Enantioselective approaches to potential MetAP-2 reversible inhibitors

[reaction: see text] Enantioselective deprotonation of 4-substituted cyclohexanones and highly stereoselective conjugate addition of higher order mixed cuprates were the key steps in a concise synthesis of fumagalone-related molecules. The origin of the (low) biological activity of the new compounds as compared to fumagalone is briefly discussed.     

Intramolecular [4 + 2] cycloadditions of 1,3-enynes or arylalkynes with alkenes with highly reactive cationic phosphine Au(I) complexes

New Au(I) complexes with bulky, biphenyl phosphines are the most reactive catalysts for the cyclizations of enynes. 1,6-Enynes with an aryl ring at the alkyne give 2,3,9,9a-tetrahydro-1H-cyclopenta[b]naphthalenes by a 5-exo-dig cyclization followed by a Nazarov-type ring expansion. 1,8-Dien-3-ynes also cyclize by a 5-exo-dig pathway to form hydrindanes.     

Dosage de traces de fer total dans les vins

Résumé Le dosage électrophotocolorimétrique des traces de fer total dans les vins au moyen de l'orthophénanthroline a été peu étudié jusqu'à présent. Sous un titre général le mémoire expose les conclusions auxquelles ont abouti diverses recherches consacrées à l'étude du dosage en question. L'application raisonnée de la méthode deBencze a permis d'établir une technique d'évaluation photocolorimétrique du fer dans les vins et les jus de fruits. Intéressante par sa simplicité et sa rapidité d'exécution, la technique en question indique le moyen de doser cet élément directement dans les liquides obtenus à partir des vins, suivant le procédé du traitement oxydatif au perhydrol. Ce traitement a permis de revaloriser le dosage du fer au point de vue de la rapidité par rapport à la minéralisation sèche, sans apporter en même temps des complications dans les manipulations analytiques et sans affecter la sensibilité et la précision de la réaction colorimétrique.

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Summary There has been little study of the electrophotocolorometric determination of the total iron content of wines by means of orthophenanthroline. Under a general title, the paper gives the general conclusions reached as a result of various studies of this determination. An intelligent application of theBencze method has resulted in a photocolorimetric evaluation of iron in wines and fruit juices. Characterized by simplicity and rapidity, this technique provides a means of determining this element directly in the liquids obtained from wines after oxidative treatment with perhydrol. This procedure compares, favorably with respect to speed with mineralization by the dry method, but is free from the complications in the analytical manipulations and there is no adverse effect on the sensitivity and the precision of the colorimetric reaction.

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Zusammenfassung Die elektrokolorimetrische Bestimmung der geringen Gesamtmengen an Eisen in Wein mit Hilfe von o-Phenanthrolin wurde bisher nur wenig untersucht. Die beim Studium dieses Verfahrens gesammelten Erfahrungen werden in Form eines allgemeinen Überblicks mitgeteilt. Die Anwendung der Methode vonBencze führte zur Ausarbeitung einer Arbeitsvorschrift zur kolorimetrischen Bestimmung des Eisens in Wein und Fruchtsäften. Diese ist wegen der Einfachheit und Geschwindigkeit ihrer Durchführung von praktischem Interesse. In der durch Oxydation des Weines mit Wasserstoffperoxyd erhaltenen Lösung kann das Eisen unmittelbar bestimmt werden. Diese Art des Aufschlusses ist besser geeignet als die trockene Veraschung, ohne die Empfindlichkeit oder die Genauigkeit der Farbreaktion zu beeinträchtigen.

