A practical oxidative method for the cleavage of hydrazide N[bond]N bonds

The selective N-oxidation of the most nucleophilic amino nitrogen atom in hydrazides is central to the development of an unprecedented methodology for the cleavage of their N[bond]N bonds under oxidative conditions. Treatment of a series of hydrazides 1-9 with peracids such as magnesium monoperoxyphtalate hexahydrate (MMPP.6 H(2)O) or meta-chloroperbenzoic acid (m-CPBA) afforded the corresponding amides 10-16 in good-to-excellent yields (80-92 %). The extension of the methodology to carbamate-like substrates such as 17 and 18 was also investigated, but in this case the process is synthetically useless in view of the low yields observed of carbamates 19 and 20 (approximately 15 %). Experiments carried out with equivalent amounts of oxidant produced nitrones, such as 26, proceeding from the dialkylamino moiety, and (1)H NMR experiments indicated that this product is formed by fast conversion of the parent hydrazide, without detection of the expected hydrazide N-oxides. In addition, the over oxidation of 26 into nitronate 25 proceeds through an unknown intermediate. This oxidative N[bond]N bond cleavage by peracids is an alternative method for the deamination of hydrazides, and constitutes the only solution compatible with substrates carrying functionalities sensitive to reducing conditions.     

Intracellular oxidation of dipeptides. Base-promoted elimination from N-halodipeptides to 2-[N-alkyl-N-(2-N-alkylimino-2-alkyl-ethanoyl)amino]-2,2-dialkylethanoic acids

One of the possible ways of intracellular oxidation of peptides is via the formation of the corresponding (N-X)-dipeptides, that then undergo base-promoted elimination to yield intermediate 2-[N-alkyl-N-(2-N-alkylimino-2-alkylethanoyl)amino]-2,2-dialkylethanoic acids, which subsequently hydrolyze. Such an elimination process is general-base catalyzed, with Br?nsted beta values ranging from 0.26 to 0.31, which suggests an essentially constant degree of proton transfer at the TS. For (N-X)-dipeptides, the ratio k(N-Br)/k(N-Cl) ranges from 2.5 to 15, suggesting a structural dependence of the degree of N-X bond breaking at the TS. The values of beta and k(N-Br)/k(N-Cl) support a concerted asynchronous A(xh)D(H)D(N) mechanism, its TS changing from reactant-like to slightly nitrenium-like depending on the structure of the starting dipeptide. As a consequence of the antiperiplanarity requirements of the reaction, the steric interaction between the leaving group and the substituent on the C bearing the H to be eliminated controls the reaction rate. Such steric interaction is rather important, as indicated by the steric crossed-interaction coefficient (p(ssy') = 0.33). Semiempirical calculations show that bulky substituents in the vicinity of the reaction center imply additional energy requirements for the system to achieve the antiperiplanarity needed at the TS for the reaction to proceed. From the observations reported it follows that (N-X)-dipeptides lose their oxidizing power more readily than analogous (N-X)-amino acids or (N-X)-amines, opening a possible pathway to lessen intracellular halogen-based oxidative stress.     

Atomic spectrometry and flow injection analysis: a synergic combination

The combination of flow-injection techniques with atomic spectrometry (flame atomic absorption and emission spectrometry and inductively-coupled plasma/atomic emission spectrometry) is reviewed, with particular reference to the more recent contributions. The considerable growth in the number of directly couple pre-concentration and matrix isolation is noted, together with the increasing number of reports of indirect methods for metals, inorganic anions and even drug molecules. Many developments are motivated by a desire to increase the performance of the spectrometry over that obtained with conventional methods of sample introduction. Conflicting statements concerning the possible benefits of reduced uptake rate, of air compensation and of peak-area measurement are examined critically. The conflicting requirements of obtaining freedom from stable-compound interferences coupled with god detection limits are discussed, as are means of obtaining the best detection limits. Modifications to nebuliser and spray-chamber design are suggested for maximising peak height (to obtain detection limits) and for working with reduced uptake rates (to reduce stable-compound interferences in flame-based spectrometries). The single well-stirred tank model is used to model nebuliser response and results are presented for the flow-injection behaviour of a Philips Scientific SP9 instrument under conditions of low flow rate which show reasonable agreement with the model. With the instrument, the best detection limits are obtained on the basis of peak-height measurements at the flow rate producing maximum signal-to-noise ratio.     

Permanently oriented antibody immobilization for digoxin determination with a flow-through fluoroimmunosensor

This paper reports a new flow-through fluoroimmunosensor, the function of which is based on antibodies immobilized on an inmunoreactor of controlled-pore glass (CPG), for determination of digoxin, used in the treatment of congestive heart failure and artery disease. The immunosensor has a detection limit of 1.20 microg L(-1) and provides high reproducibility (RSD=4.5% for a concentration of 0.0025 mg L(-1), and RSD=6.7% for 0.01 mg L(-1)). The optimum working concentration range was found to be 1.2 x 10(-3)-4.0 x 10(-2) mg L(-1). The lifetime of the immunosensor was about 50 immunoassays; if stored unused its lifetime can be extended to three months. A sample speed of about 10-12 samples per hour can be attained. Possible interference from substances with structures similar to digoxin (morphine, heroin, tebaine, codeine, pentazocine and narcotine) was investigated. No cross-reactivity was seen at the highest digoxin: interferent ratio studied (1:100). The proposed fluoroimmunosensor was successfully used to determine digoxin concentrations in human serum samples.     

