Quaternization Reaction Research Articles

Self-reinforced endocytoses of smart polypeptide nanogels for “on-demand” drug delivery

The pH and reduction dual-responsive polypeptide nanogels with self-reinforced endocytoses were prepared through ring-opening polymerization of l-glutamate N-carboxyanhydrides, deprotection of benzyl group and subsequent quaternization reaction between γ-2-chloroethyl-l-glutamate unit in polypeptide block and 2,2′-dithiobis(N,N-dimethylethylamine). The nanogels were revealed to exhibit smart pH and reduction dual-responsiveness, and excellent biocompatibilities, which expressed great potential as antitumor drug nanocarriers. Doxorubicin (DOX) as a model antitumor drug was loaded into nanogels through dispersion. DOX-loaded nanogels displayed a stable core-cross-linked structure under normal physiological condition (pH7.4), while rapidly releasing the payloads in the mimicking endosomal (pH5.3), tumor tissular (pH6.8) or intracellular reductive microenvironments (10.0mM glutathione). Confocal fluorescence microscopy demonstrated that DOX-loaded nanogels could deliver DOX into HepG2 cells (a human hepatoma cell line) more efficiently than the parent DOX-loaded micelle and free DOX. The enhanced cellular internalizations of DOX-loaded nanogels were more significant under tumor tissular acidic condition (pH6.8) ascribed to the quaternary ammonium groups in the cores. In addition, DOX-loaded nanogels exhibited improved in vitro and in vivo antitumor activities, and in vivo securities compared with DOX-loaded micelle and free DOX. These excellent features of the smart nanogels with quaternary ammonium groups were endowed with a bright prospect for intracellular targeting antitumor drug delivery.

Preparation of poly(ethylene imine) particles for versatile applications

Polyethylene imine (PEI) particles were readily prepared via a simple microemulsion polymerization method using AOT as surfactant in commercially available gasoline with moderately high yield (∼75%) depending on the MW of PEI. The aqueous solution of branched PEI crosslinked with divinyl sulfone (DVS), called c-PEI particles were in the size range of tens of nanometers to tens of micrometers and upon filtration the desired size range was readily obtained. The prepared c-PEI particles were highly positively charged depending on the used amounts of crosslinker and the extent of modifying agents such as alkyl halide for different purposes e.g., CH3I that can conveniently be used for the quaternization reaction. The prepared c-PEI particles were demonstrated to be very useful as antimicrobial materials, drug delivery materials, as a template for metal nanoparticle preparation, as a catalysis medium for the reduction of 4-nitrophenol (4-NP) to 4-amino phenol (4-AP), and for hydrogen generation from the hydrolysis of NaBH4.

Pyridine-Functionalized Luminescent Organoboron Quinolate Block Copolymers as Versatile Building Blocks for Assembled Nanostructures

Novel luminescent boron quinolate block copolymers with pyridine functionalities were prepared via RAFT polymerization and employed as building blocks for assembled nanostructures. In selective solvents, the block copolymers self-assembled into vesicles, spherical and extended branched aggregates. Quaternization reactions were performed to modify the solubility of the block copolymers and to prepare a cross-linked polymeric gel. As polymeric Lewis bases, the pyridine-functionalized block copolymers are able to form supramolecular complexes with metal ions and Lewis acids. Coordination to ZnCl2 in chloroform led to spherical micelles or larger aggregates. The supramolecular coassembly of PS-b-PBQPy-1 and zinc meso-tetraphenylporphyrin (ZnTPP) in cyclohexane as a selective solvent for PS resulted in extended branched structures with controllable emission properties. Energy transfer from the boron chromophores to the ZnTPP moieties was observed in these supramolecular complexes.

