Synthesis of a heparan sulfate mimetic library targeting FGF and VEGF via click chemistry on a monosaccharide template

A disulfated methyl 6-azido-6-deoxy-α-D-mannopyranoside template was used as a core structure for binding to the angiogenic growth factors FGF-1, FGF-2, and VEGF. The core structure was diversified in a rapid, parallel manner by employing the Cu(I)-catalyzed Huisgen azide-alkyne cycloaddition ("click") reaction. The diversity was further extended by incorporating a Swern oxidation-Wittig reaction sequence on a click adduct of propargyl alcohol. Thus, the sulfated core was linked by various spacers to selected hydrophobic or polar motifs, which were designed to probe the protein surface surrounding the cationic heparan sulfate binding sites of the growth factors in order to improve affinity and selectivity. The affinities of the compounds for the growth factors were measured by surface plasmon resonance solution affinity assays. A lead compound was identified with micromolar binding affinity toward both FGF-1 and VEGF (K(d)=84 and 49 μM, respectively) and good selectivity over FGF-2 (29- and 51-fold, respectively).     

Thermodynamic compatibility of sepiolite-filled poly(vinylidene fluoride)-polystyrene blends

Summary Inverse gas chromatography (IGC) and differential scanning calorimetry (DSC) were used to investigate the effect produced by sepiolite on the thermodynamical compatibility of poly(vinylidene fluoride)-polystyrene blends. Polymer-polymer interaction parameters were calculated from the retention data, for various polar and non-polar probes in pure and mixed stationary phases of these polymers, using sepiolite as solid support, as well as from melting point depression analysis of the sepiolite filled blends. Both techniques give us positive values of the interaction parameters, in accordance with the non-compatibility of these blends; However negative values of the interaction parameters were obtained for polystyrene-rich blends (_PS 85 wt%) and high sepiolite loadings, indicating that sepiolite acts as a compatibilizing agent for the system PVF₂/PS.     

Antimicrobial coatings produced by “tethering” biocides to the coating matrix: A comprehensive review

Covalently attached, non-leaching biocidal-moieties are being explored as an environmentally friendly option for replacing antimicrobial coatings that release biocides. This review highlights studies on antimicrobial surface treatments and coatings in which the antimicrobial agent is covalently bound (i.e. tethered) to the surface or coating matrix. In addition, test methods for measuring antimicrobial surface activity are reviewed, and a discussion of advantages and disadvantages of the various methods is provided.     

Effects of pigmentation on siloxane–polyurethane coatings and their performance as fouling-release marine coatings

Siloxane–polyurethane paints were formulated and characterized for coating properties and performance as fouling-release (FR) marine coatings. Paints were formulated at 20 and 30 pigment volume concentrations with titanium dioxide, and aminopropyl-terminated poly(dimethylsiloxane) (APT-PDMS) loadings were varied from 0 to 30% based on binder mass. The coatings were characterized for water contact angle, surface energy (SE), gloss, and pseudobarnacle (PB) adhesion. The assessment of the FR performance compared with polyurethane (PU) and silicone standards through the use of laboratory biological assays was also performed. Biofilm retention and adhesion were conducted with the marine bacterium Cellulophaga lytica, and the microalgae diatom Navicula incerta. Live adult barnacle reattachment using Amphibalanus amphitrite was also performed. The pigmented coatings were found to have properties and FR performance similar to those prepared without pigment. However, a higher loading of PDMS was required, in some cases, to obtain the same properties as coatings prepared without pigment. These coatings rely on a self-stratification mechanism to bring the PDMS to the coating surface. The slight reduction in water contact angle (WCA) and increase in pseudobarnacle release force with pigmentation suggests that pigmentation slowed or interfered with the self-stratification mechanism. However, increasing the PDMS loading is an apparent method for overcoming this issue, allowing for coatings having similar properties as those of clear coatings and FR performance similar to those of silicone standard coatings.     

