Linear Aliphatic Chains Research Articles

Di-alkylated paromomycin derivatives: Targeting the membranes of Gram positive pathogens that cause skin infections

A collection of paromomycin-based di-alkylated cationic amphiphiles differing in the lengths of their aliphatic chain residues were designed, synthesized, and evaluated against 14 Gram positive pathogens that are known to cause skin infections. Paromomycin derivatives that were di-alkylated with C7 and C8 linear aliphatic chains had improved antimicrobial activities relative to the parent aminoglycoside as well as to the clinically used membrane-targeting antibiotic gramicidin D; several novel derivatives were at least 16-fold more potent than the parent aminoglycoside paromomycin. Comparison between a di-alkylated and a mono-alkylated paromomycin indicated that the di-alkylation strategy leads to both an improvement in antimicrobial activity and to a dramatic reduction in undesired red blood cell hemolysis caused by many aminoglycoside-based cationic amphiphiles. Scanning electron microscopy provided evidence for cell surface damage by the reported di-alkylated paromomycins.

Anti-influenza active and low toxic N-phenyl-substituted β-amidoamidines structurally related to natural antibiotic amidinomycin

A set of racemic N-phenyl-substituted β-amidoamidines hydrochlorides 4, which are structurally related to natural antiviral agent amidinomycin (1), was synthesized in four steps starting from methacryloyl anilide (5). In the final step of the synthetic route, an uncommon monoacylation of β-aminoamidine 8 at the less reactive β-phenylamino-group took place. To rationalize this result, a mechanism which involves initial acylation at the more active amidine-function followed by intramolecular acyl-group transfer to β-phenylamino-group was suggested. All three β-amidoamidines 4d–f bearing long linear aliphatic chain (from n-C8H17 to n-C12H25) revealed significant in vitro activity against influenza A virus (H3N2) and modest cytotoxicity. The in vitro antiviral potency of 4d,e is 6–20 times greater than that of commercial rimantadine with lower EC50 values and higher therapeutic index. The non-toxic in vivo compounds 4d–f showed a beneficial protective effect in influenza A (H3N2) infected mice.

Alkylated-C60 based soft materials: regulation of self-assembly and optoelectronic properties by chain branching

Derivatization of fullerene (C60) with branched aliphatic chains softens C60-based materials and enables the formation of thermotropic liquid crystals and room temperature nonvolatile liquids. This work demonstrates that by carefully tuning parameters such as type, number and substituent position of the branched chains, liquid crystalline C60 materials with mesophase temperatures suited for photovoltaic cell fabrication and room temperature nonvolatile liquid fullerenes with tunable viscosity can be obtained. In particular, compound 1, with branched chains, exhibits a smectic liquid crystalline phase extending from 84 °C to room temperature. Analysis of bulk heterojunction (BHJ) organic solar cells with a ca. 100 nm active layer of compound 1 and poly(3-hexylthiophene) (P3HT) as an electron acceptor and an electron donor, respectively, reveals an improved performance (power conversion efficiency, PCE: 1.6 ± 0.1%) in comparison with another compound, 10 (PCE: 0.5 ± 0.1%). The latter, in contrast to 1, carries linear aliphatic chains and thus forms a highly ordered solid lamellar phase at room temperature. The solar cell performance of 1 blended with P3HT approaches that of PCBM/P3HT for the same active layer thickness. This indicates that C60 derivatives bearing branched tails are a promising class of electron acceptors in soft (flexible) photovoltaic devices.

