Methotrexate analogs. 7. Synthesis of two higher homologs and a positional isomer of methotrexate diethyl ester as potential antitumor agents

Analogs of methotrexate diethyl ester ( 1 ) were prepared, in which the distances separating the ester functions from each other and from the carboxamide function of the p-aminobenzoate moiety were varied via the use of methylene groups as “spacers”. The diethyl esters 3 and 4 , with D,L-α-aminoadipate and D,L-α-aminopimelate side chains in place of L-glutamate, displayed approximately the same order of activity as compound 1 against bacterial and mammalian cells in culture, and were inhibitors of the enzyme dihydrofolate reductase. When given intraperitoneally to L1210 1eukemic mice at a dose of 120 mg./kg. q3d 1,4,7, compound 4 produced a 67% increase in survival and no evidence of toxicity, whereas methotrexate diethyl ester ( 1 ) gave a 44% increase in survival at a dose of 45 mg./kg. q3d 1,4,7 but was toxic at higher doses. The positional isomer 2 was inactive.     

Novel electrophoresis mechanism based on synchronous alternating drag perturbation

We present a novel means of transporting molecules in solution by applying a zero-time-average alternating motive force to the molecules, and perturbing the molecular drag coefficient synchronously with the applied force, thus causing a net drift in a direction determined by the phase of the alternating drag perturbation relative to the alternating force. We apply an electrophoretic form of the method to transport and concentrate DNA in a gel, such that all molecules migrate on average away from the nearest electrode and toward a central region. Since an electrode does not occupy this central region, this method presents the possibility of transporting and focusing DNA and other charged molecules in regions free from electrodes and the associated electrochemistry.     

Chemical and biological studies on dihydro-s-triazines. XVII. Modifications of the three-component synthesis favoring the formation of 2-guanidino-4-methylquinazoline byproducts

A modified three-component reaction of arylamines, cyanoguanidine, and acetone is described, wherein formation of anomalous guanidinoquinazoline byproducts is greatly enhanced at the expense of the normal dihydro-s-triazines. Four new guanidinoquinazolines and four new dihydro-s-triazines were synthesized via this modification, starting from 2,4-, 2,5-, 3,4-, and 3,5-dimethoxyaniline. The guanidinoquinazoline to dihydro-s-triazine ratio was much higher with 3,4- and 3,5-dimethoxyaniline than with 2,4-dimethoxyaniline. 2,5-Dimethoxyaniline gave an unexpectedly low yield of guanidinoquinazoline, apparently because of steric hindrance. The modified three-component synthesis was also examined in detail with 2-naphthylamine.     

Phosphorus donors in highly strained silicon

The hyperfine interaction of phosphorus donors in fully strained Si thin films grown on virtual Si(1-x)Ge(x) substrates with x< or =0.3 is determined via electrically detected magnetic resonance. For highly strained epilayers, hyperfine interactions as low as 0.8 mT are observed, significantly below the limit predicted by valley repopulation. Within a Green's function approach, density functional theory shows that the additional reduction is caused by the volume increase of the unit cell and a relaxation of the Si ligands of the donor.     

Studying variations in the PCDD/PCDF profile across various food products using multivariate statistical analysis

Polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF) are widely recognized by the scientific community as persistent organic pollutants due to their toxicity and adverse effects on wildlife and human health. The actual regulation dedicated to the monitoring of dioxins in food is based on the measurement of 17 congener concentrations. The final result is reported as a toxic equivalent value that takes into account the relative toxicity of each congener. This procedure can minimize the qualitative information available from the abundances of each PCDD/PCDF congener: the characteristic contamination profile of the sample. Multivariate statistical techniques, such as principal component analysis (PCA) or linear discriminant analysis (LDA), represent an interesting way to investigate this qualitative information. Nevertheless, they have only been applied to the analysis of contamination data from food products and biological matrices infrequently. The objective of the present study was to analyze a large data set from dioxin analyses performed on various food products of animal origin. The results demonstrate the existence of differences in congener-specific patterns between the analyzed samples. Variability was first demonstrated in terms of the food type (fish, meat, milk, fatty products). Then a variability was observed that was related to the specific animal species for meat and milk samples (bovine, ovine, porcine, caprine and poultry). Some practical applications of these results are discussed. The origin(s) of the observed differences, as well as their significance, now remain to be investigated, both in terms of environmental factors and transfer through living organisms. A better knowledge of the relation between a contamination profile and its specific source and/or food product should be of great interest to scientists working in the fields of contaminant analysis, toxicology and metabolism, as well as to regulatory bodies and risk assessors in charge of final decisions regarding the eventual hazards associated with theses substances.     

Extractive electrospray ionization for direct analysis of undiluted urine, milk and other complex mixtures without sample preparation

On-line droplet-droplet extraction occurs when a sample spray intersects a reagent electrospray; this allows continuous analysis of trace amounts of compounds directly in complex matrices including undiluted urine, milk and polluted water over extended periods of time.     

High-pressure NMR study of water exchange on magnetic resonance imaging contrast agents

Abstract

The knowledge of water exchange reaction mechanism in aqueous solutions of Gd³⁺ polyaminocarboxylates is important for the understanding of the relatively slow water exchange rates measured for these complexes. Variable ressure measurements show a change of mechanism from associatively activated on [Gd(H₂O)₈]³⁺ and [Gd(PDTA)(H₂O₂)₂]^? to probably limiting dissociative on the MRI contrast agents [Gd(DOTA)(H₂O)]^?, [Gd(DTPA)(H₂O)]^2? and [Gd(DTPA-BMA)(H₂O)].