Combining Ring Opening Polymerization And "Click" Chemistry For Preparing Pendant Functionalized Amphiphilic Block Copolymers

Aliphatic polyesters belong to the category of biodegradable polymers and have been broadly used in medical products such as sutures, bone screws, tissue engineering scaffolds and drug delivery systems. An example of an aliphatic biodegradable polyester is PCL (Poly(s-caprolactone)) which has been extensively used for the development of biomedical devices and tissue engineering scaffolds. However, the high crystallinity, low melting point, low degradation rate and lack of functional groups limit its further applications in biomedical areas. Attachment of functional groups along the chain is highly desirable to tailor the macroscopic properties of these aliphatic polyesters, e.g. crystallinity, hydrophilicity, biodegradation rate, bioadhesion and mechanical properties. Moreover, pendant functional groups can be used to covalently attach molecules or probes of biological interest.For the time being, functional groups can be attached onto PCL by the following strategies. In the first approach, this can be established by abstraction of protons from the polyester by treatment with a base, such as lithium diisopropyl amide (LDA), followed by subsequent addition of an electrophilic reagent, such as a halogen- or a carbonyl-containing compound. The main drawback of this method is the possibility of side reactions, such as chain scission and racemization. The second strategy relies on the ring opening polymerization (ROP) of s-caprolactone substituted mainly in theα- orγ-position. Their synthesis is, however, usually a multistep process involving protection and deprotection of the functional groups before and after the polymerization, which may result in low overall yields as well as degradation.To solve the above problems, in this paper, pendant functional (carbobenzyloxy, carboxyl or aldehyde group) biodegradable amphiphilic block copolymers were synthesized by combining ring opening polymerization and postpolymerization modification via thio-bromo click chemistry. The main contents were as follows:1. Various biodegradable amphiphilic MPEG114-b-PaBrCLm diblock copolymers were synthesized by ROP of aBrCL with hydroxyl-terminated macroinitiator MPEG using Sn(Oct)2 as catalyst. These copolymers were characterized by differential scanning calorimetry (DSC),1H NMR, IR, and gel permeation chromatography.2. Benzyl 2-mercaptoacetate was reacted with pendant bromo of MPEG114-b-PαBrCLm by thio-bromo click chemistry, and thus obtains biodegradable amphiphilic block copolymers bearing many pendant functional carbobenzyloxy groups (MPEG114-b-PαBrCLm-g-HSCH2COOBnx, for convenience, we coded this polymer as MPEG114-b-PαBrCLm-g-Cbzx).1H NMR, IR and GPC studies confirmed the copolymers structure. Tg and Tm of this copolymers were determined by DSC.3.3-mercaptopropanoic acid and 2-(4-formylphenoxy)ethyl mercaptopropanoate were reacted respectively with pendant bromo of PEG114-b-PαBrCLm by thio-bromo click chemistry, and thus obtains biodegradable amphiphilic block copolymers bearing many pendant functional groups, MPEG114-b-PαBrCLm-g-HSCH2CH2COOHx and MPEG114-PαBrCLm-g-aldehydex。1H NMR and GPC studies confirmed the copolymers structure.