Iron oxide superparamagnetic nanocarriers bearing amphiphilic N‐heterocyclic choline analogues as potential antimicrobial agents

Magnetic nanoparticles represent an advanced tool in biomedicine because they can be simultaneously functionalized and guided using a magnetic field. Iron oxide magnetic nanoparticles precoated with oleic acid and bearing novel antimicrobial N‐heterocyclic choline analogues, namely O‐, N‐ and O,N‐bis‐undecyl‐substituted N‐(2‐hydroxyethyl)‐1,2,3,4‐tetrahydroisoquinolinium derivatives, have been obtained as potential biomedical agents for drug delivery and antimicrobial therapy. Structural and size determinations for the novel synthesized magnetic nanosystems were carried out based upon magnetogranulometry, dynamic light‐scattering measurements and X‐ray diffraction analysis. The most expected iron oxide core diameter was 6.2–10.5 nm. The magnetization analyses showed that the particles are superparamagnetic at room temperature. Aqueous magnetic fluids of the synthesized nanoparticles were examined in vitro concerning Gram‐positive (Staphylococcus aureus MSCL 334, Bacillus cereus MSCL 330) and Gram‐negative (Escherichia coli MSCL 332, Pseudomonas aeruginosa MSCL 331, Proteus mirabilis MSCL 590) bacterial strains and fungi (Candida albicans MSCL 378, Aspergillus niger MSCL 324). It was found that the samples have magnetic properties and possess antimicrobial activity. The minimum inhibitory concentration against S. aureus for the most active magnetic fluid was determined as 16 µg ml^?1. Copyright © 2015 John Wiley & Sons, Ltd.     

Oligomerization state of photosynthetic core complexes is correlated with the dimerization affinity of a transmembrane helix

In the Rhodobacter (Rba.) species of photosynthetic purple bacteria, a single transmembrane α-helix, PufX, is found within the core complex, an essential photosynthetic macromolecular assembly that performs the absorption and the initial processing of light energy. Despite its structural simplicity, many unresolved questions surround PufX, the most important of which is its location within the photosynthetic core complex. One proposed placement of PufX is at the center of a core complex dimer, where two PufX helices associate in the membrane and form a homodimer. Inability for PufX of certain Rba. species to form a homodimer is thought to lead to monomeric core complexes. In the present study, we employ a combination of computational and experimental techniques to test the hypothesized homodimerization of PufX. We carry out a systematic investigation to measure the dimerization affinity of PufX from four Rba. species, Rba. blasticus , Rba. capsulatus , Rba. sphaeroides , and Rba. veldkampii , using a molecular dynamics-based free-energy method, as well as experimental TOXCAT assays. We found that the four PufX helices have substantially different dimerization affinities. Both computational and experimental techniques demonstrate that species with dimeric core complexes have PufX that can potentially form a homodimer, whereas the one species with monomeric core complexes has a PufX with little to no dimerization propensity. Our analysis of the helix-helix interface revealed a number of positions that may be important for PufX dimerization and the formation of a hydrogen-bond network between these GxxxG-containing helices. Our results suggest that the different oligomerization states of core complexes in various Rba. species can be attributed, among other factors, to the different propensity of its PufX helix to homodimerize.     

Synthesis of Lipid A and Inner Core LPS ligands containing 4-amino-4-deoxy-l-arabinose units

Attachment of 4-amino-4-deoxy-l-arabinose to phosphates or sugar hydroxyl groups of lipopolysaccharide contributes to bacterial resistance against common antibiotics. For a detailed study of antigenic properties and binding interactions, Ara4N-containing inner core ligands related to Burkholderia and Proteus LPS have been synthesized in good yields. Glycosylation at position 8 of allyl glycosides of oct-2-ulosonic acids (Ko, Kdo) has been accomplished using an N-phenyltrifluoroacetimidate 4-azido-4-deoxy-l-arabinosyl glycosyl donor followed by azide reduction and global deprotection. The β-l-Ara4N-(1→8)-α-Kdo disaccharide was further extended into the branched β-l-Ara4N-(1→8)[α-Kdo-(2→4)]-α-Kdo trisaccharide via a regioselective glycosylation of a protected triol intermediate. Synthesis of Ara4N-modified lipid A - part structure occurring in the LPS of Burkholderia, Pseudomonas and Klebsiellla strains was accomplished using the H-phosphonate approach. The stereocontrolled assembly of the phosphodiester linkage connecting glycosidic centres of two aminosugars was elaborated employing an anomeric H-phosphonate of cyclic silyl-ether protected 4-azido-4-deoxy-β-l-arabinose which was coupled to the hemiacetal of the lipid A GlcN-disaccharide backbone. Conditions for global deprotection which warrant the integrity of "double anomeric" phosphodiester linkage were successfully developed. Introduction of thiol-terminated spacer at the synthetic ligands allows both coupling to BSA and immobilization on gold nanoparticles as well as generation of glycoarrays.     

