Mechanistic implications in the Morita-Baylis-Hillman alkylation: isolation and characterization of an intermediate

An intermediate phosphonium salt has never been isolated from the Morita-Baylis-Hillman (MBH) reaction. Due to the weakly basic counterion produced in the MBH alkylation and allylation reactions, the reaction can be stopped after electrophilic attack on the zwitterionic enolate and an intermediate isolated. Upon analysis of the crystal structure, a trans geometry is observed, suggesting that there is no electrostatic interaction between phosphorus and oxygen in the zwitterionic enolate that undergoes alkylation, thus giving new mechanistic insight into the MBH reaction.     

Submicron streptavidin patterns for protein assembly

Micron and submicron-scale features of aldehyde functionality were fabricated in polymer films by photolithography to develop a platform for protein immobilization and assembly at a biologically relevant scale. Films containing the pH-reactive polymer poly(3,3'-diethoxypropyl methacrylate) and a photoacid generator (PAG) were patterned from 500 nm to 40 mum by exposure to 365 nm (i-line) light. Upon PAG activation and hydrolysis of acetals, aldehyde groups formed. After the films were incubated with a biotinylated aldehyde reactive probe, the X-ray photoelectron spectroscopy results were consistent with biotin being attached to the surface. The background was subsequently passivated by flood exposure and incubation with an aminooxy-terminated poly(ethylene glycol), resulting in a 98% reduction in nonspecific protein adsorption. Protein patterning and assembly was demonstrated using streptavidin, biotinylated anthrax toxin receptor-1, and the protective antigen moiety of anthrax toxin and confirmed by fluorescence microscopy and atomic force microscopy (AFM). AFM demonstrated that 500 nm protein features were achieved. Because of the abundance of biotinylated proteins, this methodology provides a platform for protein immobilization and assembly for various applications in biotechnology.     

Observation of phenyl-fused porphyrinoids during the ESI mass spectrometric analysis of meso-pentafluorophenyl-substituted porphyrin and corrole

The results of ESI(+) and ESI(-) mass spectrometry/mass spectrometry investigations of meso-tetrakisphenylporphyrin (TPP) and meso-trisphenylcorrole (TPC) in comparison with their meso-tetrakis(pentafluorophenyl)-substituted analogs T(F)PP and T(F)PC are reported. The fragmentation patterns of TPP and TPC show the expected loss of meso-aryl radicals. Analyzing the meso-pentafluorophenyl substituted analogs T(F)PP and T(F)PC, we found ESI(-) to be an excellent ionization mode. Rich and well-defined HF-elimination fragmentation patterns unique to the presence of meso-tetrafluorophenyl groups and evocative for the formation of fragments with direct covalent o-phenyl-to-beta-linkages are observed. A computation of the feasibility and relative energies of the resulting species corroborates the interpretation of the experimental findings. The computations indicate the presence of cooperative interactions between the linkages that direct the linkage formations to occur in a unidirectional fashion. MS/MS/MS experiments also provide indications for the regioselectivity of the fusions. Our observations further detail earlier reports of similar HF-eliminations and allow a generalization of the findings. The results presented may also point to strategies towards the bulk synthesis of novel porphyrinoid structures.     

The RNase a superfamily: Generation of diversity and innate host defense

Summary The Ribonuclease A superfamily includes an extensive network of distinct and divergent gene lineages. Although all ribonucleases of this superfamily share invariant structural and catalytic elements and some degree of enzymatic activity, the primary sequences have diverged significantly, ostensibly to promote novel function. We will review the literature on the evolution and biology of the RNase A ribonuclease lineages that have been characterized specifically as involved in host defense including: (1) RNases 2 and RNases 3, also known as the eosinophil ribonucleases, which are rapidly-evolving cationic proteins released from eosinophilic leukocytes, (2) RNase 7, an anti-pathogen ribonuclease identified in human skin, and (3) RNase 5, also known as angiogenin, another rapidly-evolving ribonuclease known to promote blood vessel growth with recently-discovered antibacterial activity. Interestingly, some of the characterized anti-pathogen activities do not depend on ribonuclease activity per se. We discuss the ways in which the anti-pathogen activities characterized in vitro might translate into experimental confirmation in vivo. We will also consider the possibility that other ribonucleases, such as the dimeric bovine seminal ribonuclease and the frog oocyte ribonucleases, may have host defense functions and therapeutic value that remain to be explored. (190 words)     

Imprecise singing is widespread

There has been a recent surge of research on the topic of poor-pitch singing. However, this research has not addressed an important distinction in measurement: that between accuracy and precision. With respect to singing, accuracy refers to the average difference between sung and target pitches. Precision, by contrast, refers to the consistency of repeated attempts to produce a pitch. A group of 45 non-musician participants was asked to vocally imitate unfamiliar 5-note melodies, as well as to sing a series of familiar melodies from memory (e.g., Happy Birthday). The results showed that singers were more accurate than they were precise, and that a majority of participants could justifiably be categorized as imprecise singers. Accuracy and precision measures were correlated with one another, and conditional-probability analyses suggested that accuracy predicted precision more so than the converse. Finally, performance differences across groups of singers were greater for the imitation of unfamiliar tone sequences than for the recall of familiar melodies.     

