Enzymatic Synthesis of Organic‐Polymer‐Grafted DNA

To create bioorganic hybrid materials, interdisciplinary work in the fields of chemistry, biology and materials science is conducted. DNA block copolymers are promising hybrid materials due to the combination of properties intrinsic to both the polymer and the nucleic acid blocks. Until now, the coupling of DNA and organic polymers has been exercised post‐synthetically in solution or on solid support. Herein, we report the first enzyme‐catalysed synthesis of DNA–organic polymer chimeras. For this purpose, four novel 2′‐deoxyuridine triphosphates carrying polymer‐like moieties linked to the nucleobase were synthesised. Linear polyethylene glycol monomethyl ethers of different sizes ( 1 ) and branched polyamido dendrons with varying terminal groups ( 2 ) were chosen as building blocks. We investigated the ability of DNA polymerases to accept the copolymers in comparison to the natural substrate and showed, through primer extensions, polymerase chain reactions and rolling circle amplification, that these building blocks could serve as a surrogate for the natural thymidine. By this method, DNA hybrid materials with high molecular weight, modification density, and defined structure are accessible.     

Biological–synthetic hybrid block copolymers: Combining the best from two worlds

Although biopolymers and synthetic polymers share many common features, each of these two classes of materials is also characterized by a distinct and very specific set of advantages and disadvantages. Combining biopolymer elements with synthetic polymers into a single macromolecular conjugate is an interesting strategy for synergetically merging the properties of the individual components and overcoming some of their limitations. This article focuses on a special class of biological–synthetic hybrids that are obtained by site‐selective conjugation of a protein or peptide and a synthetic polymer. The first part of the article gives an overview of the different liquid‐phase and solid‐phase techniques that have been developed for the synthesis of well‐defined, that is, site‐selectively conjugated, synthetic polymer–protein hybrids. In the second part, the properties and potential applications of these materials are discussed. The conjugation of biological and synthetic macromolecules allows the modulation of protein binding and recognition properties and is a powerful strategy for mediating the self‐assembly of synthetic polymers. Synthetic polymer–protein hybrids are already used as medicines and show significant promise for bioanalytical applications and bioseparations. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1–17, 2005     

Chromatographic performance of molecularly imprinted polymers: Core‐shell microspheres by precipitation polymerization and grafted MIP films via iniferter‐modified silica beads

In this work, two different surface imprinting formats have been evaluated using thiabendazole (TBZ) as model template. The first format is a thin film of molecularly imprinted polymer (MIP) grafted from preformed silica particles using an immobilized iniferter‐type initiator (inif‐MIP). The second format is molecularly imprinted polymer microspheres with narrow particle size distribution and core‐shell morphology prepared by precipitation polymerization in a two‐step procedure. For the latter format, polymer microspheres (the core particles) were obtained by precipitation polymerization of divinylbenzene‐80 (DVB‐80) in acetonitrile. Thereafter, the core particles were used as seed particles in the synthesis of MIP shells by copolymerization of DVB‐80 and methacrylic acid in the presence of TBZ in a mixed solvent porogen (acetonitrile/toluene). The materials were characterized by elemental microanalysis, nitrogen sorption porosimetry and scanning (and transmission) electron microscopy. Thereafter, the imprinted materials were assessed as stationary phases in liquid chromatography. From this study it can be concluded that grafted MIP beads can be obtained in a simple and direct manner, consuming only a fraction of the reagents used typically to prepare imprinted particles from a monolithic imprinted polymer. Such materials can be used in the development of in‐line molecularly imprinted solid‐phase extraction methods. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1058–1066, 2010     

High‐Molecular‐Weight Polynucleotides by Transferase‐Catalyzed Living Chain‐Growth Polycondensation

We present terminal deoxynucleotidyl transferase‐catalyzed enzymatic polymerization (TcEP) for the template‐free synthesis of high‐molecular‐weight, single‐stranded DNA (ssDNA) and demonstrate that it proceeds by a living chain‐growth polycondensation mechanism. We show that the molecular weight of the reaction products is nearly monodisperse, and can be manipulated by the feed ratio of nucleotide (monomer) to oligonucleotide (initiator), as typically observed for living polymerization reactions. Understanding the synthesis mechanism and the reaction kinetics enables the rational, template‐free synthesis of ssDNA that can be used for a range of biomedical and nanotechnology applications.     

