Lipase Catalyzed Preparation of Functional Aliphatic Polyesters and an Insight into Corresponding Structure and Property Control

Author:Rao Zi Kun

Supervisor:hao jian yuan


Degree Year:2019





Functional aliphatic polyesters belong to the family of biodegradable polymers.Compared with traditional polyesters like PLA,PLGA,and PCL,many possibilities to tune physico-chemical characteristics have made functional polyesters prevailing in such biomedical fields as drug delivery or tissue engineering scaffolds.Presently,functional monomers can be homopolymerized or copolymerized to give functional polyesters.However,high temperature(>120℃)required in traditional methods usually results in lots of side reactions,inducing discoloration of final products.Besides,classical chemical catalysts usually lack of chemical,stereo-and regio-selectivity,which makes the polymerization processes complicated and less controllable.Moreover,the introduction of organo-metallic catalysts may also bring about potential toxic side effects when they are entrapped in final products.Due to the advantages of mild reaction conditions,unique chemical,regio-and stereo-selectivity and few byproducts,enzymatic catalysis is superior in obtaining structurally well-defined functional polyesters over classical chemical catalysis.However,major works of enzyme catalysis at present have been focused on the basic reaction conditions including selection of enzymes,solvents or monomers and regulation of temperatures,reaction durations or vacuum degrees.It is still scarce in macromolecular design,regulation of polymer structures and corresponding performances.As there are increasing requirements for versatility,biocompatibility and biosafety in biodegradable materials,it is increasingly important to have biomaterials with well-regulated structures and properties.We herein aim at attaining novel functional polyesters with controllable structures and performances through enzymatic polymerization of biocompatible monomers.First of all,the backbone of traditional OEG-grafted polycarbonates is too stiff with dense “C=O” groups,which makes it hard for these macromolecules to self-assemble into nanospheres in aqueous solution(mostly in the form of sticks or random coils).Under the catalysis of N435,we for the first time obtained a three-component polyester with polyethylene glycol(PEG)segments attached to both side chains and backbones by copolymerization of PEG400,diol-3mEG and diethyl succinate.Introducing PEG into backbones perfectly enhances the flexibility of the backbones,and all these new flexible polyesters will self-assemble into nanospheres in water under low temperatures(4℃)by physical winding or crosslinking.When temperature is heated to about 18℃,the nanospheres will shrink and decrease in size.Further increasing the temperature to LCST point will result in serious dehydration and shrinking of nanospheres,these nanospheres will also aggregate with each other into micron-sized particles.On the other hand,by tuning the feeding ratio of PEG in diols,the LCST can be precisely regulated to around body temperature.Meanwhile,the phase transition sensitivity in respond to increasing temperature is significantly accelerated with increasing PEG ratio in backbones.In order to overcome the problem that concentration has a great influence on the self-assembly behaviors of linear polyester molecules,we design to synthesize a dendritic,narrow distributed,structurally regular amphiphilic polyol-polyester by lipase catalysis.Polyol-polyesters obtained by polymerization of saccharide and diacid is rich in hydroxyls,which can potentially be a kind of “smart” biomaterial.However,no regular dendritic polyol-polyesters have been obtained by means of lipase catalysis so far.Herein our article,apart from obtaining structurally regular dendritic trimethylolethane(TME)polyester through facile lipase catalysis,we have had a deep insight into chain growth mechanisms by having comparison with glycerol-based polyester.TME polyesters will undergo long period of dendritic growth,giving regular dendritic scaffolds,while glycerol polyesters undergo long time of grafted growth and form into randomly branched scaffolds due to selective catalysis of primary hydroxyls.Besides,the influences of temperatures and monomer feed ratios on scaffolds forming have also been discussed in detail.Thereby,the structure design and control method in lipase catalyzed triol-polyesters is built for the first time.To clarify the influences of diacid carbon chain length on structures and properties of lipase catalyzed polyol-polyesters,we further discussed the polymerization of TME with adipic acid,suberic acid and sebacic acid.Dendritic molecules of high generations usually show different physical properties(such as crystallinity)from dendritic molecules of low generations,and high generation dendritic molecules tend to have much more loading capacity,therefore,the reaction time and monomer feeding amounts have been adjusted to achieve high generation TME polyester.It is revealed in the results that increasing atmospheric reaction time and monomer feed amounts can effectively increase the generation of TME polyester while keeping low polydispersity.However,in our reaction system,longer carbon chains of sebacic acid than suberic or adipic acid will reduce steric hindrance of “dendritic growth”,thereby,reaction sites of dendritic growth are randomized,leading to the irregularity of scaffolds and increase of polydispersity.Based on the data of differential scanning calorimetry(DSC),products with higher molecular weights in all TME-polyester groups display weaker cold crystallinity,which is resulted from the generation increase of dendritic TME polyesters.Finally,the self-assembly behaviors in aqueous solution of all TME polyester groups have been studied.All TME-Cn products can form into micelles with diameters ranging from several nanometers to several tens of nanometers.Only poly(TME-adipic acid)(TME-C6)can form regular spherical micelles in diluted solution(0.001mg/ml).When the concentration is raised above Critical Massive Aggregation Concentration(CMAC)(about 0.01 mg/ml),all the TME based polyesters will form large micelle aggregations with average diameters around 400-500 nm,but only DLS curves of TME-C6 is independent of polymer concentration(0.02-0.5 mg/ml).Therefore,the aggregation of TME-C6 polyester is the most stable one.In summary,we have obtained various linear or dendritic functional polyesters by lipase catalysis,their self-assembly behaviors in water are studied as well.Based on investigation results of polymerization mechanisms,the method of scaffolds design and control of triol polyesters is set up for the first time.Meanwhile,it is also unprecedented that a series of structurally regular and controllable TME polyesters are synthesized simply by lipase catalysis,and unimolecular micelles are also attained.Compared with the dendritic glycerol polyesters reported in the literatures,TME-polyesters is narrower in molecular weight distribution.The obtained dendritic unimolecular micelles can potentially be applied as carriers of drugs or catalysts or nanoreactors.Immeasurable prospects as growth templates of nanomaterials can also be expected.