Synthesis and evaluation of lipophilic BTBP ligands for An/Ln separation in nuclear waste treatment: the effect of alkyl substitution on extraction properties and implications for ligand design

Four new 6,6′-bis(1,2,4-triazin-3-yl)-2,2′-bipyridine (BTBP) ligands, which contain either additional alkyl groups on the pyridine rings or seven-membered aliphatic rings attached to the triazine rings, have been synthesized, and the effects of the additional alkyl substitution in the 4- and 4′-positions of the pyridine rings on their extraction properties with LnIII and AnIII cations in simulated nuclear waste solutions have been studied. The speciation of ligand 13 with some trivalent lanthanide nitrates was elucidated by 1H NMR spectroscopic titrations and ESI-MS. Although 13 formed both 1:1 and 1:2 complexes with LaIII and YIII, only 1:2 complexes were observed with EuIII and CeIII. Quite unexpectedly, both alkyl-substituted ligands 12 and 13 showed lower solubilities in certain diluents than the unsubstituted ligand CyMe4-BTBP. Compared to CyMe4-BTBP, alkyl-substitution was found to decrease the rates of metal-ion extraction of the ligands in both 1-octanol and cyclohexanone. A highly efficient (DAm > 10) and selective (SFAm/Eu > 90) extraction was observed for 12 and 13 in cyclohexanone and for 13 in 1-octanol in the presence of a phase-transfer agent. The implications of these results for the design of improved extractants for radioactive waste treatment are discussed.

Towards the total synthesis of mycaperoxide B: probing biosynthetic rationale

Studies towards the biomimetic synthesis of mycaperoxide B (1) are described. We have established the synthesis of four diastereoisomers of mycaperoxide B methyl ester (1a) by employing a Michael addition across an α,β-unsaturated ester precursor 2 as the key step. This result strongly suggestsstereocontrol in the addition of the hydroperoxide functionality to the E double bond and discloses the importance of choosing the correct geometry of the α,β-unsaturated double bond when attempting to synthesise mycaperoxide B. Four diastereoisomeric tetrahydrofurans derived from an intramolecular rearrangement of the 1,2-dioxolane enolate 12 were also isolated and characterised.

Synthesis and incorporation into cyclic peptides of tolan amino acids and their hydrogenated congeners: construction of an array of A–B-loop mimetics of the Cε3 domain of human IgE

The disruption of the human immunolobulin E–high affinity receptor I (IgE–FcεRI) protein–protein interaction (PPI) is a validated strategy for the development of anti asthma therapeutics. Here, we describe the synthesis of an array of conformationally constrained cyclic peptides based on an epitope of the A–B loop within the Cε3 domain of IgE. The peptides contain various tolan (i.e., 1,2-biarylethyne) amino acids and their fully and partially hydrogenated congeners as conformational constraints. Modest antagonist activity (IC50 660 μM) is displayed by the peptide containing a 2,2′-tolan, which is the one predicted by molecular modeling to best mimic the conformation of the native A–B loop epitope in IgE.

Correlation between Fourier series expansion and Hückel orbital theory

The Fourier series can be used to describe periodic phenomena such as the one-dimensional crystal wave function. By the trigonometric treatements in Hückel theory it is shown that Hückel theory is a special case of Fourier series theory. Thus, the conjugated π system is in fact a periodic system. Therefore, it can be explained why such a simple theorem as Hückel theory can be so powerful in organic chemistry. Although it only considers the immediate neighboring interactions, it implicitly takes account of the periodicity in the complete picture where all the interactions are considered. Furthermore, the success of the trigonometric methods in Hückel theory is not accidental, as it based on the fact that Hückel theory is a specific example of the more general method of Fourier series expansion. It is also important for education purposes to expand a specific approach such as Hückel theory into a more general method such as Fourier series expansion.

Preparation and ring-opening reactions of N-diphenylphosphinyl vinyl aziridines

Predominantly (E)-N-diphenylphosphinyl vinyl aziridines are prepared by a reaction of N-diphenylphosphinyl imines with α-bromoallyllithium in the presence of freshly fused ZnCl2. These aziridines undergo a ring-opening reaction with a variety of carbon and heteronucleophiles, in good yield, and generally with good regioselectivity.

