temperature by using DBU as an organocatalyst. Latent reactive maleimide functionalities of copolymers were activated via retro Diels-Alder reaction. Quantitative functionalization of the pendant maleimide groups by thiol containing molecules was achieved under mild conditions via nucleophilic thiol-ene "click" chemistry.