Pseudodiproline (Pro-Cyp) Oligomers Fold into Helical Polyproline Type secondary structures.

The synthesis and conformational properties of oligo-proline mimetics composed of dimeric and tetrameric Pro-Cyp constructs linked by a hydroxymethylene unit are reported. Oligomers were studied both in the solid state and in solution, unveiling right-handed helical conformation depending on the configuration of the vicinally substituted trans-cyclopentane carboxylic acid unit (Cyp). Unlike polyproline oligomers, the alternating synthetic Pro-Cyp counterparts are not stabilized by n-π* interactions but rely instead on the steric demands of the extended backbone conformation within the hydroxymethylene-linked Pro-Cyp repeating units.

Opening a Pandora's Flask on a Prototype Catalytic Direct Arylation Reaction of Pentafluorobenzene: The Ag2CO3/Pd(OAc)2/PPh3 System.

Direct C-H functionalization reactions have opened new avenues in catalysis, removing the need for prefunctionalization of at least one of the substrates. Although C-H functionalization catalyzed by palladium complexes in the presence of a base is generally considered to proceed by the CMD/AMLA-6 mechanism, recent research has shown that silver(I) salts, frequently used as bases, can function as C-H bond activators instead of (or in addition to) palladium(II). In this study, we examine the coupling of pentafluorobenzene 1 to 4-iodotoluene 2a (and its analogues) to form 4-(pentafluorophenyl)toluene 3a catalyzed by palladium(II) acetate with the commonplace PPh3 ligand, silver carbonate as base, and DMF as solvent. By studying the reaction of 1 with Ag2CO3/PPh3 and with isolated silver (triphenylphosphine) carbonate complexes, we show the formation of C-H activation products containing the Ag(C6F5)(PPh3)n unit. However, analysis is complicated by the lability of the Ag-PPh3 bond and the presence of multiple species in the solution. The speciation of palladium(II) is investigated by high-resolution-MAS NMR (chosen for its suitability for suspensions) with a substoichiometric catalyst, demonstrating the formation of an equilibrium mixture of Pd(Ar)(κ1-OAc)(PPh3)2 and [Pd(Ar)(µ-OAc)(PPh3)]2 as resting states (Ar = Ph, 4-tolyl). These two complexes react stoichiometrically with 1 to form coupling products. The catalytic reaction kinetics is investigated by in situ IR spectroscopy revealing a two-term rate law and dependence on [Pdtot/nPPh3]0.5 consistent with the dissociation of an off-cycle palladium dimer. The first term is independent of [1], whereas the second term is first order in [1]. The observed rates are very similar with Pd(PPh3)4, Pd(Ph)(κ1-OAc)(PPh3)2, and [Pd(Ph)(µ-OAc)(PPh3)]2 catalysts. The kinetic isotope effect varied significantly according to conditions. The multiple speciation of both AgI and PdII acts as a warning against specifying the catalytic cycles in detail. Moreover, the rapid dynamic interconversion of AgI species creates a level of complexity that has not been appreciated previously.

Polygonapholine: A Total Synthesis Questions the Identity for the Purported Structure of the Natural Product.

Polygonapholine was isolated in 1997 from the Polygonatum alte-lobatum rhizome. Based on spectroscopic data, it was assigned a structure comprising an unusual cis-2,6-disubstituted bis-aryl morpholine ring to which is attached a (Z)-4-hydroxycinnamate as an amide and an (E)-4-hydroxycinnamate as an ester. Being a meso compound, polygonapholine should not exhibit an optical rotation as reported. A total synthesis of the purported morpholine alkaloid presented herein reveals discrepancies between the synthetic and the natural product casting doubt on the originally proposed structure.

Design of Pseudodiproline Dimers as Mimetics of Pro-Pro Units: Stereocontrolled Synthesis, Configurational Relevance, and Structural Properties.

