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This study demonstrates that chiral‐at‐iron complexes, in which all coordinated ligands are achiral and the overall chirality the consequence of a stereogenic iron center, are capable of catalyzing asymmetric transformations with very high enantioselectivities. The catalyst is based on a previously reported design (J. Am. Chem. Soc. 2017, 139, 4322), in which iron(II) is surrounded by two configurationally inert achiral bidentate N‐(2‐pyridyl)‐substituted N‐heterocyclic carbenes in a C 2‐symmetric fashion and complemented by two labile acetonitriles. By replacing mesityl with more bulky 2,6‐diisopropylphenyl substituents at the NHC ligands, the steric hindrance at the catalytic site was increased, thereby providing a markedly improved asymmetric induction. The new chiral‐at‐iron catalyst was applied to the inverse electron demand hetero‐Diels‐Alder reaction between β,γ‐unsaturated α‐ketoester and enol ethers provide 3,4‐dihydro‐2H‐pyrans in high yields with excellent diastereoselectivities (up to 99 : 1 dr) and excellent enantioselectivities (up to 98 % ee). Other electron rich dienophiles are also suitable as demonstrated for a reaction with a vinyl azide., A chiral‐at‐iron complex, in which all coordinated ligands are achiral and the overall chirality is exclusively due to a stereogenic iron center, catalyzes hetero‐Diels‐Alder reactions with high diastereoselectivities (up to 99 : 1 dr) and enantioselectivities (up to 98 % ee). Key for this excellent stereocontrol are bulky 2,6‐diisopropylphenyl substituents at the N‐heterocyclic carbene ligands which increase the steric hindrance at the catalytic site.

We herein report the synthesis, structures, coordination ability, and mechanism of formation of silicon analogs of crown ethers. An oligomerization of 2D2 (I) (2Dn,=(Me4Si2O)n) was achieved by the reaction with GaI3 and MIx (M=Li, Na, Mg, Ca, Sr). In these reactions the metal cations serve as template and the anions (I−/[GaI4]−) are required as nucleophiles. In case of MIx=LiI, [Li(2D3)GaI4] (1) is formed. In case of MIx=NaI, MgI2, CaI2, and SrI2 the compounds [M(2D4)(GaI4)x] (M=Mg2+ (3), Ca2+ (4), Sr2+ (5) are obtained. Furthermore the proton complex [H(2D3)][Ga2I7] (6) was isolated and structurally characterized. All complexes were characterized by means of multinuclear NMR spectroscopy, DOSY experiments and, except for compound 3, also by single crystal X‐ray diffraction. Quantum chemical calculations were carried out to compare the affinity of M+ to 2Dn and other ligands and to shed light on the formation of larger rings from smaller ones., All‐silicon versions of crown ethers were isolated and characterized. These silicon‐based macrocycles are obtained from 2D2/s‐block metaliodide/gallium(III)‐iodide (2D2=(Me4Si2O)2) Lewis‐acid systems which enable s‐block metal templated Si−O bond activation and subsequent oligomerization. The coordination ability of these macrocycles is evaluated and a mechanism of formation is suggested by means of DFT calculations.

Mining microbial genomes including those of Streptomyces reveals the presence of a large number of biosynthetic gene clusters. Unraveling this genetic potential has proved to be a useful approach for novel compound discovery. Here, we report the heterologous expression of two similar P450-associated cyclodipeptide synthase-containing gene clusters in Streptomyces coelicolor and identification of eight rare and novel natural products, the C3-guaninyl indole alkaloids guanitrypmycins. Expression of different gene combinations proved that the cyclodipeptide synthases assemble cyclo-l-Trp-l-Phe and cyclo-l-Trp-l-Tyr, which are consecutively and regiospecifically modified by cyclodipeptide oxidases, cytochrome P450 enzymes, and N-methyltransferases. In vivo and in vitro results proved that the P450 enzymes function as key biocatalysts and catalyze the regio- and stereospecific 3α-guaninylation at the indole ring of the tryptophanyl moiety. Isotope-exchange experiments provided evidence for the non-enzymatic epimerization of the biosynthetic pathway products via keto-enol tautomerism. This post-pathway modification during cultivation further increases the structural diversity of guanitrypmycins.

