Isocyanide Controlled Synthesis,drug Loading,and Antibacterial Performance Of Topological Poly(phenyl Isocyanide)s

Helical polymers have a special helical structure,which are widely found in life,and play a key role in the operation of the body.With the continuous development of polymer science,helical polymers of different functions are designed and prepared and applied in many fields,such as chiral resolution,asymmetric catalysis,drug carriers,luminescent materials,conductive materials,etc.The topological structure of polymers often includes linear,ring,star,grafting,hyperbranched,trapezoidal,trapezoidal,etc.,and the study of the structure and performance of these polymers is a hot spot in the field of polymer science.Living polymerization is an essential tool to prepare topological polymers.The work content of this paper is based on the study of helical polyisocyanide,so living/controlled polymerization of various isocyanide monomers using acetylene palladium catalyst as initiator system.Using this polymerization method can not only design synthesis of a variety of different topology and versatility of helical polymer,and the polymer riser integrity is good,molecular weight,molecular weight distribution is controllable.The specific research contents are as follows:(1)With the emergence of various resistant bacteria and the abuse of antibiotics has caused serious side effects.Therefore,developing efficient and safe antibacterial systems are imminent.Herein,a series of well-defined antimicrobial materials-helical poly(phenyl guanidinium isocyanide)block copolymers(DL-P3-van,L-P3-van and D-P3-van)to connect vancomycin into the polymer through disulfide bond were synthesized with different conformations.These antimicrobial materials not only have broad-spectrum antimicrobial activity,low resistance trend and good proteolytic stability,but also overcome the intrinsic resistance of vancomycin to Gram-negative bacteria with a 100-fold increase in antimicrobial activity.Interestingly,we found that the conformation of the antimicrobial material promoted the antimicrobial activity,and experimentally show that the left-handed helix conformation is five-fold more active than the right-handed helical conformation material,this provides a new research idea for the application of nano-chiral materials in antibacterial field.(2)In order to simulate the helical structure and function of biopolymers,shellcrosslinking nanoparticles(P4)were prepared with a left-handed helical poly(phenylborate isocyanide)as the core,hydrophilic polyisocyanide as the shell,and cysteamine as the crosslinking agent.The presence of phenylborate groups and disulfide bonds in the crosslinking agent in the nucleus of the nanoparticles makes the nanoparticles have a good dual stimulus response to glutathione(GSH)and H2O2.However,under normal physiological conditions,chiral nanoparticles have good stability.Due to the helicity of the nucleus and the presence of phenylboric acid groups,the nanoparticles have a high loading capacity of anticancer drugs,and the encapsulation rate can reach68%.In addition,it has good penetration ability and fast drug release performance to tumor cells.The material has great potential in nanocarriers of anti-tumor drugs.(3)Controlled synthesis of high graft density bottlebrush polymers carrying polymer side chains on each backbone atom remains a serious challenge.Herein,we have prepared a series of well-defined macromonomers poly(L-lactic acid)(PLLA)and poly(D-lactic acid)(PDLA)with polymerizable phenylisocyanide at the end of the chain,and then polymerized the phenylisocyanide groups at the end of these macromonomers with an alkyne-palladium(II)catalyst.The bottlebrush polymer with PLLA or PDLA side chains on each main chain atom was obtained.The polymerization is performed in a living/controlled manner with a maximum degree of polymerization up to 250.The chiral macromonomer induced asymmetric polymerization and formed the main chain of phenylisocyanide with a preferred one-handed helix structure and high optical activity.It is worth noting that both the macromonomer and the phenylisocyanide backbone were non-luminescent,while the synthetic bottlebrush polymer shows interesting photoluminescence properties.In addition,the one-handed helical structure of the backbone induced a well-defined optical activity and tunable circularly polarized luminescence behavior(CPL).