Ultrasound‐assisted synthesis of benzoxazine monomers: thermal and mechanical properties of polybenzoxazines

AbstractA series of benzoxazine monomers (P‐aea2–P‐aea8) were prepared from appropriate aromatic diamines containing linear aliphatic ether chains with phenol and formaldehyde through the Mannich reaction under ultrasonication and conventional methods. Based on the reaction performance, the ultrasonication method has been found to be more facile and convenient for the synthesis of benzoxazine monomer than the conventional method. The synthesized monomers undergo curing at a lower temperature than that of conventional benzoxazine (Ba‐A) monomer as evidenced from differential scanning calorimetric analysis. The presence of an aliphatic ether core in the benzoxazine monomer aids in lowering the curing temperature, which seems to vary linearly with chain length. Thermally polymerized benzoxazine (poly(P‐aeas)) shows an enhanced tensile and flexural strength. Copyright © 2012 Society of Chemical Industry

Structural aspects of polyanion and hydrophobically modified polycation multilayers on hydrophilic or hydrophobic surfaces

Multilayer films of carboxymethylcellulose (CMC), a polyanion, and bromide salts of poly(4-vinylpyridine) quaternized with linear aliphatic chains of 2 (ethyl) and 5 (pentyl) carbon atoms, coded as QPVP-C2 and QPVP-C5, respectively, were fabricated by layer-by-layer (LbL) self-assembly onto Si/SiO2 wafers (hydrophilic substrate) or polystyrene, PS, films (hydrophobic substrate). The films were characterized by means of ex situ and in situ ellipsometry, atomic force microscopy (AFM), contact angle measurements and sum frequency generation vibrational spectroscopy (SFG). Antimicrobial tests were used to assess the exposure of pyridinium moieties to the aqueous medium. In situ ellipsometry indicated that for Si/SiO2 the chains were more expanded than the PS films and both substrates systems composed of QPVP-C5 were thicker than those with QPVP-C2. For dried layers, the alkyl side group size had a small effect on the thickness evolution, regardless of the substrate. At pH 2 the multilayers showed high resistance, evidencing that the build-up is driven not only by cooperative polymer–polymer ion pairing, but also by hydrophobic interactions between the alkyl side chains. The LbL films became irregular as the number of depositions increased. After the last deposition, the wettability of QPVP-C2 or QPVP-C5 terminated systems on the Si/SiO2 wafers and PS films were similar, except for QPVP-C2 on Si/SiO2 wafers. Unlike the morphology observed for LbL films on Si/SiO2 wafers, PS induced the formation of porous structures. SFG showed that in air the molecular orientation of pyridinium groups in multilayers with QPVP-C5 was stronger than in those containing QPVP-C2. The exposure of pyridinium moieties to the aqueous medium was more pronounced when the LbL were assembled on Si/SiO2 wafers.

Transparent Large-Strain Thermoplastic Polyurethane Magnetoactive Nanocomposites

Organically modified superparamagnetic MnFe(2)O(4)/thermoplastic polyurethane elastomer (TPU) nanocomposites (0.1-8 wt %) were prepared by solvent mixing followed by solution casting. Linear aliphatic alkyl chain modification of spherical MnFe(2)O(4) provided compatibility with the TPU containing a butanediol extended polyester polyol-MDI. All MnFe(2)O(4)/TPU nanocomposite films were superparamagnetic and their saturation magnetization, σ(s), increased with increasing MnFe(2)O(4) content. All nanocomposite films exhibited large deformations (>10 mm) under a magneto-static field. This is the first report of large actuation of magnetic nanoparticle nanocomposites at low-loading levels of 0.1 wt % (0.025 vol %). The maximum actuation deformation of the MnFe(2)O(4)/TPU nanocomposite films increased exponentially with increasing nanoparticle concentration. An empirical correlation between the maximum displacement, saturation magnetization, and magnetic nanoparticle loading is proposed. The cyclic deformation actuation of a 6 wt % surface modified MnFe(2)O(4)/TPU, in a low magnetic field 151 < B(y) < 303 Oe, exhibited excellent reproducibility and controllability. MnFe(2)O(4)/TPU nanocomposite films (0.1-2 wt %) were transparent and semitransparent over the wavelengths from 350 to 700 nm.

