Development of a dual cell, flow-injection sample holder, and NMR probe for comparative ligand-binding studies

NMR based ligand screening is becoming increasingly important for the very early stages of drug discovery. We have proposed a method that makes highly efficient use of a single sample of a scarce target, or one with poor or limited solubility, to screen an entire compound library. This comparative method is based on immobilizing the target for the screening procedure. In order to support the method, a dual cell, flow injection probe with a single receiver coil has been constructed. The flow injection probe has been mated to a single high performance pump and sample handling system to enable the automated analysis of large numbers of compound mixes for binding to the target. The probe, having an 8 mm 1H/2H dual tuned coil and triple axis gradients, is easily shimmed and yields NMR spectra of comparable quality to a standard 5 mm high-resolution probe. The lineshape in the presence of a solid support is identical to that in glass NMR tubes in a 5 mm probe. Control spectra of each cell are identical and well separated, while ligand binding in a complex mixture can be readily detected in 20-30 min, thus paving the way for use of the probe for actual drug discovery efforts.     

Funktionen vom Betrage Eins in abstrakten Hardy-Algebren

Ohne Zusammenfassung     

Alkali Metal- and Ammonium Picrate Extraction and Complex Forming Capabilities of d-Glucose and d-Mannose-based Lariat Ethers

The alkali metal- and ammonium picrate extracting ability of d-glucose- and d-mannose-based 15-crown-5 ethers and related lariat ethers was investigated in dichloromethane – water system. A heteroatom was waried in the crown ether containing a 4,6-O-benzylidene-α-d-glucopyranoside unit 6, (X=O), 2 (X=S) and 8a (X=NH). Extracting ability of the latter species (8a) was excellent (97–99%) in regard of all cations (Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺ and NH₄⁺) examined, it was not, howewer, selective. Introduction of a side arm on the nitrogen atom of 8a decreased the extracting ability, but increased the selectivity. In this series of compounds (8b–f, 4), 4 with a pyridylethyl substituent allowed the extraction of sodium picrate in 72%. The glucose-based macrocycles 8a, 8e and 8f formed a stronger complex with the cations examined than the mannose-based analogues 9a, 9e and 9f, that can be explained by the all-gauche conformation of the former ones. It was pointed out that in the case of crowns with tertiary amine moieties, the basicity increases the quantity of the picrates extracted. According to complex forming measurements by FAB-MS, the best sodium ion selectivity was achieved by the γ-hydroxypropyl substituted lariat ether (8e). Possible structures of the complexes formed by the two types of monosacharides with sodium cation were evaluated by molecule modelling calculations.     

Sum frequency generation studies at poly(ethylene terephthalate)/silane interfaces: hydrogen bond formation and molecular conformation determination

To better understand the effects of interfacial molecular orientation on adhesion to plastics, the interfaces between poly(ethylene terephthalate) (PET) and different silane coupling agents were probed using sum frequency generation (SFG) vibrational spectroscopy. The polymer/air interface was dominated by the ester carbonyl, methylene, and phenyl groups. Upon contacting the PET film with the amino-functional silane 3-aminopropyltrimethoxysilane (ATMS), the ester carbonyl stretch shifted to a lower energy indicating the formation of hydrogen bonds between the polymer surface and the silane molecules. This shift was not observed when silanes that contained no hydrogen bond donors, such as (3-glycidoxypropyl)-trimethoxysilane and n-butyltrimethoxysilane, were placed into contact with the PET surface. Further evidence of silane ordering at the interface was observed as vibrational peaks attributed to the C-H stretching of the silane methoxy headgroups dominated the PET/silane spectra. It was determined that the conformation of the ATMS molecules at the interface was such that the amino endgroups were oriented toward the interface while the methoxy headgroups were directed toward the silane bulk.     