β-Substituted chiral γ-aminobutyric acids feature important biological activities and are valuable intermediates for the synthesis of pharmaceuticals. Herein, an efficient catalytic enantioselective approach for the synthesis of β-substituted γ-aminobutyric acid derivatives through visible-light-induced photocatalyst-free asymmetric radical conjugate additions is reported. Various β-substituted γ-aminobutyric acid analogues, including previously inaccessible derivatives containing fluorinated quaternary stereocenters, were obtained in good yields (42-89 %) and with excellent enantioselectivity (90-97 % ee). Synthetically valuable applications were demonstrated by providing straightforward synthetic access to the pharmaceuticals or related bioactive compounds (S)-pregabalin, (R)-baclofen, (R)-rolipram, and (S)-nebracetam.

A novel method for the catalytic asymmetric dearomatization by visible-light-activated [2+2] photocycloaddition with benzofurans and one example of a benzothiophene is reported, thereby providing chiral tricyclic structures with up to four stereocenters including quaternary stereocenters. The benzofurans and the benzothiophene are functionalized at the 2-position with a chelating N-acylpyrazole moiety which permits the coordination of a visible-light-activatable chiral-at-rhodium Lewis acid catalyst. Computational molecular modeling revealed the origin of the unusual regioselectivity and identified the heteroatom in the heterocycle to be key for the regiocontrol.

Multicomponent reactions allow the construction of molecular complexity in an economical fashion, fluorinated compounds play an important role in pharmaceuticals and agrochemicals, whereas visible light is an abundant and sustainable source of energy for activating chemical transformations. Here we report a visible-light-induced asymmetric three-component fluoroalkylation reaction scheme catalyzed by a chiral-at-rhodium Lewis acid. The photoredox process is mediated by the inexpensive, commercially available organic photoredox mediator 4,4′-difluorobenzil, which upon activation by visible light induces the generation of perfluoroalkyl radicals from their sulfinates via single electron transfer oxidation. The fluorinated radicals are trapped by electron-rich C−C double bonds to deliver α-oxy carbon-centered radicals, followed by a subsequent stereocontrolled reaction with acceptor-substituted alkenes. This three-component fluoroalkylation scheme provides a range of complex fluoroalkyl-containing chiral compounds under dual C−C bond formation with high enantioselectivities (up to 98 % ee) and modest diastereoselectivities (up to 6:1 dr). Excellent diastereoselectivities (up to >38:1:1 dr) for natural chiral compound derivatives are observed. Broad substrate scope (25 examples), excellent functional group tolerance, scalability of the reaction, along with the option to recover the chiral catalyst and photoredox mediator reveal the practicability of this methodology in organic synthesis for the rapid synthesis of fluorinated chiral molecules.

Wir prasentieren die erste Superbase, MHPN, mit zwei wechselwirkenden Phosphorylidfunktionalitaten. Anders als klassische Protonenschwamme weist diese neuartige Verbindungsklasse zwei Kohlenstoffatome als Basizitatszentren auf, die durch ein Naphthalinruckgrat in raumliche Nahe gezwungen werden. Das Bisylid zeigt einen experimentellen pKBH+-Wert von 33.3±0.2 auf der Acetonitrilskala und eine theoretische Protonenaffinitat in der Gasphase von 277.9 kcal mol−1 (M062X/6-311+G**//M062X/6-31G*+ZPVE). Dieser Wert ist um 15 kcal mol−1 hoher als fur das entsprechende Monoylid. Der Ursprung der ungewohnlich hohen Basizitat von MHPN wurde mit NMR-spektroskopischen Methoden, Kristallstrukturanalysen und theoretischen Berechnungen untersucht, wobei ein schneller Austausch des “aciden” Protons zwischen den beiden basischen Kohlenstoffatomen eine grose Rolle spielt.

