Z/E-photoisomerizations of olefins with 4npi- or (4n + 2)pi-electron substituents: zigzag variations in olefin properties along the T(1) state energy surfaces

[Figure: see text]. A quantum chemical study has been performed to assess changes in aromaticity along the T1 state Z/E-isomerization pathways of annulenyl-substituted olefins. It is argued that the point on the T1 energy surface with highest substituent aromaticity corresponds to the minimum. According to Baird (J. Am. Chem. Soc. 1972, 94, 4941), aromaticity and antiaromaticity are interchanged when going from S0 to T1. Thus, olefins with S0 aromatic substituents (set A olefins) will be partially antiaromatic in T1 and vice versa for olefins with S0 antiaromatic substituents (set B olefins). Twist of the C=C bond to a structure with a perpendicular orientation of the 2p(C) orbitals (3p*) in T1 should lead to regaining substituent aromaticity in set A and loss of aromaticity in set B olefins. This hypothesis is verified through quantum chemical calculations of T1 energies, geometries (bond lengths and harmonic oscillator measure of aromaticity), spin densities, and nucleus independent chemical shifts whose differences along the T1 PES display zigzag dependencies on the number of -electrons in the annulenyl substituent of the olefin. Aromaticity changes are reflected in the profiles of the T1 potential energy surfaces (T1 PESs) for Z/E-isomerizations because olefins in set A have minima at 3p* whereas those in set B have maxima at such structures. The proper combination (fusion) of the substituents of set A and B olefins could allow for design of novel optical switch compounds that isomerize adiabatically with high isomerization quantum yields.     

Participation d'un groupe amide a la formation de sels de dioxolanne-1,3 ylium-2; Modele biomimetique de reaction de peptidation

An amide group is shown to be capable of intramolecular participation in the formation of an 1,3-dioxolan 2-ylium cation giving a tricyclic organic cation of a new type $\text{5a}$,$\text{b}$. This cation may be considered as a model of an electrophilic intermediate which might be formed from a peptidyl t-RNA during protein biosynthesis.The tricyclic salt $\text{5a}$,$\text{b}$ reacts with water and methanol like a classical dioxolenium salt. An amide acetal $\text{18}$ can be obtained from dimethylamine and 5a; hydrolysis of $\text{18}$ does not lead to the corresponding amide $\text{20}$ but to the cleavage of the CN. bond.     

Molecular fluorescence excitation-emission matrices relevant to tissue spectroscopy

In vivo and ex vivo studies of fluorescence from endogenous and exogenous molecules in tissues and cells are common for applications such as detection or characterization of early disease. A systematic determination of the excitation-emission matrices (EEM) of known and putative endogenous fluorophores and a number of exogenous fluorescent photodynamic therapy drugs has been performed in solution. The excitation wavelength range was 250-520 nm, with fluorescence emission spectra collected in the range 260-750 nm. In addition, EEM of intact normal and adenomatous human colon tissues are presented as an example of the relationship to the EEM of constituent fluorophores and illustrating the effects of tissue chromophore absorption. As a means to make this large quantity of spectral data generally available, an interactive database has been developed. This currently includes EEM and also absorption spectra of 35 different endogenous and exogenous fluorophores and chromophores and six photosensitizing agents. It is intended to maintain and extend this database in the public domain, accessible through the Photochemistry and Photobiology website (http://www.aspjournal. com/).     

Reaction de Knoevenagel et de Wittig-Horner En Presence D'oxydes Metalliques. Modification de la Selectivite Du Catalyseur Par Addition De Solvants Ou De Sels Metalliques

MgO et ZnO, modified by addition of a solvent or a metal salt, give very selective reactions by an interfacial solid-liquid process.     

Development and characterization of a small electromembrane extraction probe coupled with mass spectrometry for real-time and online monitoring of in vitro drug metabolism

A small and very simple electromembrane extraction probe (EME-probe) was developed and coupled directly to electrospray ionization mass spectrometry (ESI-MS), and this system was used to monitor in real time in vitro metabolism by rat liver microsomes of drug substances from a small reaction (incubation) chamber (37 °C). The drug-related substances were continuously extracted from the 1.0 mL metabolic reaction mixture and into the EME-probe by an electrical potential of 2.5 V. The extraction probe consisted of a 1-mm long and 350-μm ID thin supported liquid membrane (SLM) of 2-nitrophenyl octyl ether. The drugs and formed metabolites where extracted through the SLM and directly into a 3 μL min^?1 flow of 60 mM HCOOH inside the probe serving as the acceptor solution. The acceptor solution was directed into the ESI-MS-system, and the MS continuously monitored the drug-related substances extracted by the EME-probe. The extraction efficiency of the EME-probe was dependant on the applied electrical potential and the length of the SLM, and these parameters as well as the volume of the reaction chamber were set to the values mentioned above to avoid serious depletion from the reaction chamber (soft extraction). Soft extraction was mandatory in order not to affect the reaction kinetics by sample composition changes induced by the EME-probe. The EME-probe/MS-system was used to establish kinetic profiles for the in vitro metabolism of promethazine, amitriptyline and imipramine as model substances.     

Structure‐Based Design of Inhibitors of the Aspartic Protease Endothiapepsin by Exploiting Dynamic Combinatorial Chemistry

Structure‐based design (SBD) can be used for the design and/or optimization of new inhibitors for a biological target. Whereas de novo SBD is rarely used, most reports on SBD are dealing with the optimization of an initial hit. Dynamic combinatorial chemistry (DCC) has emerged as a powerful strategy to identify bioactive ligands given that it enables the target to direct the synthesis of its strongest binder. We have designed a library of potential inhibitors (acylhydrazones) generated from five aldehydes and five hydrazides and used DCC to identify the best binder(s). After addition of the aspartic protease endothiapepsin, we characterized the protein‐bound library member(s) by saturation‐transfer difference NMR spectroscopy. Cocrystallization experiments validated the predicted binding mode of the two most potent inhibitors, thus demonstrating that the combination of de novo SBD and DCC constitutes an efficient starting point for hit identification and optimization.     

Discriminant of a Germ {Phi}: (C2, 0)->(C2, 0) and Seifert Fibred Manifolds

Let f and g be two analytic function germs without common branches.We define the Jacobian quotients of (g, f), which are ‘firstorder invariants’ of the discriminant curve of (g, f),and we prove that they only depend on the topological type of(g, f). We compute them with the help of the topology of (g,f). If g is a linear form transverse to f, the Jacobian quotientsare exactly the polar quotients of f and we affirm the resultsof D. T. Lê, F. Michel and C. Weber.