Metal ion catalysis in the beta-elimination reactions of N-[2-(4-pyridyl)ethyl]quinuclidinium and N-[2-(2-pyridyl)ethyl]quinuclidinium in aqueous solution

Catalysis of the beta-elimination reaction of N-[2-(4-pyridyl)ethyl]quinuclidinium (1) and N-[2-(2-pyridyl)ethyl]quinuclidinium (2) by Zn(2+) and Cd(2+) in OH(-)/H(2)O (pH = 5.20-6.35, 50 degrees C, and mu = 1 M KCl) has been studied. In the presence of Zn(2+), the elimination reactions of both isomers occur from the Zn(2+)-complexed substrates (C). The equilibrium constants for the dissociation of the Zn(2+)-complexes are as follows: K(d) = 0.012 +/- 0.003 M (isomer 1) and K(d) = 0.065 +/- 0.020 M (isomer 2). The value of k(C)(H2O) for isomer 1 is 4.81 x 10(-6) s(-1). For isomer 2 both the rate constants for the "water" and OH(-)-induced reaction of the Zn(2+)-complexed substrate could be measured, despite the low concentration of OH(-) in the investigated reaction mixture [k(C)H2O)= 1.97 x 10(-6) s(-1) and k(C)(OH-)= 21.9 M(-1) s(-1), respectively]. The measured metal activating factor (MetAF), i.e., the reactivity ratio between the complexed and the uncomplexed substrate, is 8.1 x 10(4) for the OH(-)-induced elimination of 2. This high MetAF can be compared with the corresponding proton activating factor (Alunni, S.; Conti, A.; Palmizio Errico, R. J. Chem. Soc., Perkin Trans. 2 2000, 453), PAF = 1.5 x 10(6) and is in agreement with an E1cb irreversible mechanism (A(xh)D(E)* + D(N)) (Guthrie, R. D.; Jencks, W. P. Acc. Chem. Res. 1989, 22, 343). A value of k(C)(H2O)>or= 23 x 10(-7) s(-1) is estimated for the Cd(2+)-complexed isomer 2, while catalysis by Cd(2+) has not been observed for isomer 1.     

Elucidating interactions of ionic liquids with polymer films using confocal Raman spectroscopy

We report on the molecular interactions between room-temperature ionic liquids (RTILs) and Nafion and PDMS membranes, proving that in contact with these polymers RTILs behave like electrolytes rather than solvents.     

Structural researches on metal complexes with ligands containing the pyridoxal moiety: X-ray structure of chloro(N-pyridoxylidene-N′-salicyloylhydrazinato) copper(II) Monohydrate

Summary The x-ray crystal structure of the title complex is described Crystals are monoclinic, space groupP2₁/n, with unit-cell dimensions:a=18.070(2),b=13.471(2),c=6.788(2) Å,=94.70(1),Z=4. The structure was solved from diffractometer data by Patterson and Fourier methods and refined by least-squares techniques toR=5.0% for 2451 independent reflections. It consists of complex molecules, in which the copper atom square planar coordination comprises the chlorine atom, Cu-Cl=2.240(3) Å, and the organic ligand which acts as terdentate through the oxygen atom [Cu-O=1.948(3) Å] and a nitrogen atom, [Cu-N=1.933(5) Å] from the hydrazidic chain and the oxygen atom, [Cu-O = 1.894(4) Å] from the pyridoxal group.     

CH...O and CH...F links form the cage structure of dioxane-trifluoromethane

The molecular beam Fourier transform microwave spectrum of 1,4-dioxane-trifluoromethane has been assigned and measured. The two subunits form a cage stabilized by one C-H...O and two C-H...F weak hydrogen bonds. The C-H...O link involves the axial lone pair of one of the two equivalent ring oxygens, while the two C-H...F bridges connect trifluoromethane to the two axial hydrogens in positions 3 and 5. The dissociation energy has been estimated from the D(J) centrifugal distortion parameter to be approximately 6.8 kJ/mol.     

Negative ion chemical ionization mass spectra of (η6-arene)Cr(CO)3

The negative ion chemical ionization mass spectra, with ammonia and methane as reagent gases, of the (η⁶-arene)Cr(CO)₃ complexes, where the arene is C₆H₅COCH₃, C₆H₅COC₂H₅, C₆H₅COC₃H₇, C₆H₅COC(CH₃)₃, 2-CH₃C₆H₄COC₃H₇, C₆H₅COOCH₃, C₆H₅CH₃, 1,3,5-(CH₃)₃C₆H₃ and C₆H₅CH₂COC₂H₅, are reported. Similar behaviour is observed with the two reagent gases, but ammonia shows a much higher abundance for the ions produced by reactions of [NH₂]^? with sample molecules. The compounds containing the C₆H₅CO group display an abundant [M]^{? ˙}, whereas the other compounds exhibit [M? H]^? as base peak, produced by ion/molecule reactions. A comparison of the negative ion chemical ionization mass spectra of the (η⁶-arene)Cr(CO)₃ complexes with those of the corresponding ligands shows the strong electron withdrawing power of the Cr(CO)₃ group in the gas phase.     

