RESUMEN
The in-depth analytical characterization of polymers, in particular regarding intended biomedical applications, is becoming increasingly important to elucidate their structure-property relationships. Specifically, end group analysis of e.g. polymers featuring a 'stealth effect' towards the immune system is of particular importance because of their use in coupling reactions to bioactive compounds. Herein, we established a liquid chromatography (LC) protocol to analyse bicyclo[6.1.0]nonyne-functionalized poly(2-alkyl-2-oxazoline)s (POx)s as promising functional polymers that can be applied in strain-promoted click reactions. This work involved the synthesis of poly(2-methyl-2-oxazoline) (PMeOx) and poly(2-ethyl-2-oxazoline) (PEtOx) by living cationic ring-opening polymerization (CROP) with different molar masses ranging from 2 up to 17.5 kDa and, to our knowledge, the first liquid chromatographic analysis of PMeOx. The developed analytical protocol enables the quantitative determination of post-polymerization reaction sequences with respect to the conversion of the ω-end groups. All synthesized polymers were straightforwardly analysed on a C18-derivatized silica monolithic column under reversed-phase chromatographic conditions with a binary mobile phase gradient comprising a mixture of acetonitrile and water. Subsequent mass spectrometry of collected elution fractions enabled the confirmation of the desired ω-end group functionalities and the identification of synthetic by-products.
RESUMEN
Partially hydrolysed poly(2-oxazoline)s possess unique properties. However, much of the focus in this area has been on water soluble poly(2-oxazoline)s. Where hydrophobic poly(2-oxazoline)s have been used, this is often for selective hydrolysis. However, hydrolysis of very hydrophobic polymers could lead to interesting solution behaviour. Herein, we describe universal conditions for the hydrolysis of poly(2-alkyl-2-oxazoline)s suitable for both hydrophobic and hydrophilic 2-oxazolines. We show that the system utilised gives comparable rates to that of water alone for poly(2-ethyl-2-oxazoline). In addition, poly(2-fatty acid-2-oxazoline) was hydrolysed using the developed system and was found to proceed in a controlled manner allowing the targeting of specific degrees of hydrolysis, albeit much slower than for poly(2-ethyl-2-oxazoline). Finally, we demonstrate the partial functionalisation of poly(2-oxazoline)-poly(ethylene imine) co-polymers via aza-Michael addition.
RESUMEN
Cyclic ether, such as 1,3-dioxolane (DOL), are promising solvent for low-temperature electrolytes because of the low freezing point. Their use in electrolytes, however, is severely limited since it easily polymerizes in the presence of lithium inorganic salts. The trace water plays a key role via providing the source (proton) for chain initiation, which has, unfortunately, been neglected in most cases. In this work, we present an electrophile, trimethylsilyl isocyanate (Si-NCO), as the water scavenger, which eliminates moisture by a nucleophilic addition reaction. Si-NCO allows DOL to maintain liquid over a wide temperature range even in high-concentration electrolyte. Electrolyte with Si-NCO additive shows promising low-temperature performance. Our finding expands the use of cyclic ether solvents in the presence of inorganic salts and highlights a large space for unexplored design of water scavenger with electrophilic feature for low-temperature electrolytes.
RESUMEN
Photochemical techniques have recently been revitalized as they can readily be adapted to different polymerization modes to yield a wide range of complex macromolecular structures. However, the implementation of the photoinduced cationic methods in the polymerization of cyclic siloxane monomers has scarcely been investigated. Octamethylcyclotetrasiloxane (D4) is an important monomer for the synthesis of polydimethylsiloxane (PDMS) and its copolymers. In this study, the cationic ring-opening polymerization (ROP) of D4, initiated by diphenyl iodonium hexafluorophosphate (DPI), has been studied. Both direct and indirect initiating systems acting at broad wavelength using benzophenone and pyrene were investigated. In both systems, photochemically generated protonic acids and silylium cations are responsible for the polymerization. The kinetics of the polymerization are followed by viscosimetry and GPC analyses. The reported approach may overcome the problems associated with conventional methods and therefore represents industrial importance for the fabrication of polysiloxanes.