Photohemolysis Sensitized by the Furocoumarin Derivative Alloimperatorin and its Hydroperoxide Photooxidation Product

The dark and photosensitized effects of alloimperatorin methyl ether 1 (hereafter simply alloimperatorin) and its photooxygenation product alloimperatorin hydroperoxide 2 were investigated on human erythrocytes. The results reveal that the furocoumarin 1 photosensitizes efficiently the hemolysis of erythrocytes. The rate of photohemolysis increases on raising the temperature of the postirradiated incubation from 4°C to 37°C. Thermal activation of the photohemolysis and inhibition by 2,6‐di‐tert‐butyl‐p‐cresol (BHT) suggest that the furocoumarin 1 photosensitizes lipid peroxidation, increasing permeability in the erythrocyte membrane. The hydroperoxide 2 induces dark and photosensitized hemolysis more efficiently than the furocoumarin 1. The rate of hemolysis induced by 2 increases with the incubation temperature and decreases in the presence of tert‐butanol and BHT. The hydroperoxide 2 photosensitizes the formation of lipid peroxidation products as shown by the reaction with thiobarbituric acid. This process is diminished by BHT. Our data imply that the photohemolysis sensitized by the furocoumarin 1 is caused by the in situ‐formed photooxygenation product 2. Such hydroperoxides are potent hemolytic agents in the dark and especially on photosensitization.     

Electronic Metal–Support Interactions in Single‐Atom Catalysts

The synthesis of single‐atom catalysts and the control of the electronic properties of catalytic sites to arrive at superior catalysts is a major challenge in heterogeneous catalysis. A stable supported single‐atom silver catalyst with a controllable electronic state was obtained by anti‐Ostwald ripening. An electronic perturbation of the catalytic sites that is induced by a subtle change in the structure of the support has a strong influence on the intrinsic reactivity. The higher depletion of the 4d electronic state of the silver atoms causes stronger electronic metal–support interactions, which leads to easier reducibility and higher catalytic activity. These results may improve our understanding of the nature of electronic metal–support interactions and lead to structure–activity correlations.     

Linear polyurethanes derived from alditols and diisocyanates

A set of linear [m,n]‐type polyurethanes was synthesized by polycondensation in solution from hexamethylene diisocyanate and 4,4′‐methylene‐bis(phenyl isocyanate) with alditols. Threitol, arabinitol, and xylitol bearing the secondary hydroxy groups blocked as methyl ethers were used. Either regioregular or nonregioregular polymers (depending on the configuration of the alditol) were obtained in high yields and with number‐average molecular weights within the 20,000–30,000 range. All these polyurethanes were amorphous with T_g being highly dependent on the aliphatic or aromatic nature of the diisocyanate used, but scarcely depending on the chemical structure of the alditol moiety. They were found to be stable up to near 300 °C, decomposing at higher temperatures through a complex three‐stage mechanism. Polyurethanes obtained from threitol did not show significant enhancement of hydrolytic degradability as compared with polyurethanes obtained from 1,4‐butanediol. Conversely, polyurethane prepared from xylitol and hexamethylendiisocyanate was found to be almost fully hydrolyzed in 1 month when incubated in water either at 80 °C and pH 7.4 or at 37 °C and pH 10. It was concluded that the alditol size seems to be of prime importance in determining the hydrodegradability of these sugar containing polyurethanes. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4109–4117, 2007     

Poly(ethylene terephthalate) copolymers containing 1,4-cyclohexane dicarboxylate units

Poly(ethylene terephthalate-co-1,4-cyclohexane dicarboxylate) copolymers, abbreviated as PETCHD, containing from 2 up to 40 mole% of the cycloaliphatic diacid, as well as the two parent homopolymers, PET and PECHD, were prepared from comonomer mixtures by a two-step melt-polycondensation procedure. Polymer intrinsic viscosities varied from 0.6 to 0.8 dL g⁻¹ with weight-average molecular weights spanning in the range from 30,000 to 70,000. The copolymers were found to have a random microstructure and a composition according to that used in their corresponding feeds. Thermal and mechanical properties of PETCHD were evaluated as a function of composition. Copolymers were found to be crystalline for all examined compositions although they crystallize from the melt only when the cycloaliphatic comonomer composition was below 20 mole%. Both melting and glass transition temperatures of the copolyesters decreased rapidly with the content in CHD units, whereas the thermal stability appeared to be barely affected by copolymerization. Incorporation of 1,4-cyclohexane dicarboxylate units increased the Young’s modulus and the maximum tensile strength of these materials but elongation to break drastically diminished. Preliminary X-ray diffraction studies revealed that PETCHD copolyesters seem to adopt the same crystal structure as PET.