An Efficient and Modular Route to Sequence‐Defined Polymers Appended to DNA

Inspired by biological polymers, sequence‐controlled synthetic polymers are highly promising materials that integrate the robustness of synthetic systems with the information‐derived activity of biological counterparts. Polymer–biopolymer conjugates are often targeted to achieve this union; however, their synthesis remains challenging. We report a stepwise solid‐phase approach for the generation of completely monodisperse and sequence‐defined DNA–polymer conjugates using readily available reagents. These polymeric modifications to DNA display self‐assembly and encapsulation behavior—as evidenced by HPLC, dynamic light scattering, and fluorescence studies—which is highly dependent on sequence order. The method is general and has the potential to make DNA–polymer conjugates and sequence‐defined polymers widely available.     

One‐Step Synthesis of 2,5‐Diaminoimidazoles and Total Synthesis of Methylglyoxal‐Derived Imidazolium Crosslink (MODIC)

Here we describe a general method for the synthesis of 2,5‐diaminoimidazoles, which involves a thermal reaction between α‐aminoketones and substituted guanylhydrazines without the need for additives. As one of the few known ways to access the 2,5‐diaminoimidazole motif, our method greatly expands the number of reported diaminoimidazoles and further supports our previous observations that these compounds spontaneously adopt the non‐aromatic 4(H) tautomer. The reaction works successfully on both cyclic and acyclic amino ketone starting materials, as well as a range of substituted guanylhydrazines. Following optimization, the method was applied to the efficient synthesis of the advanced glycation end product (AGE) methylglyoxal‐derived imidazolium crosslink (MODIC). We expect that this method will enable rapid access to a variety of biologically important 2,5‐diaminoimidazole‐containing products.     

Synthesis and Morphogenesis of Organic and Inorganic Polymers by Means of Biominerals and Biomimetic Materials

We have studied the simultaneous synthesis and morphogenesis of polymer materials with hierarchical structures from nanoscopic to macroscopic scales. The morphologies of the original materials can be replicated to the polymer materials. In general, it is not easy to achieve the simultaneous synthesis and morphogenesis of polymer material even using host materials. In the present work, four biominerals and three biomimetic mesocrystal structures are used as the host materials or templates and polypyrrole, poly(3‐hexylthiopehene), and silica were used as the precursors for the simultaneous syntheses and morphogenesis of polymer materials. The host materials with the hierarchical structure possess the nanospace for the incorporation of the monomers. After the incorporation of the monomers, the polymerization reaction proceeds in the nanospace with addition of the initiator agents. Then, the dissolution of the host materials leads to the formation and morphogenesis of the polymer materials. The scheme of the replication can be classified into the three types based on the structures of the host materials (types I–III). The type I template facilitates the hierarchical replication of the whole host material, type II mediates the hierarchical surface replication, and type III induces the formation of the two‐dimensional nanosheets. Based on these results, the approach for the coupled synthesis and morphogenesis can be applied to a variety of combinations of the templates and polymer materials.     

Automated Synthesis of Well‐Defined Polymers and Biohybrids by Atom Transfer Radical Polymerization Using a DNA Synthesizer

A DNA synthesizer was successfully employed for preparation of well‐defined polymers by atom transfer radical polymerization (ATRP), in a technique termed AutoATRP. This method provides well‐defined homopolymers, diblock copolymers, and biohybrids under automated photomediated ATRP conditions. PhotoATRP was selected over other ATRP methods because of mild reaction conditions, ambient temperature, tolerance to oxygen, and no need to introduce reducing agents or radical initiators. Both acrylate and methacrylate monomers were successfully polymerized with excellent control in the DNA synthesizer. Diblock copolymers were synthesized with different targeted degrees of polymerization and with high retention of chain‐end functionality. Both hydrophobic and hydrophilic monomers were grafted from DNA. The DNA‐polymer hybrids were characterized by SEC and DLS. The AutoATRP method provides an efficient route to prepare a range of different polymeric materials, especially polymer‐biohybrids.     

