Solvent-free oxidation of benzyl alcohol using titania-supported gold–palladium catalysts: Effect of Au–Pd ratio on catalytic performance

The oxidation of benzyl alcohol with molecular oxygen under solvent-free conditions has been investigated using a range of titania-supported Au–Pd alloy catalysts to examine the effect of the Au–Pd ratio on the conversion and selectivity. The catalysts have been compared at high reaction temperature (160 °C) as well as at 100 °C, to determine the effect on selectivity since at lower reaction temperature the range of by-products that are formed are limited. Under these conditions the 2.5 wt.% Au–2.5 wt.% Pd/TiO₂ was found to be the most active catalyst, whereas the Au/TiO₂ catalyst demonstrated the highest selectivity to benzaldehyde. Toluene, formed via either a hydrogen transfer process or an oxygen transfer process, was observed as a major by-product under these forcing conditions.     

Structure–Property Relationships in Aligned Electrospun Barium Titanate Nanofibers

Barium titanate nanofibers were uniaxially aligned by electrospinning onto a rotating copper wire drum and alignment was maintained during calcination of the fibers. Two methods for maintaining alignment during calcination were tested, by either using carbon tape or a peeling off method to remove the aligned fibers from the mandrel followed by calcination. The carbon tape removal method led to the formation of shorter aligned nanowires while the peeling off method resulted in longer nanofibers. Additionally, the effects of calcination temperature and time on crystal structure were also examined. The degree of tetragonality in the barium titanate nanofibers increased at higher calcination temperatures and times. Piezoelectricity was confirmed in the nanofibers calcined using piezoeresponse force microscopy, yielding a d₃₃ value of 15.5 pm/V. Using the methods presented here, large quantities of aligned piezoelectric barium titanate and other ceramic fibers or wires can be produced to fulfill their demand in novel microelectronics.     

Time and shear dependent rheology of maleated polyethylene and its nanocomposites

Dipole-dipole and/or hydrogen-bonding interactions between the pendant functional groups within maleated high-density polyethylene (PE-g-MAn) establish a physical polymer network, whose formation kinetics and shear-sensitivity are revealed by dynamic oscillatory testing. The pronounced time and shear dependent viscoelastic properties of PE-g-MAn were not observed for a corresponding imide derivative, PE-g-imide, presumably due to weakened functional group associations in the latter material.The melt compounding of PE-g-MAn with onium-ion exchanged montmorillonite clay (NR₄⁺-MM) resulted in a partially exfoliated hybrid nanocomposite structure, whose viscoelastic behaviour differed significantly from that of the unfilled polymer. The presence of dispersed clay platelets altered the extent of functional group associations, thereby changing the dynamics of network formation.     

Health benefits of CLA – lessons from pig models in biomedical research

The objective of this review is to highlight the use of pig models for investigating safety, efficacy and the mechanisms of action of conjugated linoleic acid (CLA). Although CLA elicits positive effects in animal models and in vitro systems, a consistent concern in terms of translational research is that the health benefits observed by using these model systems cannot be extrapolated directly into humans. Conversely, the similarities between pigs and humans make the pig an ideal model for examining the health benefits of dietary supplements, functional foods and nutraceuticals. We have developed pig models of viral and bacterial infection to examine the preventive role of dietary CLA supplementation on virally induced immunosuppression and gut health, respectively. Results from these studies indicate that CLA significantly enhances the immune function while limiting the catabolic effects of uncontrolled immune and inflammatory responses. The scientific findings in pig models and human clinical trials demonstrate that CLA modulates immune responses in pigs and humans. Pig models of immunomodulation represent significant improvements over other animal models and in vitro systems because they mimic more closely the compartmentalization of the human immune system and the clinical presentation of human infectious, immune and inflammatory diseases.     

Microbial Production of Natural and Unnatural Monolignols with Escherichia coli

Phenylpropanoids and phenylpropanoid-derived plant polyphenols find numerous applications in the food and pharmaceutical industries. In recent years, several microbial platform organisms have been engineered towards producing such compounds. However, for the most part, microbial (poly)phenol production is inspired by nature, so naturally occurring compounds have predominantly been produced to date. Here we have taken advantage of the promiscuity of the enzymes involved in phenylpropanoid synthesis and exploited the versatility of an engineered Escherichia coli strain harboring a synthetic monolignol pathway to convert supplemented natural and unnatural phenylpropenoic acids into their corresponding monolignols. The performed biotransformations showed that this strain is able to catalyze the stepwise reduction of chemically interesting unnatural phenylpropenoic acids such as 3,4,5-trimethoxycinnamic acid, 5-bromoferulic acid, 2-nitroferulic acid, and a “bicyclic” p-coumaric acid derivative, in addition to six naturally occurring phenylpropenoic acids.     