Comparison of chromium and nickel uptake of plants grown in different soils

The chromium and nickel uptake of ryegrass has been examined in pot experiments in extremely different soils, poor sandy and fertile black chernozem. The effect of calcium carbonate doses and nitrogen supply on heavy metal uptake of the plant has been studied for chromium and nickel loadings (0–100 mg/kg Cr³⁺ or Ni²⁺) applied as inorganic salts. The ability to uptake Cr³⁺ and Ni²⁺ differs significantly and is highly affected by the characteristics of soils, and depends on the metal investigated. The heavy metal uptake of the plant differs significantly in acid, colloid deficient sandy soils; while artificial chromium contamination did not modify the dry-matter production in the pots in either soil, a large quantity of nickel reduced the yields significantly. Nitrogen application did not change significantly the uptake of heavy metals. Lime application reduced the Ni²⁺ uptake of plants considerably, especially in sandy soil. In case of a calcium carbonate addition the dry-matter production of the plant was not affected by nickel. In chernozem soil the effect of lime application – i.e., the reduction of nickel uptake – was of a lesser degree. The significantly lesser Cr³⁺ uptake was further limited by a calcium carbonate application for both soils studied. A graphic presentation of these effects is given.     

On-line delta(18)O measurement of organic and inorganic substances

A method for the automated sample conversion and on-line oxygen isotope ratio (delta(18)O) determination for organic and inorganic substances is presented. The samples are pyrolytically decomposed at 1400 degrees C in the presence of nickelized graphite. With the system presented organic as well as inorganic samples such as nitrates, sulphates and phosphates of 50-100 &mgr;g O can be analyzed for their delta(18)O values with a standard deviation usually better than 0.5 per thousand. Additionally, carbon isotope ratios of organic substances and nitrogen isotope ratios of inorganic nitrogenous compounds are available in the same sample run. Data for international and some inter-laboratory reference materials are presented to show the accuracy and reliability of the method. The effect of some additives on the CO yield was checked for substances which do not pyrolyze completely. Copyright 1999 John Wiley & Sons, Ltd.     

Synthesis of Large Platelets of Egyptian Blue via Pseudomorphosis after NaRUB-18

A colored platy substrate with appreciable aspect ratio can improve the hiding power while extending the color range of pearlescent pigments. One of the oldest synthetic pigments, Egyptian blue, possesses a layered structure and a platy morphology, making it a promising colored substrate for pearlescent pigments, which derives its blue color from Cu^II. Unfortunately, existing synthesis routes are either not technically benign or lack the natural platy morphology. Here, we introduce a new synthesis route starting with large, square-shaped platelets of a synthetic layered sodium silicate (NaRUB-18). As evidenced by Rietveld refinement and scanning electron microscopy, NaRUB-18 can be converted with conservation of this attractive morphology (pseudomorphosis) into Egyptian blue.     

How to make mathematics relevant to first-year engineering students: perceptions of students on student-produced resources

Many approaches to make mathematics relevant to first-year engineering students have been described. These include teaching practical engineering applications, or a close collaboration between engineering and mathematics teaching staff on unit design and teaching. In this paper, we report on a novel approach where we gave higher year engineering and multimedia students the task to ‘make maths relevant’ for first-year students. This approach is novel as we moved away from the traditional thinking that staff should produce these resources to students producing the same. These students have more recently undertaken first-year mathematical study themselves and can also provide a more mature student perspective to the task than first-year students. Two final-year engineering students and three final-year multimedia students worked on this project over the Australian summer term and produced two animated videos showing where concepts taught in first-year mathematics are applied by professional engineers. It is this student perspective on how to make mathematics relevant to first-year students that we investigate in this paper. We analyse interviews with higher year students as well as focus groups with first-year students who had been shown the videos in class, with a focus on answering the following three research questions: (1) How would students demonstrate the relevance of mathematics in engineering? (2) What are first-year students' views on the resources produced for them? (3) Who should produce resources to demonstrate the relevance of mathematics? There seemed to be some disagreement between first- and final-year students as to how the importance of mathematics should be demonstrated in a video. We therefore argue that it should ideally be a collaboration between higher year students and first-year students, with advice from lecturers, to produce such resources.