Synthesis and Properties of Partially Fluorinated Poly(arylene ether) Block Copolymers Containing Ammonium Groups as Anion Conductive Membranes

Abstract Synthesis and properties of aromatic block copolymers containing fluorinated phenylene and biphenylene groups and ammonium-substituted fluorene groups are reported. High-molecular-weight poly(arylene ether) block copolymers were prepared from the corresponding telechelic oligomers and were chloromethylated. Quaternization reaction of the chloromethylated precursors with trimethylamine provided the title ammonium-substituted block copolymers (QPE-bl-4). The QPE-bl-4 membrane with the highest ion-exchange capacity (IEC = 1.3 mequiv g−1) showed high hydroxide ion conductivity (45 mS cm−1) at 80 °C due to its phase-separated morphology with interconnected ion-transporting pathway. The accelerated stability test in aqueous KOH solution containing hydrazine revealed that the ammonium groups decomposed to certain extent while the polymer main chains were rather robust to maintain the self-supporting membranes.

Electrochemical Behavior of Polyvinyl Chloride Electrode Modified by Platinum Micro Particles

This paper deals with the use of PVC (polyvinyl chloride) that we modify by a quaternization reaction using triethylamine (TEA) with 5% and 50%/w. The choice of such material is justified as far or PVC is the highest tonnage in annual worldwide production an additional great advantage is the lower price in the worldwide polymer market. This modified PVC contains alkylammonium sites having the object of increasing the ionic conductivity of the medium particularly when the platinum micro particles are incorporated platinum micro particles makes the conductivity of the electrode surface more exiting The modified PVC dissolved in tetrahydrofuran used for films deposition on carbon vitreous electrode type RVC 2000. A succession of electrodes have been developed and characterized represented and numerous parameters have been optimized, such as the influence of the thickness of the modified PVC film in comparison with the various electrochemical processes taking place at the electrode surface, specifically the pH of the electrolytic solution, the amount of the incorporated platinum

PH and reduction dual-responsive nanogel cross-linked by quaternization reaction for enhanced cellular internalization and intracellular drug delivery

A novel pH and reduction dual-responsive nanogel with improved cellular internalization was prepared through atom transfer radical polymerization and subsequent quaternization reaction. Doxorubicin (DOX), a model anticancer drug, was loaded into the nanogel via dispersion. The DOX-loaded nanogel presented a stable core-cross-linked structure under physiological conditions, but quickly released its payload in an acidic (pH 6.8) and reductive (10.0 mM glutathione) environment. Confocal fluorescence microscopy and fluorescence flow cytometry revealed that the DOX-loaded nanogel could deliver DOX into the cytoplasm and nucleus of cells, more efficiently than that of free DOX. The improved cellular internalization was more significant under acidic and reductive conditions, which was analogous to the pH and reductive conditions in endosomes and cytoplasm. In vitro cytotoxicity studies demonstrated that the pH and reduction responsive DOX-loaded nanogel could inhibit cellular proliferation more efficiently than free DOX. This dual-bioresponsive nanogel with quaternary ammonium salt group has appeared to be highly promising in the further development of intracellular drug transporters.

Quaternized amino poly(glycerol-methacrylate)s for enhanced pDNA delivery

Linear and 8-arm amino poly(glycerol methacrylate)s (PGOHMAs) were synthesized from poly(glycidyl methacrylate)s (PGMA)s via ring opening reactions with methylethylamine (MEA), diethylamine (DEA) and dipropylamine (DPA), respectively. Further modification of tertiary amine groups of amino PGOHMAs by quaternization reaction with methyl iodide resulted in partially quaternized PGOHMAs, namely, QPGOHMAs. QPGOHMA/plasmid DNA (pDNA) complexes at different nitrogen-to-phosphate (N/P) ratios were then prepared. In addition, eight-arm star-shaped MEA-modified PGMA (S8-MEA) was also used to complex with pDNA as a positive control to compare with QPGOHMA/pDNA complexes. QPGOHMA/pDNA complexes were spherical in shape as observed by scanning electron microscopy (SEM), and smaller in size than S8-MEA/pDNA complexes as suggested by dynamic light scattering (DLS). Interestingly, gel electrophoresis and ethidium bromide displacement assay indicated that QPGOHMAs could condense pDNA at lower N/P ratios than that of S8-MEA. In vitro experiments on Huh-7 cells showed that QPGOHMAs displayed lower cytotoxicity and better transfection efficacy compared to S8-MEA. The cellular uptake analysis revealed that QPGOHMAs enhanced the cellular uptake level of pDNA. Overall, amino PGOHMAs modified by quaternization were proved to be effective gene delivery systems for gene therapy.