     

Biological UV dosimeters in the assessment of the biological hazard from environmental radiation

To determine the impact of environmental UV radiation, biological dosimeters that weight directly the incident UV components of sunlight have been developed, improved and evaluated in the frame of the BIODOS project. Four DNA-based biological dosimeters ((i) phage T7, (ii) uracil thin layer, (iii) spore dosimeter and (iv) DLR-biofilm) have been assessed from the viewpoint of their biological relevance, spectral response and quantification of their biological effectiveness. The biological dosimeters have been validated by comparing their readings with weighted spectroradiometer data, by comparison with other biological doses, as well as with the determined amounts of DNA UV photoproducts. The data presented here demonstrate that the biological dosimeters are potentially reliable field dosimeters for measuring the integrated biologically effective irradiance for DNA damage.     

Single molecule spectroscopy as a probe for dye-polymer interactions

Experimental (Single Molecule Spectroscopy) and theoretical (quantum-chemical calculations and Monte Carlo and molecular dynamics simulations) techniques are combined to investigate the behavior and dynamics of a polymer-dye molecule system. It is shown that the dye molecule of interest (1,1'-dioctadecyl-3,3,3',3'-tetramethylindo-dicarbocyanine) adopts two classes of conformations, namely planar and nonplanar ones, when embedded in a poly(styrene) matrix. From an in-depth analysis of the fluorescence lifetime trajectories, the planar conformers can be further classified according to the way their alkyl side chains interact with the surrounding poly(styrene) chains.     

Single particle dynamics in ionic liquids of 1-alkyl-3-methylimidazolium cations

Ionic dynamics in room temperature molten salts (ionic liquids) containing 1-alkyl-3-methylimidazolium cations is investigated by molecular-dynamics simulations. Calculations were performed with united atom models, which were used in a previous detailed study of the equilibrium structure of ionic liquids [S. M. Urahata and M. C. C. Ribeiro, J. Chem. Phys. 120, 1855 (2004)]. The models were used in a systematic study of the dependency of several single particle time correlation functions on anion size (F-, Cl-, Br-, and PF6-) and alkyl chain length (1-methyl-, 1-ethyl-, 1-butyl-, and 1-octyl-). Despite of large mass and size of imidazolium cations, they exhibit larger mean-square displacement than anions. A further detailed picture of ionic motions is obtained by using appropriate projections of displacements along the plane or perpendicular to the plane of the imidazolium ring. A clear anisotropy in ionic displacement is revealed, the motion on the ring plane and almost perpendicular to the 1-alkyl chain being the less hindered one. Similar projections were performed on velocity correlation functions, whose spectra were used to relate short time ionic rattling with the corresponding long time diffusive regime. Time correlation functions of cation reorientation and dihedral angles of the alkyl chains are discussed, the latter decaying much faster than the former. A comparative physical picture of time scales for distinct dynamical processes in ionic liquids is provided.     

Simple and condensed β-lactams-I : The application of diketene in β-lactam synthesis. The synthesis and functional group manipulations of diethyl 3-acetyl-4-oxoazetidine-2,2-dicarboxylates

Acylation of the N-substituted diethyl aminomalonates 3a–3d with diketene furnished the ring tautomers 6a–6d of the expected acetoacetyl derivatives 5. By treatment with iodine and sodium ethoxide compounds 6a–6d are smoothly converted into the β-lactam derivatives 2a–2d. Deethoxycarbonylation of the ethylene ketals 7a–7d of the latter furnishes mixtures of the corresponding diastereomeric monoesters 8 and10. The ethoxycarbonyl groups of the trans esters 8 are more reactive than those of the cis isomers 10. This permits, under appropriate conditions, selective alkaline hydrolysis and NaBH₄ reduction of the trans esters 8 in the presence of the cis esters 10. Reduction of the cis ester 10c under more forceful conditions furnishes the trans hydroxymethyl derivative 11c.     

