Structure and catalytic activity of some soluble polyethylene glycol-peptide conjugates

Soluble catalysts for the Juliá-Colonna asymmetric epoxidation reaction have been constructed in three different ways, using NH₂-PEG-OMe as the support system: suitable solvents have been identified and it is shown that the degree of helicity of the conjugates correlates with the extent of conversion and (to a lesser extent) the enantioselectivity of epoxidation.     

Asymmetric hydrogenation of alkyl(vinyl)thioethers: a promising approach to α-chiral thioethers

This paper describes the enantioselective hydrogenation of vinylthioethers. We show that thioether derivatives of maleic esters can be hydrogenated with full conversion and up to 60% ee, and that α-thioether cinnamic acids can be hydrogenated in 51% ee with modest conversion.     

Will the real Kasner metric please stand up

The Kasner metric is one of the more widely studied metrics. Its usefulness for the construction of cosmological models and its utility for certain studies of elementary particles has made it particularly attractive for exploitation. Because of its simplicity it has been rediscovered many times and is itself very closely related to metrics given several years earlier by Weyl, Levi-Civita, and Wilson. The form in which Kasner presented it has been virtually forgotten in favor of the dynamic form of the synchronous Bianchi I metric. Kasner metrics may be either static or dynamic. To each static metric there is acognate dynamic metric andvice versa, and the two are related by a complex coordinate transformation. The characterization of a Kasner metric is by means of a set of parameters. It is possible for these to take on complex values with interesting consequences, In the discussion a curious error in the original paper is rectified and some new Kasner metrics are presented. The discussion throughout is confined to the vacuum metric.     

Preservation mechanisms of trehalose in food and biosystems

The stability or shelf-life of food and biomaterials has always been a critical issue in the food and pharmaceutical industry. Trehalose (alpha-D-glucopyranosyl-alpha-D-glucopyranoside), a non-reducing diglucose sugar found in nature, confers to certain plant and animal cells the ability to survive dehydration for decades and to restore activity soon after rehydration. The interaction between trehalose and cell membranes or proteins, however, remains a debated subject, and a significant amount of work has been done to elucidate the mechanisms resulting in this unique behavior of preservation. This study shows how an interfacial phenomena approach has led to the use of trehalose as an excipient during freeze drying of a variety of products in the pharmaceutical industry. It also suggests opportunities as an ingredient for dried and processed food, as well as a non-toxic cryoprotectant of vaccines and organs for surgical transplants.     

Accuracy and long-term reproducibility of lead isotopic measurements by multiple-collector inductively coupled plasma mass spectrometry using an external method for correction of mass discrimination

The precision of isotopic measurements of Pb by thermal ionization mass spectrometry (TIMS) is limited by the fact that this element does not possess an invariant isotope ratio that can be used for the correction of mass fractionation by internal normalization. Multiple-collector inductively coupled plasma mass spectrometry (MC-ICPMS) can overcome this limitation, because with plasma ionization, elements with overlapping mass ranges are thought to display identical mass discrimination. With respect to Pb, this can be exploited by the addition of Tl to the sample solutions; the mass discrimination factor obtained for Tl can then be used for the correction of the measured Pb isotope ratios. In this article we present the results of a detailed study that investigates the accuracy and precision of such an external correction technique for mass discrimination based upon the results of multiple analyses of a mixed standard solution of NIST SRM-981 Pb and SRM-997 Tl. Our data indicate that normalization of the Pb isotope ratios to the certified isotopic composition of SRM-997 Tl produces Pb isotopic results that are significantly lower than recently published reference values by TIMS. This systematic offset can be eliminated by renormalization of the Pb data to a different Tl isotopic composition to obtain an empirically determined mass discrimination factor for Pb that generates accurate results. It is furthermore shown that a linear law is least suited for the correction of mass discrimination, whereas a power or exponential law function provide significantly more accurate and precise results. In detail, it appears that a power law may provide the most appropriate correction procedure, because the corrected Pb isotope ratios display less residual correlations with mass discrimination compared to the exponentially corrected data. Using an exponential or power law correction our results, obtained over a period of over seven months, display a precision (2σ) of better than 60 parts per million (ppm) for ²⁰⁸Pb/²⁰⁶Pb and ²⁰⁷Pb/²⁰⁶Pb and of better than 350 ppm for ²⁰⁶Pb/²⁰⁴Pb, ²⁰⁷Pb/²⁰⁴Pb/²⁰⁴Pb, and ²⁰⁸Pb/²⁰⁴Pb. This represents a significant improvement compared to conventional TIMS techniques and demonstrates the potential of MC-ICPMS for routine, high-precision measurements of Pb isotopic compositions.     