Reactions of R(1) SnCl3 (R(1) =CMe2 CH2 C(O)Me) with (SiMe3 )2 Se yield a series of organo-functionalized tin selenide clusters, [(SnR(1) )2 SeCl4 ] (1), [(SnR(1) )2 Se2 Cl2 ] (2), [(SnR(1) )3 Se4 Cl] (3), and [(SnR(1) )4 Se6 ] (4), depending on the solvent and ratio of the reactants used. NMR experiments clearly suggest a stepwise formation of 1 through 4 by subsequent condensation steps with the concomitant release of Me3 SiCl. Furthermore, addition of hydrazines to the keto-functionalized clusters leads to the formation of hydrazone derivatives, [(Sn2 (μ-R(3) )(μ-Se)Cl4 ] (5, R(3) =[CMe2 CH2 CMe(NH)]2 ), [(SnR(2) )3 Se4 Cl] (6, R(2) =CMe2 CH2 C(NNH2 )Me), [(SnR(4) )3 Se4 ][SnCl3 ] (7, R(4) =CMe2 CH2 C(NNHPh)Me), [(SnR(2) )4 Se6 ] (8), and [(SnR(4) )4 Se6 ] (9). Upon treatment of 4 with [Cu(PPh3 )3 Cl] and excess (SiMe3 )2 Se, the cluster fragments to form [(R(1) Sn)2 Se2 (CuPPh3 )2 Se2 ] (10), the first discrete Sn/Se/Cu cluster compound reported in the literature. The derivatization reactions indicate fundamental differences between organotin sulfide and organotin selenide chemistry.

Nuclear magnetic resonance spectroscopy has proven to be powerful for the study of dynamic processes. A new pulse sequence, SirX, is designed to provide boundary conditions that simplify the McConnell equations. Both an initial rate approximation and a whole curve fitting to the time course of magnetization can be used to calculate the exchange rate. These methods were used to study the exchange kinetics of N,N-dimethylacetamide. As compared with the well-established exchange spectroscopy suitable to studies of slow exchange, SirX has the advantage of being less time consuming and capable of providing more reliable kinetic data. Furthermore, by setting the observation on X-nuclei with larger chemical shift dispersion as compared with an observation on (1)H resonance, SirX extends the upper limit of a reliable determination of exchange rates.

Herein we describe an easily accessible class of superbasic proton sponges based on the 1,8-bisphosphazenylnaphthalene (PN) proton pincer motif and P-alkyl substituents ranging from methyl (TMPN) to n-butyl (TBPN), isopropyl (TiPrPN) and cyclopentyl (TcyPPN). These neutral bases with a pK(BH)(+) value (MeCN) of ~30 were accessible via a Kirsanov condensation using commercially available 1,8-diaminonaphthalene, and in case of TMPN and TBPN, simple one-pot procedures starting from trisalkylphosphanes can be performed. Furthermore, the known pyrrolidinyl-substituted superbase TPPN previously synthesized via a Staudinger reaction could also be prepared by the Kirsanov strategy allowing its preparation in a larger scale. The four alkyl-substituted proton sponges were structurally characterized in their protonated form; molecular XRD structures were also obtained for unprotonated TiPrPN and TcyPPN. Moreover, we present a detailed description of spectroscopic features of chelating bisphosphazenes including TPPN and its hyperbasic homologue P2-TPPN on which we reported recently. The four alkyl-substituted superbases were investigated with respect to their basic features by computational means and by NMR titration experiments revealing unexpectedly high experimental pK(BH)(+) values in acetonitrile between 29.3 for TMPN and 30.9 for TBPN. Besides their thermodynamic basicity, we exemplarily studied the kinetic basicity of TMPN and TPPN by means of NMR-spectroscopic methods. Furthermore, the competing nucleophilic versus basic properties were examined by reacting the proton sponges with ethyl iodide. Insight into the coordination chemistry of chelating superbases was provided by reacting TMPN with trimethylaluminum and trimethylgallium to give cationic complexes of Group XIII metal alkyls that were structurally characterized.

