Magnetic Surfactants and Polymers with Gadolinium Counterions for Protein Separations.

New magnetic surfactants, (cationic hexadecyltrimethlyammonium bromotrichlorogadolinate (CTAG), decyltrimethylammonium bromotrichlorogadolinate (DTAG), and a magnetic polymer (poly(3-acrylamidopropyl)trimethylammonium tetrachlorogadolinate (APTAG)) have been synthesized by the simple mixing of the corresponding surfactants and polymer with gadolinium metal ions. A magnetic anionic surfactant, gadolinium tri(1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate) (Gd(AOT)3), was synthesized via metathesis. Both routes enable facile preparation of magnetically responsive magnetic polymers and surfactants without the need to rely on nanocomposites or organic frameworks with polyradicals. Electrical conductivity, surface tensiometry, SQUID magnetometry, and small-angle neutron scattering (SANS) demonstrate surface activity and self-aggregation behavior of the magnetic surfactants similar to their magnetically inert parent analogues but with added magnetic properties. The binding of the magnetic surfactants to proteins enables efficient separations under low-strength (0.33 T) magnetic fields in a new, nanoparticle-free approach to magnetophoretic protein separations and extractions. Importantly, the toxicity of the magnetic surfactants and polymers is, in some cases, lower than that of their halide analogues.

Sensing and inactivation of Bacillus anthracis Sterne by polymer-bromine complexes.

We report on the performance of brominated poly(N-vinylpyrrolidone) (PVP-Br), brominated poly(ethylene glycol) (PEG-Br), and brominated poly(allylamine-co-4-aminopyridine) (PAAm-APy-Br) for their ability to decontaminate Bacillus anthracis Sterne spores in solution while also allowing for the sensing of the spores. The polymers were brominated by bromine using carbon tetrachloride or potassium tribromide as solvents, with bromine loadings ranging from 1.6 to 4.2 mEq/g of polymer. B. anthracis Sterne spores were exposed to increasing concentrations of brominated polymers for 5 min, while the kinetics of the sporicidal activity was assessed. All brominated polymers demonstrated spore log-kills of 8 within 5 min of exposure at 12 mg/mL aqueous polymer concentration. Sensing of spores was accomplished by measuring the release of dipicolinic acid (DPA) from the spore using time-resolved fluorescence. Parent, non-brominated polymers did not cause any release of DPA and the spores remained viable. In contrast, spores exposed to the brominated polymers were inactivated and the release of DPA was observed within minutes of exposure. Also, this release of DPA continued for a long time after spore inactivation as in a controlled release process. The DPA release was more pronounced for spores exposed to brominated PVP and brominated PEG-8000 compared to brominated PAAm-APy and brominated PEG-400. Using time-resolved fluorescence, we detected as low as 2500 B. anthracis spores, with PEG-8000 being more sensitive to low spore numbers. Our results suggest that the brominated polymers may be used effectively as decontamination agents against bacterial spores while also providing the sensing capability.

Nonleaching Biocidal N-Halamine-Functionalized Polyamine-, Guanidine-, and Hydantoin-Based Coatings.

Fibrous materials with inherent antimicrobial properties can help in real-time deactivation of microorganisms, enabling multiple uses while reducing secondary infections. Coatings with antiviral polymers enhance the surface functionality for existing and potential future pandemics. Herein, we demonstrated a straightforward route toward biocidal surface creation using polymers with nucleophilic biguanide, guanidine, and hydantoin groups that are covalently attached onto a solid support. Biocidal poly(N-vinylguanidine) (PVG) and poly(allylamine-co-4-aminopyridine-co-5-(4-hydroxybenzylidene)hydantoin) (PAH) were introduced for coating applications along with commercially available polyvinylamine (PVAm) and poly(hexamethylene biguanide) (PHMB). Nonleaching coatings were created by first fabricating bifunctional siloxane or isocyanate precursor coatings on the cotton, nylon-cotton, and glass fiber fabric, followed by the polymer attachment. The developed grafting methods ensured the stability of the coating and the reuse of the material while maintaining the biocidal properties. Halogenation of polymer-coated fabric was conducted by aqueous solutions of sodium hypochlorite or in situ generation of hypobromous acid (HOBr), resulting in surfaces coated by N-halamines with high contents of active > N-Cl or > N-Br groups. The polymer-coated fabrics were stable in multiple laundry cycles and maintained hydrophilic character after coating and halogenation. Halogenated polymer-coated fabrics completely inactivated human respiratory coronavirus based on a contact-killing mechanism and were shown to be reusable after recharging with bromine or chlorine.

