Mechanism of palladium-catalyzed diene cyclization/hydrosilylation: direct observation of intramolecular carbometalation

The results of kinetic, deuterium-labeling, and low-temperature NMR studies have established a mechanism for the palladium-catalyzed cyclization/hydrosilylation of dimethyl diallylmalonate (1) with triethylsilane involving rapid, irreversible conversion of the palladium silyl complex [(phen)Pd(SiEt(3))(NCAr)](+) [BAr(4)](-) [Ar = 3,5-C(6)H(3)(CF(3))(2)] (4b) and 1 to the palladium 5-hexenyl chelate complex [(phen)Pd[eta(1),eta(2)-CH(CH(2)SiEt(3))CH(2)C(CO(2)Me)(2)CH(2)CH=CH(2)]](+) [BAr(4)](-) (5), followed by intramolecular carbometalation of 5 to form the palladium cyclopentylmethyl complex trans-[(phen)Pd[CH2CHCH2C(CO2Me)2CH2CHCH2SiEt3](NCAr)]+ [BAr4]- (6), and associative silylation of 6 to release 3 and regenerate 4b.     

Determination of erythrocyte deformability and its correlation to cellular ATP release using microbore tubing with diameters that approximate resistance vessels in vivo

A novel method is described for measuring the deformability of red blood cells (RBCs) in tubing whose diameters approximate forces encountered in vivo. Here, RBCs from rabbits are loaded into a 50 cm section of 75 microm id microbore tubing and connected to a syringe pump. This section of tubing is then connected to a 15 cm section of 25 microm id tubing. As buffer is pumped through the flow system, the RBCs are evacuated from both sections of tubing. However, the inability of the RBCs to move freely through the 25 mirom id section of tubing results in a buildup of cells at the inlet of this portion of tubing. The continued force output by the syringe pump results in a deformation of the RBCs until all of the cells are eventually evacuated from the flow system. It was found that a measurement of the time required to reach half of the maximum pressure (1/2 P(max)) may be used as an indicator of the RBC deformability. For a given sample, a simple buffer results in less time to reach 1/2 P(max) (6.9 +/- 0.2 s) than deformable RBCs (21.6 +/- 0.8 s). To verify that the increased amount of time to reach 1/2 P(max) is indeed due to the RBCs, various hematocrits of an RBC sample were investigated and, as expected, it was found that a 12% RBC hematocrit had a higher 1/2 P(max) value (26.0 s +/- 2.2 s) when compared to a 7% hematocrit (19.1 +/- 0.3 s). In addition, RBCs chemically stiffened with glutaraldehyde were shown to be 25% less deformable than normal RBCs. Finally, a study was performed to examine the relationship between RBC deformability and ATP release and it was found that ATP release increased as a function of RBC deformability. This method greatly simplifies deformability measurements, employing only a syringe pump and microbore tubing, and may lead to a more complete understanding of the physiological significance of erythrocyte deformability.     

What is the nature of polyacetylene neutral and anionic chains HC(2n)H and HC(2n)H(-) (n = 6-12) that have recently been observed?

The optimized geometries, adiabatic electron affinities, and IR-active vibrational frequencies have been predicted for the long linear carbon chains HC(2n)H. The B3LYP density functional combined with the DZP basis set was used in this theoretical study. The computed physical properties are discussed. The predicted electron affinities form a remarkably regular sequence: 1.78 (HC(12)H), 2.08 (HC(14)H), 2.32 (HC(16)H), 2.53 (HC(18)H), 2.69 (HC(20)H), 2.83 (HC(22)H), and 2.95 eV (HC(24)H). The predicted structures display an alternating triple and very short single bond pattern, with the degree of bond alternation significantly less for the radical anions.     