RESUMEN
Novel copolymer brushes of quaternized sodium alginate-g-(2-ethyl-2-oxazoline)n are achieved by the grafting reaction of 2-ethyl-2-oxazoline (EOX) from benzyl bromide groups in quaternized sodium alginate (QSA). The average number of (EOX)n structural units is mediated from 1 to 5 by changing the molar ratio of the EOX monomer to benzyl bromide side groups. There exists obvious microphase separation between the QSA backbone and (EOX)n segments in the copolymer brushes due to their thermodynamic incompatibility. The strong hydrogen-bonding interaction between -OH groups in the backbone and NâCâO groups in (EOX)n segments is helpful for the construction of reversible supramolecular networks. The copolymer brushes show low cytotoxicity for HeLa cells and good antibacterial properties for Escherichia coli and Staphylococcus aureus for the contribution of hydrophilic (EOX)n segments and antibacterial activity of the quaternary ammonium. The antiprotein behavior of polymer surfaces is improved after rearrangement of (EOX)n segments by tetrahydrofuran (THF) vapor induction. These copolymer brushes have good prospects for biomedical applications.
Asunto(s)
Alginatos , Polímeros , Alginatos/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Escherichia coli , Células HeLa , Humanos , Enlace de Hidrógeno , Polímeros/farmacologíaRESUMEN
Hydrophilic poly(2-oxazoline)s represent a promising alternative to replace poly(ethylene glycol) in the biomedical field. For that purpose, reliable analytical protocols to confirm identity and quantity of impurities are required. In particular, side products deriving from chain transfer reactions occurring during the cationic ring-opening polymerization and incomplete end-capping processes may be present. The analytical approach must hence be capable of separating polymers according to minor changes regarding their end group. We demonstrate that liquid chromatography, relying on a monolithic C18-modified silica column and isocratic as well as gradient elution using water / acetonitrile mixtures and varying detectors, can accomplish such demanding high resolution separations. Poly(2-ethyl-2-oxazoline)s (PEtOx) with acetyl, hydroxyl, and phthalimide ω-end groups were investigated. Identification of side products was achieved through coupling with electrospray ionization mass spectrometry. UV / Vis detection was applied to quantify chain transfer products in PEtOx comprising biphenyl moieties. In addition, gradient elution enabled the separation of PEtOx into macromolecules according to their specific degrees of polymerization in molar mass ranges around 2,000 g mol-1.
Asunto(s)
Cromatografía Liquida , Polímeros , Peso Molecular , Polímeros/síntesis química , ProtonesRESUMEN
The incorporation of an amino group into a bifunctional initiator for the cationic ring-opening polymerization (CROP) is achieved in a two-step reaction. Detailed kinetic studies using 2-ethyl-2-oxazoline demonstrate the initiators' eligibility for the CROP yielding well-defined polymers featuring molar masses of about 2000 g mol-1 . Deprotection of the phthalimide moiety subsequent to polymerization enables the introduction of a cyclooctyne group in central position of the polymer which is further exploited in a strain-promoted alkyne-azide click reaction (SpAAC) with a Fmoc-protected azido lysine representing a commonly used binding motif for site specific polymer-protein/peptide conjugation. In-depth characterization via electrospray ionization mass spectrometry (ESI) confirms the success of all post polymerization modification steps.
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Oxazoles , Cinética , Poliaminas , PolimerizacionRESUMEN
Commonly, volumetric shrinkage occurs during polymerizations due to the shortening of the equilibrium Van der Waals distance of two molecules to the length of a (significantly shorter) covalent bond. This volumetric shrinkage can have severe influence on the materials' properties. One strategy to overcome this volumetric shrinkage is the use of expanding monomers that show volumetric expansion during polymerization reactions. Such monomers exhibit cyclic or even oligocyclic structural motifs with a correspondingly dense atomic packing. During the ring-opening reaction of such monomers, linear structures with atomic packing of lower density are formed, which results in volumetric expansion or at least reduced volumetric shrinkage. This review provides a concise overview of expanding monomers with a focus on the elucidation of structure-property relationships. Preceded by a brief introduction of measuring techniques for the quantification of volumetric changes, the most prominent classes of expanding monomers will be presented and discussed, namely cycloalkanes and cycloalkenes, oxacycles, benzoxazines, as well as thiocyclic compounds. Spiroorthoesters, spiroorthocarbonates, cyclic carbonates, and benzoxazines are particularly highlighted.