Multifunctional polymeric guanidine and hydantoin halamines with broad biocidal activity.

Prolonged and excessive use of biocides during the coronavirus disease era calls for incorporating new antiviral polymers that enhance the surface design and functionality for existing and potential future pandemics. Herein, we investigated previously unexplored polyamines with nucleophilic biguanide, guanidine, and hydantoin groups that all can be halogenated leading to high contents of oxidizing halogen that enables enhancement of the biocidal activity. Primary amino groups can be used to attach poly(N-vinylguanidine) (PVG) and poly(allylamine-co-4-aminopyridine-co-5-(4-hydroxybenzylidene)hydantoin) (PAH) as well as a broad-spectrum commercial biocide poly(hexamethylene biguanide) (PHMB) onto a solid support. Halogenation of polymer suspensions was conducted through in situ generation of excess hypobromous acid (HBrO) from bromine and sodium hydroxide or by sodium hypochlorite in aqueous solutions, resulting in N-halamines with high contents of active > N-Br or > N-Cl groups. The virucidal activity of the polymers against human respiratory coronavirus HCoV-229E increased dramatically with their halogenation. Brominated PHMB-Br showed activation activity value > 5 even at 1 mg/L, and complete virus inhibition was observed with either PHMB-Br or PAH-Br at 10 mg/mL. Brominated PVG-Br and PAH-Br possessed fungicidal activity against C. albicans, while PHMB was fungistatic. PHMB, PHMB-Br and PAH polymers demonstrated excellent bactericidal activity against the methicillin-resistant S. aureus and vancomycin-resistant E. faecium. Brominated polymers (PHMB-Br, PVG-Br, PAH-Br) were not toxic to the HeLa monolayers, indicating acceptable biocompatibility to cultured human cells. With these features, the N-halamine polymers of the present study are a worthwhile addition to the arsenal of biocides and are promising candidates for development of non-leaching coatings.

Antiviral properties of polymeric aziridine- and biguanide-modified core-shell magnetic nanoparticles.

Polycationic superparamagnetic nanoparticles (∼150-250 nm) were evaluated as virucidal agents. The particles possess a core-shell structure, with cores consisting of magnetite clusters and shells of functional silica covalently bound to poly(hexamethylene biguanide) (PHMBG), polyethyleneimine (PEI), or PEI terminated with aziridine moieties. Aziridine was conjugated to the PEI shell through cationic ring-opening polymerization. The nanometric core-shell particles functionalized with biguanide or aziridine moieties are able to bind and inactivate bacteriophage MS2, herpes simplex virus HSV-1, nonenveloped infectious pancreatic necrosis virus (IPNV), and enveloped viral hemorrhagic septicaemia virus (VHSV). The virus-particle complexes can be efficiently removed from the aqueous milieu by simple magnetocollection.

Capture and electrochemical conversion of CO2 in molten alkali metal borate-carbonate blends.

A family of blended compositions of molten mixed lithium and sodium borate (Li1.5Na1.5BO3) and eutectic lithium-potassium carbonate (Li1.24K0.76CO3) salts has been introduced as reversible carbon dioxide absorbents and as media for CO2 electrolysis for carbon conversion. Material properties, temperature effects and kinetics of CO2 uptake were examined. Li, Na borate can absorb up to 7.3 mmol g-1 CO2 at 600 °C. The blended borate-carbonate compositions are molten in the 550-600 °C temperature range, with viscosity adjustable to within a 10-1000 Pa s window depending on the borate/carbonate ratio. The blends can withstand cyclic temperature and CO2 pressure swings without significant deterioration of their CO2 uptake capabilities. Addition of eutectic carbonate into mixed Li, Na borate salts lowers overall CO2 uptake due to the lower solubility of CO2 in carbonate. However, addition of the eutectic lowers the temperature of the pressure swing operation and dramatically accelerates the CO2 uptake during the initial stage of the absorption, potentially enabling a faster cycling. Electroreduction of CO2 and carbon deposition on a galvanized steel cathode was more effective with increasing carbonate fraction in the molten alkali borate/carbonate blend. Blended borate/carbonate compositions with 50-60% borate content possessed sufficiently high loading capacity for CO2 and simultaneously enabled maximum carbon product yield and Coulombic efficiency. Most of the recovered carbon product was shown to be in the form of multiwalled carbon nanotube.

