The stereoselective coordination chemistry of the helicating ligand N,N '-bis(-2,2 '-dipyridyl-5-yl)carbonyl-(S/R,S/R)-1,2-diphenylethylenediamine

Enantiomerically pure N,N'-bis(-2,2'-dipyridyl-5-yl)carbonyl-(S/R,S/R)-1,2-diphenylethylenediamine has been synthesised by linking two 2,2'-bipyridine units by (R,R)- and (S,S)-1,2-diphenylethylenediamine. The ligands possess a hindered rotation between the bipyridine chromophores, which are held together by intramolecular hydrogen bonds. ES mass spectroscopy confirmed that reaction with Fe(II), Co(III) and Cd(II) afforded dinuclear complexes. CD spectroscopy implied that enantiopure ligands conferred helicity to the metals centre giving a dominant triple helicate diastereoisomer (with the RR isomer giving a P helicate). H-1 NMR spectroscopy of the cadmium complex confirmed the presence of a single diastereoisomer. (C) 2003 Elsevier B.V. All rights reserved.

Synthesis of a tetraoxy-bis-nortaxadiene, en route to taxol, using a cascade radical cyclisation sequence

Concise syntheses of the substituted enynediones 28a, 33b and 36 starting from the cyclohexenealdehyde 18, corresponding to ring A in the taxanes, and the vinylstannane 24, are described. Treatment of 36 with Bu3SnH–AIBN did not lead to the oxy-substituted taxadiene 37 expected from a tandem radical macrocyclisation–radical transannulation sequence; instead, a mixture of unidentified products resulted. When the PMB ether 33b corresponding to the alcohol 36 was treated with Bu3SnH–AIBN under similar conditions, p-anisaldehyde was isolated, as a major by-product, but no evidence for the formation of a taxadiene could be observed. In contrast, the iododienynedione 41, i.e., deoxy 36, underwent a tandem radical macrocyclisation–transannulation sequence, when treated with Bu3SnH–AIBN, leading to the tetraoxy-bis-nortaxadiene 42 in 44% yield. Attempts to synthesise the alcohol 28b from the silyl ether 28a en route to the iodide 28c instead gave the substituted tetrahydrofuran 29 via an intramolecular oxy-Michael reaction.

A Concise Approach to a Gelsemine Core Structure using an Oxygen to Carbon Bridge Swapping Strategy

A tricyclic core structure related to gelsemine was synthesized from an oxabicyclo[3.2.1]octanone by a three-step bridge swapping strategy involving elimination of the bridging ether oxygen and intramolecular Michael addition of a tethered cyanoacetamide unit.

Palladium-mediated reductive coupling, a stereoselective approach to the 8-dehydropumiliotoxin skeleton

Reductive cyclisation of ail E-vinyl bromide with ail allylic acetate proceeds under palladium catalysis 10 give the 8-dehydropumiliotoxin skeleton, a potential advanced precursor to 8-deoxypumiliotoxin alkaloids. Control of the stereochemistry of the E-vinyl bromide precursor is achieved readily using the Kogen or Bruckner bromophosphonate reagents and the reductive cyclisation proceeds with retention of the vinyl bromide stereochemistry. The mechanism for the cyclisation involves an in situ conversion of the allylic acetate to ail allyl stannane followed by ail intramolecular Stille-type coupling.

Palladium catalysed formal 6-endo-trig approaches to pumiliotoxin alkaloids: interception of the elusive cyclopropyl intermediate

Intramolecular Heck cyclisation of (E)-vinyl bromides leads to indolizidines, related to pumiliotoxin alkaloids, in which the stereochemistry of the trisubstituted double bond undergoes inversion. A cyclopropyl intermediate, which is believed to be responsible for the double bond inversion, has been intercepted by forcing an 'early' beta-hydride elimination on this species. The relative stereochemistry of this cyclopropyl intermediate determines the regioselectivity of the final beta-hydride elimination. In this case all three beta-hydride eliminations were stereochemically permitted, giving rise to a mixture of three isomeric products, differing in the position of a double bond. (Z)-Vinyl bromides were found to be less reactive than (E)-vinyl bromides, but on cyclisation gave the required conjugated diene, with inversion of the vinyl bromide stereochemistry, as the sole reaction product. This methodology will allow rapid stereoselective access to the diene-based pumiliotoxin alkaloids.