Stereocontrolled methods are described for the synthesis of hitherto unreported pseudodiproline dimers in which a cyclopentane carboxylic acid is linked to a pyrrolidine residue by a stereochemically defined hydroxymethylene tether. These proline-cyclopentane (Pro-Cyp) dimers have interesting structural characteristics as seen in their X-ray crystal structures as well as their nuclear magnetic resonance (NMR) spectra in CDCl3. They can be considered to be novel Pro-Pro mimetics, which can be used to replace natural diproline sequences with potential applications in medicinal chemistry. They also represent a new concept in the peptidomimetic design of chimeric proline-based amino acids as carbocyclic hydroxyethylene isosteres of inhibitor molecules, in which the stereodefined bridging hydroxyl group can simulate a tetrahedral intermediate in an enzyme complex.

Building Large Structures with Curved Aromatic Surfaces by Complexing Metals with Phosphangulene.

Phosphangulene (1) is a hexacyclic triarylphosphine with a distinctive conical shape and an electron-rich aromatic surface that is geometrically and electronically complementary to fullerenes such as C60 and C70. As a result, suitable derivatives of phosphangulene can cocrystallize with fullerenes or even bind them in solution. Surprisingly, previous work has largely overlooked the potential of phosphangulene to form complexes with metals, which offers a simple way to create large molecular structures with curved aromatic surfaces. To explore this approach, we have prepared and characterized a series of complexes of phosphangulene with Ag+ and Cu+. Our results show that Phang ligands are exceptional for many reasons. In particular, they can yield metal complexes with unique coordination, and the metal centers hold the concave aromatic surfaces of multiple ligands in various divergent arrays. Moreover, the rigid conical structure of phosphangulene gives the complexes an awkward shape that cannot be packed efficiently without complementary partners. As a result, metal complexes of phosphangulene are predisposed to cocrystallize with fullerenes, thereby yielding materials in which metals and fullerenes are brought together in ordered arrangements.

Configurationally flexible zinc complexes as catalysts for rac-lactide polymerisation.

Zn(N(SiMe3)2)2 was reacted with pyridinemethanol and R,R-N,N'-di(methylbenzyl)-2,5-diiminopyrrole (L1H) to afford the dimeric complex (L1)2Zn2(µ-OR)2. The complex showed moderate activity in rac-lactide polymerization to heterotactic polymer (Pr = 0.75). 2,4-Di-tert-butyl-6-aminomethyl-phenol ligands with amino = N,N,N',N'-tetramethyldiethylenetriamine (L2H) or di-(2-picoly)amine (L3H) were reacted with ZnEt2 to form (L2)ZnEt and with Zn(N(SiMe3)2)2 to form the respective amide complexes. All complexes, including (L1)2Zn2(µ-OR)2 were characterised by X-ray diffraction studies. (L2)ZnEt was unreactive toward ethanol, but the amide complexes afforded (L2)ZnOEt and (L3)ZnOEt upon reaction with ethanol, which were used in rac-lactide polymerization without isolation. All complexes racemise readily at room temperature and show apparent Cs-symmetry in their NMR spectra. The ethoxide complexes were highly active in lactide polymerization, with (L3)ZnOEt reaching full conversion in 15 min at 0.5 mM catalyst concentration at room temperature. In both cases, introduction of a second donor arm on the central nitrogen introduced a slight bias for isotactic monomer enchainment (Pm = 0.55-0.60), which for (L3)ZnOEt was dependent on catalyst concentration.

Self-complementary nickel halides enable multifaceted comparisons of intermolecular halogen bonds: fluoride ligands vs. other halides.