Antifouling and antibiofouling pH responsive block copolymer based membranes by selective surface modification.

Antifouling and antibacterial membranes are prepared by selective surface modification of pH responsive polystyrene-b-poly(4-vinylpyridine) (PS-P4VP) diblock copolymers by quaternization and zwitterionization reactions on a P4VP moiety. Nanoporous membranes based on the self-assembly of 2-(4'-hydroxybenzeneazo) benzoic acid (HABA)-PS-P4VP supramolecular complexes and nonsolvent induced phase separation are first prepared and the surfaces are functionalized by crosslinking with diiodobutane vapors and reacting with propane sultone vapors at moderate temperature and under vacuum conditions. Selective functionalization of surfaces is carried out to enhance the antifouling and antibiofouling properties of the membrane and to retain its pH switching behavior. The membranes are thoroughly characterized by various instrumental techniques such as Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, quartz crystal microbalance, contact angle, etc. Antifouling and antibacterial properties are proven by analyzing the adsorption of bovine serum albumin protein and bacterial cell attachment and killing efficiency. The actual membrane performance is assessed in terms of water flux under different pressures and pHs and Congo red dye rejection efficiency.

Quaternized poly(arylene ether) ionomers containing triphenyl methane groups for alkaline anion exchange membranes

A series of hydroxide ion conductive poly(arylene ether) ionomers containing functionalized triphenyl methane groups and various backbones were prepared via polycondensation, chloromethylation, quaternization, and subsequent alkalization reaction. The structures of the poly(arylene ether)s (PAEs), chloromethylated poly(arylene ether)s (CMPAEs) and quaternized ammonium-substituted poly(arylene ether)s (QPAEs) were confirmed using 1H NMR and FT-IR techniques. Thermal stabilities of the PAEs, CMPAEs and QPAEs were evaluated by thermal gravimetric analysis (TGA). The water uptakes, swelling ratios, ion exchange capacities (IECs), hydroxide conductivities and chemical stabilities of the membranes derived from the synthesized ionomers were assessed as anion exchange membranes. The IEC of the ionomers ranged from 0.57 to 2.59 mmol g−1, which can be controlled by chloromethylation reaction conditions. The hydroxide conductivities of the QPAE membranes increase dramatically with increasing temperature. The QPAE-a membrane with an IEC value of 2.59 mmol g−1 displayed the highest hydroxide conductivities of 14.9 and 84.6 mS cm−1 at 20 °C and 80 °C, respectively. The hydroxide transport activation energy for the QPAE membranes ranged from 18.07 to 24.07 kJ mol−1. The first degradation temperatures of the QPAE membranes were around 185 °C. The tensile strength varied from 18 to 41 MPa at 25 °C. The QPAE membrane retained 86% of its mechanical properties and 83% of its hydroxide conductivity after being conditioned with 1 M NaOH at 60 °C for 120 h. In particular, QPAE-a retains 87% of its original IEC under very harsh conditions of 6 M NaOH at 60 °C for 168 h. These properties of the ionomer membranes demonstrate their potential as anion exchange membranes for alkaline fuel cells.