RESUMEN
Fluorescent hydroxyapatite (HAp) nanoparticles have received significant attention in biomedical fields due to their outstanding advantages, such as low immunogenicity, excellent biocompatibility and biodegradability. However, fluorescent HAp nanoparticles with well controlled size and morphology are coated with hydrophobic molecules and their biomedical applications are largely restricted by their poor dispersibility in physiological solutions. Therefore, surface modification of these hydrophobic fluorescent HAp nanoparticles to render them water dispersibility is of utmost importance for biomedical applications. In this work, we reported for the first time for preparation of water-dispersible hydrophilic fluorescent Eu3+-doped HAp nanoparticles (named as HAp-PEOTx) through the cationic ring-opening polymerization using hydrophilic and biocompatible 2-ethyl-2-oxazoline (EOTx) as the monomer. The characterization techniques, such as nuclear magnetic resonance (NMR) spectroscopy, transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) have been used to characterize these samples. Results confirmed that we could successfully obtain the hydrophilic fluorescent HAp-PEOTx composites through the strategy described above. These fluorescent HAp-PEOTx composites display great water dispersibility, unique fluorescent properties and excellent biocompatibility, making them promising for in vitro bioimaging applications.
Asunto(s)
Durapatita/química , Nanopartículas/química , Poliaminas/química , PolimerizacionRESUMEN
A series of phenolic-acid-based 2-oxazoline monomers with methoxy-substituted phenyl and cinnamyl side chains is synthesized and polymerized in a microwave reactor at 140 °C using methyl tosylate as the initiator. The obtained poly(2-oxazoline)s are characterized by NMR spectroscopy, MALDI-TOF mass spectrometry, and size-exclusion chromatography (SEC). Kinetic studies reveal that the microwave-assisted polymerization is fast and completed within less than ≈10 min for low monomer-to-initiator ratios of ≤25. Polymers with number-average molar masses of up to 6500 g mol-1 and low dispersity (1.2-1.3) are produced. The aryl methyl ethers are successfully cleaved with aluminum triiodide/N,N'-diisopropylcarbodiimide to give a poly(2-oxazoline) with pendent catechol groups.
Asunto(s)
Hidroxibenzoatos/química , Oxazoles/química , Cinética , Microondas , Polimerizacion , Polímeros/síntesis química , Polímeros/químicaRESUMEN
The unsaturated bicyclic acetal levoglucosenyl methyl ether was readily obtained from sustainable feedstock (cellulose) and polymerized by cationic ring-opening polymerization to produce a semicrystalline thermoplastic unsaturated polyacetal with relatively high apparent molar mass (up to ca. 36â kg mol-1 ) and decent dispersity (ca. 1.4). The double bonds along the chain can undergo hydrogenation and thiol-ene reactions as well as crosslinking, thus making this polyacetal potentially interesting as a reactive functional material.
RESUMEN
During the last decades, poly(2-oxazoline)s (POx) have gained increased interest due to their versatility. In particular, cationic ring-opening polymerization (CROP) enables the synthesis of well-defined polymers bearing quantitative α- and ω-functionalities. In contrast to small initiating groups, the introduction of more sophisticated, respectively demanding groups remains challenging. To fulfill this challenge, the initiator should comply with one major requirement in order to yield well-defined polymers: a fast and complete initiation. The straight forward two-step synthesis of a novel initiator containing a 4-(trifluoromethyl)benzenesulfonate (fluorylate, TosCF3 ) counter-ion is herein presented to accomplish the introduction of a sophisticated functional 3-(2-(2-ethoxy)ethoxy)ethoxy)prop-1-ene (TEG) initiating group. Kinetic studies are conducted in acetonitrile and chlorobenzene using the hydrophilic 2-ethyl-2-oxazoline (EtOx) as well as the hydrophobic 2-octyl-2-oxazoline (OctOx) as monomers to examine the influences of the solvent as well as the different monomers. In particular, the initiator efficiency is determined by 1 H and 19 F nuclear magnetic resonance spectroscopy and compared to the corresponding tosylate (TEGTos) and triflate (TEGTf). It is shown that the fluorylate combines the stability of the tosylate and an enhanced propagation rate comparable to the triflate.