The syntheses of three series of complexes designed with self-complementary motifs for formation of halogen bonds between an iodotetrafluorophenyl ligand and a halide ligand at square-planar nickel are reported, allowing structural comparisons of halogen bonding between all four halides C6F4I···X-Ni (X = F, Cl, Br, I). In the series trans-[NiX(2,3,5,6-C6F4I)(PEt3)2] 1pX and trans-[NiX(2,3,4,5-C6F4I)(PEt3)2] (X = F, Cl, Br, I) 1oX, the iodine substituent on the benzene ring was positioned para and ortho to the metal, respectively. The phosphine substituents were varied in the series, trans-[NiX(2,3,5,6-C6F4I)(PEt2Ph)2] (X = F, I) 2pX. Crystal structures were obtained for the complete series 1pX, and for 1oF, 1oCl, 1oI and 2pI. All these complexes exhibited halogen bonds in the solid state, of which 1pF exhibited unique characteristics with a linear chain, the shortest halogen bond d(C6F4I···F-Ni) = 2.655(5) Å and the greatest reduction in halogen bond distance (I···F) compared to the sum of the Bondi van der Waals radii, 23%. The remaining complexes form zig-zag chains of halogen bonds with distances also reduced with respect to the sum of the van der Waals radii. The magnitude of the reductions follow the pattern F > Cl ∼ Br > I, 1pX > 1oX, consistent with the halogen bond strength following the same order. The variation in the I···X-Ni angles is consistent with the anisotropic charge distribution of the halide ligand. The temperature dependence of the X-ray structure of 1pF revealed a reduction in halogen bond distance of 0.055(7) Å on cooling from 240 to 111 K. Comparison of three polymorphs of 1oI shows that the halogen bond geometry may be altered significantly by the crystalline environment. The effect of the halogen bond on the 19F NMR chemical shift in the solid state is demonstrated by comparison of the magic-angle spinning NMR spectra of 1pF and 1oF with that of a complex incapable of halogen bond formation, trans-[NiF(C6F5)(PEt3)2] 3F. Halogen bonding causes deshielding of δiso in the component of the tensor perpendicular to the nickel coordination plane. The results demonstrate the potential of fluoride ligands for formation of halogen bonds in supramolecular structures.

NAD+ analog reveals PARP-1 substrate-blocking mechanism and allosteric communication from catalytic center to DNA-binding domains.

PARP-1 cleaves NAD+ and transfers the resulting ADP-ribose moiety onto target proteins and onto subsequent polymers of ADP-ribose. An allosteric network connects PARP-1 multi-domain detection of DNA damage to catalytic domain structural changes that relieve catalytic autoinhibition; however, the mechanism of autoinhibition is undefined. Here, we show using the non-hydrolyzable NAD+ analog benzamide adenine dinucleotide (BAD) that PARP-1 autoinhibition results from a selective block on NAD+ binding. Following DNA damage detection, BAD binding to the catalytic domain leads to changes in PARP-1 dynamics at distant DNA-binding surfaces, resulting in increased affinity for DNA damage, and providing direct evidence of reverse allostery. Our findings reveal a two-step mechanism to activate and to then stabilize PARP-1 on a DNA break, indicate that PARP-1 allostery influences persistence on DNA damage, and have important implications for PARP inhibitors that engage the NAD+ binding site.

Capacitance-Assisted Sustainable Electrochemical Carbon Dioxide Mineralisation.

An electrochemical cell comprising a novel dual-component graphite and Earth-crust abundant metal anode, a hydrogen producing cathode and an aqueous sodium chloride electrolyte was constructed and used for carbon dioxide mineralisation. Under an atmosphere of 5 % carbon dioxide in nitrogen, the cell exhibited both capacitive and oxidative electrochemistry at the anode. The graphite acted as a supercapacitive reagent concentrator, pumping carbon dioxide into aqueous solution as hydrogen carbonate. Simultaneous oxidation of the anodic metal generated cations, which reacted with the hydrogen carbonate to give mineralised carbon dioxide. Whilst conventional electrochemical carbon dioxide reduction requires hydrogen, this cell generates hydrogen at the cathode. Carbon capture can be achieved in a highly sustainable manner using scrap metal within the anode, seawater as the electrolyte, an industrially relevant gas stream and a solar panel as an effective zero-carbon energy source.

Conserved asymmetry underpins homodimerization of Dicer-associated double-stranded RNA-binding proteins.