Lassopeptide gehoren zu den ribosomal synthetisierten und posttranslatorisch modifizierten Peptiden. Ihr gemeinsames Erkennungsmerkmal ist ein N-terminaler Makrolactamring, der von einem C-terminalen Schwanz durchfadelt wird. Diese “Lassofaltung” wird durch sterische Wechselwirkungen aufrechterhalten. In dieser Studie werden die Isolierung und Charakterisierung der Xanthomonine I–III, der ersten Lassopeptide mit einem nur aus sieben Aminosauren bestehenden Makrolactamring, sowie die Kristallstruktur von Xanthomonin I und die NMR-spektroskopisch ermittelte Struktur von Xanthomonin II beschrieben. Insgesamt wurden 25 Xanthomonin-II-Varianten generiert, um Aspekte der Biosynthese, der Stabilisierung und der Aufrechterhaltug der Lassofaltung zu testen. Diese Mutagenesestudie offenbart die Einschrankungen, die ein so kleiner Ring fur das Durchfadeln bedeutet, und zeigt, dass jede Stopselaminosaure groser als Serin eine hitzestabile Lassofaltung in Xanthomonin II aufrechterhalten kann.

The probe-based discovery of the first small-molecule inhibitor of the repair enzyme 8-oxo-dGTPase (MTH1) is presented, which is an unconventional cyclometalated ruthenium half-sandwich complex. The organometallic inhibitor with low-nanomolar activity displays astonishing specificity, as verified in tests with an extended panel of protein kinases and other ATP binding proteins. The binding of the organometallic inhibitor to MTH1 is investigated by protein crystallography.

Die Verwendung einer metallorganischen Sonde zur Entwicklung des ersten niedermolekularen Inhibitors des Re- paraturenzyms 8-Oxo-dGTPase wird beschrieben. Dabei handelt es sich um einen unkonventionellen cyclometallierten Ruthenium-Halbsandwichkomplex. Der niedrig nanomolare metallorganische Inhibitor weist eine erstaunliche Spezifitt auf, was durch Tests in umfangreichen Kinase- und ATPase- Panels verifiziert wird. Die Bindung des metallorganischen Inhibitors an MTH1 wird durch Proteinkristallographie un- tersucht. Ein signifikanter Teil der im menschliche Genom kodierten Proteine bindet und verwendet purinbasierte Nukleoside oder Nukleotide wie ATP, GTP, NAD(P), FAD, PAPS und Coenzym A. (1) Diese Proteine umfassen wichtige Enzym- klassen wie Kinasen, ATPasen, Ligasen, Helikasen und Chaperone, sind an einer Vielzahl von zellulren Prozessen beteiligt, bilden den Ursprung fr viele menschliche Erkran- kungen, und stellen daher wichtige Enzymtargets fr die Entwicklung von Wirkstoffen dar. Unsere Arbeitsgruppe hat krzlich eine Strategie fr die Entwicklung hochpotenter und selektiver ATP-nachahmender Hemmer von Proteinkinasen eingefhrt, welche auf der Verwendung von substitutions- inertenbergangsmetallkomplexen basiert. (2, 3) Aufgrund

How to simplify a complex thing: A salt of the heaviest intermetalloid cluster known to date, [K([2.2.2]crypt)]4 [Pd@Pd2 Pb10 Bi6 ]⋅2 en, resulted from a reaction of [Pd(PPh3 )4 ] with [K([2.2.2]crypt)]2 (Pb2 Bi2 )⋅2 en in ethane-1,2-diamine (en). The electron number of the ternary intermetalloid anion accords with Wade-Mingos rules, as the [Pd(η(3) -Bi3-x Pbx )]((x+1)-) (x=0, 1) 14-electron fragments formed in situ are isolobal with Pb atoms.

A previous study showed that together with the festuclavine synthase FgaFS, the old yellow enzyme FgaOx3 from Aspergillus fumigatus catalyzed the conversion of chanoclavine-I aldehyde to festuclavine in the biosynthesis of ergot alkaloids. In the absence of FgaFS, a mixture containing two compounds with a ratio of 7:3 was detected in the enzyme assay of FgaOx3. NMR experiments including (DQF)-COSY, HSQC, HMBC and NOESY identified their structures as E/Z isomers of N-methyl-N-[(5R,10R)-10-(2-oxo-propyl)-2,4,5,10-tetrahydrobenzo[cd]indol-5-yl]formamide and proved the migration of the formyl group at C-8 in chanoclavine I-aldehyde to N-6 in the identified products. Copyright © 2011 John Wiley & Sons, Ltd.

