(57)Fe ENDOR spectroscopy on the iron-sulfur cluster involved in substrate reduction of heterodisulfide reductase

Heterodisulfide reductase (Hdr) from methanogenic archea is an iron-sulfur protein that catalyzes the reversible two-electron reduction of the mixed disulfide CoM-S-S-CoB to the thiol coenzymes, coenzyme M (CoM-SH) and coenzyme B (CoB-SH). It is unusual that this enzyme uses an iron-sulfur cluster to mediate disulfide reduction in two one-electron steps via site-specific cluster chemistry. Upon half-reaction of the oxidized enzyme with CoM-SH in the absence of CoB-SH, an iron-based paramagnetic intermediate is formed, designated CoM-Hdr. In this Communication we report 57Fe pulsed ENDOR at two very different frequencies, 9 and 94 GHz, that identify the iron sites of CoM-Hdr. We find direct evidence for a [4Fe-4S]3+ cluster, and we determine the sign of the 57Fe hyperfine couplings. The 57Fe isotropic hfc values suggest a complex interaction between the cluster and the CoM-SH substrate.     

New pentacyclic triterpene saponins with strong anti-leishmanial activity from the leaves of Maesa balansae

Six new triterpene saponins bearing an oxygen bridge between C-13 and C-28 and with pronounced anti-leishmanial activity were isolated from the methanolic extract of leaves of the Vietnamese medicinal plant Maesa balansae. The structure was established on the basis of detailed NMR (COSY, NOESY, HMQC, HMBC, TOCSY and DEPT) and FAB-MS studies along with chemical degradation. All saponins identified contained the same pentaglycosidic side chain, but a different esterification pattern on the triterpenoid part. Biological evaluation of the individual compounds against visceral leishmaniasis (Leishmania infantum amastigotes) revealed a much better activity in vitro compared to the reference compound Pentostam^®, which is currently used as first-line treatment for leishmaniasis.     

Functional single-wall carbon nanotube nanohybrids--associating SWNTs with water-soluble enzyme model systems

We succeeded in integrating single-wall carbon nanotubes (SWNTs), several water-soluble pyrene derivatives (pyrene(-)), which bear negatively charged ionic headgroups, and a series of water-soluble metalloporphyrins (MP(8+)) into functional nanohybrids through a combination of associative van der Waals and electrostatic interactions. The resulting SWNT/pyrene(-) and SWNT/pyrene(-)/MP(8+) were characterized by spectroscopic and microscopic means and were found to form stable nanohybrid structures in aqueous media. A crucial feature of our SWNT/pyrene(-) and SWNT/pyrene(-)/MP(8)(+) is that an efficient exfoliation of the initial bundles brings about isolated nanohybrid structures. When the nanohybrid systems are photoexcited with visible light, a rapid intrahybrid charge separation causes the reduction of the electron-accepting SWNT and, simultaneously, the oxidation of the electron-donating MP(8)(+). Transient absorption measurements confirm that the radical ion pairs are long-lived, with lifetimes in the microsecond range. Particularly beneficial are charge recombination dynamics that are located deep in the Marcus-inverted region. We include, for the first time, work devoted to exploring and testing FeP(8)(+) and CoP(8)(+) in donor-acceptor nanohybrids.     

Untersuchungen zu Struktur und physikalischen Eigenschaften von Oxiden der LaPd2O4-Familie

Investigations on Structure and Physical Properties of some New Members of the LaPd₂O₄ Family The new mixed valent oxopalladates MPd₂O₄ (M = Pr, Nd, Gd, Y) have been synthesized from the binary oxides in presence of a solid oxygen carrier (KClO₃) by applying hydrostatic pressure (ca. 2 GPa). According to X-ray investigations these oxides crystallize in space group I 4₁/a (No. 88) and are isotypic to LaPd₂O₄ (PrPd₂O₄: a = 5.8382(2), c = 10.1687(5) Å; NdPd₂O₄: a = 5.8419(3), c = 10.1949(6) Å; GdPd₂O₄: a = 5.7799(3), c = 10.0677(8) Å; YPd₂O₄: a = 5.7359(3), c = 9.9829(8) Å). The crystal structure consists of square planar PdO₄ units which are stacked to form columnar arrangements along [1 00] and [0 10], respectively. The PdO₄ squares are connected via common corners to a three-dimensional framework. By substitution of Pr³⁺, Nd³⁺, Gd³⁺ and Y³⁺ for lanthanum the Pd? Pd distances decrease and the electrical conductivities increase. The oxopalladates investigated in this work are black, paramagnetic and semiconducting. At ambient pressure they decompose at temperatures above 880 K into elemental palladium and the binary rare earth oxides.     

Hit-optimization using target-directed dynamic combinatorial chemistry: development of inhibitors of the anti-infective target 1-deoxy-d-xylulose-5-phosphate synthase

Target-directed dynamic combinatorial chemistry (tdDCC) enables identification, as well as optimization of ligands for un(der)explored targets such as the anti-infective target 1-deoxy-d-xylulose-5-phosphate synthase (DXPS). We report the use of tdDCC to first identify and subsequently optimize binders/inhibitors of the anti-infective target DXPS. The initial hits were also optimized for their antibacterial activity against E. coli and M. tuberculosis during subsequent tdDCC runs. Using tdDCC, we were able to generate acylhydrazone-based inhibitors of DXPS. The tailored tdDCC runs also provided insights into the structure–activity relationship of this novel class of DXPS inhibitors. The competition tdDCC runs provided important information about the mode of inhibition of acylhydrazone-based inhibitors. This approach holds the potential to expedite the drug-discovery process and should be applicable to a range of biological targets.

