Universal Soluble Polymer Supports with Precisely Controlled Loading Capacity for Sequence‐Defined Oligomer Synthesis

Soluble supports, with optimal molecular structures for iterative oligomer synthesis, were prepared by atom transfer radical copolymerization of styrene with Fmoc‐amino ethyl methacrylate. Size exclusion chromatography and nuclear magnetic resonance indicated formation of copolymers with controlled chain lengths, chain ends, dispersity, and comonomer compositions. These polymers were afterward subjected to two subsequent modifications steps: (a) the debromination of their ω‐chain ends via a tributyltin hydride treatment and (b) the removal of the Fmoc‐protecting groups in acidic conditions, thus leading to bromine‐free copolymers with a precise primary amine loading capacity. These universal amine‐containing precursors were then derived into a variety of functional supports. A glycine‐loaded Wang‐type soluble polystyrene support was prepared in two steps and tested for peptide synthesis as well as for the preparation of digital oligo(alkoxyamine amide)s. In both cases, it was possible to obtain uniform sequence‐defined oligomers as evidenced by electrospray ionization tandem mass spectrometry. However, each type of oligomer required specific experimental conditions and therefore soluble supports with an adapted loading capacity for optimal synthesis. Furthermore, the amine‐containing universal precursors were also transformed into soluble supports for iterative phosphoramidite chemistry. A support was specifically conceived for the iterative synthesis of abiotic digital oligo(phosphodiester)s and another one was designed for oligonucleotide synthesis. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 403–410     

Preparation of Information‐Containing Macromolecules by Ligation of Dyad‐Encoded Oligomers

A simplified strategy for preparing non‐natural information‐containing polymers is reported. The concept relies on the successive ligation of oligomers that contain minimal sequence motifs. It was applied here to the synthesis of digitally‐encoded poly(triazole amide)s, in which propyl and 2‐methyl propyl motifs are used to code 0 and 1, respectively. A library of four oligo(triazole amide)s containing the information dyads 00, 01, 10, and 11 was prepared. These oligomers contain two reactive functions, that is, an alkyne and a carboxylic acid. Thus, they can be linked to another with the help of a reactive spacer containing azide and amine functions. Using two successive chemoselective steps, that is, azide‐alkyne Huisgen cycloaddition and carboxylic acid‐amine coupling, monodisperse polymers can be obtained. In particular, the library of dyads permits the implementation of any desired sequence using a small number of steps. As a proof‐of‐concept, the synthesis of molecular bytes 00000000 and 00000110 is described.     

Red Ionic Water‐Soluble Imidazolium‐Containing Polydiacetylene

Synthesis of a water‐soluble polydiacetylene has been achieved by topochemical polymerization in the solid state of the bis(N‐methylimidazolium)diacetylene monomer. Structural characterization for the monomer by X‐ray diffraction and NMR spectroscopy supports a photopolymerization initiated at the surface. Characterization of the polymer (NMR, UV and Raman spectroscopy, and dynamic light scattering) is given along with a molecular modelling interpretation of the polymerization in the solid state.

     

Synthesis of water‐soluble allyl‐functionalized oligochitosan and its modification by thiol–ene addition in water

A novel, straightforward and versatile chemical pathway has been studied to functionalize water‐soluble chitosan oligomers. This metal‐free methodology is based on the epoxy‐amine reaction of the allyl glycidyl ether with chitosan, followed by thiol‐ene radical coupling reaction of ω‐functional mercaptans, using 4,4′‐Azobis(4‐cyanovaleric acid) as a free radical initiator. Both reactions were entirely carried out in water. In a preliminary step, chitosan depolymerization was carried out using H₂O₂ in an acetic medium under 100 W microwave irradiation, optimizing the yield of water‐soluble oligomers. Functionalization by six different thiols bearing alcohol, carboxylic acid, ester, and amino groups was then performed, leading to a range of functional oligochitosans with different grafting efficiencies. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 39–48     

固相合成及组合化学用的高聚物载体

综述了用于固相合成及组合化学的高聚物载体的制备方法、特征、应用和最新进展,重点介绍了目前广泛用作固相载体的交联聚苯乙烯树脂、聚酰胺树脂和TentaGel树脂,并对几类新型载体如聚乙二醇、聚四氢呋喃衍生物交联剂改性的聚苯乙烯树脂、非芳环体系的POEPOP,树脂和SPOCC树脂作了简要的概述。     

Synthesis and Characterization of Uncharged Water‐Soluble Star Polymers Containing a Porphyrin Core

Uncharged water‐soluble porphyrins were prepared by reaction between tetrakis(p‐hydroxyphenyl)porphyrin and chlorinated poly(ethylene glycol) methyl ethers of different molecular weights. Water‐solubility was achieved by binding four poly(ethylene glycol) branches to a porphyrin core to give star polymers with molecular weights in the range 2000–21 000 Da. Structural characterization of these star polymers was performed by means of gel permeation chromatography, NMR spectroscopy, and MALDI‐TOF analysis.     