The solution and solid-state structures of 3,3′-diethyl-4,4′,8,8′,9,9′,10,10′-octamethyl-6,6′-di-p-tolyl-bisBODIPY, a potent fluorescent dye, were examined by X-ray diffraction and NMR spectroscopy. The crystallographic analysis resulted in two different conformations for the fluorophor with dihedral angles between the C9N2B subunits of 91.9 and 96.8°. The presence of two different conformations is a consequence of the crystal packing as the 3D structure is composed of alternating layers of BisBODIPY molecules with and without cocrystallized solvent. In solution NMR spectroscopic studies the compound displays intramolecular and distance dependant through space C–F and F–F couplings, which were used to analyze the solution structure. This analysis suggests a single minimum conformation and a rigid, but unstrained structure in solution. The fluorescence properties of the BisBODIPY and in particular the high quantum yields found for this class of luminophores are qualitatively in agreement with the latter result, and better described by the solution structure than by the solid-state structure.

The class of nonribosomally assembled siderophores encompasses a multitude of structurally diverse natural products. The genome of the erythromycin-producing strain Saccharopolyspora erythraea contains 25 secondary metabolite gene clusters that are mostly considered to be orphan, including two that are responsible for siderophore assembly. In the present study, we report the isolation and structural elucidation of the hydroxamate-type tetrapeptide siderophore erythrochelin, the first nonribosomal peptide synthetase-derived natural product of S. erythraea. In an attempt to substitute the traditional activity assay-guided isolation of novel secondary metabolites, we have employed a dedicated radio-LC-MS methodology to identify nonribosomal peptides of cryptic gene clusters in the industrially relevant strain. This methodology was based on transcriptome data and adenylation domain specificity prediction and resulted in the detection of a radiolabeled ornithine-inheriting hydroxamate-type siderophore. The improvement of siderophore production enabled the elucidation of the overall structure via NMR and MS(n) analysis and hydrolysate-derivatization for the determination of the amino acid configuration. The sequence of the tetrapeptide siderophore erythrochelin was determined to be D-alpha-N-acetyl-delta-N-acetyl-delta-N-hydroxyornithine-D-serine-cyclo(L-delta-N-hydroxyornithine-L-delta-N-acetyl-delta-N-hydroxyornithine). The results derived from the structural and functional characterization of erythrochelin enabled the proposal of a biosynthetic pathway. In this model, the tetrapeptide is assembled by the nonribosomal peptide synthetase EtcD, involving unusual initiation- and cyclorelease-mechanisms.

The conformation of [bis-(N,N′-difluoroboryl)]-3,3′-diethyl-4,4′,8,8′,9,9′,10,10′-octamethyl-2,2′-bidipyrrin (1) in solution was studied by analyzing the 13C19F and 19F19F through-space spin–spin couplings. The 1H and 13C NMR spectra were assigned on the basis of nuclear Overhauser effect spectroscopy (NOESY), heteronuclear single-quantum correlation (HSQC), and heteronuclear multiple-bond correlation (HMBC) experiments. The 19F spectrum of 1 was compared with that of 2-ethyl-1,3,5,6,7-pentamethyl-4,4-difluoro-4-bor-3a,4a-diaza-s-indacen (2). The 19F19F through-space spinspin coupling in 1 was thus assigned and the coupling constant was obtained by simulating the coupling patterns. The obtained conformation of 1 was compared with those of the known complexes [bis-(N,N′-difluoroboryl)]-3,3′,8,8′,9,9′-hexaethyl-4,4′,10,10′-tetramethyl-6,6′-(4-methylphenyl)-2,2′-bidipyrrin (3)and [bis-(N,N′-difluoroboryl)]-9,9′-diethyl-4,4′,8,8′,10,10′-hexamethyl-3,3′-bis(methoxycarbonylethyl)-2,2′-bidipyrrin (4). The conformational dynamics of 1, 3, and 4 was surveyed by observing the temperature dependence of the through-space coupling constants between 253 and 333 K. The 13C19F and 19F19F through-space spin–spin couplings thus confirm similar conformations of different BisBODIPYs in solution in contrast to earlier findings in the solid state. Copyright © 2009 John Wiley & Sons, Ltd.