Double-stranded RNA-binding domains (dsRBDs) are commonly found in modular proteins that interact with RNA. Two varieties of dsRBD exist: canonical Type A dsRBDs interact with dsRNA, while non-canonical Type B dsRBDs lack RNA-binding residues and instead interact with other proteins. In higher eukaryotes, the microRNA biogenesis enzyme Dicer forms a 1:1 association with a dsRNA-binding protein (dsRBP). Human Dicer associates with HIV TAR RNA-binding protein (TRBP) or protein activator of PKR (PACT), while Drosophila Dicer-1 associates with Loquacious (Loqs). In each case, the interaction involves a region of the protein that contains a Type B dsRBD. All three dsRBPs are reported to homodimerize, with the Dicer-binding region implicated in self-association. We report that these dsRBD homodimers display structural asymmetry and that this unusual self-association mechanism is conserved from flies to humans. We show that the core dsRBD is sufficient for homodimerization and that mutation of a conserved leucine residue abolishes self-association. We attribute differences in the self-association properties of Loqs, TRBP and PACT to divergence of the composition of the homodimerization interface. Modifications that make TRBP more like PACT enhance self-association. These data are examined in the context of miRNA biogenesis and the protein/protein interaction properties of Type B dsRBDs.

Redox Couple Involving NOx in Aerobic Pd-Catalyzed Oxidation of sp3-C-H Bonds: Direct Evidence for Pd-NO3-/NO2- Interactions Involved in Oxidation and Reductive Elimination.

NaNO3 is used in oxidative Pd-catalyzed processes as a complementary co-catalyst to common oxidants, e.g., CuII salts, in C-H bond activation and Wacker oxidation processes. NaNO3 and NaNO2 (with air or O2) assist the sp3-C-H bond acetoxylation of substrates bearing an N-directing group. It has been proposed previously that a redox couple is operative. The role played by NOx anions is examined in this investigation. Evidence for an NOx anion interaction at PdII is presented. Palladacyclic complexes containing NOx anions are competent catalysts for acetoxylation of 8-methylquinoline, with and without exogenous NaNO3. The oxidation of 8-methylquinoline to the corresponding carboxylic acid has also been noted at PdII. 18O-Labeling studies indicate that oxygen derived from nitrate appears in the acetoxylation product, the transfer of which can only occur by interaction of 18O at Pd with a coordinating-acetate ligand. Nitrated organic intermediates are formed under catalytic conditions, which are converted to acetoxylation products, a process that occurs with (50 °C) and without Pd (110 °C). A catalytically competent palladacyclic dimer intermediate has been identified. Head-space analysis measurements show that NO and NO2 gases are formed within minutes on heating catalytic mixtures to 110 °C from room temperature. Measurements by in situ infrared spectroscopy show that N2O is formed in sp3-C-H acetoxylation reactions at 80 °C. Studies confirm that cyclopalladated NO2 complexes are rapidly oxidized to the corresponding NO3 adducts on exposure to NO2(g). The investigation shows that NOx anions act as participating ligands at PdII in aerobic sp3-C-H bond acetoxylation processes and are involved in redox processes.

DNA recognition for virus assembly through multiple sequence-independent interactions with a helix-turn-helix motif.

The helix-turn-helix (HTH) motif features frequently in protein DNA-binding assemblies. Viral pac site-targeting small terminase proteins possess an unusual architecture in which the HTH motifs are displayed in a ring, distinct from the classical HTH dimer. Here we investigate how such a circular array of HTH motifs enables specific recognition of the viral genome for initiation of DNA packaging during virus assembly. We found, by surface plasmon resonance and analytical ultracentrifugation, that individual HTH motifs of the Bacillus phage SF6 small terminase bind the packaging regions of SF6 and related SPP1 genome weakly, with little local sequence specificity. Nuclear magnetic resonance chemical shift perturbation studies with an arbitrary single-site substrate suggest that the HTH motif contacts DNA similarly to how certain HTH proteins contact DNA non-specifically. Our observations support a model where specificity is generated through conformational selection of an intrinsically bent DNA segment by a ring of HTHs which bind weakly but cooperatively. Such a system would enable viral gene regulation and control of the viral life cycle, with a minimal genome, conferring a major evolutionary advantage for SPP1-like viruses.

Photochemical pump and NMR probe to monitor the formation and kinetics of hyperpolarized metal dihydrides.