Reductively and hydrolytically dual degradable nanoparticles by “click” crosslinking of a multifunctional diblock copolymer

In this study, we report the synthesis of dual degradable nanoparticles by crosslinking a multifunctional amphiphilic block copolymer through “click” chemistry. Poly(ethylene glycol)-block-poly((ε-caprolactone)-co-(5,5-dibromomethyl trimethylene carbonate)) (mPEG-b-PDBTCL), an amphiphilic block copolymer with multiple bromo groups, was synthesized first by the ring-opening copolymerization of 5,5-dibromomethyl trimethylene carbonate (DBTC) and ε-caprolactone (CL) in the presence of methoxyl poly(ethylene glycol) as macroinitiator and stannous octanoate (Sn(Oct)2) as catalyst. Then the pendant bromo groups were partially transformed to the azide form by reacting with sodium azide under room temperature, to give partially azidated mPEG-b-PDBTCL (mPEG-b-PDBTCL-N3). Then “click” crosslinking was carried out using mPEG-b-PDBTCL-N3 as precursor and propargyl 3,3′-dithiopropionate as crosslinker, resulting in star-shaped nanoparticles bearing multiple bromo groups in the core. This kind of core crosslinked nanoparticle is biodegradable due to the hydrolysis of the poly(ester-carbonate) core. Additionally, depending on the redox-sensitive disulfide crosslinkers, the stable nanoparticles will dissociate into free block copolymers in the presence of 1,4-dithiothreitol (DTT). Furthermore, ammonium groups were introduced into the core covalently by the quaternization reaction between the remaining bromomethyl groups and N,N-dimethylbutylamine. These dual degradable nanoparticles are expected to have potential applications as smart nanovessels for both drug and gene delivery.

Structure–rheology relationship in complex quaternized polysulfones/solvent/nonsolvent systems

Polymer chains consisting of water-soluble polysulfones with various amounts of ionic chlorine have been prepared via the quaternization reaction of chloromethylated polysulfones with N,N-dimethylethanolamine. Rheological investigations have reflected the importance of electrostatic interactions, hydrogen bonding, and association phenomena from the ternary systems consisting of a proton-acceptor polymer (polysulfones with different ionic chlorine content), a proton-donor solvent (N,N-dimethylformamide), and a proton-donor solvent (methanol). The specific interactions, the polyelectrolyte effect induced by enhanced dissociation of the ionizable groups and mixed solvents’ quality modify the rheological functions, i.e., dynamic viscosity, elastic shear modulus and viscous shear modulus, as well as the thermodynamic parameters obtained from the rheological properties, such as apparent energy of activation and flow activation entropy. These results were correlated with the surface properties of the polysulfonic films formed from solutions in solvent/nonsolvent mixtures.

Adsorption of Aqueous Cr(VI) by Novel Fibrous Adsorbent with Amino and Quaternary Ammonium Groups

A novel fibrous adsorbent functionalized with both amino and quaternary ammonium groups (QAPAN) was prepared through a simple two-step route (i.e., amination followed by quaternization reactions) f...

Synthesis of Novel Imidazolium and Benzimidazolium Salts from Halomethyl Derivatives of 4-Pyrones

A series of mono- and bis-benzimidazolium and imidazolium salts of 4-pyrone derivatives has been synthesized in good yields, by various quaternization reactions of halomethyl derivatives of 4H-pyran-4-ones. These salts can be used as novel precursors of functionalized N-heterocyclic carbenes and some of them as novel ionic liquids. Keywords: 4-pyrones, benzimidazolium salts, imidazolium salts, KI, kojic acid, substitution reactions, ionic, thermal stability, transformations, synthetic

Synthesis and characterization of cationic silsesquioxane hybrids by hydrolytic condensation of triethoxysilane derived from 2-(dimethylamino)ethyl acrylate