Background Cell-penetrating peptides (CPPs) could potentially be used as vectors for intracellular delivery of proteins, peptides and nucleic acids. The present study examined different CPPs, such as TAT-derived and arginine rich sequences, as well as model amphiphilic peptide, with respect to transfection efficiency of pegylated polyethylenimine (PEI) in A549, Calu-3 cells and in mice after intra-tracheal administration. Methods The conjugates were prepared by the coupling of CPPs to PEI via a heterobifunctional polyethylene glycol (PEG) linker, resulting in the bioconjugates CPP-PEG-PEI. Structures were successfully confirmed by 1H-nuclear magnetic resonance and diffusion-ordered spectroscopy. Unmodified PEI 25 kDa was compared with pegylated PEI, and aggregation tendency in cell culture medium, interaction with mucin and stability against heparin was assayed. After evaluating transfection efficiency of the polymers in two different lung cell lines, luciferase reporter gene expression was determined in mouse lungs. Results All conjugates showed superior transfection efficiency compared to unmodified PEI 25 kDa. The conjugates sizes were generally < 300 nm, thus enabling them to penetrate through the mucus lining of the lung and reach the target cells. Coupling of CPPs to PEG-PEI, however, did not significantly improve transfection efficiency in A549 cells, calu-3 cells and in mouse lungs. Conclusions We show that small and stable polyplex size achieved by pegylation is favourable for successful pulmonary gene delivery. Compared to PEI 25 kDa, pegylated PEI and CPP-PEG-PEI displayed enhanced transfection efficiency both in vitro and in vivo. Copyright © 2008 John Wiley & Sons, Ltd.

The stereochemistry of γ-butyrolactons tetrahydro-6a-phenylfuro[3,4-b]furan-2(3H)-one (1), 1,4,5,9b-tetrahydro-3a-methylnaphtho[2,1-b]furan-2(3aH)-one (2), 1,4,5,9 b-tetrahydro-3a-methylfuro[2,3-c]quinolin-2(3aH)-one (3) and hexahydro-furo[3,2-c]benzofuran-2-one (4) was studied using DPFGSE-NOE experiments. Compounds 1–3 contain two stereocenters, while 4 contains three. Both 1H and 13C spectra showed a single diastereomer of all the compounds. Routine 2D experiments (DQF)-COSY, HMQC/HSQC, and HMBC were used to assign 1H and 13C spectra completely. Diastereotopic methylene protons with resolved 1H NMR signals as well as protons of cyclohexane served as references for the construction of the spatial arrangement in the molecules. NOE contacts between protons attached to the stereocenter and the diastereotopic protons were thus used to determine the configuration of the molecules. Vicinal coupling constants 3J assisted the assignment of the conformational arrangement of the cyclohexane ring of 4. Copyright © 2007 John Wiley & Sons, Ltd.

Reactions of the binary Zintl anion (Pb2Bi2)2- with Ln(Me4Cp)3 (Ln: La, Ce, Nd, Gd, Sm, Tb) in presence of [2.2.2]crypt in en/toluene yields ten [K([2.2.2]crypt)]+ salts of Ln-doped semimetal clusters with 13 or 14 surface atoms.

A single weak-binding event is multiplied into an efficient receptor site for protein surfaces (10(-1) to10(6) M(-1) in buffered aqueous solution) in a biomimetic fashion. This has hitherto been done with natural host/guest pairs, but not with artificial receptors. The organic reaction presented is one of very few that enable chemists to fuse multiple ionic building blocks covalently in highly polar solution; this one-pot reaction proceeds with virtually quantitative yield. According to this concept, other building blocks with aldehyde groups can likewise be multiplied into monodisperse functional dendrimers. Small basic proteins are bound by octameric dendrimers in 1:1 or 1:2 complexes with millimolar to submicromolar affinities. The complexation event is studied independently in buffered aqueous solution by three different spectroscopic methods (PFG-LED, UV/Vis, and fluorescence). Potential new applications include recombinant protein purification through Arg tags on immobilized dendrimers and on/off switching of protein function by reversible active-site capping of enzymes.