Electron attachment to SF(6) and lifetimes of SF(6)(-) negative ions

We study the process of low-energy electron capture by the SF(6) molecule. Our approach is based on the model of Gauyacq and Herzenberg [J. P. Gauyacq and A. Herzenberg, J. Phys. B 17, 1155 (1984)] in which the electron motion is coupled to the fully symmetric vibrational mode through a weakly bound or virtual s state. By tuning the two free parameters of the model, we achieve an accurate description of the measured electron attachment cross section and good agreement with vibrational excitation cross sections of the fully symmetric mode. An extension of the model provides a limit on the characteristic time of intramolecular vibrational relaxation in highly excited SF(6)(-). By evaluating the total vibrational spectrum density of SF(6)(-), we estimate the widths of the vibrational Feshbach resonances of the long-lived negative ion. We also analyze the possible distribution of the widths and its effect on the lifetime measurements, and investigate nonexponential decay features in metastable SF(6)(-).

Positron-molecule interactions: Resonant attachment, annihilation, and bound states

This article presents an overview of current understanding of the interaction of low-energy positrons with molecules with emphasis on resonances, positron attachment, and annihilation. Measurements of annihilation rates resolved as a function of positron energy reveal the presence of vibrational Feshbach resonances (VFRs) for many polyatomic molecules. These resonances lead to strong enhancement of the annihilation rates. They also provide evidence that positrons bind to many molecular species. A quantitative theory of VFR-mediated attachment to small molecules is presented. It is tested successfully for selected molecule (e.g., methyl halides and methanol) where all modes couple to the positron continuum. Combination and overtone resonances are observed and their role is elucidated. Molecules that do not bind positrons and hence do not exhibit such resonances are discussed. In larger molecules, annihilation rates from VFR far exceed those explicable on the basis of single-mode resonances. These enhancements increase rapidly with the number of vibrational degrees of freedom, approximately as the fourth power of the number of atoms in the molecule. While the details are as yet unclear, intramolecular vibrational energy redistributio (IVR) to states that do not couple directly to the positron continuum appears to be responsible for these enhanced annihilation rates. In connection with IVR, experimental evidence indicates that inelastic positron escape channels are relatively rare. Downshifts of the VFR from the vibrational mode energies, obtained by measuring annihilate rates as a function of incident positron energy, have provided binding energies for 30 species. Their dependence upon molecular parameters and their relationship to positron-atom and positron-molecule binding-energy calculations are discussed. Feshbach resonances and positron binding to molecules are compared with the analogous electron-molecul (negative-ion) cases. The relationship of VFR-mediated annihilation to other phenomena such as Doppler broadening of the gamma-ray annihilation spectra, annihilation of thermalized positrons in gases, and annihilation-induced fragmentation of molecules is discussed. Possible areas for future theoretical and experimental investigation are also discussed.

Sequential C-H and C-Ru bond formation and cleavage during the thermally induced rearrangement of aryl ruthenium(II) complexes with [C6H3(CH2NMe2)(2)-2,6](-) as a bidentate eta(2)-C,N coordinated ligand. The crystal structures of the isomeric pairs [RuCl{eta(6)-C10H14}{eta(2)-C,N-C6H3(CH2NMe2)(2)-2,n}] (n = 4 or 6) and [Ru(eta(5)-C5H5){(eta(2)-C,N-C6H3(CH2NMe2)(2)-2,n} (PPH3)] (n = 4 or 6)

New air-stable ruthenium(II) complexes that contain the aryldiamine ligand [C6H3(CH2-NMe2)(2)-2,6](-) (NCN) are described. These complexes are [RuCl{eta(2)-C,N-C6H3(CH2NMe2)(2)-2,6}(eta(6)-C10H14)] (2; C10H14 = p-cymene = C6H4Me-Pr-i-4), [Ru{eta(2)-C,N-C6H3(CH2NMe2)(2)-2,6}(eta(5)-C5H5)(PPh3)] (5), and their isomeric forms [RuCl{eta(2)-C,N-C6H3(CH2NMe2)(2)-2,4}(eta(6)-C10H14)] (3) and [Ru{eta(2)-C,N-C6H3(CH2NMe2)(2)-2,4}(eta(5)-C5H5)(PPh3)] (6), respectively. Complex 2 has been prepared from the reaction of [Li(NCN)](2) with [RuCl2(eta(6)-C10H14)](2), whereas complex 5 has been prepared by the treatment of [RuCl{eta(3)-N,C,N-C6H3(CH2NMe2)(2)-2,6}(PPh3)] (4) with [Na(C5H5)](n). Both 2 and 5 are formally 18-electron ruthenium(II) complexes in which the monoanionic potentially tridentate coordinating ligand NCN is eta(2)-C,N-bonded, In solution (halocarbon solvent at room temperature or in aromatic solvents at elevated temperature), the intramolecular rearrangements of 2 and 5 afford complexes 3 and 6, respectively. This is a result of a shift of the metal-C-aryl bond from position-1 to position-3 on the aromatic ring of the NCN ligand. The mechanism of the isomerization is proposed to involve a sequence of intramolecular oxidative addition and reductive elimination reactions of both aromatic and aliphatic C-H bonds. This is based on results from deuterium labeling, spectroscopic studies, and some kinetic experiments. The mechanism is proposed to contain fully reversible steps in the case of 5, but a nonreversible step involving oxidative addition of a methyl NCH2-H bond in the case of 2. The solid-state structures of complexes 2, 3, 5, and 6 have been determined by single-crystal X-ray diffraction. A new dinuclear 1,4-phenylene-bridged bisruthenium(II) complex, [1,4-{RuCl(eta(6)-C10H14)}(2){C-6(CH2NMe2)(4)-2,3,5,6-C,N,C',N'}] (9) has also been prepared from the dianionic ligand [C-6(CH2NMe2)(4)-2,3,5,6](2-) (C2N4). The C2N4 ligand is in an eta(2)-C,N-eta(2)-C',N'-bis(bidentate) bonding mode. Compound 9 does not isomerize in solution (halocarbon solvent), presumably because of the absence of an accessible C-aryl-H bond. Complex 9 could not be isolated in an analytically pure form, probably because of its high sensitivity to air and very low solubility, which precludes recrystallization.