A generic approach to the impurity profiling of drugs using standardised and independent capillary zone electrophoresis methods coupled to electrospray ionisation mass spectrometry

Three standardised, capillary zone electrophoresis-electrospray ionisation mass spectrometry (CZE-ESI-MS) methods were developed for the analysis of six drug candidates and their respective process-related impurities comprising a total of 22 analytes with a range of functional groups and lipophilicities. The selected background electrolyte conditions were found to be: 60/40 v/v 10 mM ammonium formate pH 3.5/organic, 60/40 v/v 10 mM ammonium acetate pH 7.0/organic and 10 mM piperidine, pH 10.5, where the organic solvent is 50/50 v/v methanol/acetonitrile. The coaxial sheath flow consisted of either 0.1% v/v formic acid in 50/50 v/v methanol/water, or 10 mM ammonium acetate in 50/50 v/v methanol/water, depending on the mixture being analysed. Factor analysis and informational theory were used to quantify the orthogonality of the methods and predict their complementarities. The three selected CZE-ESI-MS methods allowed the identification of 21 out of 22 of all the drug candidates and their process-related impurities and provided orthogonality with four established high-performance liquid chromatography-mass spectrometry (HPLC-MS) methods. These methodologies therefore form the basis of a generic approach to impurity profiling of pharmaceutical drug candidates and can be applied with little or no analytical method development, thereby offering significant resource and time savings.     

Electrostatic influence on rotational mobilities of sol-gel-encapsulated solutes by NMR and EPR spectroscopies

The rotational mobilities of small solute molecules encapsulated in tetramethyl orthosilicate (TMOS) sol-gels have been investigated by EPR spectroscopy of encapsulated nitroxide probes and by high-resolution NMR spectroscopic measurements of transferred NOE's (trNOE's), of T(1)'s, and of T(1)'s in the rotating frame (T(1)rho). The two spectroscopic methods are sensitive to motions on different time scales and hence, are nicely complementary. Suites of neutral, positively, and negatively charged nitroxide probes (EPR) and of simple diamagnetic small molecules (NMR) were selected to disclose influences of electrostatic interactions with the sol-gel walls and to probe the presence of multiple populations of molecules in distinct regions of the sol-gel pores. For neutral and negatively charged solute probes, both techniques disclose a single population with a significantly increased average rotational correlation time, which we interpret at least in part as resulting from exchange between free-volume and transiently immobilized surface populations. The electrostatic attraction between cationic probes and the negatively charged sol-gel walls causes the positively charged probes to be more effectively immobilized and/or causes a greater percentage of probes to undergo this transient immobilization. The EPR spectra directly disclose a population of cationic probes which are immobilized on the X-band EPR time scale: tau(c) greater than or approximately equal 10(-7) s. However, NMR measurements of trNOE's and of T(1)rho demonstrate that this population does exchange with the free-volume probes on the slower time scale of NMR. This approach is equally applicable to the study of solutes within other types of confined spaces, as well.     

Hexagonal Si−Ge Class of Semiconducting Alloys Prepared by Using Pressure and Temperature

Multi-anvil and laser-heated diamond anvil methods have been used to subject Ge and Si mixtures to pressures and temperatures of between 12 and 17 GPa and 1500–1800 K, respectively. Synchrotron angle dispersive X-ray diffraction, precession electron diffraction and chemical analysis using electron microscopy, reveal recovery at ambient pressure of hexagonal Ge−Si solid solutions (P6₃/mmc). Taken together, the multi-anvil and diamond anvil results reveal that hexagonal solid solutions can be prepared for all Ge−Si compositions. This hexagonal class of solid solutions constitutes a significant expansion of the bulk Ge−Si solid solution family, and is of interest for optoelectronic applications.     

A simple,efficient, regioselective and one-pot preparation of N-hydroxy- and N–O-protected hydroxyindoles via cycloaddition of nitrosoarenes with alkynes. Synthetic scope,applications and novel by-products

The thermal reaction between nitrosoarenes and alkynes under alkylating conditions produces N-alkoxyindoles as the major products in moderate to good yields and excellent regioselectivity. Various electrophiles are used affording different N–O-protected hydroxyindoles in a multi-component fashion. Privileged acetylenic substrates used in reactions with substituted nitrosoarenes are arylalkynes or propiolates. Potentially bioactive compounds and other classes of highly functionalizable indole products were prepared. Reactions between o-carbomethoxy-nitrosoarenes and arylacetylenes provided tricyclic compounds containing an acylaziridine indoline skeleton.