Sequence-defined multifunctional polyethers via liquid-phase synthesis with molecular sieving

Synthetic chemists have devoted tremendous effort towards the production of precision synthetic polymers with defined sequences and specific functions. However, the creation of a general technology that enables precise control over monomer sequence, with efficient isolation of the target polymers, is highly challenging. Here, we report a robust strategy for the production of sequence-defined synthetic polymers through a combination of liquid-phase synthesis and selective molecular sieving. The polymer is assembled in solution with real-time monitoring to ensure couplings proceed to completion, on a three-armed star-shaped macromolecule to maximize efficiency during the molecular sieving process. This approach is applied to the construction of sequence-defined polyethers, with side-arms at precisely defined locations that can undergo site-selective modification after polymerization. Using this versatile strategy, we have introduced structural and functional diversity into sequence-defined polyethers, unlocking their potential for real-life applications in nanotechnology, healthcare and information storage

Author Correction: Sequence-defined multifunctional polyethers via liquid-phase synthesis with molecular sieving

Correction to: Nature Chemistry https://doi.org/10.1038/s41557-018-0169-6, published online 3 December 2018

Aligned macrocycle pores in ultrathin films for accurate molecular sieving

Jiang Z, Dong R, Evans AM, et al. Aligned macrocycle pores in ultrathin films for accurate molecular sieving. Nature. 2022;609(7925):58-64.Polymer membranes are widely used in separation processes including desalination1, organic solvent nanofiltration2,3 and crude oil fractionation4,5. Nevertheless, direct evidence of subnanometre pores and a feasible method of manipulating their size is still challenging because of the molecular fluctuations of poorly defined voids in polymers6. Macrocycles with intrinsic cavities could potentially tackle this challenge. However, unfunctionalized macrocycles with indistinguishable reactivities tend towards disordered packing in filmshundreds of nanometresthick7-9, hindering cavity interconnection and formation of through-pores. Here, we synthesized selectively functionalized macrocycles with differentiated reactivities that preferentially aligned to create well-defined pores across an ultrathin nanofilm. The ordered structure was enhanced by reducing the nanofilm thickness down to several nanometres. This orientated architecture enabled direct visualization of subnanometre macrocycle pores in the nanofilm surfaces, with the size tailored to angstromprecision by varying the macrocycle identity. Aligned macrocycle membranes provided twice the methanol permeance and higher selectivity compared to disordered counterparts. Used in high-value separations, exemplified here by enriching cannabidiol oil, they achieved one order of magnitude faster ethanol transport and threefold higher enrichment than commercial state-of-the-art membranes. This approach offers a feasible strategy for creating subnanometre channels in polymer membranes, and demonstrates their potential for accurate molecular separations. © 2022. The Author(s)

Supramolecular ABC Miktoarm Star Terpolymer Based on Host–Guest Inclusion Complexation

A facile strategy for the construction of supramolecular star-shaped ABC terpolymer was proposed and realized via the molecular recognition between β-cyclodextrin- (β-CD-) based host and adamantane- (AD-)­modified guest. In the first step, β-CD with two different functional groups was prepared, which was further used to construct a diblock copolymer host via “click” reaction with <i>alkynyl</i>-poly­(ethylene glycol) (<i>alkynyl</i>-PEG) and atom transfer radical polymerization (ATRP) of dimethylaminoethyl methacrylate (DMAEMA) monomer. On the other hand, the AD-modified polymeric guest was obtained by ATRP of methyl methacrylate (MMA) using an AD-modified initiator. Because of the molecular recognition between β-CDs and adamantyl moieties, the polymeric host and guest formed a star-shaped ABC miktoarm terpolymer via a simple mixing procedure. The resultant ABC miktoarm star-shaped terpolymer was characterized by two-dimensional NMR spectroscopy. This amphiphilic ABC miktoarm terpolymer could self-assemble into micelles in aqueous solution, and the reversible transition between assembly and disassembly of this supramolecular ABC miktoarm star terpolymer could be readily controlled by adding the competitive host or guest