Preparation and modification of chitosan particles for Rhizomucor miehei lipase immobilization

Chitosan particles, suitable as immobilization support, were prepared by precipitation and modified by reductive amination in order to graft linear aliphatic chains of 12 carbon atoms to their native amine groups. Their physical characterization was performed by different techniques: differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), air–water contact angle analysis, among others. Lipases from Rhizomucor miehei (RM) were immobilized by adsorption at low ionic strength onto different modified chitosan microspheres. Their ability to catalyze the acidolysis reaction between sunflower oil and palmitic and stearic free fatty acids was evaluated in a solvent medium. Effects of modification conditions on the particles hydrophobic character, lipase adsorption and acidolysis activity were investigated. Modified particles were bigger and more hydrophobic than unmodified ones. The most active biocatalyst achieved a change in the composition of palmitic and stearic acid from a value of 9.6% in the original oil to 49.1% in the final structured lipids, representing an almost 3-fold enzyme hyperactivation. This high conversion was maintained during 7 reuse cycles (168 total hours). The results demonstrated that the chitosan modification was effective in order to adsorb and hyperactivate RM lipases.

Protein Adsorption onto Polyelectrolyte Layers: Effects of Protein Hydrophobicity and Charge Anisotropy

Ellipsometry was used to investigate the influence of ionic strength (I) and pH on the adsorption of bovine serum albumin (BSA) or beta-lactoglobulin (BLG) onto preabsorbed layers of two polycations: poly(diallyldimethylammonium chloride) (PDADMAC) or poly(4-vinylpyridine bromide) quaternized with linear aliphatic chains of two (QPVP-C2) or five (QPVP-C5) carbons. Comparisons among results for the three polycations reveal hydrophobic interactions, while comparisons between BSA and BLG-proteins of very similar isoelectric points (pI)-indicate the importance of protein charge anisotropy. At pH close to pI, the ionic strength dependence of the adsorbed amount of protein (Gamma) displayed maxima in the range 10 < I < 25 mM corresponding to Debye lengths close to the protein radii. Visualization of protein charge by Delphi suggested that these ionic strength conditions corresponded to suppression of long-range repulsion between polycations and protein positive domains, without diminution of short-range attraction between polycation segments and locally negative protein domains, in a manner similar to the behavior of PE-protein complexes in solution. (1-4) This description was consistent with the disappearance of the maxima at pH either above or below pI. In the former case, Gamma values decrease exponentially with I(1/2), due to screening of attractions, while in the latter case adsorption of both proteins decreased at low I due to strong repulsion. Close to or below pI both proteins adsorbed more strongly onto QPVP-C5 than onto QPVP-C2 or PDADMAC due to hydrophobic interactions with the longer alkyl group. Above pI, the adsorption was more pronounced with PDADMAC because these chains may assume more loosely bound layers due to lower linear charge density.

ChemInform Abstract: Environmentally Friendly Liquid Phase Oxidation: Enhanced Selectivity in the Aerial Oxidation of Alkyl Aromatics, Epoxidations and the Baeyer-Villiger Oxidation Using Novel Silica Supported Transition Metal Ions.

Active transition metal species (Co, Cu, Cr, Ni or Mn) supported on a chemically modified silica gel are used as heterogeneous catalysts in a range of liquid phase oxidation reactions: alkyl aromatic side chain oxidations, epoxidations of alkenes and Baeyer–Villiger oxidations of linear ketones to esters and cyclic ketones to lactones. The catalyst employs metal centres bound to the silica surface via a hydrophobic spacer chain and is thus chemically robust and has a relatively high loading for a supported reagent (c 0.4 mmol g−1). The Cr version of the catalyst promotes the oxidation of ethylbenzene to acetophenone in a solvent-free system at a rate of 5.5% h−1 (>370 turnover h−1). It is also active for the oxidation of p-chlorotoluene and p-xylene to p-chlorobenzoic acid and p-toluic acid respectively. Cyclohexene is converted to its oxide at room temperature at a rate of c 28% h−1 (c 12 turnover h−1) using either the Ni or Cu versions of the catalyst. The room temperature Baeyer–Villiger oxidation of cyclohexanone is achieved at a rate of 44% h−1 (49 turnover h−1) using the Ni-containing catalyst. The same material also promotes the Baeyer–Villiger oxidation of linear aliphatic ketones and aromatic side chains. All the above systems use either air or molecular oxygen as the oxidant rather than peroxides or peracids. © 1999 Society of Chemical Industry

