Ground and Excited-Electronic-State Dissociations of Hydrogen-Rich and Hydrogen-Deficient Tyrosine Peptide Cation Radicals

We report a comprehensive study of collision-induced dissociation (CID) and near-UV photodissociation (UVPD) of a series of tyrosine-containing peptide cation radicals of the hydrogen-rich and hydrogen-deficient types. Stable, long-lived, hydrogen-rich peptide cation radicals, such as [AAAYR + 2H]^+● and several of its sequence and homology variants, were generated by electron transfer dissociation (ETD) of peptide-crown-ether complexes, and their CID-MS³ dissociations were found to be dramatically different from those upon ETD of the respective peptide dications. All of the hydrogen-rich peptide cation radicals contained major (77%–94%) fractions of species having radical chromophores created by ETD that underwent photodissociation at 355 nm. Analysis of the CID and UVPD spectra pointed to arginine guanidinium radicals as the major components of the hydrogen-rich peptide cation radical population. Hydrogen-deficient peptide cation radicals were generated by intramolecular electron transfer in Cu^II(2,2′:6′,2″-terpyridine) complexes and shown to contain chromophores absorbing at 355 nm and undergoing photodissociation. The CID and UVPD spectra showed major differences in fragmentation for [AAAYR]^+● that diminished as the Tyr residue was moved along the peptide chain. UVPD was found to be superior to CID in localizing C_α-radical positions in peptide cation radical intermediates.

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Total synthesis of iejimalide A-D and assessment of the remarkable actin-depolymerizing capacity of these polyene macrolides

A concise and convergent total synthesis of the highly cytotoxic marine natural products iejimalide A-D (1-4) is reported, which relies on an effective ring-closing metathesis (RCM) reaction of a cyclization precursor containing no less than 10 double bonds. Because of the exceptional sensitivity of this polyunsaturated intermediate and its immediate precursors toward acid, base, and even gentle warming, the assembly process hinged upon the judicious choice of protecting groups and the careful optimization of all individual transformations. As a consequence, particularly mild protocols for Stille as well as Suzuki reactions of elaborate coupling partners have been developed that hold considerable promise for applications in other complex settings. Moreover, a series of non-natural "iejimalide-like" compounds has been prepared, differing from the natural lead in the polar head groups linked to the macrolide's N-terminus. With the aid of these compounds it was possible to uncover the hitherto unknown effect of iejimalide and analogues on the actin cytoskeleton. Their capacity to depolymerize this microfilament network rivals that of the latrunculins which constitute the standard in the field. Structural modifications of the peptidic terminus in 2 are thereby well accommodated, without compromising the biological effects. The iejimalides hence constitute an important new class of probe molecules for chemical biology in addition to their role as promising lead structures for the development of novel anticancer agents.     

Near-field ultrasound tomography

In this paper, a near-field tomographic solution is introduced to solve the imaging problem of fluid objects assumed to be weakly heterogeneous (Born approximation) and excited by spherical waves. The solution to the forward problem is based on the Huygens-Fresnel principle which describes the scattered field as the result of the interference scheme of all the secondary spherical waves. From the derivation of the scattered field, a new Fourier transform that has been called the elliptical Fourier transform is defined: It differs from the standard Fourier transform in that instead of a plane wave decomposition, a harmonic ellipsoidal wave decomposition is obtained. Based on this spectral analysis, a near-field Radon transform is designed that complements the "far-field tools" published in diffraction tomography literature. Then, assuming that the measuring distance is greater than one wavelength, the feasibility of reconstructing either the impedance or the velocity maps of an acoustical (perfect fluid) model is demonstrated. Numerical simulations were performed which confirmed the validity of the theory presented here; a theory which has many potential applications in future wave theory research.     

Tristhienylphenylamine--extended dithiafulvene hybrids as bifunctional electroactive species

Extended hybrid conjugated systems based on a trithienylphenylamine core with 1, 2 and 3 peripheral dithiafulvenyl units have been synthesized and studied by cyclic voltammetry and UV-Vis. absorption spectroscopy. Theoretical calculations have also been undergone. The behaviour of these derivatives which depends on the number of dithiafulvene moieties grafted of the central core is cleared up. One polymer, obtained from derivative 3 presents polyelectrochromic properties.     

Intercalation synthesis of functional hybrid materials based on layered simple hydroxide hosts and ionic liquid guests--a pathway towards multifunctional ionogels without a silica matrix?

