Electron spin resonance detection of radiosterilization of pharmaceuticals: application to four nitrofurans

The detection and dosimetry of radiosterilization of pharmaceuticals is a growing concern to numerous government regulatory agencies worldwide. In the absence of suitable detection methods, attention was focused on electron spin resonance (ESR) spectrometry. This paper reports experimental data on ESR dosimetry of irradiated nitrofurans (nitrofurantoin, nifuroxazide, nifurzide and nifurtoinol). Whereas the ESR spectrum of a non-irradiated sample shows no signal, a signal, that is dependent on the irradiation dose is observed with irradiated samples. The number of free radicals was calculated by comparing the second integral from radiosterilized samples and a Bruker strong pitch reference; the values were in the range 1.1 x 10(18)-1.5 x 10(19) radicals mol-1 (G = 0.003-0.03). In addition to qualitative detection, ESR spectrometry can be used for dose determination. When a bi-exponential function is applied to the variation of the peak-to-peak amplitude versus dose, the function correlates well with the data. However, an exponential function, easier to use than a bi-exponential function, will probably be sufficient for dose determination by retrospective dosimetry. Decay of radicals upon storage was modelled using a bi-exponential function. From this, the time limit from the irradiation (25 kGy) for identification of irradiated nitrofurans by ESR can be evaluated. With regard to the commercial aspects of drugs, radicals should be detected up to 2 years after irradiation. The kinetic decrease makes discrimination between irradiated and non-irradiated nitrofurans possible even after storage for up to 2 years, except for nifurtoinol.     

Synthesis of isoxazolo[4,5-d]pyridazin-4(5H)-ones and 4-acyl-5-hydroxy-3(2H)-pyridazinones

The title compounds were prepared from ethyl 5-acyl- or 5-(1-hydroxyethenyl)isoxazole-4-carboxylates which in turn were prepared from ethyl 3-methylamino-2-butenoate or 3(2H)-furanones.     

Factors controlling the regioselectivity of additions to α-enones—III: Reactions of 3-aryl α-enones with phosphorylated anions

Reaction of phosphonoester 2 and phosphononitrile 3 with chalcone and p-methoxychaleone in THF-t-BuOK at room temperature gives only the product resulting from CC double bond attack. The same reagents with benzalacetone lead to mixture of products resulting from CC double bond and carbonyl attack, though phosphine oxide 4 gives only the products of CC attack. Dypnone gives products of carbonyl attack with 3 and does not react with 2.These results are discussed in terms of perturbation theory: C₄ attack increases with delocalization of the reagent's negative charge and lowering of the α-enone LUMO level.     

Additions radicalaires du tétrahydrothiophène à des dérivés éthyléniques: Préparation de tétrahydrothiophènes substitués en 2

Di-t-butyl peroxide induces a free radical addition of tetrahydrothiophene to ethylenic compounds. The main products arise from an α-attack of the substrate. This reaction seems to be an interesting synthesis of these heterocycles.     

Rearrangement of 5-trimethylsilylthebaine on treatment with L-selectride: an efficient synthesis of (+)-bractazonine

Treatment of 5-trimethylsilylthebaine with L-Selectride gave rise to a rearrangement to 10-trimethylsilylbractazonine through migration of the phenyl group, whereas treatment of thebaine with strong Lewis acids is known to lead to a similar rearrangement through migration of the alkyl bridge to give, after reduction, (+)-neodihydrothebaine. It is suggested that the rearrangement of the alkyl group of thebaine is favored due to the formation of a tertiary benzylic cation. However, for 5-trimethylsilylthebaine, the lithium ion of L-Selectride acts as the Lewis acid and the beta-silyl effect dominates in the stabilization of any positive charge. This rearrangement provides a clear example of the greater relative migratory aptitude of phenyl groups over alkyl groups, and provides an efficient synthesis of (+)-bractazonine from thebaine.     

Reactivity of stable trifluoroacetaldehyde hemiaminals. 2. Generation and synthetic potentialities of fluorinated iminiums

Under Lewis acid activation, hemiaminals of trifluoroacetaldehyde and related (fluoroalkyl)aldehydes generate iminium species that can react with various nucleophiles to provide fluorinated amines.     

The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design

Bifunctional derivatives of the alkaloid galanthamine, designed to interact with both the active site of the enzyme acetylcholinesterase (AChE) and its peripheral cation binding site, have been assayed with Torpedo californica AChE (TcAChE), and the three-dimensional structures of their complexes with the enzyme have been solved by X-ray crystallography. Differences were noted between the IC(50) values obtained for TcAChE and those for Electrophorus electricus AChE. These differences are ascribed to sequence differences in one or two residues lining the active-site gorge of the enzyme. The binding of one of the inhibitors disrupts the native conformation of one wall of the gorge, formed by the loop Trp279-Phe290. It is proposed that flexibility of this loop may permit the binding of inhibitors such as galanthamine, which are too bulky to penetrate the narrow neck of the gorge formed by Tyr121 and Phe330 as seen in the crystal structure.     

Conversion directe des phospholes en dihydro-6,7 phosphepines dans la sphere de coordination du tungstene

In the presence of AlCl₃, [1-β-chloroethyl-3,4-dimethylphosphole]pentacarbonyltungsten($\text{1}$) rearranges into [1-chloro-3,4-dimethyl-6,7-dihydrophosphepin]pentacarbonyltungsten ($\text{3}$).     

Determination de la structure de perfluoroalcenes a chaines longues par R.M.N. du19F : lère Partie : pefluoroalcenes-1

After a review of 1-perfluoroalkene R_FCFCF₂ synthesis, with R_FC₄F₉, C₅F₁₁, C₆F₁₃, we have studied their fine structures by ¹⁹F N.M.R. This study has led us to first generalize the rules set for the chemical shifts and coupling constants of olefinic fluorine atoms of fluoropropene and their derivatives. Then, we have been able to determinate unambiguously the chemical shifts of the difluoromethylene groups of the perfluorinated chains. We have thus shown, by irradiation, that inversions may take place in the chemical shifts of the CF₂ groups at the β and γ position of the double bond.     

STRUCTURE OF DYE AGGREGATES AND THE MECHANISM(S) OF PHOTOSENSITIZATION OF AgBr*,†

Abstract— This paper reports the present conclusions of an extended investigation on photo-sensitization of silver bromide. A general molecular packing structure for dye aggregates on the AgBr (111) surface is proposed. This structure, along with the observed spectral absorption displacements of small aggregates, is used to elucidate the phenomena of antisensitization and supersensitization. Supersensitization is seen as a partitioning of large dye aggregates into small aggregates by a deliberately added second component or by gaps between the aggregates. This partitioning isolates antisensitizing dye in a small fraction of the aggregates and minimizes its effect. The smallest aggregates are least likely to contain an antisensitizer, and show the highest quantum efficiency for photoconductivity and photographic action. Photoconductivity measurements establish that supersensitization occurs before the electron appears in the AgBr phase.
The question of direct electron injection vs. energy transfer as mechanisms for AgBr photosensitization is examined in terms of radiationless transfer to surface Ag₂S on AgBr. The absorption of surface Ag₂S is shown to be adequate for acceptance of Förster transfer from the dye, and surface Ag₂S is known to be photographically active. However, this mechanism is inefficient, and inadequate to account for observed high efficiency infrared sensitization. Direct electron injection is seen as the more probable mechanism for efficient dye sensitization of AgBr.