Polystyrene-graft-polyglycerol resins: a new type of high-loading hybrid support for organic synthesis

The preparation of a dendritic graft polymer by a very efficient synthesis of polyglycerol directly on a polystyrene resin is presented. This one-step process can be performed on a multigram scale to provide a chemically stable polymeric support. The resulting hybrid polymers were fully characterized by diverse analytical methods (NMR, IR, ESEM, UV detection of cleaved protecting groups, and mass-spectrometric methods). They combine a high loading capacity (up to 4.3 mmol g(-1)) with good swelling properties in a wide range of solvents (including water), which is the major drawback for many existing solid phase supports. In comparison to the widely employed PEGylated resins, these hybrid materials offer a 10-fold higher loading capacity. Their suitability as supports for organic synthesis and for the immobilization of reagents has been demonstrated. These materials also swell in water, and consequently, it should be possible to use these new hybrid materials for synthesis in protic solvents.     

An enhanced host–guest electro‐optical polymer system using poly(norbornene‐dicarboximides) via ROMP

High glass transition temperature poly(N‐cyclohexyl‐5‐norbornene‐2,3‐dicarboximide)s (NDI)s prepared by ring opening metathesis polymerization yielded polymers with a narrow polydispersity and well‐controlled molecular weight materials when using the Grubbs first generation initiator. Polymers produced using the Grubbs second generation initiator could not be controlled easily. By initiator selection it was also possible to synthesize polymers with either 98 or 52% trans microstructures. These materials were employed as electro‐optic (EO) polymer hosts for high molecular hyperpolarizability (β) phenyl vinylene thiophene vinylene bridge chromophores. This chromophore was modified by the incorporation of a tert‐butyldiphenylsilane group. The addition was able to further increase its EO coefficient (r₃₃) to reach 93 pm/V in a trans rich poly(NDI) produced by the Grubbs first generation initiator, compared to a benchmark chromophore / polymer combination. We investigated in detail the relationship between polymer microstructure and their absolute molecular weight on forming the best host–guest with the high β chromophore. Our results indicate that by utilizing a very simple host–guest system a high r₃₃ can be realized. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Effect of a Set of Acids and Polymerization Conditions on the Architecture of Polycarbonates Obtained via Ring Opening Polymerization

Polycarbonate‐based polymers with a well‐defined architecture have become interesting materials due to their large range of applications. Ring opening polymerization (ROP) has been largely applied to make branched polycarbonates. The polymer architectures obtained via this method are strictly related with the polymerization mechanisms involved which depend on the polymerization conditions chosen. Hereby, we evaluate the catalytic activity of three acids, fumaric, trifluoroacetic, and methanesulfonic on the Cationic ROP of trimethylene carbonate (TMC) over a trifunctional initiator, trimethylol propane (TMP), under different reaction conditions. In‐detail characterization of the polymers showed the co‐existence of two polymerization mechanisms: the activated monomer (AM), which produces a tri‐armed branched polycarbonate with inclusion of the TMP initiator (TMP‐PTMC), and a combined AM/Activated Chain End (ACE) mechanism, which produces a linear polycarbonate (L‐PTMC). Such mixtures were identified for nearly all the reaction variables investigated, together with other side reactions. Upon optimization of the synthesis, the polymerizations in toluene with TFA at 35 °C and equimolar acid/initiator ratio were optimal, avoiding side reactions, but still resulting in a polymer mixture composed of ～69% TMP‐PTMC and 31% of a polycarbonate linear polymer. The occurrence of such mixed polymer architectures is commonly overlooked in literature regarding CROP of branched polycarbonates. We demonstrate the importance of performing a full characterization for a successful detection of polymer mixtures having different (number of) end‐functionalities, which are critical for further use in advanced applications, such as in the biomedical or pharmaceutical filed. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1502–1511     

Bio‐Inspired Renewable Surface‐Initiated Polymerization from Permanently Embedded Initiators

Herein, we describe a simple and robust approach to repeatedly modify surfaces with polymer brushes through surface‐initiated atomic transfer radical polymerization (SI‐ATRP), based on an initiator‐embedded polystyrene sheet that does not rely on specific surface chemistries for initiator immobilization. The surface‐grafted polymer brushes can be wiped away to expose fresh underlying initiator that re‐initiates polymerization. This strategy provides a facile route for modification of molded or embossed surfaces, with possible applications in the preparation of fluidic devices and polymer‐embedded circuits.     

