Synthesis Of Biodegradable Polymers With Metal-free Organic Catalysts

We have systematically studied the synthesis of biodegradable polymers with metal-freeorganic catalysts, such as weak Br nsted acid (salicylic acid), strong Lewis acid(tris(pentafluorophenyl)borane) and super base(1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)phophoranylidenamino]-2Λ5,4Λ5-catenadi(phosphazene)) in this PhD thesis. Biodegradable polymers based onε-caprolactone, δ-valerolactone, l-lactide and trimethylene carbonate cyclic monomers havebeen prepared with those organic metal-free catalysts proceeding ring-opening polymerization.The polymerization kinetic, mechanism and the biodegradability have also been studied. Theresults are as follows:1) We have synthesized poly(ε-caprolactone-co-tert-butyl methacrylate)(CL-co-BMA)random copolymer via hybrid copolymerization with1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)phophoranylidenamino]-2Λ5,4Λ5-catenadi(phosphazene)(t-BuP4) as the catalyst. The copolymer has been hydrolyzedinto poly(ε-caprolactone-co-methacrylic acid)(CL-co-MAA), a PCL-based copolymer withpendent carboxyl groups. Nuclear magnetic resonance (NMR), Fourier transform infrared(FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermogravimetric analysis(TGA) measurements indicate that cyclic ester and vinyl monomer form a random copolymer.The degradation of the copolymer has also been studied using quartz crystal microbalancewith dissipation (QCM-D).2) We have synthesized poly(ε-caprolactone-co-tert-butyl glycidyl ether)(CL-co-BGE)random copolymer with1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)phophoranylidenamino]-2Λ5,4Λ5-catenadi(phosphazene)(t-BuP4) as thecatalyst. The hydrolysis of the resulting polymer yields an amphiphilicpoly(ε-caprolactone-co-glycidol)(CL-co-GD) copolymer. By use of quartz crystalmicrobalance with dissipation (QCM-D), we have investigated the enzymatic degradation ofpolymers in PBS buffer. It shows that the polymeric surface exhibits higher degradation rateas the hydrophilic GD units increase. Laser Light Scattering (LLS) indicates the amphiphiliccopolymer can be self-assemble in water to form nanoparticles.(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide)(MTT) assay experimentsdemonstrate that the CL-co-GD copolymer has a low cytotoxicity.3) We have synthesized poly(l-lactide-co-2-(2-methoxyethoxy)ethyl methacrylate)(LA-co-MEO2MA) containing both degradable and protein resistant units via hybrid copolymerization with(1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)phophoranylidenamino]-2Λ5,Λ5-catenadi(phosphazene)(t-BuP4) as the catalyst. Nuclear magnetic resonance (NMR)and differential scanning calorimetry (DSC) show that LA-co-MEO2MA is a randomcopolymer. The studies of quartz crystal microbalance with dissipation (QCM-D) demonstratethat the copolymer enzymaticlly degrades much faster than poly(l-lactide)(PLA)homopolymer due to its lower crystallinity. We have also investigated the adsorption ofbovine serum albumin (BSA), lysozyme or fibrinogen on a LA-co-MEO2MA surface in realtime by use of QCM-D and surface plasmon resonance (SPR). Our studies reveal that thepolymer is protein resistant depending on MEO2MA content.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay experimentsdemonstrate that the polymer has a low cytotoxicity.4) Ring-opening polymerization (ROP) of ε-caprolactone (CL) using salicylic acid (SAA)as the organocatalyst and benzyl alcohol (BnOH) as the initiator in bulk at80°C successfullyproceeded to give a narrowly distributed poly(ε-caprolactone)(PCL). In addition,2-hydroxyethyl methacrylate (HEMA), propargyl alcohol (PGA),6-azido-1-hexanol (AHA)and methoxy poly(ethylene glycol)(mPEG) were also used as functional initiators. The1HNMR, SEC, MALDI-TOF MS measurements of the PCL clearly indicate the presence of theinitiator residue at the chain end, implying that the SAA-catalyzed ROP of CL was throughthe activated monomer mechanism. The kinetic experiments confirmed the controlled/livingnature of the SAA-catalyzed ROP of CL. Furthermore, the block copolymerization of CL andδ-valerolactone (VL) successfully proceeded to give PCL-b-PVL.5) Narrowly distributed poly(ε-caprolactone)(PCL) was synthesized by the ring-openingpolymerization (ROP) of ε-caprolactone (CL) using tris(pentafluorophenyl)borane (B(C6F5)3)as acidic catalyst and benzyl alcohol (BnOH) as the initiator in bulk at80°C. The use offunctional initiators such as2-hydroxyethyl methacrylate (HEMA), propargyl alcohol (PGA),6-azido-1-hexanol (AHA) and methoxy poly(ethylene glycol)(mPEG) leads toend-functionalized PCLs.1H NMR, SEC and MALDI-TOF MS measurements clearlyindicate the presence of the initiator residue at the chain end of the obtained PCLhomopolymers. The study on polymerization kinetics confirm the controlled/living nature ofthe B(C6F5)3-catalyzed ROP of CL. Accordingly, the block copolymerization of CL withδ-valerolactone (VL) and trimethylene carbonate (TMC) successfully proceeded to givePCL-b-PVL and PCL-b-PTMC copolymers. Macrocyclic PCL was also prepared by theintramolecular click reaction of the heterotelechelic α-azido,ω-enthynyl-PCL.