A new family of silsesquioxane hybrids was synthesized by hydrolytic condensation of a triethoxysilane precursor, R-Si(OCH2CH3)3, R = -CH2CH2CH2N[CH2CH2COOCH2CH2N(CH3)2]2, derived from 2-(dimethylamino)ethyl acrylate. Condensation of the triethoxysilane precursor proceeded as a homogeneous system in methanol in the presence of aqueous HF solution (3.2 %) to afford the water-soluble silsesquioxane hybrid having a high density of chemically bonded peripheral tertiary amino groups on the outermost surface, as confirmed by nuclear magnetic resonance and Fourier transform infrared analyses. The relatively low polydispersity (M w/M n = 1.33) and a reasonable molecular weight (M n = 2700), corresponding to species having 6–12 silicon atoms, were confirmed by size exclusion chromatography. The size of the silsesquioxane hybrid (1.7 nm) was also determined by X-ray diffraction. Co-condensation of tetraethoxysilane (TEOS) with the triethoxysilane precursor was carried out under different feed ratios, and water-soluble products were obtained in the cases of TEOS molar ratio up to 40 %. Quaternization reaction of the tertiary amine-containing hybrids with methyl iodide led to cationic silsesquioxane hybrids containing quaternized amine functionalities, which showed good solubility in polar solvents. Scanning force microscopy measurements indicated the formation of the cationic silsesquioxane hybrids having relatively narrow size distribution with average particle diameter (about 2.0 nm) without aggregation.

Multi-functionality of cationic porphyrin-immobilized polymeric microspheres prepared by synchronously synthesizing and immobilizing pyridylporphyrin on surfaces of polymeric microspheres

Pyridylporphyrin (PyP) was synchronously synthesized and immobilized on the surfaces of crosslinked polystyrene microspheres (CPS microspheres) via an Adler reaction between solid–liquid phases, resulting in PyP-immobilized microspheres, PyP-CPS microspheres. Then the cationic porphyrin-immobilized microspheres, MPyP-CPS microspheres (“M” represents methyl group that comes from iodomethane), was prepared via the quaternization reaction of PyP-CPS microspheres with iodomethane as reagent. In the current work, the efficiency of the above route to immobilize pyridylporphyrin PyP on CPS microspheres was first researched by a comparison method, and then the multi-functionality of the cationic porphyrin-immobilized microspheres MPyP-CPS were mainly tested and examined from many aspects. The investigation results show that: (1) the above route to immobilize pyridylporphyrin on the surfaces of CPS microspheres is highly efficient, and the immobilization amount of PyP on CPS microspheres can get up to about 0.2 mmol g−1; (2) the cationic porphyrin-immobilized microspheres MPyP-CPS are a kind of multifunctional polymeric microspheres because of their special surface structure, and they can be used to construct different host-guest systems, resulting in many applications. MPyP-CPS microspheres can used as triphase-transfer catalysis in organic synthesis, can coordinate to transition metal ion to form immobilized metalloporphyrin catalysts to be used in the green catalytic oxidations, can be used as support of heteropoly acid to prepare heterogenous heteropoly acid catalyst, and MPyP-CPS microspheres also can used as solid adsorbent in the removal of toxic chromate ion from water medium. In a word, the polymeric microspheres supporting cationic porphyrin, MPyP-CPS microspheres, will have vast application prospect in various fields because they have special surface chemical structure.

Synthesis and characterization of luminescent tricationic salts of mesitylene and stilbazolium moieties

A series of luminescent tricationic salts having mesitylene and stilbazolium moieties with various organic counterions were synthesized by using quaternization and metathesis reactions. Their chemical structures were characterized by 1H, 19F and 13C NMR spectroscopy, and elemental analysis. Their crystalline and amorphous properties were examined by differential scanning calorimetry, polarized optical microscopy, and variable-temperature X-ray diffraction studies. Their thermal stabilities were determined by thermogravimetric analyses, which were in the broad temperature ranges of 239–317°C in nitrogen. Their optical properties were studied by UV–Vis and photoluminescent spectroscopy. The light-emission properties were dependent on the polarity of organic solvents (positive solvatochromism) but independent on the chemical structures of organic counterions. They emitted blue light in various organic solvents in a broad range of wavelengths of 470–497nm, but emitted green light in a narrow range of wavelengths of 506–515nm in their solid states.

Synthesis of mesomeric betaine compounds with imidazolium-enolate structure.