Asunto(s)
Oxazoles/síntesis química , Sulfonamidas/química , Iones/química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Oxazoles/químicaRESUMEN
Fluorescent silica nanoparticles (FSNPs) have attracted great interest for potential applications in biological and biomedical fields because they possess higher fluorescence quantum yield and better fluorescence stability as comparison with small organic fluorescent molecules. The encapsulation of covalent linkage with fluorescent organic dyes or fluorescent metal complexes has demonstrated to be the commonly adopted strategies for fabrication of FSNPs previously. However, it is still challengeable to obtain FSNPs based polymer composites with intensive fluorescence and good water dispersibility through a one-pot surface modification strategy. In this paper, we developed a facile method to fabricate novel FSNPs based polymer composites (PhE@MSNs-PEtOx) through introducing the aggregation-induced emission (AIE) dye (PhE-OH) and poly(2-ethyl-2-oxazoline) (PEtOx) onto mesoporous silica nanoparticles (MSNs) based on cationic ring opening polymerization (CROP). The resulting PhE@MSNs-PEtOx composites possess strong fluorescence emission, excellent hydrophilicity and biocompatibility. These features make the final FSNPs based polymer composites great potential for biomedical applications. Taken together, we have developed for the first time that FSNPs based polymer composites can be facilely prepared through the one-pot introduction of AIE dyes and hydrophilic PEtOx on MSNs. Moreover, the novel FSNPs based composites could also be utilized for other biomedical applications considered their properties.
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Colorantes/química , Nanopartículas/química , Polimerizacion , Dióxido de Silicio/química , Animales , Cationes , Línea Celular , Supervivencia Celular , Fluorescencia , Ratones , Nanopartículas/ultraestructura , Imagen Óptica , Espectroscopía de Fotoelectrones , Espectroscopía de Protones por Resonancia Magnética , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie , TermogravimetríaRESUMEN
The reversible addition-fragmentation chain-transfer (RAFT) process represents a sophisticated polymerization technique for the preparation of tailored and well-defined polymers from acrylates, acrylamides, and (meth)acrylates. The direct switching from other methods, such as cationic polymerizations, without the need for tedious functionalization and purification steps remains challenging. Within this study, it is demonstrated that poly(2-oxazoline) (P(Ox)) macro chain-transfer agents (macro-CTAs) can be prepared through the quenching of the cationic ring-opening polymerization with a carbonotrithioate salt. The end-functionalization of the P(Ox)s is observed to be almost quantitative and the macro-CTAs could be directly used for RAFT polymerization without further purification. This one-pot procedure could be extended to a variety of (multi)block copolymers consisting of different 2-oxazolines and acrylates with good-to-excellent control. Kinetic studies revealed the controlled polymerization of block copolymers, which are further accessible for α- and ω-end-functionalization. The simplicity and versatility of the approach promise a straightforward access to block copolymers from cationic and controlled radical polymerizations.
Asunto(s)
Oxazoles/síntesis química , Cationes/química , Radicales Libres/química , Estructura Molecular , Oxazoles/química , PolimerizacionRESUMEN
Depending on the degree of grafting (DG) and the side chain degree of polymerization (DP), graft copolymers may feature properties similar to statistical copolymers or to block copolymers. This issue is approached by studying aqueous solutions of PMMA-g-OEtOx graft copolymers comprising a hydrophobic poly(methyl methacrylate) (PMMA) backbone and hydrophilic oligo(2-ethyl-2-oxazoline) (OEtOx) side chains. The graft copolymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) copolymerization of methyl methacrylate (MMA) and OEtOx-methacrylate macromonomers of varying DP. All aqueous solutions of PMMA-g-OEtOx (9% ≤ DG ≤ 34%; 5 ≤ side chain DP ≤ 24) revealed lower critical solution temperature behavior. The graft copolymer architecture significantly influenced the aggregation behavior, the conformation in aqueous solution and the coil to globule transition, as verified by means of turbidimetry, dynamic light scattering, nuclear magnetic resonance spectroscopy, and analytical ultracentrifugation. The aggregation behavior of graft copolymers with a side chain DP of 5 was significantly affected by small variations of the DG, occasionally forming mesoglobules above the cloud point temperature (Tcp), which was around human body temperature. On the other hand, PMMA-g-OEtOx with elongated side chains assembled into well-defined structures below the Tcp (apparent aggregation number (Nagg = 10)) that were able to solubilize Disperse Orange 3. The thermoresponsive behavior of aqueous solutions thus resembled that of micelles comprising a poly(2-ethyl-2-oxazoline) (PEtOx) shell (Tcp > 60 °C).
