Rigid orthogonal bis-TEMPO biradicals with improved solubility for dynamic nuclear polarization

The synthesis and characterization of oxidized bis-thioketal-trispiro dinitroxide biradicals that orient the nitroxides in a rigid, approximately orthogonal geometry are reported. The biradicals show better performance as polarizing agents in dynamic nuclear polarization (DNP) NMR experiments as compared to biradicals lacking the constrained geometry. In addition, the biradicals display improved solubility in aqueous media due to the presence of polar sulfoxides. The results suggest that the orientation of the radicals is not dramatically affected by the oxidation state of the sulfur atoms in the biradical, and we conclude that a biradical polarizing agent containing a mixture of oxidation states can be used for improved solubility without a loss in performance.     

Targeting orphan nuclear receptors for treatment of metabolic diseases and autoimmunity

The nuclear receptor (NR) superfamily is composed of 48 members in humans and includes receptors for steroid hormones, thyroid hormone, various lipids and oxysterols. This superfamily has been a rich source of drug targets for myriad diseases including inflammation, cancer, and metabolic disorders. Approximately half of the superfamily have well characterized natural ligands whereas the remaining receptors are considered orphan receptors and remain a focus of a number of investigators assessing their ability to be regulated by ligands. Here, we review recent discoveries that yield important insight into the druggability of three orphan nuclear receptors: the retinoic acid receptor-like orphan receptors (RORs), peroxisome proliferator-activated receptor γ (PPARγ), and liver receptor homolog-1 (LRH-1).     

Role of magnetic shear on the electrostatic current driven ion-cyclotron instability in the presence of parallel electric field

Recent observation and theoretical investigations have led to the significance of electrostatic ion cyclotron (EIC) waves in the electrodynamics of acceleration process. The instability is one of the fundamental of a current carrying magnetized plasma. The EIC instability has the lowest threshold current among the current driven instabilities. On the basis of local analysis where inhomogeneities like the magnetic shear and the finite width current channel, have been ignored which is prevalent in the magnetospheric environment. On the basis of non-local analysis interesting modification has been incorporated by the inclusion of magnetic shear. In this paper we provide an analytical approach for the non-local treatment of current driven electrostatic waves in presence of parallel electric field. The growth rate is significantly influenced by the field aligned electron drift. The presence of electric field enhances the growth of EIC waves while magnetic shear stabilizes the system.     

Assessing Crystallisation Kinetics of Zr Metal–Organic Frameworks through Turbidity Measurements to Inform Rapid Microwave-Assisted Synthesis

Controlling the crystallisation of metal-organic frameworks (MOFs), network solids of metal ions or clusters connected by organic ligands, is often hindered by the significant number of synthetic variables inherent to their synthesis. Coordination modulation, the addition of monotopic competing ligands to solvothermal syntheses, can allow tuning of physical properties (particle size, porosity, surface chemistry), enhance crystallinity, and select desired phases, by modifying the kinetics of self-assembly, but its mechanism(s) are poorly understood. Herein, turbidity measurements were used to assess the effects of modulation on the solvothermal synthesis of the prototypical Zr terephthalate MOF UiO-66 and the knowledge gained was applied to its rapid microwave synthesis. The studied experimental parameters—temperature, reagent concentration, reagent aging, metal precursor, water content, and modulator addition—all influence the time taken for onset of nucleation, and subsequently allow microwave synthesis of UiO-66 in as little as one minute. The simple, low cost turbidity measurements align closely with previously reported in situ synchrotron X-ray diffraction studies, proving their simplicity and utility for probing the nucleation of complex materials while offering significant insights to the synthetic chemist.     

Spinning Sidebands in Slow-Magic-Angle-Spinning NMR Spectra Arising from TightlyJ-Coupled Spin Pairs

Complex spinning sidebands are observed in magic-angle-spinning (MAS) NMR spectra arising from isolated tightlyJ-coupled spin pairs under slow spinning conditions. Such spinning sidebands are sensitive to the magnitude and relative orientation of the chemical-shift tensors, the dipolar-coupling tensor, and the sign of the indirect spin–spin (J) coupling. We show that it is possible to extract information concerning such NMR parameters from an analysis of the observed spinning sidebands. As an example, numerical simulations are carried out to reproduce observed³¹P MAS NMR spectra of a phosphole tetramer (1) ando-bis(diphenylphosphino)benzene (2), so that invaluable information concerning the orientations of the phosphorus chemical-shift tensors and the sign ofJ(³¹P,³¹P) can be deduced. Simulations are carried out by numerically evaluating the spin-density matrix of the spin system.     

Photothermal ionisation spectroscopy of oxygen-related shallow defects in crystalline silicon

Shallow thermal donors are electrically active oxygen-related thermally formed defects observed in oxygen-rich silicon annealed between 300 ° and 600 ° C. Seven donors have been identified with an average central-cell correction of only 5 meV. In view of their molecule-like nature this close agreement to the effective mass theory prediction for a hydrogen-like donor in silicon is of interest. It is shown that these centres are not correlated to the residual impurities phosphorus and boron but rather to the presence of nitrogen. Nitrogen-doped oxygen-rich samples show increased shallow thermal donor growth and a reduction in the growth of other oxygen-related donors in comparison to normally nitrogen-undoped oxygen-rich samples. A reduction in shallow thermal donor concentration at high nitrogen concentrations is reported.     

P-AMINOBENZOIC ACID CAN SENSITIZE THE FORMATION OF PYRIMIDINE DIMERS IN DNA: DIRECT CHEMICAL EVIDENCE

Thymine-containing photoproducts with chromatographic properties similar to those of cyclobutyl pyrimidine dimers can be formed in [³H]-thymine-labeled DNA in solution by 313 nm ultraviolet radiation in the presence of para-aminobenzoic acid (PABA), a compound used in sunscreen preparations. In the absence of PABA, similar fluences of 313 nm radiation do not produce significant numbers of these photoproducts. The thymine-containing photoproducts can be reversed by 254 nm radiation so that the tritium label migrates with the mobility of thymine monomer, a behavior characteristic of thymine-containing cyclobutyl pyrimidine dimers. This result supports previous, but less direct, data from other laboratories indicating that PABA can sensitize dimer formation in the DNA of bacterial and mammalian cells.     

Endoscopic microsuture repair of vocal fold defects

The presence of a nonvibratory segment of vocal folds after microlaryngeal surgery is often a cause of poor voice result. The etiology of a nonvibratory segment is due to full thickness epithelial defect followed by secondary wound closure and scar contracture. To reduce scar contracture and nonvibratory segment of the vocal folds, primary repair with a 6-0 chromic endo-knot suture technique was used to close defects and approximate microflaps of the vocal folds. This was done in 18 patients with epithelial defects after resection of benign vocal fold lesions. The pathologic findings included severe polypoid degeneration (n = 7), fusiform laryngeal polyps (n = 5), sulcus vocalis (n = 2), cyst (n = 2), and keratosis (n = 2). Voice was improved in all patients after surgery. Comparison of vocal fold vibration before and after surgery showed improvements in configuration, amplitude, and mucosal wave. Vocal folds that were sutured all had good vibratory characteristics; none had a nonvibrating segment at the site of suture placement. Voice and healing after microsuture technique were near normal by Day 10 and return of mucosal wave was often complete by Day 14. Endoscopic microsuture closure of microflaps of the vocal folds edge is safe and affords the surgeon an opportunity for primary repair with improved functional result.