Polypeptoids by Living Ring‐Opening Polymerization of N‐Substituted N‐Carboxyanhydrides from Solid Supports

The nucleophilic living ring‐opening polymerization of N‐substituted glycine N‐carboxyanhydrides using solid‐phase synthesis resins is reported. By variation of experimental parameters, products with near Poisson distributions are obtained. As opposed to reversible deactivation radical polymerization, the living polymerization is demonstrated to be viable to high monomer conversion and through multiple monomer addition steps. Successful preparation of a multiblock copolypeptoid is proof for a highly living and robust character of the solid‐phase peptoid polymerization.

     

A Water‐Soluble Polycarbonate With Dimethylamino Pendant Groups Prepared by Enzyme‐Catalyzed Ring‐Opening Polymerization

A water‐soluble polycarbonate with dimethylamino pendant groups, poly(2‐dimethylaminotrimethylene carbonate) (PDMATC), is synthesized and characterized. First, the six‐membered carbonate monomer, 2‐dimethylaminotrimethylene carbonate (DMATC), is prepared via the cyclization reaction of 2‐(dimethylamino)propane‐1,3‐diol with triphosgene in the presence of triethylamine. Although the attempted ring‐opening polymerization (ROP) of DMATC with Sn(Oct)₂ as a catalyst fails, the ROP of DMATC is successfully carried out with Novozym‐435 as a catalyst to give water‐soluble aliphatic polycarbonate PDMATC with low cytotoxicity and good degradability.     

Thermoresponsive Synergistic Hydrogen Bonding Switched by Several Guest Units in a Water‐Soluble Polymer

Thermoresponsive synergistic hydrogen bonding (H‐bonding) switched by several guest units in a water‐soluble polymer is reported. Adjusting the distribution of guest units can effectively change the synergistic H‐bonding inside polymer chains, thus widely switch the preorganization and thermoresponsive behavior of a water‐soluble polymer. The synergistic H‐bonding is also evidenced by converting less polar aldehyde groups into water‐soluble oxime groups, which bring about the lowering‐down of cloud point and an amplified hysteresis effect. This is a general approach toward the wide tunability of thermosensitivity of a water‐soluble polymer simply by adjusting the distribution of several guest H‐bonding units.     

Synthesis and antibacterial activities of water‐soluble methacrylate polymers containing quaternary ammonium compounds

New water‐soluble methacrylate polymers with pendant quaternary ammonium (QA) groups were synthesized and used as antibacterial materials. The polymers with pendant QA groups were obtained by the reaction of the alkyl halide groups of a previously synthesized functional methacrylate homopolymer with various tertiary alkyl amines containing 12‐, 14‐, or 16‐carbon alkyl chains. The structures of the functional polymer and the polymers with QA groups were confirmed with Fourier transform infrared and ¹H and ¹³C NMR. The degree of conversion of alkyl halides to QA sites in each polymer was determined by ¹H NMR to be over 90% in all cases. The number‐average molecular weight and polydispersity of the functional polymer were determined by size exclusion chromatography to be 32,500 g/mol and 2.25, respectively. All polymers were thermally stable up to 180 °C according to thermogravimetric analysis. The antibacterial activities of the polymers with pendant QA groups against Staphylococcus aureus and Escherichia coli were determined with broth‐dilution and spread‐plate methods. All the polymers showed excellent antibacterial activities in the range of 32–256 μg/mL. The antibacterial activity against S. aureus increased with an increase in the alkyl chain length for the ammonium groups, whereas the antibacterial activity against E. coli decreased with increasing alkyl chain length. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5965–5973, 2006     

Synthesis of phenylquinoxaline oligomers containing pendant electron‐donating and electron‐withdrawing groups

A series of extended 6‐substituted quinoxaline AB monomer mixtures, 2‐(4‐fluorophenyl)‐3‐[4‐(4‐hydroxyphenoxy)phenyl]‐6‐substituted quinoxaline and 3‐(4‐fluorophenyl)‐2‐[4‐(4‐hydroxyphenoxy)phenyl]‐6‐substituted quinoxaline, were prepared and polymerized to afford phenylquinoxaline oligomers. High‐molecular‐weight polymers could not be obtained because of the formation of cyclic oligomers. On the basis of matrix‐assisted laser desorption/ionization time‐of‐flight analysis and molecular modeling results, the formation of a cyclic dimer could be a favorable process resulting in low‐molecular‐weight oligomers. They were completely soluble and amorphous, with glass‐transition temperatures varying from 165 to 266 °C, and they had thermooxidative stability, with samples displaying 5% weight loss temperatures of 419–511 °C in nitrogen. The thermal properties of the monomers and resultant polymers dramatically depended on the polarity of the substituents. The monomers and resultant oligomers displayed high fluorescence in tetrahydrofuran solutions and N‐methyl‐2‐pyrrolidinone solutions, respectively. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 6465–6479, 2005     