Synthesis and Antibiofilm Activity of a Second‐Generation Reverse‐Amide Oroidin Library: A Structure–Activity Relationship Study

A second-generation library of 2-aminoimidazole-based derivatives incorporating a "reversed amide" (RA) motif in comparison to the marine natural product oroidin were synthesized and subsequently assayed for antibiofilm activity against the medically relevant Gram-negative proteobacteria P. aeruginosa and A. baumannii. Most notably, an in-depth activity profile is reported for the most active subclass of derivatives that bear linear aliphatic chains off the amide bond. Additionally, further structural modifications of the core template, such as removal of the amide bond or substitution with a triazole isostere, resulted in the discovery of analogues with antibiofilm activities that varied with respect to their inhibition and dispersal properties of P. aeruginosa and A. baumannii biofilms.

Lysozyme binding to poly(4-vinyl- N-alkylpyridinium bromide)

The adsorption behavior of polycations at ionic strengths ( I ) ranging from 0.001 to 0.1 onto silicon wafers was studied by means of ellipsometry, contact angle measurements and atomic force microscopy (AFM). Polycations chosen were bromide salts of poly(4-vinylpyridine) N-alkyl quaternized with linear aliphatic chains of 2 and 5 carbon atoms, QPVP-C2 and QPVP-C5, respectively. Under I = 0.001 the reduction of screening effects led to low adsorbed amounts of QPVP-C2 or QPVP-C5 ( 1.0 ± 0.1 mg / m 2 ) , arising from the adsorption of extended chains. Upon increasing I to 0.1, screening effects led to conformational changes of polyelectrolyte chains in solution and to higher adsorbed amount values ( 1.9 ± 0.2 mg / m 2 ) . Advancing contact angle θ a measurements performed with water drops onto QPVP-C2 and QPVP-C5 adsorbed layers varied from ( 45 ± 2 ) ° to ( 50 ± 5 ) ° , evidencing the exposure of both hydrophobic alkyl groups and charged moieties. The adsorption of lysozyme (LYZ) molecules to QPVP-C5 layers was more pronounced than to QPVP-C2 films. Antimicrobial effect of LYZ bound to QPVP-C2 or QPVP-C5 layers or to Si wafers was evaluated with enzymatic assays using Micrococcus luteus as substrates. The adsorption behavior of QPVP-C2 and QPVP-C5 at the water–air interface was studied by means of surface tension measurements. Only QPVP-C5 was able to reduce water surface tension. Mixtures of LYZ and QPVP-C5 were more efficient in reducing surface tension than pure LYZ solution, evidencing co-adsorption at liquid–air interface. Moreover, antimicrobial action observed for mixtures of LYZ and QPVP-C5 was more pronounced than that measured for pure LYZ. Hydrophobic interaction between LYZ and QPVP-C5 in solution seems to drive the binding and to preserve LYZ secondary structure.

The aggregative behavior of hydrophobically modified chitosans with high substitution degree in aqueous solution

Abstract Nowadays chitosan, CHIT, is becoming one of the most interesting raw materials because of the actual and potential applications in several technological fields due to its chemical versatility, natural abundance and ecological compatibility. By applying a very versatile and quantitative amination reaction, linear aliphatic chains of length variable from five to 12 carbon atoms have been grafted on the chitosan backbone at 10% in mole of the glycosidic units. Newtonian viscosity and fluorescence probe emission have been used to analyze the intra- and inter-aggregation properties of these modified chitosans, C n -CHITs, and to compare them with those of chitosan itself. Viscosity in the dilute concentration range showed that for CHIT and C5-CHIT the behavior is quite similar highlighting that the insertion of this short aliphatic chain does not modify the rigidity and/or the interaction with the solvent. For C6, C8, and C10-CHIT, the increasing length of the pendant promotes a progressively more efficient intra-aggregation of the polymer as shown by the reduction of its hydrodynamic radius. Converging evidences are obtained by the analysis of the fluorescence spectra of pyrene, used as probe, in the aqueous solutions of the grafted polymers, which show how different is the environment in which pyrene is located, if short or long chained polymers are analyzed. In fact, the spectra in CHIT, C5-CHIT, and C6-CHIT are quite similar among them and indicate a scant hydrophobic quality of the aggregates for these short grafted polymers even in concentrated solution. In contrast, the presence of C8-CHIT, C10-CHIT, and C12-CHIT concentrated solutions gives rise to a progressive and evident modification of the pyrene spectra, which resemble those of this fluorescent probe in a hydrocarbon solvent, thus indicating the formation of well-defined hydrophobic pools. However, in the limit of very concentrated solutions, the specificity of the grafted chains of different length is lost.