Tailor–made Covalent Organic‐Inorganic Polyoxometalate Hybrids: Versatile Platforms for the Elaboration of Functional Molecular Architectures

Post‐functionalization of organically modified polyoxometalates (POMs) is a powerful synthetic tool to devise functional building blocks for the rational elaboration of POM‐based molecular materials. In this personal account we focus on iodoaryl‐terminated POM platforms, describe reliable routes to the synthesis of covalent organic‐inorganic POM‐based hybrids and their integration into advanced molecular architectures or multi‐scale assemblies as well as their immobilization onto surfaces. Valorisation of the remarkable redox properties of POMs in the fields of artificial synthesis and molecular electronic is especially considered.     

Functional copolymer/organo‐MMT nanoarchitectures. VII. Interlamellar controlled/living radical copolymerization of maleic anhydride with butyl methacrylate via preintercalated RAFT agent–organoclay complexes

We have developed a new approach for the synthesis of polymer nanocomposites using a bifunctional reversible addition–fragmentation chain transfer (RAFT) agent, two types of organo‐montmorillonites (O‐MMT), such as a non‐reactive dimethyldidodecyl ammonium (DMDA)‐MMT and a reactive octadecyl amine (ODA)‐MMT organoclays, maleic anhydride (MA), and n‐butyl methacrylate (BMA) monomers and a radical initiator. This method includes the following stages: (1) synthesis of RAFT intercalated O‐MMTs by a physical or chemical interaction of the RAFT agent having two pendant carboxylic groups [S,S′‐bis(α,α′‐dimethyl‐α″‐acetic acid) trithiocarbonate] with surface alkyl amines of O‐MMT containing tertiary ammonium cation or primary amine groups through strong H‐bonding and compexing/amidization reactions, respectively, and (2) utilization of these well dispersed and intercalated RAFT…O‐MMT complexes and amide derivative of RAFT…ODA‐MMT as new modified RAFT agents in radical‐initiated interlamellar controlled/living complex‐radical copolymerization of MA‐BMA monomer pair. Nanostructure and compositions of the synthesized RAFT…O‐MMT complexes and functional copolymer/O‐MMT hybrids were confirmed by FTIR, GPC, XRD, thermal (DSC‐TGA), SEM, and TEM morphology analyses. This simple and versatile method can be applied to a wide range of monomer/comonomer systems for the preparation of completely exfoliated macromolecular nanoarchitectures. Copyright © 2011 John Wiley & Sons, Ltd.     

Poly(styrene‐co‐glycerol dimethacrylate): Synthesis,characterization, and application as a resin for gel‐phase peptide synthesis

An efficient cross‐linked polymer support for solid‐phase synthesis was prepared by introducing glycerol dimethacrylate cross‐linker to polystyrene network using free radical aqueous suspension polymerization. The support was characterized by various spectroscopic methods. Morphological feature of the resin was analyzed by microscopy. The polymerization reaction was investigated with respect to the effect of amount of cross‐linking agent, which in turn vary the swelling, loading, and the mechanical stability of the resin. The solvent uptake of the polymer was studied in relation to cross‐linking and compared with Merrifield resin. The stability of the resin was tested in different synthetic conditions used for solid‐phase peptide synthesis. Hydroxy group of the support was derivatized to chloro and then amino groups using different reagents and reaction conditions. Efficiency of the support was tested and compared with TentaGel? resin by following different steps involved in the synthesis of the 65–74 fragment of acyl carrier protein. The results showed that the poly(styrene‐co‐glycerol dimethacrylate) (GDMA‐PS) is equally efficient as TentaGel resin in peptide synthesis. The purity of the peptides was analyzed by HPLC and identities were determined by mass spectroscopy and amino acid analysis. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4382–4392, 2005     

Filler effect on properties of “All‐Acrylic” copolymer/clay elastomeric materials synthesized by “in situ” nitroxide mediated polymerization