High-throughput purification of combinatorial libraries I: a high-throughput purification system using an accelerated retention window approach

We have developed a high-throughput purification system to purify combinatorial libraries at a 50-100-mg scale with a throughput of 250 samples/instrument/day. We applied an accelerated retention window method to shorten the purification time and targeted one fraction per injection to simplify data tracking, lower QC workload, and simplify the postpurification processing. First, we determined the accurate retention time and peak height for all compounds using an eight-channel parallel LC/UV/MS system, and calculated the specific preparative HPLC conditions for individual compounds. The preparative HPLC conditions include the compound-specific gradient segment for individual compounds with a fixed gradient slope and the compound-specific UV or ELSD threshold for triggering a fraction collection device. A unique solvent composition or solvent strength was programmed for each compound in the preparative HPLC in order to elute all compounds at the same target time. Considering the possible deviation of the predicted retention time, a 1-min window around the target time was set to collect peaks above a threshold based on UV or ELSD detection. Dual column preparative instruments were used to maximize throughput. We have purified more than 500 000 druglike compounds using this system in the past 3 years. We report various components of this high-throughput purification system and some of our purification results.     

A convenient two-step synthesis of 6-methylenesubstituted-4-trichloromethyl-2-methylsulfanyl pyrimidines

This work reports a two-step synthetic strategy to obtain a series of 6-methylenesubstituted-4-trichloromethyl-2-methylsulfanylpyrimidines from the cyclization of 5-bromo-4-methoxy-1,1,1-trichloro-pent-3-en-2-ones with 2-methyl-2-pseudothiourea sulfate, followed by nucleophilic substitution of 6-bromomethyl-4-trichloromethyl-2-methylsulfanylpyrimidine with a series of nucleophiles. Alternative strategies to obtain 6-halomethyl-4-trichloro[fluoro]methyl-2-methylsulfanyl pyrimidines have been addressed.     

Electrostatics of phosphatidic acid monolayers: Insights from computer simulations

In this paper, we argue that many of the fascinating electrostatic effects that take place in amphiphilic systems are strongly related to the particular organization of the oxygen atoms within each individual molecule. In particular, we focus on two effects: charge inversion and dielectric overscreening. For that purpose, we present molecular dynamics simulations of phosphatidic acid (DMPA²⁻) in the presence of divalent counterions. Our results show that the many oxygens present in DMPA²⁻ cooperatively create strong binding sites for counterions, which in some cases lead to charge inversion. We also present an analysis of the role of interfacial water and relate our analysis to the phenomenon of dielectric overscreening. Several experimental implications are discussed in the conclusions.     

OPTICAL AND THERMAL CHARACTERIZATION OF NATURAL (Sepia officinalis) MELANIN

Abstract The optical properties and the thermal diffusivity of natural cuttlefish ( Sepia officinalis ) melanin have been measured. The optical absorption and scattering properties of melanin particles were determined at 580 nm and 633 nm, using photometric and photothermal techniques. For the photometric studies, the absorption and the transport scattering coefficients were determined from the measurements of diffuse reflectance and transmittance. The scattering anisotropy was obtained from an additional measurement of the total attenuation coefficient and independently obtained by goniometry. For photothermal studies, pulsed photothermal radiometry was used to deduce the absorption and transport scattering coefficients via a model based on optical diffusion theory. Pulsed photothermal radiometry was also used to provide the thermal diffusivity of solid melanin pressed pellets.