Target-directed dynamic combinatorial chemistry was used for hit-identification and subsequent hit-optimization for the anti-infective target 1-deoxy-d-xylulose-5-phosphate synthase resulting in novel inhibitors with low micromolar affinities.     

Vollständige13C-NMR-Zuordnung von gluco- und idokonfigurierten 1,2-O-Alkyliden-furanurono-6,3-lactonen durch 2D-1H-13C-korrelierte NMR-Spektroskopie

1,2-O-Isopropylidene- and 1,2-O-benzylidene--D-glucofuranurono-6,3-lactones and the readily accessible 1,2-O-isopropylidene- and 1,2-O-benzylidene--L-idofuranurono-6,3-lactones were investigated by NMR spectroscopy. By means of a 2D-¹H-¹³C-correlated NMR experiment all resonances of the sugar carbons could be unambiguously assigned.

     

The Isoinversion Principle—a General Model of Chemical Selectivity

A large number of successful methods for chirality transfer, using either stoichiometric or catalytic chiral auxiliaries, are in use today. However, there is a lack of practical and dynamic selectivity models, i.e. models which take into account the entire reaction sequence, and which allow simple and reliable assessment, optimization and prediction of selectivity in asymmetric syntheses. The models that are available are either too strongly biased to the steric requirement of the particular molecules reacting, but do not go beyond classical considerations of static facial differentiation, or they take a demanding, theoretical approach, which because of its inherent limitations and the great theoretical effort required has not yet found its way into the practical world of the synthetic chemist. The “Isoinversion Principle”, developed on the basis of Eyring's theory, closes this gap. With its aid, the synthetic chemist can determine the characteristic isoinversion temperature T_i for the reaction type of interest from a few temperature-dependent measurements of selectivity parameters. T_i then affords information on interesting questions such as optimization etc. The advantage of this method is that it is useful not only for stereoselectivity, but for any kind of process where selectivity in general (regio-,chemo-, etc) is generated at two or more stages of a reaction sequence, regardless of whether these reactions involve the ground state or a diabatic photoprocess. The present review will demonstrate that this generation of selectivity at two or more stages of a reaction sequence occurs more commonly than is generally thought.     

Generalized Virasoro algebra: left-symmetry and related algebraic and hydrodynamic properties

Motivated by the work of Kupershmidt (J. Nonlin. Math. Phys. 6 (1998), 222 –245) we discuss the occurrence of left symmetry in a generalized Virasoro algebra. The multiplication rule is defined, which is necessary and sufficient for this algebra to be quasi-associative. Its link to geometry and nonlinear systems of hydrodynamic type is also recalled. Further, the criteria of skew-symmetry, derivation and Jacobi identity making this algebra into a Lie algebra are derived. The coboundary operators are defined and discussed. We deduce the hereditary operator and its generalization to the corresponding 3–ary bracket. Further, we derive the so-called ρ–compatibility equation and perform a phase-space extension. Finally, concrete relevant particular cases are investigated.     

Lithium Halomethylcarbenoids: Preparation and Use in the Homologation of Carbon Electrophiles

α‐Halomethyllithium carbenoids are useful homologating reagents which – reacting under proper reaction conditions as carbanions – enable the installation via nucleophilic addition of a reactive halomethyl fragment onto a preformed carbon–heteroatom bond. The pronounced thermolability represented – since seminal studies by Köbrich – the Achilles' heel of these reagents: the use of Barbier‐type methodologies (i.e., the electrophile should be present in the reaction mixture prior to the formation of the carbenoid) was pivotal in order to suppress decomposition through α‐elimination processes. Nowadays, the use of low temperatures (?78 °C) guarantees reliable procedures and, significantly, the employment of microreactor technologies allows external trapping to be performed even at higher temperatures as reported by Luisi. We will discuss the α‐halomethyllithium‐mediated homologations of a series of carbon electrophiles such as carbonyl compounds, imines, esters, Weinreb amides, and isocyanates.

     

Electrophile-induced bromocyclization of gamma,delta-unsaturated ketimines to intermediate 1-pyrrolinium salts and their selective conversion into novel 5-alkoxymethyl-2-aryl-3-chloropyrroles and 2-aroylpyrroles

N-(1-Aryl-2,2-dichloropent-4-enylidene)amines were efficiently transformed into 5-bromomethyl-1-pyrrolinium bromides via electrophile-induced bromocyclization. The latter pyrrolinium salts were converted into novel 5-alkoxymethyl-2-aryl-3-chloropyrroles by reaction with alkoxides in the corresponding alcohol or in THF. This chemistry clearly deviates from the corresponding gamma,delta-unsaturated alpha,alpha-dialkylaldimines under similar conditions. Furthermore, treatment of 5-bromomethyl-1-pyrrolinium bromides with sodium hydroxide in water afforded a new entry into 2-aroylpyrroles by an unexpected ring transformation of intermediate aziridine derivatives, which could be isolated as well.