Optimization Of Synthetic Process Of Poly(β-malic Acid)and Properties Of A New Crystalline Poly(β-benzyl Malate)

Poly(β-malic acid)(PMLA)is a biodegradable polyester which is connected by ester bonds with malic acid as the sole monomer.It was proved to be biocompatibility and non-immunogenic.PMLA has three configurations ofα,βandγ.Only theβis present in body,and the synthetic route ofβ-PMLA is the most complex.However,there are little research on the total synthesis of poly(β-malic acid).The synthesis of poly(β-malic acid)by chemical synthesis was based on the preparation of the same monomer benzyl-β-malolactonate(MLABn)that is the key intermediate to prepare PMLA.In this work,MLABn was synthesized from L-aspartic acid and malic acid,respectively.The MLABn that synthesized from(L)or(D)-malic acid and L-aspartic acid was optically active and racemic,respectively.The yield of MLABn from malic acid(31.2%)was nearly seven times as much as the L-aspartic acid(4.5%)by optimizing the reaction conditions.During the anionic ring-opening polymerization,we investigated the relationship between the monomer/initiator ratio and the polymerization time.Meanwhile,the relationship between the initiator/monomer addition order and the molecular weight of PBM was studied.PBM-1 was soluble in most organic solvents which was prepared from L-aspartic acid.In contrast,the PBM-2 prepared from L or D-malic acid had very poor solubility in many organic solvents.The XRD patterns revealed that the atomic arrangement of PBM-1 was unordered.As for PBM-2,it had high crystallinity on account of the obvious diffraction peaks which were strongly in favor of that the internal atoms arranged more orderly and regular.The glass transition temperature(T_g)of PBM-1 was19℃.There was an obvious endothermic peak at 190℃which was the melting temperature(T_m)of PBM-2.The degradation rates of PBM-1 and PBM-2 were 42.4%and8.2%at 37℃,71.9%and 15.1%at 50℃after 100 days,respectively.Histological results showed that both PBM-1 and PBM-2 had no inflammatory response to the tissue.The cell cycle assay showed that the crystallized material PBM-2 had no significant effect on the cell viability.Finally,the MLABn which synthesized from L or D-malic acid were mixed together for polymerization to obtain the PMLA.It was difficult to synthesize PMLA from PBM-2 unless the temperature was raised.The partial hydrogenation of PBM could give an amphiphilic block copolymer and it could form the certain size of the nanomicelles by self-assembling in water.It was confirmed that a hydrogenation degree was 77%of PBM which would obtain the well-formed nanomicelles.The remaining benzene ring can also combine the paclitaxel which carries the benzene ring byπ-πstacking effect to enhance the bioavailability of the drug.The synthesis routes of PMLA from malic acid not only had shorter route and higher yield,but the polymerization time was faster than L-aspartic acid.In the process of synthesis,we prepared a crystalline PBM whose internal atoms arranged more orderly and regular with the increased hardness and strength.The study on partially hydrogenated PBM provided an important working basis for its application in drug carriers.The next step,we will carry out the application of partially hydrogenated PBM as a drug carrier and polymerize different optically active monomers in different proportions to prepare materials with controllable degradability.We will further explore its application in medical materials and tissue engineering.