Synthesis and preliminary biological evaluation of a new pyridocarbazole derivative covalently linked to a thymidine nucleoside as a potential targeted antitumoral agent. I

The therapy of human cancer is one of the more pursued goals by medicinal chemistry research. Most of the compounds clinically used as a treatment owe their efficacy to their cytotoxic interaction (direct or indirect) with nuclear DNA. This interaction results in the inhibition of DNA synthesis and the degradation of nucleic strands. Ellipticine is a naturally occurring 6H-pyrido[4,3-b]carbazole alkaloid endowed with antitumor activity, and several ellipticine derivatives have been used in clinical trials. We previously reported some 1,4-dimethyl-9H-carbazole derivatives structurally related to ellipticine. The purpose of our research was to transform the pyridocarbazole in a prodrug so that it would have more penetration in the tumor cells and block their replication. Our prodrug is slowly hydrolyzed in human plasma in the corresponding acid. From these preliminary results, we deduce that our compound can block cellular replication. Our hypothesis is that the antitumoral activity is probably related to the induction of damage to DNA, without cellular lysis in the short term.     

Evolutionarily conserved functional mechanics across pepsin-like and retroviral aspartic proteases

The biological function of the aspartic protease from HIV-1 has recently been related to the conformational flexibility of its structural scaffold. Here, we use a multistep strategy to investigate whether the same mechanism affects the functionality in the pepsin-like fold. (i) We identify the set of conserved residues by using sequence-alignment techniques. These residues cluster in three distinct regions: near the cleavage-site cavity, in the four beta-sheets cross-linking the two lobes, and in a solvent-exposed region below the long beta-hairpin in the N-terminal lobe. (ii) We elucidate the role played by the conserved residues for the enzymatic functionality of one representative member of the fold family, the human beta-secretase, by means of classical molecular dynamics (MD). The conserved regions exhibit little overall mobility and yet are involved into the most important modes of structural fluctuations. These modes influence the substrate-catalytic aspartates distance through a relative rotation of the N- and C-terminal lobes. (iii) We investigate the effects of this modulation by estimating the reaction free energy at different representative substrate/enzyme conformations. The activation free energy is strongly affected by large-scale protein motions, similarly to what has been observed in the HIV-1 enzyme. (iv) We extend our findings to all other members of the two eukaryotic and retroviral fold families by recurring to a simple, topology-based, energy functional. This analysis reveals a sophisticated mechanism of enzymatic activity modulation common to all aspartic proteases. We suggest that aspartic proteases have been evolutionarily selected to possess similar functional motions despite the observed fold variations.     

Synthesis of a ditopic cyclophane based on the cyclobutane ring by chalcone photocycloaddition

The intramolecular photocycloaddition of chalcones to give cyclobutanes has proven to be a fast and simple method to shrink a cyclophane ring to a tricyclic system, in order to prepare potential ditopic receptors. In particular, the chalcone 1, having dioxyethylene chains as spacers, is converted in high yield to the cyclobutane 2. NOESY spectroscopy indicates that the formation of 2 occurs by a head-to-head syn ring closure.     

ASV determination of cadmium complexation in seawater. Methodology evaluation

The methodology for using DPASV to study cadmium complexation in seawater is evaluated using EDTA as a model ligand and by analysing natural samples. The results show that the methodology gives an accurate evaluation of metal complexation when inert complexes are studied, both as regards the ligand concentration and the conditional stability constant; the error for both the parameters is lower than 10% at a ligand concentration of about 10(-8) M and a conditional stability constant of 10(9) M-1. Cadmium complexes with ligands present in natural seawater show an evident kinetic lability that may lead to underestimation of the conditional stability constant when a working electrode characterised by a very thick diffusion layer is used. The conditional stability constant in one water sample of the Adriatic coast ranged between 0.14 and 1.4 l/nmol using a rotating disk electrode at rotation rates of 300 and 6000 rpm. The results of cadmium complexation obtained for samples collected in coastal seawater show that the ligands present low specificity for the metal.     

A general NMR method for rapid, efficient, and reliable biochemical screening

High-throughput screening is usually the method of drug-lead discovery. It is now well accepted that, for a functional assay, quality is more important than quantity. The ligand-based or protein-based NMR screening methodologies for detecting compounds binding to the macromolecular target of interest are now well established. A novel and sensitive NMR method for rapid, efficient, and reliable biochemical screening is presented. The method named 3-FABS (three fluorine atoms for biochemical screening) requires the labeling of the substrate with a CF(3) moiety and utilizes (19)F NMR spectroscopy for the detection of the starting and enzymatically modified substrates. The method allows for high-quality screening of large compound or natural product extract collections and for measuring their IC(50) values. Applications of this technique to the screening of inhibitors of the Ser/Thr kinase AKT1 and the protease trypsin are presented. In addition, an interesting application of 3-FABS to functional genomics is also presented.