Synthesis of Poly(lactide)s with Modified Thermal and Mechanical Properties

The use of poly(lactide)‐based materials is, in part, limited by their physical and mechanical properties. This article reviews the methods that have been employed to enable enhancement of the materials properties through synthetic manipulation of the polymer structure including block copolymer synthesis and modification of the lactide monomer structure, focusing on the application of ring‐opening polymerization. In turn the effect of these structural modifications on the properties of the resultant materials are reported.

     

Robust decoupling techniques to extend quantum coherence in diamond

We experimentally demonstrate over 2 orders of magnitude increase in the room-temperature coherence time of nitrogen-vacancy centers in diamond by implementing decoupling techniques. We show that equal pulse spacing decoupling performs just as well as nonperiodic Uhrig decoupling and also allows us to take advantage of revivals in the echo to explore the longest coherence times. At short times, we can extend the coherence of particular quantum states out from T2*=2.7 μs out to an effective T2>340 μs. For preserving arbitrary states we show the experimental importance of using pulse sequences that compensate the imperfections of individual pulses for all input states through judicious choice of the phase of the pulses. We use these compensated sequences to enhance the echo revivals and show a coherence time of over 1.6 ms in ultrapure natural abundance 13C diamond.     

Influence of quantum size effects on island coarsening

Surface x-ray scattering and scanning-tunneling microscopy experiments reveal novel coarsening behavior of Pb nanocrystals grown on Si(111)-(7 x 7). It is found that quantum size effects lead to the breakdown of the classical Gibbs-Thomson analysis. This is manifested by the lack of scaling of the island densities. In addition, island decay times tau are orders of magnitude faster than expected from the classical analysis and have an unusual dependence on the growth flux F (i.e., tau is approximately 1/F). As a result, a highly monodispersed 7-layer island height distribution is found after coarsening if the islands are grown at high rather than low flux rates. These results have important implications, especially at low temperatures, for the controlled growth and self-organization of nanostructures.     

Binding thermodynamics of metal ions to HIV-1 ribonuclease H domain

Journal of Thermal Analysis and Calorimetry - Metal–protein interactions are not necessarily tight in many transient biological processes, such as cellular signaling, enzyme regulation, and...     

Structural and Computational Analysis of 2‐Halogeno‐Glycosyl Cations in the Presence of a Superacid: An Expansive Platform

An expansive NMR‐based structural analysis of elusive glycosyl cations derived from natural and non‐natural monosaccharides in superacids is disclosed. For the first time, it has been possible to explore the consequence of deoxygenation and halogen substitution at the C2 position in a series of 2‐halogenoglucosyl, galactosyl, and mannosyl donors in the condensed phase. These cationic intermediates were characterized using low‐temperature in situ NMR experiments supported by DFT calculations. The 2‐bromo derivatives display intramolecular stabilization of the glycosyl cations. Introducing a strongly electron‐withdrawing fluorine atom at C2 exerts considerable influence on the oxocarbenium ion reactivity. In a superacid, these oxocarbenium ions are quenched by weakly coordinating SbF₆^? anions, thereby demonstrating their highly electrophilic character and their propensity to interact with poor nucleophiles.     

A novel and highly stereoselective route for the synthesis of non-racemic 3-substituted isoindolin-1-one targets

A new, versatile and highly stereoselective approach for the synthesis of non-racemic 3-substituted isoindolin-1-ones is described from a readily available chiral template. The potential of this new protocol is demonstrated through the synthesis of an enantiomerically enriched 3-alkyl N-H isoindolin-1-one target with an e.e. of 98%.     

Near‐Infrared Photoluminescence and Electrochemiluminescence from a Remarkably Simple Boron Difluoride Formazanate Dye

A boron difluoride formazanate dye that exhibits near‐infrared photoluminescence and electrochemiluminescence was produced via a straightforward two‐step synthesis. Examination of its solid‐state structure suggested that the N‐aryl substituents have significant quinoidal character, which narrows the S₁–S₀ energy gap and leads to the unique optoelectronic properties observed. Cyclic voltammetry studies revealed two oxidation waves and two reduction waves that were electrochemically reversible. Electrochemiluminescence properties were examined in the presence of tri‐n‐propylamine, leading to maximum intensity at 910 nm, at least 85 nm (1132 cm^?1) red‐shifted compared to all other organic dyes. This work sets the stage for the development of future generations of dyes for emerging applications, including single‐cell imaging, that require near‐infrared photoluminescence and electrochemiluminescence.     

