Synthesis and X-ray structure of 11-N-benzylamido-9,10-dihydro-9,10-ethenoanthracene

As a part of studies on MDR reversing agents, the structure of a benzylamido-9,10-dihydro-9,10-ethenoanthracene is reported: C₂₄ H₁₉ N O; orthorhombic; space group: Pca2₁; a = 9.214(2), b = 18.624(4), c = 10.170(2) Å; 1745.2(6) ų; Z = 4. The three nonplanar rings from the 9,10-dihydro-9,10-ethenoanthracene skeleton of the molecule adopt a boat conformation. The benzamide side-chain is extended (conformation, trans-trans-gauche). The molecules in the crystal are joined by infinite chains of H-bonds N14–H14···O13.     

Site of protonation of nicotine and nornicotine in the gas phase: pyridine or pyrrolidine nitrogen?

The gas-phase basicities (GBs) of nornicotine, nicotine, and model pyrrolidines have been measured by FT-ICR. These experimental GBs are compared with those calculated (for the two sites of protonation in the case of nicotine and nornicotine) at the B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d,p) level, or those estimated from substituent effects on the GBs of 2-substituted pyrrolidines, 2-substituted N-methylpyrrolidines, and 3-substituted pyridines. It is found that, in contrast to the Nsp(3) protonation in water, in the gas phase nornicotine is protonated on the pyridine nitrogen, because the effects of an intramolecular CH.Nsp(3) hydrogen bond and of the polarizability of the 3-(pyrrolidin-2-yl) substituent add up on the Nsp(2) basicity, while the polarizability effect of the 2-(3-pyridyl) substituent on the Nsp(3) basicity is canceled by its field/inductive electron-withdrawing effect. The same structural effects operate on the Nsp(3) and Nsp(2) basicities of nicotine, but here, the polarizability effect of the methyl group puts the pyrrolidine nitrogen basicity very close to that of pyridine. Consequently, protonated nicotine is a mixture of the Nsp(3) and Nsp(2) protonated forms.     

Influence of pH on the photochemical and electrochemical reduction of the dinuclear ruthenium complex, [(phen)2Ru(tatpp)Ru(phen)2)Cl4, in water: proton-coupled sequential and concerted multi-electron reduction

The dinuclear ruthenium complex [(phen)2Ru(tatpp)Ru(phen)2]4+ (P; in which phen is 1,10-phenanthroline and tatpp is 9,11,20,22-tetraaza tetrapyrido[3,2-a:2'3'-c:3',2'-l:2',3']-pentacene) undergoes a photodriven two-electron reduction in aqueous solution, thus storing light energy as chemical potential within its structure. The mechanism of this reduction is strongly influenced by the pH, in that basic conditions favor a sequential process involving two one-electron reductions and neutral or slightly acidic conditions favor a proton-coupled, bielectronic process. In this complex, the central tatpp ligand is the site of electron storage and protonation of the central aza nitrogen atoms in the reduced products is observed as a function of the solution pH. The reduction mechanism and characterization of the rich array of products were determined by using a combination of cyclic and AC voltammetry along with UV-visible reflectance spectroelectrochemistry experiments. Both the reduction and protonation state of P could be followed as a function of pH and potential. From these data, estimates of the various reduced species' pKa values were obtained and the mechanism to form the doubly reduced, doubly protonated complex, [(phen)2Ru(H2tatpp)Ru(phen)2]4+ (H2P) at low pH (< or =7) could be shown to be a two-proton, two-electron process. Importantly, H2P is also formed in the photochemical reaction with sacrificial reducing agents, albeit at reduced yields relative to those at higher pH.     

Capillary electrophoresis combined with microdialysis in the human spinal cord: a new tool for monitoring rapid peroperative changes in amino acid neurotransmitters within the dorsal horn

A method originally developed for the separation of the three neurotransmitters gamma-aminobutyric acid (GABA), glutamate (Glu) and L-aspartate (L-Asp) in microdialysis samples from rat brain (Sauvinet et al., Electrophoresis 2003, 24, 3187-3196) was applied to human spinal dialysates obtained during peroperative microdialysis from patients undergoing surgery against chronic pain. Molecules were tagged on their primary amine function with the fluorogene agent, naphthalene-2,3-dicarboxaldehyde (NDA), and, after separation by capillary electrophoresis (CE, 75 mmol/L borate buffer, pH 9.2, containing 70 mmol/L sodium dodecyl sulfate and 10 mmol/L hydroxypropyl-beta-cyclodextrin, + 25 kV voltage), were detected by laser-induced fluorescence detection (LIFD) using a 442 nm helium-cadmium laser. The complete method, including microdialysis sampling and analysis by CE-LIFD, has been validated for the analysis of human spinal microdialysates. The analytical detection limits were 1, 3.7 and 17 nmol/L for GABA, Glu and L-Asp respectively. This method allows an accurate measurement of the three amino acid neurotransmitters during an in vivo monitoring performed as rapidly as every minute in the human spinal dorsal horn. In addition, the effect of a brief peroperative electrical stimulation of the dorsal rootlets was investigated. The results obtained illustrate the advantages of combining microdialysis with CE-LIFD for studying neurotransmitters with such a high sampling rate.     

