Enzyme Mimetic-catalyzed "Living"/Controlled Radical Polymerization And Its Application In Preparation Of Functional Materials

Enzymes are environmentally friendly,non-toxic and renewable natural products.Biocatalysts,such as enzymes,create a smart platform for polymerization and materials used in biomedical science,which act as a bioinspired catalyst in an ATRP process under moderate temperature.“Living”/controlled radical polymerization as a robust and versatile polymerization strategy for the synthesis of various kinds of functional polymer materials has gained significant attention in the past few decades,which can be classified as atom transfer radical polymerization?ATRP?,reversible addition-fragmentation chain transfer?RAFT?polymerization,and so on.However,enzymatic biocatalysis has certain limitations,that is,high cost,harsh application conditions,and difficulty in separation,etc.Due to the limitation factors of enzyme,enzyme immobilization has been proved to be a robust technology.However,the enzyme activity will be decreased during enzyme immobilization.Biomimetic catalyst candidate provide a novel approach to this goal,which could be easily separated from reaction mixture after polymerization and will not adhere to resulting polymers as same as enzymes.Based on the abovementioned backgrounds,we first employed ATRP process catalyzed by DhHP-6 to construct an amphiphilic non-viral gene vector.Then,biomimetic catalyst was also employed on RAFT polymerization to produce polymers with precise control of molecular weight,specific molecular structure,and narrow polydispersity index?M_w/M_n?.Firstly,to avoid using transition metal catalysts in polymer gene vectors,we have synthesized a series of water soluble polymers via enzymatic ATRP,as previously reported.Herein,we report a series of amphiphilic block polymers with different molecular weight synthesized from a double head initiator HEBIB utilizing mimic enzyme catalysts.Finally,the pendant epoxy groups were decorated with amine moieties to obtain non-viral polycations which were evaluated for gene delivery.The synthesized vector has the ability to bind to pDNA at N/P=0.75 with particle sizes ranged from 200 nm to 300 nm.The transfection efficiency of amphiphilic block polymer?PCL-b-PGEA?is comparable to PEI 25 kDa and possessed a relatively lower cytotoxicity when compared to PEI 25 kDa,which may due to the combination of enzyme catalysis and the good biocompatibility of the polymer gene vectors.More importantly,enzyme or mimic enzyme catalysis can basically reduce the use of transition metal catalysis in ATRP and provide a promising platform for synthesizing materials.Secondly,we present a promising strategy to construct well-defined polymers by combining the advantages of RAFT polymerization and the initiation step that catalytically generate radicals by BSA-Cu₃?PO₄?₂·3H₂O hybrid nanoflowers,ACAC,and H₂O₂ ternary system.Significantly,unlike free enzymes usually adhere to products,employing Cu₃?PO₄?₂·3H₂O hybrid nanoflowers in a heterogeneous system could avoid complicated purification processes after polymerization.We take advantage of Cu₃?PO₄?₂·3H₂O hybrid nanoflowers to produce primary radicals in the chain initiation step.More specifically,Cu₃?PO₄?₂·3H₂O hybrid nanoflowers could catalyze ACAC to generate ACAC radicals?ACAC·?in the presence of H₂O₂,which could be further used to initiate RAFT polymerization in a mixed solvent of DMF and H₂O.Such nanobiocatalysts enjoy the advantages of mild reaction temperature,good control over polymer synthesis,low cytotoxicity,easy separation,and high efficiency activity.Finally,we prepared nanoflowers by employing PPL as the organic component and Cu₃?PO₄?₂ as the inorganic component,which exhibited enhanced activity under a relative high temperature and much more recycling times compared with free enzyme.