Isonitrile-responsive and bioorthogonally removable tetrazine protecting groups.

In vivo compatible reactions have a broad range of possible applications in chemical biology and the pharmaceutical sciences. Here we report tetrazines that can be removed by exposure to isonitriles under very mild conditions. Tetrazylmethyl derivatives are easily accessible protecting groups for amines and phenols. The isonitrile-induced removal is rapid and near-quantitative. Intriguingly, the deprotection is especially effective with (trimethylsilyl)methyl isocyanide, and serum albumin can catalyze the elimination under physiological conditions. NMR and computational studies revealed that an imine-tautomerization step is often rate limiting, and the unexpected cleavage of the Si-C bond accelerates this step in the case with (trimethylsilyl)methyl isocyanide. Tetrazylmethyl-removal is compatible with use on biomacromolecules, in cellular environments, and in living organisms as demonstrated by cytotoxicity experiments and fluorophore-release studies on proteins and in zebrafish embryos. By combining tetrazylmethyl derivatives with previously reported tetrazine-responsive 3-isocyanopropyl groups, it was possible to liberate two fluorophores in vertebrates from a single bioorthogonal reaction. This chemistry will open new opportunities towards applications involving multiplexed release schemes and is a valuable asset to the growing toolbox of bioorthogonal dissociative reactions

The search for habitable worlds: 1. The viability of a starshade mission

As part of NASA's mission to explore habitable planets orbiting nearby stars, this paper explores the detection and characterization capabilities of a 4-m space telescope plus 50-m starshade located at the Earth-Sun L2 point, a.k.a. the New Worlds Observer (NWO). Our calculations include the true spectral types and distribution of stars on the sky, an iterative target selection protocol designed to maximize efficiency based on prior detections, and realistic mission constraints. We carry out both analytical calculations and simulated observing runs for a wide range in exozodiacal background levels ({\epsilon} = 1 - 100 times the local zodi brightness) and overall prevalence of Earth-like terrestrial planets ({\eta}\oplus = 0.1 - 1). We find that even without any return visits, the NWO baseline architecture (IWA = 65 mas, limiting FPB = 4\times10-11) can achieve a 95% probability of detecting and spectrally characterizing at least one habitable Earth-like planet, and an expectation value of ~3 planets found, within the mission lifetime and {\Delta}V budgets, even in the worst-case scenario ({\eta}\oplus = 0.1 and {\epsilon} = 100 zodis for every target). This achievement requires about one year of integration time spread over the 5 year mission, leaving the remainder of the telescope time for UV-NIR General Astrophysics. Cost and technical feasibility considerations point to a "sweet spot" in starshade design near a 50-m starshade effective diameter, with 12 or 16 petals, at a distance of 70,000-100,000 km from the telescope.Comment: Refereed and accepted to PASP, scheduled for publication in the May 2012 issue (Vol. 124, No. 915

Metal-free α-amination of secondary amines: Computational and experimental evidence for azaquinone methide and azomethine ylide intermediates

We have performed a combined computational and experimental study to elucidate the mechanism of a metal-free α-amination of secondary amines. Calculations predicted azaquinone methides and azomethine ylides as the reactive intermediates and showed that iminium ions are unlikely to participate in these transformations. These results were confirmed by experimental deuterium-labeling studies and the successful trapping of the postulated azomethine ylide and azaquinone methide intermediates. In addition, computed barrier heights for the rate-limiting step correlate qualitatively with experimental findings. © 2013 American Chemical Society

Radial Distribution of Dust Grains Around HR 4796A

We present high-dynamic-range images of circumstellar dust around HR 4796A that were obtained with MIRLIN at the Keck II telescope at lambda = 7.9, 10.3, 12.5 and 24.5 um. We also present a new continuum measurement at 350 um obtained at the Caltech Submillimeter Observatory. Emission is resolved in Keck images at 12.5 and 24.5 um with PSF FWHM's of 0.37" and 0.55", respectively, and confirms the presence of an outer ring centered at 70 AU. Unresolved excess infrared emission is also detected at the stellar position and must originate well within 13 AU of the star. A model of dust emission fit to flux densities at 12.5, 20.8, and 24.5 um indicates dust grains are located 4(+3/-2) AU from the star with effective size, 28+/-6 um, and an associated temperature of 260+/-40 K. We simulate all extant data with a simple model of exozodiacal dust and an outer exo-Kuiper ring. A two-component outer ring is necessary to fit both Keck thermal infrared and HST scattered-light images. Bayesian parameter estimates yield a total cross-sectional area of 0.055 AU^2 for grains roughly 4 AU from the star and an outer-dust disk composed of a narrow large-grain ring embedded within a wider ring of smaller grains. The narrow ring is 14+/-1 AU wide with inner radius 66+/-1 AU and total cross-sectional area 245 AU^2. The outer ring is 80+/-15 AU wide with inner radius 45+/-5 AU and total cross-sectional area 90 AU^2. Dust grains in the narrow ring are about 10 times larger and have lower albedos than those in the wider ring. These properties are consistent with a picture in which radiation pressure dominates the dispersal of an exo-Kuiper belt.Comment: Accepted by Astrophysical Journal (Part1) on September 9, 2004. 13 pages, 10 figures, 2 table

Long-term photometry and periods for 261 nearby pulsating M giants

We present the results of a 5.5-year CCD photometric campaign that monitored 261 bright, southern, semi-regular variables with relatively precise Hipparcos parallaxes. The data are supplemented with independent photoelectric observations of 34 of the brightest stars, including 11 that were not part of the CCD survey, and a previously unpublished long time-series of VZ Cam. Pulsation periods and amplitudes are established for 247 of these stars, the majority of which have not been determined before. All M giants with sufficient observations for period determination are found to be variable, with 87% of the sample (at S/N >= 7.5) exhibiting multi-periodic behaviour. The period ratios of local SRVs are in excellent agreement with those in the Large Magellanic Cloud. Apparent K-band magnitudes are extracted from multiple NIR catalogues and analysed to determine the most reliable values. We review the effects of interstellar and circumstellar extinction and calculate absolute K-band magnitudes using revised Hipparcos parallaxes.Comment: 18 pages, 15 figures; accepted for publication in Monthly Notices of the Royal Astronomical Societ

Correlation Between the Deuteron Characteristics and the Low-energy Triplet np Scattering Parameters

The correlation relationship between the deuteron asymptotic normalization constant, $A_{S}$, and the triplet np scattering length, $a_{t}$, is investigated. It is found that 99.7% of the asymptotic constant $A_{S}$ is determined by the scattering length $a_{t}$. It is shown that the linear correlation relationship between the quantities $A_{S}^{-2}$ and $1/a_{t}$ provides a good test of correctness of various models of nucleon-nucleon interaction. It is revealed that, for the normalization constant $A_{S}$ and for the root-mean-square deuteron radius $r_{d}$, the results obtained with the experimental value recommended at present for the triplet scattering length $a_{t}$ are exaggerated with respect to their experimental counterparts. By using the latest experimental phase shifts of Arndt et al., we obtain, for the low-energy scattering parameters ($a_{t}$, $r_{t}$, $P_{t}$) and for the deuteron characteristics ($A_{S}$, $r_{d}$), results that comply well with experimental data.Comment: 19 pages, 1 figure, To be published in Physics of Atomic Nucle

How the Lewis Base F– Catalyzes the 1,3-Dipolar Cycloaddition between Carbon Dioxide and Nitrilimines

Bio-organic Synthesi