Synthesis of a Cationic Supramolecular Block Copolymer with Covalent and Noncovalent Polymer Blocks for Gene Delivery

The design and fabrication of safe and highly efficient nonviral vectors is the key scientific issue for the achievement of clinical gene therapy. Supramolecular cationic polymers have unique structures and specific functions compared to covalent cationic polymers, such as low cytotoxicity, excellent biodegradability, and smart environmental responsiveness, thereby showing great application prospect for gene therapy. However, supramolecular gene vectors are facile to be degraded under physiological conditions, leading to a significant reduction of gene transfection efficiency. In order to achieve highly efficient gene expression, it is necessary for supramolecular gene vectors being provided with appropriate biostability to overcome various cell obstacles. To this end, a novel cationic supramolecular block copolymer composed of a conventional polymer and a noncovalent polymer was constructed through robust β-cyclodextrin/ferrocene host–guest recognition. The resultant supramolecular block copolymer perfectly combines the advantages of both conventional polymers and supramolecular polymers ranging from structures to functions. This supramolecular copolymer not only has the ability to effectively condense pDNA for enhanced cell uptake, but also releases pDNA inside cancer cells triggered by H₂O₂, which can be utilized as a prospective nonviral delivery vehicle for gene delivery. The block polymer exhibited low cytotoxicity, good biostability, excellent biodegradability, and intelligent responsiveness, ascribing to the dynamic/reversible nature of noncovalent linkages. In vitro studies further illustrated that the supramolecular block polymer exhibited greatly improved gene transfection efficiency in cancer cells. This work offers an alternative platform for the exploitation of smart nonviral vehicles for specific cancer gene therapy in the future

Synthesis and Self-Assembly of Amphiphilic Aptamer-Functionalized Hyperbranched Multiarm Copolymers for Targeted Cancer Imaging

A novel targeting cancer imaging platform based on aptamer-functionalized amphiphilic hyperbranched copolymer conjugates, which can self-assemble into nanoscopic micelles with a core–shell structure and a narrow size distribution, has been designed and synthesized. The size, morphology, fluorescence performance, and cytotoxicity of micelles were studied by dynamic light scattering, transmission electron microscopy, fluorescence spectroscopy, and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. The results indicate that these micelles have low cytotoxicity against MCF-7 cells and can be easily internalized by MCF-7 cells. In addition, they also exhibit enhanced cell uptake, excellent fluorescence properties, and smart targeting capability <i>in vitro</i>, indicating great potential to be promising carriers for bioimaging and cancer specific delivery

Multicolor Fluorescent Polymers Inspired from Green Fluorescent Protein

Mimicking the green fluorescent protein (GFP), multicolor fluorescent polymers possessing enhanced fluorescence have been developed and applied to single-excitation cell imaging. The GFP core chromophore was covalently linked to the azide-functionalized amphiphilic block polymer poly­(ethylene glycol)–azide–poly­(methyl methacrylate). Through macromolecular assembly into micelles, the fluorescence enhanced and further increased with the elongation of poly­(methyl methacrylate) chain due to the segmentation effect of the polymeric framework, which could reduce strong π–π interaction and suppress the chromophore’s conformational motion. By a combination of chemically tailoring the core chromophore and macromolecular assembly strategy, multicolor fluorescent polymers showing a color palette from blue to orange were achieved under similar excitation conditions with the highest emission quantum yield approaching 8%, which is more than 80-fold larger than that of the core chromophore. Moreover, fluorescent emission color could be regulated by tuning the coassembling constitution of green and orange fluorescent polymers, generating three new types of emission color. Owing to their low cytotoxicity and good photostability, GFP-mimicking fluorescent polymers were suitable for single-excitation multicolor cell imaging, exhibiting maximum Stokes shift of 202 nm, ascribing to the effect of excited-state proton transfer (ESPT). More importantly, green, yellow, and orange fluorescent cell images were obtained from one single visual field, demonstrating identical information on examined cells, which would improve the accuracy and reliability of biological analysis