Synthesis Of Amino Acid Polymers With Controlled Structures

Amino acids with rich and diverse functional groups as well as natural chiral sources are the basic building blocks of proteins and renewable resource.Amino acid polymers are a class of polymer composed of amino acid monomers or their derivatives connected by amide bond,which have stable secondary structure similar to natural proteins(such as ?-helix or ?-sheet),excellent biocompatibility,biodegradability,and various functional pendant groups.The structure and property of amino acid polymers enable them having broad application prospects in food cosmetics,drug delivery,tissue engineering,gene transfection and other biomaterials field.Therefore,using renewable amino acid monomers as raw materials to artificially synthesize high value-added amino acid-based polymers is a very important research topic in the field of polymer science.For the synthesis of amino acid polymers,precise control of the primary structure(such as stereo-and sequence structures,molecular weight,functionalization of side chains,etc.)is a crucial factor affecting the performance and application of amino acid polymers.However,the methods for synthesizing amino acid polymers with precise primary structures are still limited so far.Therefore,it is of great significance to develop efficient and controlled methods to synthesize amino acid polymers with precise stereo-and sequence structures and functionalized side chains.The main results obtained in this dissertation are summarized as follows:1 A series of novel bifunctional single-molecule hydrogen-bonding organocatalysts based on hexafluoroalcohol(HFA)were firstly synthesized to mediate the metal-free ROP of y-benzyl-L-glutamate NCA(L-BnGluNCA)monomer.The polymerization initiated by tertiary amine-activated hydroxyl group was highly efficient and fast,affording high molecular weight(Mn)polypeptide up to 352 kDa.Though the molecular weight of polypeptides were higher than theoretical values,the polymerization still followed a relatively controlled manner.The research on polymerization mechanism indicated that the ?-helical structure formed during chain propagating of polypeptide induce the accelerated chain propagating,consequently leading to the faster chain propagation than the initiation and higher Mn.2 A series of functionalized lysine-derived ?-lactam monomers bearing pendant benzyl-protected hydroxyl,allyloxy,and oligo-ethylene glycol groups were designed and synthesized via simple and efficient cyclization methods.The functionalized lysine-based polymers were obtained via organocatalytic ring-opening polymerization(ROP)of ?-lactam monomers under mild conditions(25?),achieving high monomer conversion with the molecular weight up to 47.7 kDa.The very mild polymerization condition tolerant of a wide range of functional groups did not interfere with the allyloxy groups,and lysine-based polymer with abundant and diverse functional side chains were synthesized by thiol-ene click reaction of allyloxy groups.Then,the thermal properties and self-assembly behavior of the obtained polymer were studied.The result of differential scanning calorimetry(DSC)indicated variable glass transition temperatures of functional lysine-based polymers.And the amphiphilic lysine-based polymers can self-assemble to form spherical nanoparticles in aqueous solution,suggesting their great potential for biomedical applications.3 The control of molecular weight and side chain structures of the amino acid-based polymer can be realized via efficient organocatalytic ring-opening polymerization,but it is difficult to synthesize polymers with dual precise control over sequence and stereoconfiguration.Therefore,we designed an exponential iterative synthesis method based on orthogonal deprotections and efficient coupling reactions to attain absolute control over stereo-and sequence structure of polymers.Using serines with different configurations and different pendant groups as raw materials,we firstly synthesized five stereoisomeric dimers with different sequence.Then five monodispersed serine-based polymers with precise stereo-and sequence structures were synthesized by four iteration cycles consisting of orthogonal deprotection reactions and efficient organic reactions.Unimolecular serine-based 32 mers with molar masses up to 8.3 kDa was synthesized in only a few days.The structures of five polymers were detailly characterized by SEC,chiral HPLC,1H NMR,13C NMR and MALDI-TOF MS,and the effect of stereoconfiguration on the thermal properties of serine-based polymers was studied by DSC.