The Preparation, Characterization and X-ray Structural Analysis of Tetrakis[1-Methyl-3-(2-Propyl)-2(3H)-Imidazolethione]Cadmium(II) Hexafluorophosphate

Abstract  A new compound, [Cd(mipit)₄][PF₆]₂ has been synthesized and characterized via standard solid and solution state methods including single crystal X-ray crystallography (mipit = 1-methyl-3-(2-propyl)-2(3H)-imidazolethione). The title compound crystallizes in tetragonal space group I4 ₁ /a with a = 12.478(2) ?, b = 12.478(2) ?, c = 28.806(6) ?, and Z = 4. The complex is a high melting, colorless solid that has a distorted tetrahedral CdS₄ coordination geometry. Thermogravimetric analysis results for the title compound as well as for another potential CdS synthon and two potential CdSe synthons are reported. Graphical Abstract  The synthesis and characterization of the title compound, a new ionic homoleptic cadmium complex, tetrakis[1-methyl-3-(2-propyl)-2(3H)-imidazolethione]cadmium(II) hexafluorophosphate is reported. The results of a single crystal X-ray diffraction analysis reveal a distorted tetrahedral CdS₄ coordination sphere about the cadmium. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Magnetic Relaxometry with an Atomic Magnetometer and SQUID Sensors on Targeted Cancer Cells

Magnetic relaxometry methods have been shown to be very sensitive in detecting cancer cells and other targeted diseases. Superconducting Quantum Interference Device (SQUID) sensors are one of the primary sensor systems used in this methodology because of their high sensitivity with demonstrated capabilities of detecting fewer than 100,000 magnetically-labeled cancer cells. The emerging technology of atomic magnetometers (AM) represents a new detection method for magnetic relaxometry with high sensitivity and without the requirement for cryogens. We report here on a study of magnetic relaxometry using both AM and SQUID sensors to detect cancer cells that are coated with superparamagnetic nanoparticles through antibody targeting. The AM studies conform closely to SQUID sensor results in the measurement of the magnetic decay characteristics following a magnetization pulse. The AM and SQUID sensor data are well described theoretically for superparamagnetic particles bound to cells and the results can be used to determine the number of cells in a cell culture or tumor. The observed fields and magnetic moments of cancer cells are linear with the number of cells over a very large range. The AM sensor demonstrates very high sensitivity for detecting magnetically labeled cells does not require cryogenic cooling and is relatively inexpensive.     

Bott periodicity and realizations of chiral symmetry in arbitrary dimensions

We compute the chiral symmetries of the Lagrangian for confining “vector-like” gauge theories with massless fermions in d-dimensional Minkowski space and, under a few reasonable assumptions, determine the form of the quadratic fermion condensates which arise through spontaneous breaking of these symmetries. We find that for each type (complex, real, or pseudoreal) of representation of the gauge group carried by the fermions, the chiral symmetries of the Lagrangian, as well as the residual symmetries after dynamical breaking, exactly follow the pattern of Bott periodicity as the dimension changes. The consequences of this for the topological features of the low-energy effective theory are considered.     

Engineering the interface between glucose oxidase and nanoparticles

The behavior of glucose oxidase (GOx) on gold nanoparticles (NPs) was investigated as a function of (1) NP surface chemistry, (2) stabilizing protein additives, and (3) protein microenvironment. GOx secondary structure and unfolding was probed by circular dichroism (CD) spectroscopy and fluorescence, and GOx enzymatic activity was measured by a colorimetric assay. We also examined the activity and structure of GOx after displacement from the NP surface. Generally, GOx behavior was negatively impacted by conjugation to the NP, and conjugation conditions could vary the influence of the NP. Surface chemistry and protein microenvironment could improve behavior, but addition of stabilizing proteins negatively influenced activity. After displacement from the NPs, GOx tended to remain unfolded, indicating that the interactions with the NP were irreversible.     

Vertical anisotropic microfibers for a gecko-inspired adhesive

Geckos are able to adhere strongly and release easily from surfaces because the structurally anisotropic fibers on their toes naturally exhibit force anisotropy based on the direction of articulation. Here, semicircular fibers, with varying amounts of contact area on the two faces, are investigated to ascertain whether fiber shape can be used to gain anisotropy in shear and shear adhesion forces. Testing of 10-μm-diameter polydimethylsiloxane (PDMS) fibers against a 4-mm-diameter flat glass puck show that shear and shear adhesion forces were two to five times greater when in-plane movement caused the flat face, rather than the curved face, of the fiber to come in contact with the glass puck. The directional adhesion and shear force anisotropy results are close to theoretical approximations using the Kendall peel model and clearly demonstrate how fiber shape may be used to influence the properties of the adhesive. This result has broad applicability, and by combining the results shown here with other current vertical and angled designs, synthetic adhesives can be further improved to behave more like their natural counterparts.