Dispersion interactions in room-temperature ionic liquids: Results from a non-empirical density functional

The role of dispersion or van de Waals (VDW) interactions in imidazolium-based room-temperature ionic liquids is studied within the framework of density functional theory, using a recently developed non-empirical functional [M. Dion, H. Rydberg, E. Schroder, D. C. Langreth, and B. I. Lundqvist, Phys. Rev. Lett. 92, 246401 (2004)], as efficiently implemented in the SIESTA code [G. Roman-Perez and J. M. Soler, Phys. Rev. Lett. 103, 096102 (2009)]. We present results for the equilibrium structure and lattice parameters of several crystalline phases, finding a general improvement with respect to both the local density (LDA) and the generalized gradient approximations (GGA). Similar to other systems characterized by VDW bonding, such as rare gas and benzene dimers as well as solid argon, equilibrium distances and volumes are consistently overestimated by approximate to 7%, compared to -11% within LDA and 11% within GGA. The intramolecular geometries are retained, while the intermolecular distances and orientations are significantly improved relative to LDA and GGA. The quality is superior to that achieved with tailor-made empirical VDW corrections ad hoc [M. G. Del Popolo, C. Pinilla, and P. Ballone, J. Chem. Phys. 126, 144705 (2007)]. We also analyse the performance of an optimized version of this non-empirical functional, where the screening properties of the exchange have been tuned to reproduce high-level quantum chemical calculations [J. Klimes, D. Bowler, and A. Michaelides, J. Phys.: Condens. Matter 22, 074203 (2010)]. The results for solids are even better with volumes and geometries reproduced within 2% of experimental data. We provide some insight into the issue of polymorphism of [bmim][Cl] crystals, and we present results for the geometry and energetics of [bmim][Tf] and [mmim][Cl] neutral and charged clusters, which validate the use of empirical force fields. (C) 2011 American Institute of Physics. [doi:10.1063/1.3652897]

Synthesis of the putative structures of homopumiliotoxins 235C and 233F

A novel approach to diene based quinolizidines, using an intramolecular Heck reaction in which the vinyl bromide double bond undergoes inversion of configuration, is reported. These quinolizidines have previously been proposed as tentative structures for homopumiliotoxin alkaloids 233F and 235C. The mass spectral data of the synthetic materials were different to those of the natural products confirming that the original structures need to be revised. (C) 2004 Elsevier Ltd. All rights reserved.

Subdivision of the bacterioferritin comigratory protein family of bacterial peroxiredoxins based on catalytic activity