The synthesis of a heterocyclic mesomeric betaine by quaternization reaction of 1-butylimidazole and tetrabromo-1,4-benzoquinone is presented. The structure was verified by means of X-ray single-crystal analysis, NMR and IR spectroscopy. Inclusion complexes of the heterocyclic mesomeric betaine with randomly methylated (1.8) β-cyclodextrin were investigated by UV–vis spectroscopy. Furthermore, the reaction conditions were applied to poly(vinylimidazole) and 1,4-bis(1H-imidazol-1-yl)butane to obtain functionalized polymer networks and condensate polymers, respectively.

Synthesis of New Polyelectrolytes via Backbone Quaternization of Poly(aryloxy- and alkoxyphosphazenes) and their Small Molecule Counterparts

Novel polyelectrolytes were synthesized by quaternization of the backbone of poly(alkoxy- and aryloxyphosphazenes) with strong alkylation reagents. As models for the synthesis of these polymers, similar quaternization reactions were also carried out on small-molecule alkoxy and aryloxy cyclotriphosphazenes. The quaternized small molecules and high polymers were characterized by 1 H NMR, 31 P NMR, DSC, TGA, and AC impedance studies. The quaternized poly(alkoxyphosphazenes) showed ionic conductivities of 2.58 × 10 −4 S·cm −1 at 25 °C and 2.09 × 10 −3 S·cm −1 at 80 °C, which are among the highest values for known solvent-free ionically conducting polymers.

Facile synthesis and characterization of biodegradable antimicrobial poly(ester-carbonate)

Biodegradable antimicrobial poly(ester-carbonate)s were prepared facilely via a simple two-step process with low cost. First, poly(5,5-dibromomethyl trimethylene carbonate-co-e-caprolactone) (PDBTCL) with pendant bromo groups was synthesized by the direct ring-opening copolymerization of 5,5-dibromomethyl trimethylene carbonate (DBTC) and e-caprolactone (CL) in the presence of stannous octanoate (Sn(Oct)2) as catalyst. Then, the quaternization reaction between PDBTCL and a series of N,N-dimethyl alkylamines was performed under mild conditions, resulting in biodegradable poly(ester-carbonate)s with pendant ammonium salts (QPDBTCL). The chemical structure and composition of QPDBTCLs were characterized by 1H NMR. The influences of alkyl chain length and charge density on the antimicrobial activity of QPDBTCLs against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria were evaluated by OD600 and zone of inhibition methods. It was observed that QPDBTCLs with long alkyl chain on the ammonium groups exhibit significantly higher antimicrobial activity than those with short alkyl chain for both Gram-negative and Gram-positive bacteria. QPDBTCL with quaternary N,N-dimethyldodecylammonium groups shows strong antimicrobial activity even with very low charge density (4.3 mol%). This kind of biodegradable antimicrobial material may have potential applications as biomaterials.

Amphipathic antibacterial agents using cationic methacrylic polymers with natural rosin as pendant group

We prepared a class of novel cationic polymers as antimicrobial agents: quaternary ammonium-containing poly(N,N-dimethylaminoethyl methacrylate) with natural rosin as the pendant group (PDMAEMA-g-rosin). Different from most other amphipathic antimicrobial polymeric systems reported in the literature, our approach sandwiched the hydrophilic cationic group between the polymer backbone and bulky hydrophobic hydrophenanthrene side groups. A simple quaternization reaction was used to link the rosin ester chloride and PDMAEMA homopolymers. Both the Gram-positive bacterium Staphylococcus aureus (S. aureus) and Gram-negative bacterium Escherichia coli (E. coli) were tested against the PDMAEMA-g-rosin copolymers. PDMAEMA-g-rosin copolymers with the amphipathic structure exhibited effective antimicrobial activity against both E. coli and S. aureus. Both the degree of quaternization of rosin group and the molecular weight of PDMAEMA played roles in antimicrobial activities. Our results also indicated that conformation of hydrophobic group (particularly steric hindrance) played a role in dictating antibacterial efficacy. Scanning electron microscopy and confocal laser scanning microscopy were used to characterize morphological changes of bacteria after exposure with PDMAEMA-g-rosin copolymers. Possible mechanisms on a combination of ionic and hydrophobic interactions between bacterial cells and polymers are discussed.