Total and Semi‐Syntheses of Antimicrobial Thuggacin Derivatives

The total and semi‐synthesis of 13 new macrolactones derived from thuggacin, which is a secondary metabolite from the myxobacterium Sorangium cellulosum, are reported. The thuggacins have attracted much attention due to their strong antibacterial activity, particularly towards Mycobacterium tuberculosis. This study focuses on 1) thuggacin derivatives that cannot equilibrate by transacylation between the three natural thuggacins A–C, 2) the roles of the thiazole ring, and 3) the hexyl side chain at C2. Semi‐synthetic O‐methylation at C17 suppressed the transacylations without a substantial loss of antibacterial activity. Exchanging the C17–C25 side chain for simplified hydrophobic chains led to complete loss of antibacterial activity. Exchange of the thiazole by an oxazole ring or removal of the hexyl side chain at C2 had no substantial effect on the biological properties.     

Controlled Variable Oxidative Doping of Individual Organometallic Nanoparticles

The charging and controlled oxidative doping of single organometallic ferrocene nanoparticles is reported in aqueous sodium tetrafluoroborate using the nano‐impacts method. It is shown that ferrocene nanoparticles of approximately 105 nm diameter are essentially quantitatively oxidatively doped with the uptake of one tetrafluoroborate anion per ferrocene molecule at suitably high overpotentials. By using lower potentials, it is possible to achieve low doping levels of single nanoparticles in a controlled manner.     

In situ liquid SIMS analysis of uranium oxide

Trace analysis of nuclear materials in solid particles collected in the environment or particles in liquid slurry generated in nuclear material manufacturing processes can pinpoint elemental, organic, and isotopic signatures of nuclear fuel cycle activities and processes. Such information can support nuclear safeguards programs by increasing our ability to detect undeclared nuclear materials, routine activities for safeguarding at declared facilities, and illicit activities. However, trace radioactive material analysis in liquids and slurries is challenging using bulk approaches. For example, one drawback of sensitive analysis such as inductively coupled plasma mass spectrometry (ICP-MS) is that sample is consumed or destroyed as a result of the technical approach. We developed a vacuum compatible microfluidic interface to enable surface analysis of liquids and solid–liquid interactions using time-of-flight secondary ion mass spectrometry (ToF-SIMS). In this work, we illustrate the initial results from the analysis of liquid uranium oxide standard solutions using in situ liquid SIMS. Because the liquid SIMS analysis is almost nondestructive, the same sample can then be analyzed by other analytical techniques or saved for future reference. Consequently, multimodal analysis is possible. Our results demonstrate that in situ liquid SIMS can be used as a new approach to analyze radioactive materials in liquid and slurry forms of relevance to diverse applications.     

Synthesis of cananodine by intramolecular epoxide opening

Cananodine is a guaipyridine alkaloid with activity against liver cancer. Cananodine was synthesized using a remarkable intramolecular opening of a trisubstituted epoxide as the key step in construction of the seven-membered carbocycle of the target. The epoxide opening strategy allows all four stereoisomers of cananodine to be prepared.     

A non-metric perfectly normal hereditarily indecomposable continuum

We construct an example of a non-metric perfectly normal hereditarily indecomposable continuum. The example is constructed as an inverse limit of non-metric analogues of solenoids. Theorems needed to insure perfect normality are stated and proven. It is shown that the example cannot be embedded in a countable product of Hausdorff arcs.     

Functional connectivity between task-positive and task-negative brain areas and its relation to working memory performance

Functional brain imaging studies have identified a set of brain areas typically activated during cognitive tasks (task-positive brain areas) and another set of brain areas typically deactivated during cognitive tasks (task-negative brain areas). Negative correlations, or anticorrelations, between task-positive and task-negative brain areas have been reported at rest. Furthermore, the strength of these anticorrelations appears to be related to cognitive function. However, studies examining anticorrelations have typically employed global regression or similar analysis steps that force anticorrelated relationships to exist between brain areas. Therefore the validity of these findings has been questioned. Here we examine anticorrelations between a task-negative region in the medial frontal gyrus/anterior cingulate cortex and dorsolateral prefrontal cortex, a classic task-positive area, using an analysis that does not include global regression. Instead, we control for whole-brain correlations in the group-level analysis. Using this approach, we demonstrate that the strength of the functional connection between the medial frontal cortex and the dorsolateral prefrontal cortex is related to cognitive function and that this relationship is not an artifact of global regression.     

Constant pH Molecular Dynamics Simulations of Nucleic Acids in Explicit Solvent

The nucleosides of adenine and cytosine have pKa values of 3.50 and 4.08, respectively, and are assumed to be unprotonated under physiological conditions. However, evidence from recent NMR and X-Ray crystallography studies has revealed the prevalence of protonated adenine and cytosine in RNA macromolecules. Such nucleotides with elevated pKa values may play a role in stabilizing RNA structure and participate in the mechanism of ribozyme catalysis. With the work presented here, we establish the framework and demonstrate the first constant pH MD simulations (CPHMD) for nucleic acids in explicit solvent in which the protonation state is coupled to the dynamical evolution of the RNA system via λ-dynamics. We adopt the new functional form λ(Nexp) for λ that was recently developed for Multi-Site λ-Dynamics (MSλD) and demonstrate good sampling characteristics in which rapid and frequent transitions between the protonated and unprotonated states at pH = pKa are achieved. Our calculated pKa values of simple nucleotides are in a good agreement with experimentally measured values, with a mean absolute error of 0.24 pKa units. This work demonstrates that CPHMD can be used as a powerful tool to investigate pH-dependent biological properties of RNA macromolecules.     

Novel Copolymers of Styrene. 16. Halogen Ring-Disubstituted Methyl 2-Cyano-3-Phenyl-2-Propenoates

Electrophilic trisubstituted ethylenes, ring-disubstituted methyl 2-cyano-3-phenyl-2-propenoates, RPhCH?C(CN)CO₂CH₃, where R is 2,5-dichloro, 3,5-dichloro, 2,3-difluoro, 3-chloro-2-fluoro, 3-chloro-4-fluoro, 4-chloro-3-fluoro, 2-chloro-5-nitro, and 2-chloro-6-nitro were prepared and copolymerized with styrene. The monomers were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-disubstituted benzaldehydes and methyl cyanoacetate, and characterized by CHN analysis, IR, ¹H and ¹³C-NMR. All the ethylenes were copolymerized with styrene (M₁) in solution with radical initiation (ABCN) at 70°C. The compositions of the copolymers were calculated from nitrogen analysis and the structures were analyzed by IR, ¹H and ¹³C-NMR. The order of relative reactivity (1/r₁) for the monomers is 4-Cl-3-F (4.87) > 2,3-F₂ (4.49) > 3-Cl-4-F (3.50) > 3-Cl-2-F (2.96) > 2-Cl-5-NO₂ (2.02) > 2,5-Cl₂ (1.54) > 2-Cl-6-NO₂ (1.00) > 3,5-Cl₂ (0.41). Relatively high T_g of the copolymers in comparison with that of polystyrene indicates a decrease in chain mobility of the copolymer due to the high dipolar character of the trisubstituted ethylene monomer unit. Decomposition of the copolymers in nitrogen occurred in two steps, first in the 200–500ºC range with residue (1.5–34.5% wt), which then decomposed in the 500-800ºC range.