Troxacitabine Prodrugs for Pancreatic Cancer

Troxacitabine is a cytotoxic deoxycytidine analogue with an unnatural L-configuration, which is activated by deoxycytidine kinase (dCK). The configuration is responsible for differences in the uptake and metabolism of troxacitabine compared to other deoxynucleoside analogues. The main drawback in the use of most nucleoside anticancer agents originates from their hydrophilic nature, which property requires a high and frequent dosage for an intravenous administration. To overcome this problem several troxacitabine prodrugs modified in the aminogroup with a linear aliphatic chain with a higher lipophilicity were developed. To determine whether these prodrugs have an advantage over Troxacitabine pancreatic cancer cell lines were exposed to Troxacitabine and the lipophilic prodrugs. The addition of linear aliphatic chains to troxacitabine increased sensitivity of pancreatic cancer cell lines to the drug > 100-fold, possibly due to a better uptake and retention of the drug.

Skeletal isomerization of unsaturated fatty acids: the role of mesopores in HBeta zeolites

Fatty acids are an important class of feedstock for the production of many chemicals, such as surfactants, lubricants, biodiesel, etc. Fatty acids derived from vegetable oils and animal fats typically have linear aliphatic chain, and are therefore called linear fatty acids. Products based on branched fatty acids offer many attractive properties over those based on linear ones, e.g. low melting points and low viscosity. Catalytic skeletal isomerization of linear fatty acids to branched ones is particularly important for industrial production of branched fatty acids. This paper for the first time reveals the key properties of the most active zeolite catalysts for this reaction. Among many solid acid catalysts studied, acidic Beta zeolites were found to stand out in their performance for the reaction. In this work, several acidic Beta zeolites (HBeta) from commercial sources were evaluated for their performance in fatty acid skeletal isomerization. The activities of these zeolites under identical test conditions were found to vary in a wide range, even with similar silica to alumina molar ratios (SAR). A combination of characterization techniques was used to systematically investigate the most critical property of the zeolites responsible for the observed superior activity. All the HBeta zeolites in this study have high crystallinity. Pore size distribution of the zeolites was identified to be the most important factor that unambiguously correlates the catalyst activity to the amount of mesopores in the HBeta zeolites.

Molecular Interactions between Rubber and Asphalt

The analysis of the interactions between rubber and asphalt was carried out. The swelling rate and equilibrium of rubber penetration with the selected asphalt components were found to be dependent on these components and the rubber content in asphalt. At fixed conditions of stirring asphalt with rubber, the equilibrium swell value decreases with the increase in rubber content. From the gel permeation chromatography (GPC) analysis, it follows that the lighter asphalt components penetrate more readily into the internal matrix of the polymer. The gas chromatography-mass spectrometry (GC-MS) study allowed us to assess which components penetrated from asphalt into the rubber and which moved from rubber to asphalt. It has been found that of the nonpolar components, the n-alkanes and n-alkylbenzenes, possess the highest propensity to penetrate into rubber particles. Preferential absorption of the compounds with linear aliphatic chains into the rubber suggests that these components have a good compatibility with the linear polymeric skeleton of the rubber. During immersion of the rubber in hot asphalt, the fatty acids, which are the components of the curing system of the polymer, move from rubber to asphalt, and they are most probably concentrated in the naphthene-aromatic fraction of the asphalt. The electron paramagnetic resonance (EPR) study confirmed the effect of the immersion time of rubber in asphalt and of the shear on the swelling rate.