Modelling the active site of glyceraldehyde-3 phosphate dehydrogenase with the LSCF formalism

In the framework of a theoretical approach to the relationship between structure and reactivity of the catalytic centers of enzymes, glyceraldehyde-3 phosphate dehydrogenase (GAPDH) has been chosen as a model enzyme. In GAPDH, the proximity of His₁₇₆ increases the reactivity of Cys₁₄₉ at neutral pH; however, its presence alone is not sufficient to explain the reactivity of the catalytic Cys. In order to determine which other interactions play an important role, a study of the geometric and electronic structure of the catalytic site has been made using a hybrid quantum mechanics/molecular mechanics local self-consistent field method. This allows the computation of the electronic properties of amino acid residues in subsystems influenced by other parts of the macromolecule. The quantum subsystem was centered on the Cys₁₄₉ residue of GAPDH. The structures of GAPDH taken from the crystallographic database did not include hydrogen atoms and these had to be added taking into account the fact that, in the active site, His₁₇₆ has three tautomeric forms: δ-His protonated, ε-His protonated and His⁺. The results presented here suggest that the most stable His…Cys system in GAPDH is a strongly hydrogen-bonded Cys₁₄₉ ⁻/His₁₇₆ ⁺ ion pair. Received: 24 March 1998 / Accepted: 3 September 1998 / Published online: 23 November 1998     

Synthesis of nucleoside aminooxy acids

First nucleoside aminooxy acids were synthesized from furanoid sugar phthalimidooxy acids by N-glycosylation with uracil, thymine, N-benzoylcytosine, 6-N-benzoyladenine and 2-N-acetyl-6-O-diphenylcarbamoylguanine. Boc or Fmoc protected uridine aminooxy acid derivatives have also been prepared. As oxyamine protecting group, the phthalimido group was shown to be instable in MeOH, leading to the imide ring-opening product in a reversible way. This reaction was accelerated under acid or basic conditions. A uridine dimer linked by N-oxy amide has also been prepared by coupling of uridine aminooxy ester with uridine phthalimidooxy acid. These nucleoside aminooxy acids might constitute useful building blocks for the development of novel RNA mimics and conjugates with other biomolecules or reporter compounds.     

Cationic Homoleptic Vanadium(II), (IV), and (V) Complexes Arising from Protonolysis of [V(NEt2)4]

At least three different cationic species arise in the classic protonolysis of [V^IV(NEt₂)₄] with a borate ammonium salt. The unexpected formation of the vanadium(V ) species [V(NEt₂)₄][B(C₆H₅)₄] (shown in the picture without its counterion) underlines the problem of deducing the true oxidation state of vanadium species in Ziegler–Natta reactions.     

Characterizing the sound quality of air-conditioning noise

The aim of the psychoacoustic study presented here was to characterize listeners' preferences for a set of sounds produced by different brands and models of indoor air-conditioning units. In addition, some synthetic sounds, created by interpolation between recorded sound samples, were integrated into the set. The multidimensional perceptual space and the corresponding physical space representative of the sound set were determined with multidimensional scaling (MDS). Then the preferences for different classes of listeners were related to the physical space. The best spatial model yielded by the MDS had three common dimensions and specificities. The three dimensions are correlated with the ratio of the noisy part of the spectrum to the harmonic part (NHR), with the spectral center of gravity (SC) and with loudness (N). Two classes of listeners can be distinguished in terms of preference. For one, preference varied primarily with loudness, whereas for the other it varied more with SC and NHR. However, for one class the preference grew with the parameter NHR, while it decreased for the other class. The results replicate under different laboratory conditions and indicate the usefulness of this sound quality assessment approach for characterizing appliance noises.     

Glutamatergic alterations in the cortex of genetic absence epilepsy rats

Background  

In absence epilepsy, the neuronal hyper-excitation and hyper-synchronization, which induce spike and wave discharges in a cortico-thalamic loop are suspected to be due to an imbalance between GABA and glutamate (GLU) neurotransmission. In order to elucidate the role played by GLU in disease outcome, we measured cortical and thalamic extracellular levels of GLU and GABA. We used an in vivo quantitative microdialysis approach (no-net-flux method) in an animal model of absence epilepsy (GAERS). In addition, by infusing labelled glutamate through the microdialysis probe, we studied in vivo glutamate uptake in the cortex and thalamus in GAERS and non-epileptic control (NEC) rats. Expression of the vesicular glutamate transporters VGLUT1 and VGLUT2 and a synaptic component, synaptophysin, was also measured.