Bactericidal core-shell paramagnetic nanoparticles functionalized with poly(hexamethylene biguanide).

Bactericidal paramagnetic particles were obtained either through the attachment of a conjugate of poly(ethyleneimine) (PEI) and poly(hexamethylene biguanide) (PHMBG) to the surface of magnetite (Fe(3)O(4)) particles, or via the sol-gel encapsulation of magnetite particles with a functional silane (3-glycidoxypropyl trimethoxysilane) and subsequent binding of the polysiloxane shell by the amine/imine groups of PHMBG. The encapsulated core-shell particles possess a high saturation magnetization, which is preserved for more than 10 months while in contact with air in aqueous suspensions. The minimum inhibitory concentration (MIC) of the encapsulated particles for eight types of bacteria was size-dependent, with polydisperse submillimeter particles possessing a several-fold higher MIC than analogous particles sized below 250 nm. The encapsulated particles are biocompatible and nontoxic to mammalian cells such as mouse fibroblasts. The particles efficiently bind both glycopeptide components mimicking the gram-positive bacteria membranes and whole bacteria, and possess broad-range bactericidal activity. The cell-particle complexes can be captured, manipulated, and removed by means of a magnet.

Electrospray as a tool for drug micro- and nanoparticle patterning.

Carbamazepine (CBZ) microparticles of different sizes and shapes, including spheres, q-tips, elongated spheres, and tear-shaped particles, were formed by electrospraying solutions of different CBZ concentrations. The particle characteristics were determined by the interplay between jet formation, droplet breakup, solvent evaporation, and eventual particle solidification. The average particle size increased with increasing CBZ concentration, with particles of different shapes being observed for different CBZ concentrations. The cascade of sizes and shapes observed was interpreted in terms of Rayleigh instability theory as applied to charged jets and droplets, with the final sizes depending upon the time needed to evaporate the solvent sufficiently for CBZ to solidify; the lower the initial concentration of CBZ, the smaller the final droplets/particles that are formed.

Growth of metal-organic frameworks on polymer surfaces.

Polymer substrates have been functionalized with a MOF material (MIL-47) synthesized directly on polyacrylonitrile using in situ microwave irradiation. The growth of MIL-47 on these substrates was studied as a function of microwave irradiation time using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The conversion of nitrile to carboxylic acid groups on the PAN surface was necessary for the growth of MIL-47 on the substrate. MIL-47 crystals grew over time at the expense of a related disordered precursor phase, which lacks the long-range order of MIL-47. This work paves the way for the development of a new class of hybrid MOF-polymer materials that will extend the applications of MOFs to fields such as membrane separations, filtration, and protective textiles.

Binding of functionalized paramagnetic nanoparticles to bacterial lipopolysaccharides and DNA.

Magnetite and metallic cobalt-based nanoparticles with sizes ranging from 10 to 300 nm and surface-functionalized with poly(hexamethylene biguanide) (PHMBG) are introduced as capable lipopolysaccharide (LPS)-sequestering agents. The nanoparticles efficiently bind to whole E. coli cells and can be used to separate the cells effectively from suspension using a magnet. A fluorescence dye displacement assay shows strong affinities of the nanoparticles for lipid A, the glycolipid component of LPS responsible for septic shock. The particle-lipid A affinity is of the same order of magnitude or higher than that of polymyxin B. The affinity of smaller (< 50 nm) magnetite particles modified with PHMBG to lipid A is several-fold higher than that of their larger counterparts (> 100 nm) due to their higher surface area to volume ratio. The nanoparticles possess high saturation capacity for double-stranded lambdaDNA from E. coli, with which particle-polyelectrolyte complexes are formed. The PHMBG-modified nanoparticles are potent bactericides, inhibiting E. coli viability and growth at concentrations at < or = 10 microg/mL.