On reaction of IrI(CO)(PPh3)21 with para-hydrogen (p-H2), Ir(H)2I(CO)(PPh3)22 is formed which exhibits strongly enhanced 1H NMR signals for its hydride resonances. Complex 2 also shows similar enhancement of its NMR spectra when it is irradiated under p-H2. We report the use of this photochemical reactivity to measure the kinetics of H2 addition by laser-synchronized reactions in conjunction with NMR. The single laser pulse promotes the reductive elimination of H2 from Ir(H)2I(CO)(PPh3)22 in C6D6 solution to form the 16-electron precursor 1, back reaction with p-H2 then reforms 2 in a well-defined nuclear spin-state. The build up of this product can be followed by incrementing a precisely controlled delay (τ), in millisecond steps, between the laser and the NMR pulse. The resulting signal vs. time profile shows a dependence on p-H2 pressure. The plot of kobs against p-H2 pressure is linear and yields the second order rate constant, k2, for H2 addition to 1 of (3.26 ± 0.42) × 102 M-1 s-1. Validation was achieved by transient-UV-vis absorption spectroscopy which gives k2 of (3.06 ± 0.40) × 102 M-1 s-1. Furthermore, irradiation of a C6D6 solution of 2 with multiple laser shots, in conjunction with p-H2 derived hyperpolarization, allows the detection and characterisation of two minor reaction products, 2a and 3, which are produced in such low yields that they are not detected without hyperpolarization. Complex 2a is a configurational isomer of 2, while 3 is formed by substitution of CO by PPh3.

Synthesis of a series of new platinum organometallic complexes derived from bidentate Schiff-base ligands and their catalytic activity in the hydrosilylation and dehydrosilylation of styrene.

The synthesis and properties of a novel class of platinum complexes containing Schiff bases as O,N-bidentate ligands is described as are the solution and solid state properties of the uncomplexed ligands. The platinum complexes were prepared from [PtBr2(COD)] (COD = 1,5-cyclooctadiene) and N-(2-hydroxy-1-naphthalidene)aniline derivatives in the presence of base (NaOBu(t)). Instead of a substitution reaction to afford cationic species, the addition of the Schiff base ligands results in both the formal loss of two equivalents of bromide and addition of hydroxide to the COD ligand of the complexes. It is proposed that this reaction proceeds through a cationic platinum complex [Pt(N-O)(COD)]Br which then undergoes addition of water and loss of HBr. An example of a dinuclear platinum complex in which two cyclo-octene ligands are bridged by an ether linkage is also reported. The platinum complexes were evaluated as catalysts for the hydrogenative and dehydrogenative silylation of styrene, the resulting behaviour is substituent, time and temperature dependent.

Simultaneous recovery of organic and inorganic content of paper deinking residue through low-temperature microwave-assisted pyrolysis.

Significant amounts of paper deinking residue (DIR) has been and is still being generated from paper deinking processes, representing both an economic and environmental burden for recycled paper mills. Our research on low-temperature (<200 °C) microwave-assisted (MW-assisted) pyrolysis of DIR allows for simultaneously efficient fast separation and recovery of the organic and inorganic content of DIR at relatively low temperature and within 15 min. Our study is the first highly detailed account of the use low-temperature MW-assisted pyrolysis to effect this change. The obtained liquid and solid products were characterized by a variety of analytical techniques (e.g., attenuated total reflection infrared, gas chromatography-mass spectrometry, liquid-state nuclear magnetic resonance (NMR), X-ray diffraction, solid-state cross-polarization/magic-angle spinning (13)C NMR, and Bloch-decay (13)C NMR). The results reveal that the process efficiently separates the inorganic minerals as microwave residue (mainly calcite and kaolinite) from organic matter, and hence the microwave residue could be reused to produce new paper/cardboard products. The organic fraction bio-oil generated is energy-densified and rich in carbohydrates and is a potential source for valuable aromatic compounds.

(1)H high resolution magic-angle coil spinning (HR-MACS) µNMR metabolic profiling of whole Saccharomyces cervisiae cells: a demonstrative study.