In this work, we describe the “in situ” synthesis of “all‐acrylic” copolymer (n‐butyl acrylate‐co‐methyl methacrylate)/clay materials at different low contents of raw and modified Montmorillonite (1–4 wt % versus monomer). The cationic 2,2′ azobis‐(amidinopropane)dihydrochloride initiator was used to modified the clay by cation exchange in combination with the N‐tert‐butyl‐N‐[1‐diethylphosphono‐(2,2‐dimethylpropyl)] (SG1) nitroxide to synthesize the polymer/clay nanocomposite via nitroxide mediated controlled radical polymerization. All synthesized materials are characterized by proton nuclear magnetic resonance, size exclusion chromatography, thermogravimetric analysis and differential scanning calorimetry techniques. The thermo‐mechanical properties of the synthesized materials are also reported. The results show that a decrease in molar masses and/or slight changes in molar compositions of poly (n‐butyl acrylate‐ co‐methyl methacrylate)/clay systems can be balanced by clay loading in polymer matrix, and consequently compensated or masked clay effects on physical properties of obtained materials. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Atom Transfer Radical Polymerization in the Solid‐State

Poly(2‐vinylnaphthalene) was synthesized in the solid‐state by ball milling a mixture of the corresponding monomer, a Cu‐based catalyst, and an activated haloalkane as the polymerization initiator. Various reaction conditions, including milling time, milling frequency and added reductant to accelerate the polymerization were optimized. Monomer conversion and the evolution of polymer molecular weight were monitored over time using ¹H NMR spectroscopy and size exclusion chromatography, respectively, and linear correlations were observed. While the polymer molecular weight was effectively tuned by changing the initial monomer‐to‐initiator ratio, the experimentally measured values were found to be lower than their theoretical values. The difference was attributed to premature mechanical decomposition and modeled to accurately account for the decrement. Random copolymers of two monomers with orthogonal solubilities, sodium styrene sulfonate and 2‐vinylnaphthalene, were also synthesized in the solid‐state. Inspection of the data revealed that the solid‐state polymerization reaction was controlled, followed a mechanism similar to that described for solution‐state atom transfer radical polymerizations, and may be used to prepare polymers that are inaccessible via solution‐state methods.     

Synthesemethoden für keramische Materialien. Hochtechnologiewerkstoffe

The new developments in the field of gas phase synthesis, synthesis from the condensed phases and solid‐state synthesis allowing for the fabrication of new ceramic materials for diverse technical applications have been reviewed. The Flame Spray Pyrolysis, aqueous and non‐aqueous sol‐gel techniques, hydro‐ and solvothermal methods, polymer pyrolysis route and high pressure techniques have been considered as synthesis methods with great technical potential.     

Ring‐Opening Polymerization of Prodrugs: A Versatile Approach to Prepare Well‐Defined Drug‐Loaded Nanoparticles

The synthesis of polymer–drug conjugates from prodrug monomers consisting of a cyclic polymerizable group that is appended to a drug through a cleavable linker is achieved by organocatalyzed ring‐opening polymerization. The monomers polymerize into well‐defined polymer prodrugs that are designed to self‐assemble into nanoparticles and release the drug in response to a physiologically relevant stimulus. This method is compatible with structurally diverse drugs and allows different drugs to be copolymerized with quantitative conversion of the monomers. The drug loading can be controlled by adjusting the monomer(s)/initiator feed ratio and drug release can be encoded into the polymer by the choice of linker. Initiating these monomers from a poly(ethylene glycol) macroinitiator results in amphiphilic diblock copolymers that spontaneously self‐assemble into micelles with a long plasma circulation, which is useful for systemic therapy.     

Photo‐triggered redox frontal polymerization: A new tool for synthesizing thermally sensitive materials

A novel approach of photo‐triggered redox frontal polymerization (FP) by integrating photocaged superbase (QA‐DBU) with a peroxide initiator (dibenzoyl peroxide, BPO) is presented for the synthesis of thermally sensitive materials. Under photo‐irradiation at a localized region, the regenerated superbase can diffuse into unirradiated regions and effectively actuate redox FP in a diffusion‐controlled manner. Moreover, the redox FP can be conducted at a much lower front temperature with enhanced front velocity. Astonishingly, the front temperature can be well‐modulated by changing the concentration of latent superbase. The prepared thermally sensitive fluorescent polymer composites exhibit enhanced fluorescence emission intensity compared to that of conventional thermal FP. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 4515–4521