Biguanide-, imine-, and guanidine- based networks as catalysts for transesterification of vegetable oil.

Polycationic systems based on poly(hexamethylene biguanide) (PHMBG), branched polyethyleneimine (PEI) and poly(N-vinylguanidine) (PVG) have been evaluated as heterogeneous catalysts for the transesterification of sunflower oil by methanol. Insoluble networks are synthesized via crosslinking of PHMBG by either 4,4'-methylenebis(N,N-diglycidylaniline) or polyisocyanate prepolymer, PEI with sebacoyl chloride, and PVG with 1,4-butanediol diglycidyl ether. PHMBG and its crosslinked networks appeared to be remarkably efficient catalysts, enabling 80-100% triglyceride conversion within 0.5 h at 70 degrees C. PEI-based networks catalyzed triglyceride transesterification with rates 8- to 12-fold slower than their PHMBG-based counterparts. The PVG-based networks, which were devoid of hydrophobic moieties, appeared to be inefficient catalysts due to limited accessibility of the basic guanidine groups to reactants. The PHMBG networks were shown to be recyclable by a simple centrifugal filtration. After 15 cycles of recovery and reuse, only 10-15% decline in performance was observed.

Oxidation of betrixaban to yield N-nitrosodimethylamine by water disinfectants.

Degradation of betrixaban, an oral anticoagulant recently approved by the U.S. Food and Drug Administration (FDA), and its N-nitrosodimethylamine (NDMA) formation potential were studied mechanistically in the presence of monochloramine (NH2Cl), free chlorine, and ozone. Upon monochloramination, the formation of NDMA exceeded 1% at basic pH and was significant at circumneutral pH as well. The kinetic studies revealed that the reaction between betrixaban and monochloramine followed pseudo-first-order reaction kinetics. Increasing monochloramine concentration, its reaction time, and pH all significantly enhanced the NDMA formation yield, which also increased three-fold in the presence of bromide during monochloraminantion. The presence of nitrite inhibited the formation of NDMA under the same conditions. This study revealed a new potent and significant precursor of NDMA, indicating that monochloramination of waters containing betrixaban can lead to the formation of NDMA and other disinfection by-products such as dichloroacetonitrile (DCAN) and dimethylformamide (DMF). Moreover, chlorination of betrixaban by hypochlorite also yielded NDMA, albeit at two orders of magnitude lower yield than chloramination, while no NDMA formation was observed from ozonation of betrixaban.

Functional magnetic nanoparticles for biodefense and biological threat monitoring and surveillance.

A new methodology toward biodefense and threat surveillance by water-dispersible, bactericidal, paramagnetic nanoparticles is presented. The nanoparticles consist of magnetite clusters (approximately 70 nm) modified by polyethyleneimine (PEI) and poly(hexamethylene biguanide) (PHMBG) and are prepared by a two-step procedure at an acceptable cost. The cationic nanoparticles are colloidally stable in water at pH < or = 10, where they sequester DNA or whole microbes. The nanoparticles and bound DNA are captured by high-gradient magnetic separation. Methods of efficient extraction and quantification of the DNA by real-time PCR are developed. Broad bactericidal activity of the nanoparticles is demonstrated at concentrations far below cytotoxicity levels for mammalian cells. The levels of the DNA detection sensitivity obtained in our experiments allow us to project the applicability of the developed method for the detection of DNA molecules of various germs.

Guanidinylated polyethyleneimine-polyoxypropylene-polyoxyethylene conjugates as gene transfection agents.

Conjugates of linear and branched polyethyleneimine (PEI) and monoamine polyether Jeffamine M-2070 (PO/EO mol ratio 10/31, 2000 Da) were synthesized through polyether activation by cyanuric chloride followed by attachment to PEI and guanidinylation by 1H-pyrazole-carboxamidine hydrochloride. The resulting guanidinylated PEI-polyether conjugates (termed gPEI-Jeffamine) efficiently complexed plasmid DNA, and their polyplexes possessed enhanced colloidal stability in the presence of serum proteins. In vitro studies with mammalian CHO-1, 3T3, and Cos-7 cell lines demonstrated improved transfection efficiency of the pCMVbeta-gal plasmid/gPEI-Jeffamine polyplexes. The guanidinylation of the amino groups of PEI and the conjugation of PEI with the Jeffamine polyether enhanced the conjugates' interaction with genetic material and reduced the cytotoxicity of the polyplexes in experiments with the L929 cell line.