Hybrid Photopatterned Enzymatic Reaction (HyPER) for in Situ Cell Manipulation

The ability to design artificial extracellular matrices as cell‐instructive scaffolds has opened the door to technologies capable of studying the fate of cells in vitro and to guiding tissue repair in vivo. One main component of the design of artificial extracellular matrices is the incorporation of biochemical cues to guide cell phenotype and multicellular organization. The extracellular matrix (ECM) is composed of a heterogeneous mixture of proteins that present a variety of spatially discrete signals to residing cell populations. In contrast, most engineered ECMs do not mimic this heterogeneity. In recent years, photo‐deprotection has been used to spatially immobilize signals. However, this approach has been limited mostly to small peptides. Here we combine photo‐deprotection with enzymatic reaction to achieve spatially controlled immobilization of active bioactive signals that range from small molecules to large proteins. A peptide substrate for transglutaminase factor XIII (FXIIIa) was caged with a photo‐deprotectable group, which was then immobilized to the bulk of a cell‐compatible hydrogel. With focused light, the substrate can be deprotected and used to immobilize patterned bioactive signals. This approach offers an innovative strategy to immobilize delicate bioactive signals, such as growth factors, without loss of activity and enables in situ cell manipulation of encapsulated cells.     

Synthesis and characterization of novel antimicrobial polymers containing pendent triclosan moieties

Novel antimicrobial copolymers were produced by first converting the commodity biocide, triclosan (TCS), to an epoxy-functional derivative, 2-((5-chloro-2-(2,4-dichlorophenoxy)phenoxy) methyl)oxirane (ETCS), and then reacting ETCS with polyethylenimine (PEI). While neither ETCS or PEI showed high antimicrobial activity toward either the Gram-positive bacterium, Staphylococcus epidermidis, or the Gram-negative bacterium, Escherichia coli, some the copolymers showed very high activity toward both bacteria. Antimicrobial activity for these copolymers was found to be highly dependent on both the molecular weight of the PEI utilized and the concentration of pendent groups derived from ETCS. In general, decreasing PEI molecular weight and increasing TCS pendent group concentration increased antimicrobial activity. Surface tension measurements showed that the molecular parameters affecting antimicrobial activity also affected surface activity in a similar fashion. Thus, it was speculated that the mechanism of antimicrobial activity associated with these copolymers involves interaction of the copolymers with the bacterial cell wall. A comparison of the antimicrobial activity of the most effective copolymers to TCS showed that the copolymers were more effective toward E. coli than pure TCS when compared using an equivalent TCS content (i.e. TCS pendent group content for the copolymers). This characteristic coupled with the fact that the TCS-containing copolymers are highly aqueous soluble liquids as opposed to a crystalline solid of limited solubility may afford utility of these copolymers for a variety of applications.     

The characteristic curvature (Cc) definition and its use in assessing Cc for single ionic surfactants

The hydrophilic–lipophilic-difference (HLD) is a set of empirical equations that correlate the formulation conditions at phase inversion (HLD = 0). Based on partition studies for nonionic surfactants, the HLD can be interpreted as a normalized chemical potential difference between the surfactant dissolved in water and oil. The net-average curvature (NAC) model extrapolates this interpretation into a curvature form that has been used to fit and predict the phase behavior of surfactant-oil–water (SOW) systems. The curvature interpretation led to renaming the HLD surfactant parameter, sigma (σ), as the characteristic curvature (Cc). This work tests the validity of the curvature interpretation of the HLD, and the Cc concept, for single ionic surfactants and the use of this concept as a method to assess the Cc without the use of reference surfactants or alcohols. To this end, the net curvature of six anionic and two cationic surfactants was evaluated from solubilization data at the characteristic condition of 25°C, no added cosolvent, in the presence of an oil mixture with equivalent alkane carbon number (EACN) of zero, and as a function of salinity. These studies showed that the original HLD equation for ionic surfactant could not be interpreted as chemical potential or curvature because a salinity prefactor (coefficient) “bi” was missing. The revised equation, HLD_bi = bi∙ln(S)-k_bi∙EACN+Cc_bi -a_Tbi∙(T-25°C), could now be interpreted as a curvature expression, and it was demonstrated that Cc could be obtained from curvature using the expression Cc = Cc_bi/bi. This single surfactant method produces uncertainties that, for most surfactants, ranged from 0.2 to 1 Cc units, similar to the uncertainty obtained with the conventional method of Cc determination using mixtures of test and reference surfactants.     

