Compartmentalization And Unidirectional Cross-Domain Molecule Shuttling Of Single-chain Nanoparticles

Compartmentalization and unidirectional cross-domain molecule shuttling are omnipresent in native proteins,which play key roles in molecular recognition,enzymatic reaction,mass transport,information transfer and other functions.Nanomachinery design that emulates the biological functions is being considered as one of the most ambitious and challenging tasks in modern chemistry and nanoscience.Recent advances in control of biomacromolecule-like primary and secondary structures of synthetic polymers have provided the potential to access this goal.Synthetic polymers may be explored as nano-objects with biomimetic structures and functions.Although it is not possible to reach a level of structural/functional complexity found in biomaterials,recent progresses have opened up interesting avenues for the prepratation of materials with potential microelectronics,photovoltaics,and biotechnology applications.Mimicry of peptide chain-folding and molecule transport may lead to protein-mimic structures and functions.In this thesis,we present a nanomachinery design involving single-chain compartmentalization and cross-domain molecule shuttling using single-chain technology.First,we explore the compartmentalization of linear ABC triblock copolymer single-chain nanoparticles（SCNPs）using coordination-driven orthogonal self-assembly.A well-defined ABC-type triblock copolymer,PHisAM-b-PHPMA-b-PAEMA,was synthesized via visible light-mediated RAFT aqueous block copolymerization of histamine acrylamide hydro-chloride（HisAM）,2-aminoethylmethacrylamide hydrochloride（AEMA）and 2-hydroxy-propylmethacrylamide（HPMA）.It possesses charged imidazoliums in A-block,NH₃⁺in C-block,and nonionic hydroxyl groups in B-block,and hence water-soluble.The electrostatic repulsion and steric segregation of middle block played crucial roles in the compartment-alization.Coordination-driven orthogonal self-assembly of ABC-type triblock copolymer in A-block within pH 3.3-4.4 and C-block within pH 5.3-6.4 proceed upon neutralization,judged by ¹H NMR,UV-vis spectroscopy,dynamic light scattering（DLS）,NMR diffusion-ordered spectroscopy（DOSY）.A blank regime of pH 4.4-5.3 guarantees self-assembly independently without mutual interference,i.e.orthogonal assembly.Transmission electron microscopy（TEM）displays discrete double heads of the resulting SCNP-1.These results demonstrate the formation of dumbbell-shaped SCNP with discrete assymetric dual heads.The pH-cycling results illustrate that the dual heads are discrete and respond individually to external stimulus.Charge repulsion of residual ammonium motifs and steric segregation of hydrophilic middle block segregate effectively the heads.SCNP-1 was served as a prototype of nanomachine capable of cross-domain molecule shuttling.A novel nanomachine capable of unidirectional cross-domain molecule shuttling between the discrete dual heads has been achieved upon ascorbic acid（AA）reduction and subsequent air oxidation taking advantages of differences of Cu-NH₂ and Cu-imidazole in coordination number and ligand association.Reduction reactions proceed at a series of feed molar ratios of AA to copper centers in argon-saturated solution of SCNP-1 at pH 6.4,25℃,overnight.¹H NMR,UV-vis spectroscopy,DLS,DOSY and TEM results confirmed that quantitative reduction of copper center led to the concurrent C-head disassembly and A-head reassembly.Copper centers shuttled out of the C-head into the A-head,leading to a dumbbell-to-tadpole transformation of SCNPs,namely SCNP-2.Ox-AA entered selectively and quantitatively into reassembled A-heads.Consequently,the SCNP-based nanomachine with unidirectional cross-domain molecule shuttling has been established.To put inverse molecule-shuttling into effect,cuprous centers of SCNP-2 are oxidized via bubbling fresh air at 25℃.¹H NMR,UV-vis spectroscopy,DLS,DOSY and TEM results reveal the oxidized metal centers and C-segment refolding,with folded A-heads throughout oxidation process.Copper centers shuttle inverse from the A-head into the C-head,leading to the formation of new dumbbell-shape SCNP,SCNP-3.Ox-AA enters into the reassembled C-head.Thus,aerial oxidation is sufficient to drive the inverse molecule shuttling.All these results demonstarte the successful design of a new SCNP-based molecular machine that involve single-chain compartmentalization and unidirectional cross-domain molecule shuttling.It was validated using the dumbbell-shaped SCNP prepared by stepwise complex of the outer blocks of ABC-type linear triblock terpolymer to copper ions.Sequential AA reduction and air oxidation resulted in unidirectional and inverse molecule shuttling,leading to dumbbell-to-tadpole-to-dumbbell configurational transition and selective intake of Ox-AA into reassembled heads.This is the first demonstration of molecular machinery design capable of compartmentalization and unidirectional crossdomain molecule shuttling,which has been exemplified using a new single-chain technology.We envision that the alteration of ligand motifs and/or metal centers will lead to unprecedented machinery behaviors.This strategy provides a new technique for the development of nanotechnology,and opportunities for design of biomaterials and nanomachines.