Light-sensitive intelligent drug delivery systems.

Drug delivery systems (DDS) capable of releasing an active molecule at the appropriate site and at a rate that adjusts in response to the progression of the disease or to certain functions/biorhythms of the organism are particularly appealing. Biocompatible materials sensitive to certain physiological variables or external physicochemical stimuli (intelligent materials) can be used for achieving this aim. Light-responsiveness is receiving increasing attention owing to the possibility of developing materials sensitive to innocuous electromagnetic radiation (mainly in the UV, visible and near-infrared range), which can be applied on demand at well delimited sites of the body. Some light-responsive DDS are of a single use (i.e. the light triggers an irreversible structural change that provokes the delivery of the entire dose) while others able to undergo reversible structural changes when cycles of light/dark are applied, behave as multi-switchable carriers (releasing the drug in a pulsatile manner). In this review, the mechanisms used to develop polymeric micelles, gels, liposomes and nanocomposites with light-sensitiveness are analyzed. Examples of the capability of some polymeric, lipidic and inorganic structures to regulate the release of small solutes and biomacromolecules are presented and the potential of light-sensitive carriers as functional components of intelligent DDS is discussed.

Polydiacetylene functionalized with charged termini for device-free colorimetric detection of malathion.

We introduce 10,12-Pentacosadiynoic acid conjugated with pyridine-2-aldoxime (pralidoxime, PAM) as a positively charged amphiphilic molecule capable of forming a polymer with polydiacetylene (PDA-PAM) via 1,4-addition photopolymerization of self-assembled PAM-modified monomers. Colloidally stabilized vesicles formed by PDA-PAM and unmodified pentacosadiynoic acid via electrostatic interactions in a basic aqueous medium exhibit a colorimetric transition in the presence of malathion. The malathion detection limit, through color change observed by the naked eye, is in the mM range (liquid suspension) or at nmol/cm2 levels (solid membrane); the response to exposure to malathion was rapid, within seconds. Density functional theory (DFT) calculations on the PDA-PAM system before and after binding with the target molecule (malathion) demonstrate that the large blue absorption shift of 0.42 eV observed in the malathion-bound configuration of the polymer is due to the dissociation of the positive charge center on the pralidoxime functional group from the negative charge center on the carboxylic terminus.

Postsynthetic Functionalization of Mg-MOF-74 with Tetraethylenepentamine: Structural Characterization and Enhanced CO2 Adsorption.

Postsynthetic functionalization of magnesium 2,5-dihydroxyterephthalate (Mg-MOF-74) with tetraethylenepentamine (TEPA) resulted in improved CO2 adsorption performance under dry and humid conditions. XPS, elemental analysis, and neutron powder diffraction studies indicated that TEPA was incorporated throughout the MOF particle, although it coordinated preferentially with the unsaturated metal sites located in the immediate proximity to the surface. Neutron and X-ray powder diffraction analyses showed that the MOF structure was preserved after amine incorporation, with slight changes in the lattice parameters. The adsorption capacity of the functionalized amino-Mg-MOF-74 (TEPA-MOF) for CO2 was as high as 26.9 wt % versus 23.4 wt % for the original MOF due to the extra binding sites provided by the multiunit amines. The degree of functionalization with the amines was found to be important in enhancing CO2 adsorption, as the optimal surface coverage improved performance and stability under both pure CO2 and CO2/H2O coadsorption, and with partially saturated surface coverage, optimal CO2 capacity could be achieved under both wet and dry conditions by a synergistic binding of CO2 to the amines as well as metal centers.

Block ionomer complexes as prospective nanocontainers for drug delivery.