Theoretical study of the visible photodissociation spectrum of Ar 3 +

The photodissociation of Ar ₃ ⁺ is studied following a consistent theoretical approach from the Potential Energy Surfaces to the dynamics. Six P.E.S. are computed according to a D.I.M.-like model Hamiltonian. Transition dipole moments are determined using a similar method. The 4-D dynamics of this system is obtained with the H.W.D. method (Hemiquantal dynamic with the Whole DIM basis). All the 4 nuclear degrees of freedom and all the 6 electronic states are involved in the dynamical calculations, allowing for very general investigations. The main theoretical results are:

1. the spectrum essentially results from a Σ → Σg transition to the second excited electronic state along with a symmetric stretching motion
2. excited Ar ₃ ⁺ molecules almost all dissociate in Ar⁺ + 2 Ar
3. dissociation in Ar ₂ ⁺ + Ar requires special conditions such as low laser excitation and is predicted to increase with a specific excitation of the bending mode
4. the dominant symmetric stretching motion induces a bimodal kinetic energy distribution of the fragments.

All these points are in close agreement with experimental results.     

Mass spectra of the coordination compounds of nickel with the tetradentate Schiff bases of S-substituted thiosemicarbazides with 2,4-pentanedione and 3-oxo-2,4-pentanedione

The mass spectra of the coordination compounds of nickel(II) with the bis-S-substituted thiosemicarbazones of 2,4-pentanedione (R₂H₂L) with the general formula [NiR₂HL]X and of 3-oxo-2,4-pentanedione (H₂R₂LO) with the general formula NiR₂LO were studied. A distinguishing feature of the mass spectra of [NiR₂HL]X is the absence of molecular ion peaks. The initial point of fragmentation is the [M - HX] ions. The strongest lines in spectra of NiR₂LO are those due to the elimination of R and R-H. At the first stage the fragmentation of all the investigated compounds takes place mainly through only one of the thiosemicarbazide residues. At the second stage the 2,4-pentanedione (3-oxo-2,4-pentanedione) residue is eliminated, after which the remaining thiosemicarbazide part dissociates. A significant part of the fragmentation paths was confirmed by the peaks of the metastable ions and also by the mass spectra of the deuterated analogs.Institute of Chemistry, Academy of Sciences of the Moldavian SSR, Kishinev. Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 27, No. 2, 205–211, March–April, 1991. Original article submitted August 19, 1986.     

A proposal for the molecular basis of μ and δ opiate receptor differentiation based on modeling of two types of cyclic enkephalins and a narcotic alkaloid

Summary The molecular basis underlying the divergent receptor selectivity of two cyclic opioid peptides Tyr-c[N -d-Orn²-Gly-Phe-Leu-] (c-ORN) and [d-Pen², l-Cys⁵]-enkephalinamide (c-PEN) was investigated using a molecular modeling approach. Ring closure and conformational searching procedures were used to determine low-energy cyclic backbone conformers. Following reinsertion of amino acid side chains, the narcotic alkaloid 7-[(1R)-1-methyl-1-hydroxy-3-phenylpropyl]-6,14-endoethenotetrahydro oripavine (PEO) was used as a flexible template for bimolecular superpositions with each of the determined peptide ring conformers using the coplanarity and cocentricity of the phenolic rings as the minimum constraint. A vector space of PEO, accounting for all possible orientations for the C₂₁-aromatic ring of PEO served as a geometrical locus for the aromatic ring of the Phe⁴ residue in the opioid peptides. Although a vast number of polypeptide conformations satisfied the criteria of the opiate pharmacophore, they could be grouped into three classes differing in magnitude and sign of the torsional angle values of the tyrosyl side chain. Only class III conformers for both c-ORN and c-PEN, having tyramine dihedral angles ₁ =–150° ± 30° and ₂=–155° ± 20°, had significant structural and conformational properties that were mutually compatible while respecting the PEO vector space. Comparison of these properties in the context of the divergent receptor selectivity of the studied opioid peptides suggests that the increased distortion of the peptide backbone in the closure region of c-PEN together with the pendant ,-dimethyl group, combine to generate a steric volume which is absent in c-ORN and that may be incompatible with a restrictive topography of the receptor. The nature and stereo-chemistry of substituents adjacent to the closure region of the peptides could also modulate receptor selection by interacting with a charged () or neutral () subsite.