Improvements in ion signal reproducibility obtained using a homogeneous laser beam for on-line laser desorption/ionization of single particles

A major factor limiting on-line single particle mass spectrometry techniques from becoming more quantitative is the large shot-to-shot variability in ion intensities observed in the laser desorption/ionization (LDI) mass spectra.1,2 In previous work, lab-generated particles showed fluctuations of up to 152% in the absolute ion intensities in averaged spectra of 200-300 'identical' particles.2 Most of these fluctuations were attributed to inhomogeneities in the laser beam profile, leading to significant differences in the power each particle encountered depending on the position in the LDI laser beam where it underwent analysis. The goal of the work presented herein is to determine whether a fiber optic actually reduces the observed variability in single particle LDI mass spectral data. Initial results are presented for individual single component organic particles composed of 2,4-dihydroxybenzoic acid (2,4-DHB) analyzed using a low-power flat-top laser beam profile created by sending an ultraviolet (266 nm) DI laser through a fiber optic. Relative standard deviations of the total ion intensities for peaks in individual spectra are reduced to 31%. Single particle spectra, compared with and without laser homogenization at the same nominal laser fluence, show a marked enhancement. Specifically, the ion signal patterns of the 2,4-DHB particle spectra obtained using a homogenous LDI beam look identical to one another (i.e. only one particle type was produced with a commonly used neural network grouping algorithm), whereas without beam homogenization 25 different particle types (based on ion intensity patterns) were obtained. Future publications will explore more particle types and matrices but the initial results described herein are quite encouraging.     

Imaging the binding ability of proteins immobilized on surfaces with different orientations by using liquid crystals

We report an investigation of the binding ability of a protein immobilized on surfaces with different orientations but in identical interfacial microenvironments. The surfaces present mixed self-assembled monolayers (SAMs) of 11-[19-carboxymethylhexa(ethylene glycol)]undecyl-1-thiol, 1, and 11-tetra(ethylene glycol) undecyl-1-thiol, 2. Whereas 2 is used to define an interfacial microenvironment that prevents nonspecific adsorption of proteins, 1 was activated by two different schemes to immobilize ribonuclease A (RNase A) in either a preferred orientation or random orientations. The binding of the ribonuclease inhibitor protein (RI) to RNase A on these surfaces was characterized by using ellipsometry and the orientational behavior of liquid crystals. Ellipsometric measurements indicate identical extents of immobilization of RNase A via the two schemes. Following incubation of both surfaces with RI, however, ellipsometric measurements indicate a 4-fold higher binding ability of the RNase A immobilized with a preferred orientation over RNase A immobilized with a random orientation. The higher binding ability of the oriented RNase A over the randomly oriented RNase A was also apparent in the orientational behavior of nematic liquid crystals of 4-cyano-4'-pentylcyanobiphenyl (5CB) overlayed on these surfaces. These results demonstrate that the orientations of proteins covalently immobilized in controlled interfacial microenvironments can influence the binding activities of the immobilized proteins. Results reported in this article also demonstrate that the orientational states of proteins immobilized at surfaces can be distinguished by examining the optical appearances of liquid crystals.     

Regioselectivity in the Intramolecular Heck Reaction of a Series of Cyclic Sulfonamides: An Experimental and Computational Study

Regioselectivity in the intramolecular Heck reaction of a series of N‐sulfonyl‐2,5‐dihydro‐3‐substituted pyrroles was studied. These substrates are unbiased in terms of the formed ring size of the new heterocycle. Results indicate that high levels of regioselectivity are observed under a range of conditions, and that there is an underlying propensity for carbon–carbon bond formation at the most hindered end of the alkene. For two examples (3‐Me and 3‐tBu), DFT calculations were performed and indicate that in both cases, the modelled transition state for carbopalladation is energetically lower for the experimentally preferred isomer.     

Julia sets that are full of holes

Conclusion  Many of the most fundamental properties, such as measure and dimension, remain unknown for most Julia sets. Although there are Julia sets that are the whole Riemann sphere and so have dimension two and positive measure, no other Julia sets of measure bigger than zero have been found. Shishikura’s surprising result (1998) shows that there are other Julia sets of dimension 2, which makes it appear possible that there are other Julia sets of positive measure. Proving that a Julia set is full of holes, or porous, provides a bound on the upper box dimension, but this has so far been possible only for special classes of Julia sets. Mean porosity and mean e-porosity, both found in Koskela and Rohde (1997), provide better dimension bounds; nonuniform porosity (Roth 2006) implies measure zero, but is not known to provide dimension bounds. These notions can be used in some cases when it is not possible to prove porosity. In the end, we do not know in general which Julia sets are porous and which are not. In fact, forJ _R, little is known about its dimension or measure. There is much left to explore.     

A new and unexpected aminoisoquinoline formed under bischler-napieralski reaction conditions provides for A new synthesis of 3-aminoisoquinolines

Treatment of an amide, 1 , of a substituted 2-phenethylamine using Bischler-Napieralski reaction conditions with acetonitrile as a solvent, gave the desired dihydroisoquinoline 2 as well as an unexpected 3-aminoisoquinoline product 3 . The applicability of this finding as a method of synthesizing 3-aminoisoquinoline derivatives was examined.     

Practical synthesis of a potent hepatitis C virus RNA replication inhibitor

A practical, efficient synthesis of 1, a hepatitis C virus RNA replication inhibitor, is described. Starting with the inexpensive diacetone glucose, the 12-step synthesis features a novel stereoselective rearrangement to prepare the key crystalline furanose diol intermediate. This is followed by a highly selective glycosidation to couple the C-2 branched furanose epoxide with deazapurine.