RESUMEN
Detailed kinetic studies during the cationic ring-opening polymerization (CROP) of 2-ethyl-2-oxazoline (EtOx) are conducted using four bifunctional bromo-type initiators in N,N-dimethylformamide (DMF) at 140 °C. Serving as models to quantify chain transfer to monomer occurring during the CROP initiated by monofunctional initiators, size exclusion chromatography (SEC) resolves a second molar mass distribution with lower molar mass at initial [monomer] to [initiation site] ratios ([M]0 /[I]0 ) of 25, while the resolution is insufficient at [M]0 /[I]0 of 10. Slightly slow initiation is revealed at [M]0 /[I]0 = 25, which prohibits the derivation of chain transfer rates by fitting of the size exclusion chromatography (SEC) data. Although conventional kinetic plots give no indication of significant amounts of chain transfer, the molar mass distributions resolved by SEC can unambiguously be identified as such by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) in both the high as well as the low m/z regions of the mass spectra.
Asunto(s)
Dimetilformamida/química , Sustancias Macromoleculares/química , Oxazoles/química , Polímeros/química , Cationes/química , Cromatografía en Gel , Cinética , Peso Molecular , PolimerizacionRESUMEN
Hydroxy terminated polyepichlorohydrin (PECH) was synthesized in good yield (85-88%) with improved functionality (2.01-2.53) and desired number average molecular weight (â¼3000), using a novel catalyst-co-catalyst combination. The effect of various molar ratios (4-12) of p-toluenesulphonic acid and SnCl4 on molecular weight of PECH was investigated. Different polymerization conditions like temperature, time and monomer addition rates were found to have pronounced effect on molecular weight, polydispersity and functionality of the products. The molecular weight distribution and polydispersity of the synthesized polymers were determined by Gel permeation chromatography (GPC). Absolute value of Number average molecular weight (Mn) was established with vapor pressure osmometry and structural elucidations were carried out by FT-IR and NMR spectroscopic techniques. Terminal Hydroxyl groups were quantified by acetylation method and functionality was derived from hydroxyl value and Mn.
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The step-wise solution self-assembly of double crystalline organometallic poly(ferrocenyldimethylsilane)-block-poly(2-iso-propyl-2-oxazoline) (PFDMS-b-PiPrOx) diblock copolymers is demonstrated. Two block copolymers are obtained by copper-catalyzed azide-alkyne cycloaddition (CuAAC), featuring PFDMS/PiPrOx weight fractions of 46/54 (PFDMS30-b-PiPrOx75) and 30/70 (PFDMS30-b-PiPrOx155). Nonsolvent induced crystallization of PFDMS in acetone leads in both cases to cylindrical micelles with a PFDMS core. Afterward, the structures are transferred into water for sequential temperature-induced crystallization of the PiPrOx corona, leading to hierarchical double crystalline superstructures, which are investigated using scanning electron microscopy, wide angle X-ray scattering, and differential scanning calorimetry.
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Polímeros/química , Polímeros/síntesis química , Rastreo Diferencial de Calorimetría , Micelas , Polietilenglicoles/químicaRESUMEN
The transmembrane transport of drug loaded micelles to intracellular compartment is quite crucial for efficient drug delivery. In the current study, we investigated the cellular internalization and anticancer activity of doxorubicin loaded micelles with folate modified stealthy PEOz corona. Folate-decorated micelles incorporating doxorubicin were characterized for particle size, degree of folate decoration, drug loading content and encapsulation efficiency, morphology, and surface charge. The targeting capability and cell viability were assessed using HeLa, KB, A549 and MCF-7/ADR cell lines. In vitro study clearly illustrated the folate receptor (FR) mediated targeting of FA modified micelles to FR-positive human HeLa, KB and MCF-7/ADR cells, while specific delivery to FR-negative A549 cells was not apparently increased at the same experimental conditions. Cytotoxicity assay showed 60% and 58% decrease in IC50 values for HeLa and KB cells, while only a slight decrease for A549 cells, following treatment with folate modified formulations. The enhanced intracellular delivery of FA modified micelles in MCF-7/ADR cells was also observed. In vivo antitumor tests revealed DOX entrapped FA-PEOz-PCL micelles effectively inhibited the tumor growth and reduced the toxicity to mice compared with free DOX. The current study showed that the targeted nano-vector improved cytotoxicity of DOX and suggested that this novel PEOz endowed stealthy micelle system held great promise in tumor targeted therapy.