Low-conductivity buffers for high-sensitivity NMR measurements

The sensitivity of nuclear magnetic resonance (NMR) probes, especially the recently introduced cryogenic probes, can be substantially reduced by the electrical noise generated by conductive samples. In particular, samples of biological macromolecules, which usually contain salts to keep the pH constant and to prevent aggregation, can experience a significant reduction in sensitivity. So far this dependence has forced researchers to minimize the salt concentrations in their samples. Here we demonstrate that the decisive factor is not the salt concentration itself but the conductivity which is a function of both the concentration and the mobility of the ions in solution. We show that by choosing buffers with low ionic mobility, the sample conductivity can be dramatically reduced and the sensitivity substantially enhanced compared to the same measurement with an equal concentration of a standard NMR buffer such as phosphate. We further show that the highest sensitivity gain of one buffer over another buffer is equal to the square root of the ratio of their ion mobilities and describe a simple method to evaluate the effect of a certain buffer on the sensitivity.     

Chiral amplification by polypeptides and its relevance to prebiotic catalysis

Polyleucine prepared from scalemic Leu-NCA monomers, shows high chiral amplification in the Julia-Colonna epoxidation of chalcone.     

The isomerisation of (Z)-3-[2H1]-phenylprop-2-enone as a measure of the rate of hydroperoxide addition in Weitz-Scheffer and Julia-Colonna epoxidations

(Z)-3-[2H1]-Phenylprop-2-enone is isomerised by hydroperoxide to an equimolar mixture of the (Z)- and (E)-isomers prior to epoxidation. Poly-(L)-leucine (10 mole %) accelerates the addition of hydroperoxide by an order of magnitude and sequesters hydroperoxide from THF.     

Predicting the efficiency of UAG translational stop signal through studies of physicochemical properties of its composite mono- and dinucleotides

In this study, we explored the problem of predicting the UAG stop-codon read-through efficiency. The reported nucleotide sequences were first converted into physicochemical property vectors before being presented to a machine learning algorithm. Two sets of physicochemical properties were applied: one for mononucleosides (in terms of steric bulk, hydrophobicity and electronics) and another for dinucleotides. To the best of our knowledge, this is the first report of how dinucleotides are converted into principle components derived from NMR chemical shift data. A few efficiency prediction models were then derived and a comparison between mononucleoside and dinucleotide-based models was shown. In the derived models, the coefficients of these property based predictors lend themselves to bio-physical interpretations, an advantage which is demonstrated in this study via a prediction model based on the steric bulk factor. Although it is quite simple, the steric bulk factor model explained well the effect of sequence variations surrounding the amber stop codon and the tRNA bearing UCCU anticodon. We further proposed new alternatives at position -1 and +4 of a UAG stop codon sequence to enhance the readthrough efficiency. This research may contribute to a better understanding of the readthrough mechanisms and may also help to study the normal translation termination process.     

Use of design of experiments to optimize high-throughput semipreparative LC and LC/MS methods

This paper describes an investigation into decreasing the run time for high-throughput semipreparative RP-HPLC methods without compromising the resolution. Experimental design was used to devise a small set of experiments in which factors, including solvent flow rate, solvent/column temperature, at-column dilution, and run time were varied systematically. The results were analyzed by means of multiple regression and partial least squares to generate a model relating the factors to the results, showing which factors are important. The model was then used to determine the optimal conditions.     

Synthesis of azacridone A

[reaction: see text] The first total synthesis of the only known naturally occurring azaacridone alkaloid (1) has been achieved in 10 steps from phloroglucinol. A variety of ortholithiation reactions are described, and a method for overcoming the originally unfavorable regiochemistry of one of them is provided.     

Macroporous germanium by electrochemical deposition

Germanium is electrodeposited in a template formed from a dried suspension of silica spheres. The germanium completely fills the pores of the silica matrix. The semiconductor, as deposited, is amorphous but can be crystallized by annealing. Selective dissolution of the silica template gives a macroporous germanium-air sphere matrix, which offers interesting possibilities for photonic applications.     

Nucleotide oxidation mediated by naphthalimide excited states with covalently attached viologen cosensitizers

The ground- and excited-state interactions of polymethylene-linked 1,8-naphthalimide-viologen dyads with calf-thymus DNA have been investigated. By virtue of the covalently attached viologen, the compounds represent the first example of linked chromophore/cosensitizer systems in the photooxidation of duplex DNA. The compounds associate strongly with DNA. Analysis of ground-state spectral changes yield binding constants of 0.7-2.5 x 10(6) M-1. Upon 355 nm pulsed irradiation of the compounds in the presence of calf-thymus DNA, reduced viologen is observed within the laser pulse. Photoproducts are not observed on this time scale in the absence of DNA. Since ground-state bleaching of the naphthalimide was not observed, the results suggest that DNA nucleobases are the species being oxidized. The quantum efficiency of radical production increases with the extent of binding to DNA. Under conditions where the compounds are bound predominantly to DNA, the quantum efficiencies were found to range from 0.02 to 0.03. Although small, the values represent a substantial increase in charge-separation yield compared to 1,8-naphthalimide compounds that lack the covalently attached viologen. The mechanism of radical production and effect of number of intervening methylenes are discussed.     

Kilohertz linewidth from frequency-stabilized mid-infrared quantum cascade lasers

Frequency stabilization of mid-IR quantum cascade (QC) lasers to the kilohertz level has been accomplished by use of electronic servo techniques. With this active feedback, an 8.5-microm QC distributed-feedback laser is locked to the side of a rovibrational resonance of nitrous oxide (N(2) O) at 1176.61cm (-1) . A stabilized frequency-noise spectral density of 42Hz/ radicalHz has been measured at 100 kHz; the calculated laser linewidth is 12 kHz.