Peroxiredoxins are ubiquitous proteins that catalyze the reduction of hydroperoxides, thus conferring resistance to oxidative stress. Using high-resolution mass spectrometry, we recently reclassified one such peroxiredoxin, bacterioferritin comigratory protein (BCP) of Escherichia coli, as an atypical 2-Cys peroxiredoxin that functions through the formation of an intramolecular disulfide bond between the active and resolving cysteine. An engineered E. coli BCP, which lacked the resolving cysteine, retained enzyme activity through a novel catalytic pathway. Unlike the active cysteine, the resolving cysteine of BCP peroxiredoxins is not conserved across all members of the family. To clarify the catalytic mechanism of native BCP enzymes that lack the resolving cysteine, we have investigated the BCP homologue of Burkholderia cenocepacia. We demonstrate that the B. cenocepacia BCP (BcBCP) homologue functions through a 1-Cys catalytic pathway. During catalysis, BcBCP can utilize thioredoxin as a reductant for the sulfenic acid intermediate. However, significantly higher peroxidase activity is observed utilizing glutathione as a resolving cysteine and glutaredoxin as a redox partner. Introduction of a resolving cysteine into BcBCP changes the activity from a 1-Cys pathway to an atypical 2-Cys pathway, analogous to the E. coli enzyme. In contrast to the native B. cenocepacia enzyme, thioredoxin is the preferred redox partner for this atypical 2-Cys variant. BCP-deficient B. cenocepacia exhibit a growth-phase-dependent hypersensitivity to oxidative killing. On the basis of sequence alignments, we believe that BcBCP described herein is representative of the major class of bacterial BCP peroxiredoxins. To our knowledge, this is the first detailed characterization of their catalytic activity. These studies support the subdivision of the BCP family of peroxiredoxins into two classes based on their catalytic activity.

Photocontrolled Binding and Binding-Controlled Photochromism within Anthracene-Modified DNA

Modified DNA strands undergo a reversible light-induced reaction involving the intramolecular photodimerization of two appended anthracene tags. The photodimers exhibit markedly different binding behavior toward a complementary strand that depends on the number of bases between the modified positions. By preforming the duplex, photochromism can be suppressed, illustrating dual-mode gated behavior.

The chains of the heterodimeric amphibian skin antimicrobial peptide, distinctin, are encoded by separate messenger RNAs

Using a primer to a conserved nucleotide sequence of previously-cloned skin peptides of Phyllomedusa species, two distinct cDNAs were “shotgun” cloned from a skin secretion-derived cDNA library of the frog, Phyllomedusa burmeisteri. The two ORFs separately encode chains A and B of an analog of the previously-reported heterodimeric peptide, distinctin. LC-MS/MS analysis of native versus dithiotreitol reduced crude venom, confirmed the predicted primary sequences as well as the cystine link between the two monomers. Distinctin predominantly exists in the venom as a heterodimer (A-B), neither of the constituent peptides were detected as monomer, whereas of the two possible homodimers (A-A or B-B), only B-B was detected in comparatively low quantity. In vitro dimerization of synthetic replicates of the monomers demonstrated that besides heterodimer, both homodimers are also formed in considerable amounts. Distinctin is the first example of an amphibian skin dimeric peptide that is formed by covalent linkage of two chains that are the products of different mRNAs. How this phenomenon occurs in vivo, to exclude significant homodimer formation, is unclear at present but a “favored steric state” type of interaction between chains is most likely.

Magnetic properties of copper hexadecaphthalocyanine (F16CuPc) thin films and powders

The structural and magnetic properties of F16CuPc thin films and powder, including x-ray diffraction (XRD), superconducting quantum interference device (SQUID) magnetometry, and theoretical modelling of exchange interactions are reported. Analysis of XRD from films, with thickness ranging between 100 and 160 nm, deposited onto Kapton and a perylene-3,4,9,10-tetracarboxylic-3,4,9,10-dianhydride (PTCDA) interlayer shows that the stacking angle (defined in the text) of the film is independent of the thickness, but that the texture is modified by both film thickness and substrate chemistry. The SQUID measurements suggest that all samples are paramagnetic, a result that is confirmed by our theoretical modelling including density functional theory calculations of one-dimensional molecular chains and Green's function perturbation theory calculations for a molecular dimer. By investigating theoretically a range of different geometries, we predict that the maximum possible exchange interaction between F16CuPc molecules is twice as large as that in unfluorinated copper-phthalocyanine (CuPc). This difference arises from the smaller intermolecular spacing in F16CuPc. Our density functional theory calculation for isolated F16CuPc molecule also shows that the energy levels of Kohn-Sham orbitals are rigidly shifted similar to 1 eV lower in F16CuPc compared to CuPc without a significant modification of the intramolecular spin physics, and that therefore the two molecules provide a suitable platform for independently varying magnetism and charge transport. 

Novel synthetic route to the C-nucleoside, 2-deoxy benzamide riboside

2-Deoxy-C-nucleosides are a subcategory of C-nucleosides that has not been explored extensively, largely because the synthesis is less facile. Flexible synthetic procedures giving access to 2-deoxy-C-nucleosides are therefore of interest. To exemplify the versatility and highlight the limitations of a synthetic route recently developed to that effect, the first synthesis of 2-deoxy benzamide riboside is reported. Biological properties of this novel C-nucleoside are also discussed. (c) 2012 Elsevier Ltd. All rights reserved.