The biological ion channel gramicidin A (gA) was modified by synthetic means to obtain the tail-to-tail linked asymmetric gA-derived dimer compound 3. Single-channel current measurements for 3 in planar lipid bilayers exhibit an Eisenman I ion selectivity for alkali cations. The structural asymmetry does not lead to an observable functional asymmetry. The structure of 3 in solution without and with Cs cations was investigated by 1H-NMR spectroscopy. In CDCl3/CD3OH (1 : 1, v/v), 3 forms a mixture of double-stranded beta-helices. Upon addition of excess CsCl, the double-stranded species are converted completely into one new conformer: the right-handed single-stranded beta-helix. A combination of DQF-COSY and TOCSY was used for the assignment of the 1H-NMR spectrum of the Cs-3 complex in CDCl3/CD3OH (1 : 1, v/v). A total of 69 backbone, 27 long-range, and 64 side-chain distance restraints were obtained from NOESY together with 25 phi and 14 chi1 torsion angles obtained from coupling constants. These data were used as input for structure calculation with dyana built in sybyl 6.8. A final set of 11 structures with an average rmsd for the backbone of 0.45 A was obtained (PDB: 1TKQ). The structure of the Cs-3 complex in solution is equivalent to the bioactive channel conformation in the membrane environment.

Gradient-selected (gs) HSQC-NOESY type experiments are often applied in order to obtain NOE cross peaks in symmetrical molecules or in complex organic molecules, e.g. carbohydrates. Since the coherence-selecting gradients in these pulse sequences are separated by several delays, including the mixing time, the gs-HSQC-NOESY spectra exhibit severe signal attenuation due to diffusion effects. The respective NOE information unaffected by diffusion effects can be obtained by X-half-filtered gs-NOESY-HSQC spectra. In this paper, an X-half-filtered version of the gs-NOESY-HSQC experiment is presented and the NOE cross peak integrals of its spectra are compared with those of a standard gs-HSQC-NOESY experiment. With phenanthrene as an example of symmetrical molecules, it is shown that the relative signal attenuation of gs-HSQC-NOESY cross peaks versus gs-NOESY-HSQC cross peaks is caused by diffusion effects and follows the Stejskal-Tanner equation. In contrast, the X-half-filtered gs-NOESY-HSQC experiment provides NOE cross peaks with reasonable signal-to-noise ratios even for long-range interactions in the presence of quadrupolar relaxation. This is demonstrated by the spectra of lithium dimethylcuprate.

Paramagnetic vanadocene gives easily recordable 1H and 13C solid-state NMR signals which are shifted by more than 300 and 500 ppm (to high and low frequency, at room temperature), respectively. The strong temperature dependence of these shifts is the basis of new NMR signal shift thermometers for solutions and for the solid state. Since different signal shifts are found for the two states, primary referencing is established by using a resistance thermometer for solutions and absorbed glycol for the solid state. In the MAS experiment the sample temperature, Ts, depends linearly on the temperature set on the controller, as verified for five rotor spinning rates, νr, between 6 and 12 kHz. The slope and the intercept of the calibration curves depend on νr. In a Tsvs. νr2 plot, a non-linear correlation is found. In addition to 1H, 13C is a useful nucleus for measuring Ts. With simple spectrometer handling and favourable signal shift data, vanadocene meets the requirements of an internal temperature standard for MAS NMR studies. © 1997 John Wiley & Sons, Ltd.

The synthetic use of pseudo-homoatomic Pb-—Bi Zintl anions as an efficient approach to the first M@Pb—Bi ternary intermetalloid clusters with reasonable yields is demonstrated.

The N-heterocyclic carbene-catalyzed conjugate Umpolung of differently substituted α,β-unsaturated aldehydes, e. g. cinnamaldehydes, a-methylcinnamaldehydes, and crotonaldehydes, is described. Coupling of these compounds with a variety of electrophilic aldehydes and ketones results in the selective formation of highly substituted β- and γ-butyrolactones.