Design of Soluble Hyperbranched Polythiophenes with Tailor‐Made Optoelectronic Properties

Hyperbranched polythiophenes were prepared via a simple one‐pot synthesis approach based on oxidative coupling of branched conjugated monomers. Only small variations in the building unit and architecture lead to large differences of absorption and photoluminescence properties. Interestingly, soluble hyperbranched polythiophenes with relatively small molecular weights show enhanced absorption at low and high wavelengths compared to linear analogues, such as poly(3‐hexyl thiophenes) with high molecular weights. With this versatile approach we present a method to design tailor made, functional materials with potential applications in optoelectronics.

     

Sequence‐Defined Oligomers from Hydroxyproline Building Blocks for Parallel Synthesis Applications

The functionality of natural biopolymers has inspired significant effort to develop sequence‐defined synthetic polymers for applications including molecular recognition, self‐assembly, and catalysis. Conjugation of synthetic materials to biomacromolecules has played an increasingly important role in drug delivery and biomaterials. We developed a controlled synthesis of novel oligomers from hydroxyproline‐based building blocks and conjugated these materials to siRNA. Hydroxyproline‐based monomers enable the incorporation of broad structural diversity into defined polymer chains. Using a perfluorocarbon purification handle, we were able to purify diverse oligomers through a single solid‐phase extraction method. The efficiency of synthesis was demonstrated by building 14 unique trimers and 4 hexamers from 6 diverse building blocks. We then adapted this method to the parallel synthesis of hundreds of materials in 96‐well plates. This strategy provides a platform for the screening of libraries of modified biomolecules.     

A Water‐Soluble Conjugated Polymer for Protein Identification and Denaturation Detection

Rapid and sensitive methods to detect proteins and protein denaturation have become increasingly needful in the field of proteomics, medical diagnostics, and biology. In this paper, we have reported the synthesis of a new cationic water‐soluble conjugated polymer that contains fluorene and diene moieties in the backbone ( PFDE ) for protein identification by sensing an array of PFDE solutions in different ionic strengths using the linear discriminant analysis technique (LDA). The PFDE can form complexes with proteins by electrostatic and/or hydrophobic interactions and exhibits different fluorescence response. Three main factors contribute to the fluorescence response of PFDE , namely, the net charge density on the protein surface, the hydrophobic nature of the protein, and the metalloprotein characteristics. The denaturation of proteins can also be detected using PFDE as a fluorescent probe. The interactions between PFDE and proteins were also studied by dynamic light scattering (DLS) and isothermal titration microcalorimetry (ITC) techniques. In contrast to other methods based on conjugated polymers, the synthesis of a series of quencher or dye‐labeled acceptors or protein substrates has been avoided in our method, which significantly reduces the cost and the synthetic complexity. Our method provides promising applications on protein identification and denaturation detection in a simple, fast, and label‐free manner based on non‐specific interaction‐induced perturbation of PFDE fluorescence response.     

Comparative study on the enzymatic polymerization of N‐substituted aniline derivatives

A series of water‐soluble N‐substituted poly(alkylanilines) (PNAAs) have been enzymatically synthesized with a variety of groups, from methyl to n‐butyl, such as poly(N‐methylaniline), poly(N‐ethylaniline), poly(N‐butylaniline) and poly(N‐phenylethanolamine). The syntheses were made in the presence of poly(4‐sodium styrene sulfonate) (SPS) as a template and horseradish peroxidase (HRP) as a catalyst. The size and type of the groups have a great effect on the properties of the final polymers. UV‐vis spectroscopy and cyclic voltammetry measurements confirmed that for enzymatically synthesized PNAAs/SPS complexes, the electroactivity increased with the bulkiness of the substituents. These polymers have been studied in the doped and undoped states by FT‐IR and UV‐vis spectroscopy. Also these polymers show multiple and reversible optical transitions that can be ascribed to the formation of polaron and bipolaron states. Copyright © 2005 John Wiley & Sons, Ltd.     