Analytical method for the representation of atoms-in-molecules densities

We present analytic refinements and applications of the deformed atomic densities method [Fernández Rico, J.; López, R.; Ramírez, G. J Chem Phys 1999, 110, 4213-4220]. In this method the molecular electron density is partitioned into atomic contributions, using a minimal deformation criterion for every two-center distributions, and the atomic contributions are expanded in spherical harmonics times radial factors. Recurrence relations are introduced for the partition of the two-center distributions, and the final radial factors are expressed in terms of exponential functions multiplied by polynomials. Algorithms for the practical implementation are developed and tested, showing excellent performances. The usefulness of the present approach is illustrated by examining its ability to describe the deformation of atoms in different molecular environments and the relationship between these atomic densities and some chemical properties of molecules.     

Enantioselective hydrolysis of nitriles and amides using an immobilised whole cell system

An immobilised whole cell catalyst SP361 has been shown to hydrolyse a range of 2-alkyl arylacetonitriles 1a–3a and amides 2b, 3b with good to excellent enantioselectivity. The absolute configuration of the derived amides and/or carboxylic acids shows remarkable changes according to the structure of the nitrite substrate.     

Development of a fluoroimmunosensor for theophylline using immobilised antibody

A flowthrough theophylline fluoroimmunosensor with an antibody covalently immobilised on a solid support has been developed. The immobilisation technique proposed in this paper used Protein-A on control pore glass (Protein A-CPG) in an immunoreactor and dimethylsuberimidate as a cross-linking agent. Several supports and cross-linking reagents were tested in order to obtain oriented immobilisation and thus efficiency of the immunological reaction and reusability of the immunosensor. The immunosensor performance characteristics were established. The precision expressed as RSD, was 1.6%; the detection limit was 3 mug l(-1); the immunoreactor lifetime was established in 80 assays and there were no interferences with structurally similar compounds such as aminophylline, dihydroxypropyltheophylline and caffeine in the determination of the analyte. This fluoroimmunosensor was applied to determine theophylline in human serum samples from patients of the Puerta de Hierro Hospital in Madrid. The results obtained show that there are no significant differences between the proposed immunosensor and the high-pressure liquid chromatographic method with UV detection used by the Hospital, thus demonstrating the validity of the method.     

Analysis of herbicide residues in cereals, fruits and vegetables

The determination of herbicide residues in cereals, fruits and vegetables by chromatographic methods is reviewed. The principal chemical groups of herbicides, like phenoxyacids, benzonitriles, ureas, triazines, dinitroanilines, chloroacetamides, carbamates, uracils, glyphosate and bipyridylium compounds, are considered. This review briefly provides some basic information on food sample extraction, clean-up, derivatization and determination of herbicide residues.     

Spirolactams as conformationally restricted pseudopeptides: synthesis and conformational analysis

The synthesis of 1-(tert-butoxycarbonyl)-7-[1-(tert-butoxycarbonyl)-3-methylbutyl]-6-oxo-1,7-diazaspiro[4.5]decanes (S,S)-1a and (S,R)-1b is described. Derivatives 17a,b and 19a are prepared for use in peptide synthesis as constrained surrogates of the Pro-Leu and Gly-Leu dipeptides. The Ac-[Gly-Leu]-Met-NH(2) derivatives (S,S,S)-2a and (S,R,S)-2b, with the tripeptidic C-terminal region present in tachykinins, are also synthesized. Conformational analyses of these tripetide analogues by NMR experiments and molecular modeling calculations show that both (S,S,S)-2a and (S,R,S)-2b epimers are gamma-turn/distorted type II beta-turn mimetics.     

Generation and mid-IR measurement of a gas-phase to predict security parameters of aviation jet fuel

The worldwide use of kerosene as aviation jet fuel makes its safety considerations of most importance not only for aircraft security but for the workers’ health (chronic and/or acute exposure). As most kerosene risks come from its vapours, this work focuses on predicting seven characteristics (flash point, freezing point, % of aromatics and four distillation points) which assess its potential hazards. Two experimental devices were implemented in order to, first, generate a kerosene vapour phase and, then, to measure its mid-IR spectrum. All the working conditions required to generate the gas phase were optimised either in a univariate or a multivariate (SIMPLEX) approach. Next, multivariate prediction models were deployed using partial least squares regression and it was found that both the average prediction errors and precision parameters were satisfactory, almost always well below the reference figures.