Formulating middle-phase microemulsions using mixed anionic and cationic surfactant systems

Although mixtures of anionic and cationic surfactants can show great synergism, their potential to precipitate and form liquid crystals has limited their use. Previous studies have shown that alcohol addition can prevent liquid crystal formation, thereby allowing formation of middle-phase microemulsions with mixed anionic-cationic systems. This research investigates the role of surfactant selection in designing alcohol-free anionic-cationic microemulsions. Microemulsion phase behavior was studied for three anionic-cationic surfactant systems and three oils of widely varying hydrophobicity [trichloroethylene (TCE), hexane, and n-hexadecane]. Consistent with our hypothesis, using a branched surfactant and surfactants with varying tail length allowed us to form alcohol-free middle-phase microemulsion using mixed anionic-cationic systems (i.e., liquid crystals did not form). The anionic to cationic molar ratio required to form middle-phase microemulsions approached 1∶1 for univalent surfactants as oil hydrophobicity increased (i.e., TCE to hexane to n-hexadecane); even for these equimolar systems, liquid crystal formation was avoided. To test the use of these anionic-cationic surfactant mixtures in surfactant-enhanced subsurface remediation, we performed soil column studies: Greater than 95% of the oil was extracted in 2.5 pore volumes using an anionic-rich surfactant system. By contrast, cationic-rich systems performed very poorly (<1% oil removal), reflecting significant losses of the cationic-rich surfactant system in the porous media. The results thus suggest that, when properly designed, anionic-rich mixtures of anionic and cationic surfactants can be efficient for environmental remediation. By corollary, other industrial applications and consumer products should also find these mixtures advantageous.     

Effect of triacylglycerol structure on absorption and metabolism of isotope-labeled palmitic and linoleic acids by humans

The effect of dietary TAG structure and fatty acid acyl TAG position on palmitic and linoleic acid metabolism was investigated in four middle-aged male subjects. The study design consisted of feeding diets containing 61 g/d of native lard (NL) or randomized lard (RL) for 28 d. Subjects then received an oral dose of either 1,3-tetradeuteriopalmitoyl-2-dideuteriolinoleoyl-rac-glycerol or a mixture of 1,3-dideuteriolinoleoyl-2-tetradeuteriopalmitoyl-rac-glycerol and 1,3-hexadeuteriopalmitoyl-2-tetradeuteriolinoleoyl-rac-glycerol. Methyl esters of plasma lipids isolated from blood samples drawn over a 2-d period were analyzed by GC-MS. Results showed that absorption of the ²H-fatty acids (²H-FA) was not influenced by TAG position. The ²H-FA at the 2-acyl TAG position were 85±4.6% retained after absorption. Substantial migration of ²H-16∶0 (31.2±8.6%) from the sn-2 TAG position to the sn-1,3 position and ²H-18∶2n−6 (52.8±6.4%) from the sn-1,3 position to the sn-2 position of chylomicron TAG occurred after initial absorption and indicates the presence of a previously unrecognized isomerization mechanism. Incorporation and turnover of the ²H-FA in chylomicron TAG, plasma TAG, and plasma cholesterol esters were not influenced by TAG acyl position. Accretion of ²H-16∶0 from the sn-2 TAG position in 1-acylphosphatidylcholine was 1.7 times higher than ²H-16∶0 from the sn-1,3 TAG positions. Acyl TAG position did not influence ²H-18∶2n−6 incorporation in PC. The concentration of ²H-18∶2n−6-derived ²H-20∶4n−6 in plasma PC from subjects fed, the RL diet was 1.5 times higher than for subjects fed the NL diet, and this result suggests that diets containing 16∶0 located at the sn-2 TAG position may inhibit 20∶4n−6 synthesis. The overall conclusion is that selective rearrangement of chylomicron TAG structures diminishes but does not totally eliminate the metabolic and physiological effects of dietary TAG structure.