Functional hybrid materials on the basis of inorganic hosts and ionic liquids (ILs) as guests hold promise for a virtually unlimited number of applications. In particular, the interaction and the combination of properties of a defined inorganic matrix and a specific IL could lead to synergistic effects in property selection and tuning. Such hybrid materials, generally termed ionogels, are thus an emerging topic in hybrid materials research. The current article addresses some of the recent developments and focuses on the question why silica is currently the dominating matrix used for (inorganic) ionogel fabrication. In comparison to silica, matrix materials such as layered simple hydroxides, layered double hydroxides, clay-type substances, magnetic or catalytically active solids, and many other compounds could be much more interesting because they themselves may carry useful functionalities, which could also be exploited for multifunctional hybrid materials synthesis. The current article combines experimental results with some arguments as to how new, advanced functional hybrid materials can be generated and which obstacles will need to be overcome to successfully achieve the synthesis of a desired target material.     

Molecular editing and assessment of the cytotoxic properties of iejimalide and progeny

Systematic variation of all substructures embedded into the framework of iejimalide B (2) led to a panel of synthetic analogues of this polyunsaturated macrolide, featuring structural modifications that are not accessible by derivatization of the natural lead compound itself. The assessment of the cytotoxicity of these compounds with the aid of a monolayer proliferation assay (12 human tumor cell lines in vitro) as well as a colony formation assay (24 human tumor xenografts ex vivo) revealed the exceptional potency of 2 and several of its synthetic congeners, with IC(50) values in the picomolar range for the most sensitive cell lines. Whereas structural modifications of the macrocycle or of the side chain generally lead to a decrease in activity, changes of the peptidic terminus are not only well accommodated but engender increased tumor selectivity as well. 2 and two of the most promising analogues were selected for in vivo studies in mice, in which their activity against human tumor xenografts of breast cancer (MAXF 401) and prostate cancer (PRXF PC-3M) was tested. In contrast to a previous report in the literature however, which had claimed in vivo activity for the parent iejimalides, these tests did not show a significant therapeutic effect against the chosen solid tumors upon intraperitoneal administration.     

Can a functionalized phosphine ligand promote room temperature luminescence of the [Ru(bpy)(tpy)]2+ core?

Unexpected room temperature luminescence is observed and rationalized by highly challenging excited state calculations for a functionalized phosphine ligand coordinated on the [Ru(bpy)(tpy)](2+) core.     

Insight into the stereoselectivity of PPL-catalyzed formation of polyesters from phenyl glycidyl ether and succinic anhydride

Analysis of the stereoselectivity that would be expected in the Pig Pancreatic Lipase-catalyzed oligomerization of succinic anhydride and phenyl glycidyl ether is carried out.The results show that no stereoselection was recorded at any step of the suggested mechanism of the process: opening of the chiral epoxide into 1,2-diol, nucleophilic attack of the chiral acylenzyme by a chiral diol, or by the hydroxyl group of a growing oligomer.     

Highly efficient broadband double-sided Fresnel lens for THz range

Modern passive THz setups require effective optical elements with a large numerical aperture. Here we propose a new type of the optical element for THz applications, which is a broadband double-sided Fresnel-like lens with an optimized thickness. The optimization is performed to obtain a very low attenuation, low material cost, and small weight in the element media. It also provides achromatic properties for the assumed wavelength range. The experimental evaluation of the proposed diffractive lens by means of time-domain spectroscopy is presented and discussed.     

Enhancement of L-3-hydroxybutyryl-CoA dehydrogenase activity and circulating ketone body levels by pantethine. Relevance to dopaminergic injury

Background  

The administration of the ketone bodies hydroxybutyrate and acetoacetate is known to exert a protective effect against metabolic disorders associated with cerebral pathologies. This suggests that the enhancement of their endogenous production might be a rational therapeutic approach. Ketone bodies are generated by fatty acid beta-oxidation, a process involving a mitochondrial oxido-reductase superfamily, with fatty acid-CoA thioesters as substrates. In this report, emphasis is on the penultimate step of the process, i.e. L-3-hydroxybutyryl-CoA dehydrogenase activity. We determined changes in enzyme activity and in circulating ketone body levels in the MPTP mouse model of Parkinson's disease. Since the active moiety of CoA is pantetheine, mice were treated with pantethine, its naturally-occurring form. Pantethine has the advantage of being known as an anti-inflammatory and hypolipidemic agent with very few side effects.