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

Cinchona alkaloids with a free 6'-OH functionality are being increasingly used within asymmetric organocatalysis. This fascinating class of bifunctional catalyst offers a genuine alternative to the more commonly used thiourea systems and because of the different spacing between the functional groups, can control enantioselectivity where other organocatalysts have failed. In the main, this review covers the highlights from the last five years and attempts to show the diversity of reactions that these systems can control. It is hoped that chemists developing asymmetric methodologies will see the value in adding these easily accessible, but underused organocatalysts to their screens.

Thermodynamic Stabillity of Hydrogen-Bonded Systems in Polar and Nonpolar Environments

The thermodynamic properties of a selected set of benchmark hydrogen-bonded systems (acetic acid dimer and the complexes of acetic acid with acetamide and methanol) was studied with the goal of obtaining detailed information on solvent effects on the hydrogen-bonded interactions using water, chloroform, and n-heptane as representatives for a wide range in the dielectric constant. Solvent effects were investigated using both explicit and implicit solvation models. For the explicit description of the solvent, molecular dynamics and Monte Carlo simulations in the isothermal isobaric (NpT) ensemble combined with the free energy perturbation technique were performed to determine solvation free energies. Within the implicit solvation approach, the polarizable continuum model and the conductor-like screening model were applied. Combination of gas phase results with the results obtained from the different solvation models through an appropriate thermodynamic cycle allows estimation of complexation free energies, enthalpies, and the respective entropic contributions in solution. Owing to the strong solvation effects of water the cyclic acetic acid dimer is not stable in aqueous solution. In less polar solvents the double hydrogen bond structure of the acetic acid dimer remains stable. This finding is in agreement with previous theoretical and experimental results. A similar trend as for the acetic acid dimer is also observed for the acetamide complex. The methanol complex was found to be thermodynamically unstable in gas phase as well as in any of the three solvents. (C) 2010 Wiley Periodicals, Inc. J Comput Chem 31: 2046-2055, 2010

A further exploration of a nucleophilicity index based on the gas-phase ionization potentials

An empirical nucleophilicity index based on the gas-phase ionization potentials has been recently shown to be useful categorizing and settling the nucleophilicity power of a series of captodative ethylenes reacting in cycloaddition reactions (L.R. Domingo, E. Chamorro, P. Perez, Journal of Organic Chemistry 73 (2008) 4615-4624). In the present work, the applicability of such model is tested within a broader series of substituted alkenes, substituted aromatic compounds and simple nucleophilic molecules. This index obtained within a Koopman`s theorem framework has been evaluated here in both gas and solution phases for several well-known nucleophiles. These results are found to be linearly correlated. Finally, the feasibility of the predictive character of this index has been discussed in comparison to the available experimental nucleophilicities of some amines in water. These results further support and validate the usefulness of such approximation in the modeling of the global nucleophilicity. (C) 2008 Elsevier B.V. All rights reserved.

Study of absorption spectrum and dynamics evaluation of the indocyanine-green first singlet excited state

Excited state absorption and excited state dynamics of indocyanine-green (ICG) dissolved in dymethyl sulfoxide were measured using white-light continuum Z-scan (WLCZScan) and white-light continuum pump-probe (WLCPP) techniques. The excited state absorption spectrum, obtained through Z-scan measurements, revealed saturable absorption (SA) for wavelengths longer than 630 nm, while reverse saturable absorption (RSA) appeared, as indicated by a band at approximately 570 nm. Both processes were modeled by a three-energy-level diagram, from which the excited state cross-section values were determined. SA and RSA were also observed in pump-probe experiments, with a recovery time in the hundreds of picoseconds time scale due to the long lifetime of the first excited state of ICG. Such results contribute to the understanding of ICG optical properties, allowing application in photonics and medicine. Copyright (C) 2010 John Wiley & Sons, Ltd.

Synthesis of the C11-C23 Fragment of the Potent Antitumor Agent Dictyostatin

We wish to report here our initial efforts toward the total synthesis of the potent antitumor agent dictyostatin, describing a short and efficient synthesis of the C11-C23 fragment. ( (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Reactions of 1,2.,5-thiadiazole 1,1-dioxide derivatives with nitrogen nucleophiles. Part IV. Addition of alpha-diamines

alpha-diamines, such as ethylendiamine and o-phenylendiamine, add to 3,4-aryl-disubstituted 1,2,5-thiadiazole 1,1-dioxides to give dihydropyrazines or quinoxalines, respectively and sulfamide. The new compound acenaphtho [5,6-b]-2,3-dihydropyrazine was synthesized and characterized. The addition of ethylendiamine to 3,4-diphenyl-1,2,5-thiadiazoline 1,1-dioxide gives 3,4-disubstituted thiadiazoildine 1,1-dioxide, dihydropyrazines, or pyrazines, depending on the reaction condition used. The reactions were followed by cyclic voltammetry and NMR spectroscopy which, in some cases, allowed the detection of the thiadiazolidine intermediate. Copyright (c) 2008 John Wiley & Sons, Ltd.