Hyperpolarization of Pyridyl Fentalogues by Signal Amplification By Reversible Exchange (SABRE)

Fentanyl, also known as ‘jackpot’, is a synthetic opiate that is 50–100 times more potent than morphine. Clandestine laboratories produce analogues of fentanyl, known as fentalogues to circumvent legislation regarding its production. Three pyridyl fentalogues were synthesized and then hyperpolarized by signal amplification by reversible exchange (SABRE) to appraise the forensic potential of the technique. A maximum enhancement of -168-fold at 1.4 T was recorded for the ortho pyridyl ¹H nuclei. Studies of the activation parameters for the three fentalogues revealed that the ratio of ligand loss trans to hydride and hydride loss in the complex [Ir(IMes)(L)₃(H)₂]⁺ (IMes=1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene) ranged from 0.52 to 1.83. The fentalogue possessing the ratio closest to unity produced the largest enhancement subsequent to performing SABRE at earth's magnetic field. It was possible to hyperpolarize a pyridyl fentalogue selectively from a matrix that consisted largely of heroin (97 : 3 heroin:fentalogue) to validate the use of SABRE as a forensic tool.     

Progranulin is expressed within motor neurons and promotes neuronal cell survival

Background

Progranulin is a secreted high molecular weight growth factor bearing seven and one half copies of the cysteine-rich granulin-epithelin motif. While inappropriate over-expression of the progranulin gene has been associated with many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and development of a form of dementia (frontotemporal lobar degeneration with ubiquitin positive inclusions, FTLD-U) associated with the formation of ubiquitinated inclusions. Recent reports indicate that progranulin has neurotrophic effects, which, if confirmed would make progranulin the only neuroprotective growth factor that has been associated genetically with a neurological disease in humans. Preliminary studies indicated high progranulin gene expression in spinal cord motor neurons. However, it is uncertain what the role of Progranulin is in normal or diseased motor neuron function. We have investigated progranulin gene expression and subcellular localization in cultured mouse embryonic motor neurons and examined the effect of progranulin over-expression and knockdown in the NSC-34 immortalized motor neuron cell line upon proliferation and survival.

Results

In situ hybridisation and immunohistochemical techniques revealed that the progranulin gene is highly expressed by motor neurons within the mouse spinal cord and in primary cultures of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal microscopy coupled to immunocytochemistry together with the use of a progranulin-green fluorescent protein fusion construct revealed progranulin to be located within compartments of the secretory pathway including the Golgi apparatus. Stable transfection of the human progranulin gene into the NSC-34 motor neuron cell line stimulates the appearance of dendritic structures and provides sufficient trophic stimulus to survive serum deprivation for long periods (up to two months). This is mediated at least in part through an anti-apoptotic mechanism. Control cells, while expressing basal levels of progranulin do not survive in serum free conditions. Knockdown of progranulin expression using shRNA technology further reduced cell survival.

Conclusion

Neurons are among the most long-lived cells in the body and are subject to low levels of toxic challenges throughout life. We have demonstrated that progranulin is abundantly expressed in motor neurons and is cytoprotective over prolonged periods when over-expressed in a neuronal cell line. This work highlights the importance of progranulin as neuroprotective growth factor and may represent a therapeutic target for neurodegenerative diseases including motor neuron disease.     

Polymeric Nanoparticles Active against Dual-Species Bacterial Biofilms

Biofilm infections are a global public health threat, necessitating new treatment strategies. Biofilm formation also contributes to the development and spread of multidrug-resistant (MDR) bacterial strains. Biofilm-associated chronic infections typically involve colonization by more than one bacterial species. The co-existence of multiple species of bacteria in biofilms exacerbates therapeutic challenges and can render traditional antibiotics ineffective. Polymeric nanoparticles offer alternative antimicrobial approaches to antibiotics, owing to their tunable physico-chemical properties. Here, we report the efficacy of poly(oxanorborneneimide) (PONI)-based antimicrobial polymeric nanoparticles (PNPs) against multi-species bacterial biofilms. PNPs showed good dual-species biofilm penetration profiles as confirmed by confocal laser scanning microscopy. Broad-spectrum antimicrobial activity was observed, with reduction in both bacterial viability and overall biofilm mass. Further, PNPs displayed minimal fibroblast toxicity and high antimicrobial activity in an in vitro co-culture model comprising fibroblast cells and dual-species biofilms of Escherichia coli and Pseudomonas aeruginosa. This study highlights a potential clinical application of the presented polymeric platform.