The low sensitivity and thus need for large sample volume is one of the major drawbacks of Nuclear Magnetic Resonance (NMR) spectroscopy. This is especially problematic for performing rich metabolic profiling of scarce samples such as whole cells or living organisms. This study evaluates a (1)H HR-MAS approach for metabolic profiling of small volumes (250 nl) of whole cells. We have applied an emerging micro-NMR technology, high-resolution magic-angle coil spinning (HR-MACS), to study whole Saccharomyces cervisiae cells. We find that high-resolution high-sensitivity spectra can be obtained with only 19 million cells and, as a demonstration of the metabolic profiling potential, we perform two independent metabolomics studies identifying the significant metabolites associated with osmotic stress and aging.

Local and average structure in zinc cyanide: toward an understanding of the atomistic origin of negative thermal expansion.

Neutron diffraction at 11.4 and 295 K and solid-state (67)Zn NMR are used to determine both the local and the average structures in the disordered, negative thermal expansion (NTE) material, Zn(CN)2. Solid-state NMR not only confirms that there is head-to-tail disorder of the C≡N groups present in the solid, but yields information about the relative abundances of the different Zn(CN)4­n(NC)n tetrahedral species, which do not follow a simple binomial distribution. The Zn(CN)4 and Zn(NC)4 species occur with much lower probabilities than are predicted by binomial theory, supporting the conclusion that they are of higher energy than the other local arrangements. The lowest energy arrangement is Zn(CN)2(NC)2. The use of total neutron diffraction at 11.4 K, with analysis of both the Bragg diffraction and the derived total correlation function, yields the first experimental determination of the individual Zn­N and Zn­C bond lengths as 1.969(2) and 2.030(2) Å, respectively. The very small difference in bond lengths, of ~0.06 Å, means that it is impossible to obtain these bond lengths using Bragg diffraction in isolation. Total neutron diffraction also provides information on both the average and the local atomic displacements responsible for NTE in Zn(CN)2. The principal motions giving rise to NTE are shown to be those in which the carbon and nitrogen atoms within individual Zn­C≡N­Zn linkages are displaced to the same side of the Zn···Zn axis. Displacements of the carbon and nitrogen atoms to opposite sides of the Zn···Zn axis, suggested previously in X-ray studies as being responsible for NTE behavior, in fact make negligible contributions at temperatures up to 295 K.

Connectivity-enforcing Hough transform for the robust extraction of line segments.

Global voting schemes based on the Hough transform (HT) have been widely used to robustly detect lines in images. However, since the votes do not take line connectivity into account, these methods do not deal well with cluttered images. On the other hand, the so-called local methods enforce connectivity but lack robustness to deal with challenging situations that occur in many realistic scenarios, e.g., when line segments cross or when long segments are corrupted. We address the critical limitations of the HT as a line segment extractor by incorporating connectivity in the voting process. This is done by only accounting for the contributions of edge points lying in increasingly larger neighborhoods and whose position and directional information agree with potential line segments. As a result, our method, which we call segment extraction by connectivity-enforcing HT (STRAIGHT), extracts the longest connected segments in each location of the image, thus also integrating into the HT voting process the usually separate step of individual segment extraction. The usage of the Hough space mapping and a corresponding hierarchical implementation make our approach computationally feasible. We present experiments that illustrate, with synthetic and real images, how STRAIGHT succeeds in extracting complete segments in situations where current methods fail.

Revisiting complex moments for 2-D shape representation and image normalization.

When comparing 2-D shapes, a key issue is their normalization. Translation and scale are easily taken care of by removing the mean and normalizing the energy. However, defining and computing the orientation of a 2-D shape is not so simple. In fact, although for elongated shapes the principal axis can be used to define one of two possible orientations, there is no such tool for general shapes. As we show in the paper, previous approaches fail to compute the orientation of even noiseless observations of simple shapes. We address this problem and show how to uniquely define the orientation of an arbitrary 2-D shape, in terms of what we call its Principal Moments. We start by showing that a small subset of these moments suffices to describe the underlying 2-D shape, i.e., that they form a compact representation, which is particularly relevant when dealing with large databases. Then, we propose a new method to efficiently compute the shape orientation: Principal Moment Analysis. Finally, we discuss how this method can further be applied to normalize gray-level images. Besides the theoretical proof of correctness, we describe experiments demonstrating robustness to noise and illustrating with real images.