End group effect on the thermo‐sensitive properties of well‐defined water‐soluble polystyrenics with short pendant oligo(ethylene glycol) groups synthesized by nitroxide‐mediated radical polymerization

The effects of hydrophobic chain end groups on the cloud points of thermo‐sensitive water‐soluble polystyrenics were investigated. Well‐defined poly (4‐vinylbenzyl methoxytris(oxyethylene) ether) (PTEGSt) and poly(α‐hydro‐ω‐(4‐vinylbenzyl)tetrakis(oxyethylene)) (PHTrEGSt) were prepared by nitroxide‐mediated radical polymerization using α‐hydrido alkoxyamine initiators including two monomer‐based initiators. The polymers were reduced with (n‐Bu)₃SnH to replace the alkoxyamine end group with hydrogen. In the studied molecular weight range (M_n,GPC = 3000 to 28,000 g/mol), we found that the hydrophobic end groups decreased the cloud point by 1–20 °C depending on the molecular weight and the largest depression was observed at the lowest molar mass. The cloud points of PTEGSt and PHTrEGSt with two hydrophobic end groups, phenylethyl and alkoxyamine, exhibited a monotonic increase with the increase of molecular weight. For polymers with only one hydrophobic end group, either phenylethyl or alkoxyamine, the cloud point initially increased with the increase of molecular weight but leveled off/decreased slightly with further increasing molar mass. For polymers with essentially no end groups, the cloud point decreased with the increase of chain length, which represents the “true” molecular weight dependence of the cloud point. The observed molecular weight dependences of the cloud points of polystyrenics with hydrophobic end group(s) are believed to result from the combined end group effect and “true” molecular weight effect. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3707–3721, 2007     

Stimulus‐responsive polymers based on 2‐hydroxypropyl acrylate prepared by RAFT polymerization

Homopolymerization and diblock copolymerization of 2‐hydroxypropyl acrylate (HPA) has been conducted using reversible addition fragmentation chain transfer (RAFT) chemistry in tert‐butanol at 80 °C. PHPA homopolymers were obtained with high conversions and narrow molecular weight distributions over a wide range of target degrees of polymerization. Like its poly(2‐hydroxyethyl methacrylate) isomer, PHPA homopolymer exhibits inverse temperature solubility in dilute aqueous solution, with cloud points increasing systematically on lowering the mean chain length. The nature of the end groups is shown to significantly affect the cloud point, whereas no effect of concentration was observed over the PHPA concentration range investigated. Various thermoresponsive PHPA‐based diblock copolymers were prepared via one‐pot syntheses in which the second block was either permanently hydrophilic or pH‐responsive. Preliminary studies confirmed that poly(ethylene oxide)‐poly(2‐hydroxypropyl acrylate) (PEO₄₅‐PHPA₄₈) and poly(2‐hydroxypropyl acrylate)‐ poly(2‐hydroxyethyl acrylate) (PHPA₄₉‐PHEA₆₈)diblock copolymers formed well‐defined PHPA‐core micelles in 10 mM sodium nitrate solution at 40 °C and 70 °C with mean hydrodynamic diameters of 20 nm and 35 nm, respectively. In contrast, most other PHPA‐based diblock copolymers investigated formed larger colloidal aggregates in 10 mM NaNO₃ solution at elevated temperatures. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2032–2043, 2010     

Copper‐mediated radical polymerization on a microcellular monolith surface

High‐capacity microcellular monoliths were prepared by a two‐step process, including the synthesis of a bromoester‐functionalized scaffold by the copolymerization of a highly concentrated emulsion and an in situ surface polymerization of methyl methacrylate with atom transfer radical polymerization. The influence of various parameters, such as the feed ratio, the concentration of immobilized bromoester groups, and the presence of a spacer group on the poly(methyl methacrylate) loading, was studied. Monoliths with capacities of up to 7 mmol g^?1 were obtained. Thermogravimetric analyses, scanning electron microscopy experiments, and mercury intrusion porosimetry measurements were used for the characterization of the final materials. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1216–1226, 2004     

Scalable ambient synthesis of water‐soluble poly(β‐hydroxythio‐ether)s

Proton transfer polymerization through thiol‐epoxy “click” reaction between commercially available and hydrophilic di‐thiol and di‐epoxide monomers is carried out under ambient conditions to furnish water‐soluble polymers. The hydrophilicity of monomers permitted use of aqueous tetrahydrofuran as the reaction medium. A high polarity of this solvent system in turn allowed for using a mild catalyst such as triethylamine for a successful polymerization process. The overall simplicity of the system translated into a simple mixing of monomers and isolation of the reactive polymers in an effortless manner and on any scale required. The structure of the resulting polymers and the extent of di‐sulfide defects are studied with the help of 13C‐ and ¹H‐NMR spectroscopy. Finally, reactivity of the synthesized polymers is examined through post‐polymerization modification reaction at the backbone sulfur atoms through oxidation reaction. The practicality, modularity, further functionalizability, and water solubility aspects of the described family of new poly(β‐hydroxythio‐ether)s is anticipated to accelerate investigations into their potential utility in bio‐relevant applications. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3381–3386