Poly(amido amine)s as Gene Delivery Vectors: Effects of Quaternary Nicotinamide Moieties in the Side Chains

To evaluate the effect of quaternary nicotinamide pendant groups on gene delivery properties, a series of poly(amido amine) (co)polymers were synthesized by Michael addition polymerization of N, N-cystaminebisacrylamide with variable ratios of 1-(4-aminobutyl)-3-carbamoylpyridinium (Nic-BuNH2), and tert-butyl-4-aminobutyl carbamate (BocNH-BuNH2), yielding poly(amido amine)s (NicX-NHBoc) with X=0, 10, 30, and 50 % of quaternary nicotinamide groups in the polymer side chains. Deprotection of the pendant Boc-NH groups afforded an analogous series of polymers (NicX-NH2) with higher charge density (due to the presence of protonated primary amino groups in the side chains) and subsequent acetylation yielded a series of polymers (NicX-NHAc) of lower hydrophobicity than the Boc-protected polymers. The polymers with the Boc-protected or the acetylated amino groups showed high buffer capacity in the range pH 5.1-7.4, which is a property that can contribute to endosomal escape of polyplexes. The presence of quaternary nicotinamide groups has distinct beneficial effects on the gene vector properties of these polymers. The polymers containing 30 % of quaternary nicotinamide groups in their side chains condense DNA into small, nanosized particles (200 nm) with positive surface charge (+15 mV). Fluorescence experiments using ethidium bromide as a competitor showed that the quaternary nicotinamide groups intercalate with DNA, contributing to a more intimate polymer-DNA binding and shielding. Polyplexes of nicotinamide-functionalized poly(amido amine)s NicX-NHBoc and NicX-NHAc, formed at 12/1 polymerDNA mass ratio, efficiently transfect COS-7 cells with efficacies up to four times higher than that of PEI (Exgen 500), and with essentially absence of cytotoxicity. NicX-NH2 polymers, possessing protonated primary amino groups in their side chains, have a higher cytotoxicity profile under these conditions, but at lower 3/1 polymer-DNA mass ratio also these polymers are capable of efficient transfection, while retaining full cell viability

Quaternary amines exert anti-myocardial ischemia effects via regulation of energy metabolism and oxygen free radicals in myocardial cells in acute myocardial infarction rats

Purpose: To investigate the effect of quaternary amines on myocardial cells of a rat model of cardiac arrest, with respect to energy generation potential and oxygen free radicals. Methods: Forty-five Sprague-Dawley (SD) rats were assigned to sham, model and quaternary amine groups (each with 15 rats). After their corresponding treatments, lectrocardiogram (ECG) monitoring of the rats in the three groups at various time periods was carried out. Serum levels of myocardial enzymes, thromboxane B2 (TXB2), prostacyclin I2 (PGI2), serum carbon monoxide (CO), and changes in endothelial carbon monoxide synthase (eNOS) and endothelin (ET), were determined. Results: The levels of NO and eNOS were significantly reduced in model rats, relative to sham operation rats, while ET was significantly elevated in sham rats (p < 0.05). There were higher levels of NO and eNOS in the quaternary amine group than in model rats, but ET was higher in quaternary amine group than in model rats. Thromboxane B2 (TXB2) concentration was higher in model rats than in sham rats (p < 0.05). While PGI2 was markedly lower in quaternary group than in sham operation rats. TXB2 was lower in the quaternary amine group than in model rats, while PGI2 was significantly higher in quaternary amine group, relative to model rats (p < 0.05). Conclusion: Quaternary amines exert anti-myocardial effects by regulating energy metabolism and oxygen free radicals in myocardial cells of congestive heart failure rats, and thus are potentially useful for the management of acute myocardial infarction. Keywords: Quaternary amine; Acute myocardial infarction; Electrocardiogram; Serum myocardial enzymes; Myocardial cell

Dual antibacterial effect of immobilized quaternary ammonium and aliphatic groups on PVC

A coating comprising quaternary ammonium salts (QAS) and aliphatic moieties was formed on the poly(vinyl chloride) (PVC) surface in order to confer antibacterial activity. This was achieved by grafting mercaptopropyltrimethoxysilane onto PVC, followed by aminopropyltriethoxysilane. Betaine and dodecenyl succinic anhydride (DDSA) were bonded to free amine groups. The modified PVC samples were characterized by FT-IR, showing that the PVC surface was successfully coated. Energy dispersive X-ray spectroscopy showed the spatial distributions of the elements Si and S, indicating that the coatings were homogeneous. Betaine and DDSA coated PVC showed a better antibacterial performance than the controls. This antibacterial effect was extremely reinforced in betaine-DDSA modified PVC showing greater antibacterial activity than both treatments separately applied. Antibacterial activity against Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis was studied in the treated samples showing that the coating was effective against Gram positive and Gram negative species.Fil: Villanueva, María Emilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Salinas, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: González, Joaquín Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Teves, Sergio. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Copello, Guillermo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentin

Insoluble polyelectrolyte and ion-exchange hollow fiber impregnated therewith

The number of quaternary sites and ion exchange capacity of a polyquaternary, cross linked, insoluble copolymer of a vinyl pyridine and a dihalo organic compound is increased by about 15-35% by reaction of the polymer with an amine followed by quaternization, if required. The polymer forms spontaneously in the presence of a substrate such as within the pores of a hollow fiber. The improved resin impregnated fiber may be utilized to remove ions from waste or process steams

Catalytic enantioselective synthesis of quaternary carbon stereocentres.

Quaternary carbon stereocentres-carbon atoms to which four distinct carbon substituents are attached-are common features of molecules found in nature. However, before recent advances in chemical catalysis, there were few methods of constructing single stereoisomers of this important structural motif. Here we discuss the many catalytic enantioselective reactions developed during the past decade for the synthesis of single stereoisomers of such organic molecules. This progress now makes it possible to incorporate quaternary stereocentres selectively in many organic molecules that are useful in medicine, agriculture and potentially other areas such as flavouring, fragrances and materials

Anion selective membrane

Experimental anion permselective membranes were prepared and tested for their suitability as cell separators in a chemical redox power storage system being developed at NASA-Lewis Research Center. The goals of long-term (1000 hr) oxidative and thermal stability at 80 C in FeCl3 and CrCl3 electrolytes were met by most of the weak base and strong base amino exchange groups considered in the program. Good stability is exhibited by several of the membrane substrate resins. These are 'styrene' divinylbenzene copolymer and PVC film. At least four membrane systems produce strong flexible films with electrochemical properties (resistivity, cation transfer) superior to those of the 103QZL, the most promising commercial membrane. The physical and chemical properties of the resins are listed

Improved polyelectrolyte for ion exchange fibers

Technique increases ion exchange capacity of hollow-fiber-substrate ion exchange resins. Procedure increases number of quaternary sites on polyquaternary copolymer by 15 to 35 percent

Chemistry on the inside: green chemistry in mesoporous materials

An overview of the rapidly expanding area of tailored mesoporous solids is presented. The synthesis of a wide range of the materials is covered, both inorganically and organically modified. Their applications, in particular those relating to green chemistry, are also highlighted. Finally, potential future directions for these materials are discussed

Optimal protection of stabilised dry live bacteria from bile toxicity in oral dosage forms by bile acid adsorbent resins

We previously found that dried live bacteria of a vaccine strain can be temporarily sensitive to bile acids and suggested that Bile Adsorbing Resins (BAR) can be used in oral vaccine tablets to protect dried bacteria from intestinal bile. Here, we report a quantitative analysis of the ability of BAR to exclude the dye bromophenol blue from penetrating into matrix tablets and also sections of hard capsule shells. Based on this quantitative analysis, we made a fully optimised formulation, comprising 25% w/w of cholestyramine in Vcaps™ HPMC capsules. This gave effectively 100% protection of viability from 4% bile, with 4200-fold more live bacteria recovered from this formulation compared to unprotected dry bacteria. From the image analysis, we found that the filler material or compaction force used had no measurable effect on dye exclusion but did affect the rate of tablet hydration. Increasing the mass fraction of BAR gave more exclusion of dye up to 25% w/w, after which a plateau was reached and no further dye exclusion was seen. More effective dye exclusion was seen with smaller particle sizes (i.e. cholestyramine) and when the BAR was thoroughly dried and disaggregated. Similar results were found when imaging dye penetration into capsule sections or tablets. The predictions of the dye penetration study were tested using capsules filled with dried attenuated Salmonella vaccine plus different BAR types, and the expected protection from bile was found, validating the imaging study. Surprisingly, depending on the capsule shell material, some protection was given by the capsule alone without adding BAR, with Vcaps™ HPMC capsules providing up to 174-fold protection against 1% bile; faster releasing Vcaps Plus™ HPMC capsules and Coni Snap™ gelatin capsules gave less protection