Nanosized environmentally responsive materials are of special interest for various applications, including drug delivery. Block ionomer complexes (BIC) composed of graft-comb copolymers of Pluronic and poly(acrylic acid) (Pluronic-PAA) and a model cationic surfactant, hexadecyltrimethylammonium bromide (HTAB), were synthesized by mixing the polymer and surfactant in aqueous media. According to TEM, the resulting BIC represented spherical particles of nanoscale size (50 to 100 nm). The stability of the BIC in the aqueous dispersion depended on the lengths of the hydrophilic poly(ethylene oxide) and hydrophobic poly(propylene oxide) chains in Pluronic molecules as well as on the surface charge of the resulting complexes. The latter was controlled by changing the ratio of the Pluronic-PAA and HTAB in the BIC and by changing the pH due to reversible ionization of the PAA chains. The acidification of the media below pH 6.0 resulted in the appearance of a strong positive charge on the BIC, which in the intracellular environment can trigger interaction of such BIC with the cell membranes. An efficient solubilization of a model hydrophobic molecule, Sudan III, and a drug, Etoposide, in such BIC was demonstrated with the loading capacities of about 6 to 15% by weight of the dispersed complex. Overall, these BIC wield a promise as environmentally responsive nanocarriers for pharmaceuticals.

Template-assisted synthesis of nanogels from Pluronic-modified poly(acrylic acid).

A series of novel polymeric nanogels with core-shell morphology was developed. Block ionomer complexes of comb-graft poly(ethylene oxide)-b-poly(polypropylene oxide)-b-poly(ethylene oxide)-g-poly(acrylic acid) copolymers (Pluronic-PAA) and divalent metal cations were utilized as micellar templates for the synthesis of nanogels with sizes ranging from 100 to 200 nm in diameter. The Pluronic-PAA nanogels were confirmed to possess ionic cross-linked PAA cores and flexible hydrophilic shells from the Pluronic copolymer chains. The ionic character of the core provided for pH-dependent swelling/collapse behavior of the nanogels. These prepared nanogels are expected to be of utility as carriers for charged therapeutic or diagnostic agents.

Self-Decontaminating Fibrous Materials Reactive toward Chemical Threats.

Polymers that possess highly nucleophilic pyrrolidinopyridine (Pyr) and primary amino (vinylamine, VAm) groups were prepared by free-radical copolymerization of N,N-diallylpyridin-4-amine (DAAP) and N-vinylformamide (NVF) followed by acidic hydrolysis of NVF into VAm. The resulting poly(DAAP-co-VAm-co-NVF) copolymers were water-soluble and reacted with water-dispersible polyurethane possessing a high content of unreacted isocyanate groups. Spray-coating of the nylon-cotton (NYCO), rayon, and poly(p-phenylene terephthalamide) (Kevlar 119) fibers pretreated with phosphoric acid resulted in covalent bonding of the polyurethane with the hydroxyl groups on the fiber surface. A second spray-coating of aqueous solutions of poly(DAAP-co-VAm-co-NVF) on the polyurethane-coated fiber enabled formation of urea linkages between unreacted isocyanate groups of the polyurethane layer and the amino groups of poly(DAAP-co-VAm-co-NVF). Fibers with poly(DAAP-co-VAm-co-NVF) attached were compared with fibers modified by adsorption of water-insoluble poly(butadiene-co-pyrrolidinopyridine) (polyBPP) in terms of the stability against polymer leaching in aqueous washing applications. While the fibers modified by attachment of poly(DAAP-co-VAm-co-NVF) exhibited negligible polymer leaching, over 65% of adsorbed polyBPP detached and leached from the fibers within 7 days. Rayon fibers modified by poly(DAAP-co-VAm-co-NVF) were tested for sorption of dimethyl methylphosphonate (DMMP) in the presence of moisture using dynamic vapor sorption technique. Capability of the fibers modified with poly(DAAP-co-VAm-co-NVF) to facilitate hydrolysis of the sorbed DMMP in the presence of moisture was uncovered. The self-decontaminating property of the modified fibers against chemical threats was tested using a CWA simulant diisopropylfluorophosphate (DFP) in aqueous media at pH 8.7. Fibers modified with poly(DAAP-co-VAm-co-NVF) facilitated hydrolysis of DFP with the half-lives up to an order of magnitude shorter than that of the unmodified fibers. The presented polymers and method of multilayer coating can lead to a development of self-decontaminating textiles and other materials.