Synthesis of the Macrolactone of Migrastatin and Analogues with Potent Cell-Migration Inhibitory Activity

The synthesis of the macrolactone core of migrastatin 2, its potent anti-metastasis analogue 34, and ester derivatives 35 and 38 are reported. The approach involves the use of a dihydroxylation reaction to establish the desired C-8 stereocenter followed by a metathesis cyclization reaction. The effects of the compounds on the migration and invasion of human breast cancer cells were evaluated by using the wound-healing and the Boyden-chamber cell-migration and cell-invasion assays. The results revealed a high potency of the macrolactones 2 and 34 and the ester analogues 35 and 38, which suggests they have potential as antimetastatic agents.

Catecholase and DNase activities of copper(II) complexes containing phenolate-type ligands

Three new homodinuclear complexes containing substituted phenolate-type ligands based on the N(5)O(2) donor (2-(N,N-Bis(2-pyridylmethyl)aminomethyl)-6-(N`,N`-(2-hydroxybenzyl)(2-pyridylmethyl))aminomethyl)-4-methylphenol (H(2)L-H) were synthesized and characterized by X-ray crystallography. Potentiometric titration studies in 70% (v/v) aqueous ethanol show that all three complexes exhibit a common {Cu(II)(mu-phenoxo)(mu-OH)Cu(II)(OH)} core in solution. Kinetic studies on the oxidation reaction of 3,5-di-tert-butylcatechol revealed that the catalytic activity of the metal complexes increases toward the ligand containing an electron-donating group. In addition, these complexes also carried out DNA cleavage by hydrolytic and oxidative pathways. Copyright (C) 2010 John Wiley & Sons, Ltd.

Synthesis of Phthalocyanines-ALA Conjugates: Water-Soluble Compounds with Low Aggregation

Syntheses of two water-soluble phthalocyanines (Pc) containing 5-aminolevulinic acid (ALA) linked to the core structure are described. These compounds were prepared by using original functionalizations, and they present remarkable structural and photophysical features, indicating that they could be applied to photodynamic therapy (PDT).

Polymethine cyanine dyes in beta-cyclodextrin solution: multiple equilibria and chemical oxidation

Absorption and fluorescence spectroscopy, electrochemical techniques, and semiempirical calculations were employed to characterize the multiple complexation equilibria between two polymethine cyanine dyes (IR-786 and Indocyanine green-ICG, 5) and beta-cyclodextrin (beta-CD, L), as well as the chemical reactivity of the complexed and uncomplexed species against the oxidizing agents hypochlorite (HC) and hydrogen peroxide (HP). IR-786 dimerization is favored with the increase in beta-CD concentration in the form of (SL)(2) complexes. In the case of ICG, free dimers (D) and SL complexes are favored. Both IR-786 and ICG react and discolor in the presence of HC and HP. For IR-786, the reaction with HP and HC proceeds with observed rate constants of 10(-3) and 0.28 s(-1) and second-order rate constants (k(2)) of similar to 10(-3) and 10(4) M(-1) s(-1), respectively. The intermediate species observed in the bleaching reactions of IR-786 and ICG were shown, by cyclic voltammetry and VIS absorption, to result from one electron oxidation. IR-786 complexed with beta-CD is protected against bleaching in the presence of HP and HC by factors of 20 and 4, respectively. This protection was not observed in ICG complexes. Superdelocalizability profile of both dyes and frontier orbital analysis indicates that beta-CD does not protect ICG from oxidation by HP or HC, whereas the 2:2 IR-786/beta-Cd complex is able to avoid the oxidation of IR-786. We concluded that the decrease in the chemical reactivity of the dyes against oxidant agents in the presence of beta-CD is due to the formation of (SL)(2) complexes. Copyright (C) 2010 John Wiley & Sons, Ltd.