Heterogeneous Chemical Modification of Cellulose for Composite Materials

Two different cellulosic substrates in the form of powders and regenerated fibers were surface modified with different isocyanates in a heterogeneous organic medium. Two of these isocyanates also bore alkenyl functions which were used as a means of copolymerization in subsequent reactions involving common monomers. The third isocyanate bore instead a non reactive C18 linear aliphatic chain. The fibers modified by either the latter single reaction or the former double procedure were introduced into macromolecular matrices in order to elaborate composite materials and study their properties. All the envisaged reactions were shown to occur and the application of the fragmentation test to the corresponding composite materials provided quantitative evidence of the improvement of fiber– matrix adhesion associated with the different modifications.

Amorphous fluoropolymers from tetrafluoroethylene and bulky vinyl esters or vinyl ethers

Copolymers of tetrafluoroethylene (TFE) with vinyl esters and vinyl ethers having adamantyl or norbornyl side chains are prepared in good yield by radical polymerizations in organic solvents. The polymers are thermally stable, soluble in standard organic solvents and can have glass transition temperatures more than 100 °C higher than the corresponding copolymers with linear aliphatic side chains.

Thermodynamics of the hydrophobic effect. II. Calorimetric measurement of enthalpy, entropy, and heat capacity of aggregation of alkylamines and long aliphatic chains

The thermodynamics of long aliphatic chain alkylamine aggregation in aqueous solution was studied by isothermal titration calorimetry (ITC). Protonated alkylammonium cations with linear aliphatic chains of 10–14 carbon atoms were fully soluble in aqueous solution at the beginning of titration, but practically insoluble after deprotonation by titrating with sodium hydroxide. The alkylamines aggregated and precipitated during the reaction, enabling direct measurement of the enthalpy of aggregation. The enthalpy of aggregation became increasingly exothermic upon increasing the chain length. Hydrophobic aggregation was enthalpy-driven and entropy-opposed for alkylamines with 12–14 carbon atoms at room temperature. Direct observation of hydrophobic aggregation by ITC at constant temperature and pressure provided more accurate thermodynamic parameters than obtainable from van't Hoff analysis. Aggregation into liquid or solid phases could be distinguished by ITC, but not by van't Hoff analysis of alkylamine solubility data.

Bioorganic & Medicinal Chemistry Letters

A set of racemic N-phenyl-substituted b-amidoamidines hydrochlorides 4, which are structurally related to natural antiviral agent amidinomycin (1), was synthesized in four steps starting from methacryloyl anilide (5). In the final step of the synthetic route, an uncommon monoacylation of b-aminoamidine 8 at the less reactive b-phenylamino-group took place. To rationalize this result, a mechanism which involves initial acylation at the more active amidine-function followed by intramolecular acyl-group transfer to b-phenylamino-group was suggested. All three b-amidoamidines 4d–f bearing long linear aliphatic chain (from n-C8H17 to n-C12H25) revealed significant in vitro activity against influenza A virus (H3N2) and modest cytotoxicity. The in vitro antiviral potency of 4d,e is 6–20 times greater than that of commercial rimantadine with lower EC50 values and higher therapeutic index. The non-toxic in vivo

Inhibition of lead corrosion with saturated linear aliphatic chain monocarboxylates of sodium

The ability of sodium monocarboxylates to inhibit the aqueous corrosion of lead was investigated. Electrochemical measurements (Rp,icor) have shown that the inhibiting efficiency of these compounds, with a general formula CH3(CH2)n−2COONa (n=7–11), is dependent on the carbon chain length and the concentration. The greatest inhibiting efficiency was observed for the longest carbon chains, sodium decanoate or undecanoate at a concentration of 0.01 M.Lead carboxylates were synthesised and their solubilities were determined. The potential–pH diagram of lead in water containing undecanoate anions was drawn taking into account the presence of lead carboxylate. Metal passivation was attributed to the growth of passive layers containing metallic soap, which was confirmed by XRD analysis and SEM observations of the treated lead surfaces.