Charged nucleobases and their potential for RNA catalysis

Catalysis in living cells is carried out by both proteins and RNA. Protein enzymes have been known for over 200 years, but RNA enzymes, or "ribozymes", were discovered only 30 years ago. Developing insight into RNA enzyme mechanisms is invaluable for better understanding both extant biological catalysis as well as the primitive catalysis envisioned in an early RNA-catalyzed life. Natural ribozymes include large RNAs such as the group I and II introns; small RNAs such as the hepatitis delta virus and the hairpin, hammerhead, VS, and glmS ribozymes; and the RNA portion of the ribosome and spliceosome. RNA enzymes use many of the same catalytic strategies as protein enzymes, but do so with much simpler side chains. Among these strategies are metal ion, general acid-base, and electrostatic catalysis. In this Account, we examine evidence for participation of charged nucleobases in RNA catalysis. Our overall approach is to integrate direct measurements on catalytic RNAs with thermodynamic studies on oligonucleotide model systems. The charged amino acids make critical contributions to the mechanisms of nearly all protein enzymes. Ionized nucleobases should be critical for RNA catalysis as well. Indeed, charged nucleobases have been implicated in RNA catalysis as general acid-bases and oxyanion holes. We provide an overview of ribozyme studies involving nucleobase catalysis and the complications involved in developing these mechanisms. We also consider driving forces for perturbation of the pK(a) values of the bases. Mechanisms for pK(a) values shifting toward neutrality involve electrostatic stabilization and the addition of hydrogen bonding. Both mechanisms couple protonation with RNA folding, which we treat with a thermodynamic formalism and conceptual models. Furthermore, ribozyme reaction mechanisms can be multichannel, which demonstrates the versatility of ribozymes but makes analysis of experimental data challenging. We examine advances in measuring and analyzing perturbed pK(a) values in RNA. Raman crystallography and fluorescence spectroscopy have been especially important for pK(a) measurement. These methods reveal pK(a) values for the nucleobases A or C equal to or greater than neutrality, conferring potential histidine- and lysine/arginine-like behavior on them. Structural support for ionization of the nucleobases also exists: an analysis of RNA structures in the databases conducted herein suggests that charging of the bases is neither especially uncommon nor difficult to achieve under cellular conditions. Our major conclusions are that cationic and anionic charge states of the nucleobases occur in RNA enzymes and that these states make important catalytic contributions to ribozyme activity. We conclude by considering outstanding questions and possible experimental and theoretical approaches for further advances.     

Stable dye-labelled oligonucleotide-nanoparticle conjugates for nucleic acid detection

Metallic nanoparticles functionalized with oligonucleotides are used for a number of nucleic acid detection strategies. However, oligonucleotide-nanoparticle conjugates suffer from a lack of stability when exposed to certain conditions associated with DNA detection assays. In this study, we report the synthesis of thiol and thioctic acid-modified oligonucleotide gold nanoparticle (OGNs) conjugates functionalized with a dye label and varying spacer groups. The thioctic acid-modified conjugates exhibit increased stability when treated with dithiothreitol (DTT) compared to the more commonly used thiol modification. When the dye labelled oligonucleotide nanoparticle conjugates are exposed to the same conditions there is a pronounced increase in the stability for both thioctic acid and thiol modified sequences. These results open up the possibility of simply using a dye label to enhance the stability of oligonucleotide-nanoparticle conjugates in DNA detection assays where the enhanced stability of the conjugate system can be advantageous in more complex biological environments.     

Mining the cinnabaramide biosynthetic pathway to generate novel proteasome inhibitors

The cinnabaramides and salinosporamides are mixed PKS/NRPS natural products isolated from a terrestrial streptomycete and a marine actinomycete, respectively. They interfere with the proteasome and thus potentially inhibit the growth of cancer cells. The compounds exhibit a γ-lactam-β-lactone bicyclic ring structure attached to a cyclohexenyl unit and a PKS side chain. As a first step towards improving anticancer activity and permitting genetic approaches to novel analogues, we have cloned and characterized the cinnabaramide biosynthetic genes from Streptomyces sp. JS360. In addition to the expected PKS and NRPS genes, the cluster encodes functionalities for the assembly of the hexyl side chain precursor. The corresponding enzymes exhibit relaxed substrate specificities towards a number of synthesized precursors, enabling production of novel chlorinated cinnabaramides. These were isolated and analyzed for activity, revealing that derivatives bearing a chlorine atom in the PKS side chain show higher inhibitory potentials towards the proteasome's proteolytic subunits (especially the trypsin and chymotrypsin units) and higher cytotoxicities towards human tumor cell lines than the parent cinnabaramide A. Although their activities towards the proteasome were weaker than that of salinosporamide A, the cinnabaramides were found to inhibit the growth of various fungi with greater potency.     

Looking to the future: biomarkers in the management of pancreatic adenocarcinoma

The incidence and mortality of pancreas cancer converge. There has been little advancement in the treatment of pancreas cancer since the acceptance of gemcitabine as the standard therapy. Unfortunately, the efficacy of gemcitabine is dismal. While there is much discussion for the development of biomarkers to help direct therapy in this area, there is little action to move them into clinical practice. Herein, we review potential pancreatic cancer biomarkers and discuss the limitations in their implementation.