A 93Nb Solid‐State NMR and Density Functional Theory Study of Four‐ and Six‐Coordinate Niobate Systems

A variable B₀ field static (broadline) NMR study of a large suite of niobate materials has enabled the elucidation of high‐precision measurement of ⁹³Nb NMR interaction parameters such as the isotropic chemical shift (δ_iso), quadrupole coupling constant and asymmetry parameter (C_Q and η_Q), chemical shift span/anisotropy and skew/asymmetry (Ω/Δδ and κ/η_δ) and Euler angles (α, β, γ) describing the relative orientation of the quadrupolar and chemical shift tensorial frames. These measurements have been augmented with ab initio DFT calculations by using WIEN2k and NMR‐CASTEP codes, which corroborate these reported values. Unlike previous assertions made about the inability to detect CSA (chemical shift anisotropy) contributions from Nb^V in most oxo environments, this study emphasises that a thorough variable B₀ approach coupled with the VOCS (variable offset cumulative spectroscopy) technique for the acquisition of undistorted broad (?1/2?+1/2) central transition resonances facilitates the unambiguous observation of both quadrupolar and CSA contributions within these ⁹³Nb broadline data. These measurements reveal that the ⁹³Nb electric field gradient tensor is a particularly sensitive measure of the immediate and extended environments of the Nb^V positions, with C_Q values in the 0 to >80 MHz range being measured; similarly, the δ_iso (covering an approximately 250 ppm range) and Ω values (covering a 0 to approximately 800 ppm range) characteristic of these niobate systems are also sensitive to structural disposition. However, their systematic rationalisation in terms of the Nb? O bond angles and distances defining the immediate Nb^V oxo environment is complicated by longer‐range influences that usually involve other heavy elements comprising the structure. It has also been established in this study that the best computational method(s) of analysis for the ⁹³Nb NMR interaction parameters generated here are the all‐electron WIEN2k and the gauge included projector augmented wave (GIPAW) NMR‐CASTEP DFT approaches, which account for the short‐ and long‐range symmetries, periodicities and interaction‐potential characteristics for all elements (and particularly the heavy elements) in comparison with Gaussian 03 methods, which focus on terminated portions of the total structure.     

Enhanced Anion Binding from Unusual Coordination Modes of Bis(thiourea) Ligands in Platinum Group Metal Complexes

Treatment of a range of bis(thiourea) ligands with inert organometallic transition‐metal ions gives a number of novel complexes that exhibit unusual ligand binding modes and significantly enhanced anion binding ability. The ruthenium(II) complex [Ru(η⁶‐p‐cymene)(κS,S′,N‐ L³ ?H)]⁺ ( 2 b ) possesses juxtaposed four‐ and seven‐membered chelate rings and binds anions as both 1:1 and 2:1 host guest complexes. The pyridyl bis(thiourea) complex [Ru(η⁶‐p‐cymeme)(κS,S′,N_py‐ L⁴ )]²⁺ ( 4 ) binds anions in both 1:1 and 1:2 species, whereas the free ligand is ineffective because of intramolecular NH???N hydrogen bonding. Novel palladium(II) complexes with nine‐ and ten‐membered chelate rings are also reported.     

The stereochemical assignment of acyclic polyols: a computational study of the NMR data of a library of stereopentad sequences from polyketide natural products

The reliable stereochemical assignment of flexible molecules, such as acyclic polypropionates is an enormously challenging task. This is illustrated by the NMR chemical shifts for a complete set of sixteen diastereomeric stereopentads whose experimental data is reported here for the first time. Although the experimental spectra are very similar to each other, analysis of the similarity between the shifts of different diastereoisomers reveals that some diastereoisomers are much more distinctive than others. In addition, the NMR shifts of the sixteen compounds have also been calculated using DFT GIAO calculations, and the use of our recently developed CP3 parameter for structure assignment is illustrated for these molecules. Even in cases where the experimental spectra are very similar, our CP3 parameter makes possible the correct assignment of pairs of diastereoisomers with high confidence.     

Synthesis and bioactivity of (±)-tetrahydrohaliclonacyclamine A

The total synthesis of tetrahydrohaliclonacyclamine A (5) is described. A key step involves the hydrogenation of an unsaturated bis-piperidine incorporated into a 17-membered macrocycle to provide the cis-syn-cis stereochemistry common to haliclonacyclamines A-D. The hydrogenation product is advanced to the title compound following a five-step reaction sequence. Tetrahydrohaliclonacyclamine A is shown to bind to a variety of ion channels/GPCRs and act as a muscarinic M₁ antagonist.     

Evaluation of Raman probe for oesophageal cancer diagnostics

Early detection of (pre-)cancerous changes improves prognosis, therefore in the UK patients at high risk of developing gastrointestinal cancers are enrolled on endoscopic surveillance programmes or the Bowel Cancer Screening Programme. The current gold standard technique for the detection of pre-cancerous changes in the gastrointestinal tract is histopathological analysis of biopsy tissue collected at endoscopy. This relies upon subjective assessment of morphological changes within the excised tissue samples and poor targeting of pre-malignant lesions. Raman spectroscopy offers a number of potential advantages for in vivo assessment of tissue at endoscopy. The performance of a custom built Raman probe as a biopsy targeting tool has been evaluated using excised biopsy material. Multivariate classification models have been used to demonstrate the likely ability of a miniature, confocal, fibre optic Raman probe to be used as an optical biopsy tool at endoscopy to provide spectral information in clinically practicable timescales. This technique could facilitate improved targeting of excisional biopsy with associated clinical benefits.     

Novel bismuth and lead coordination polymers synthesized with pyridine-2,5-dicarboxylates: two single component "white" light emitting phosphors

New two-dimensional (2D) bismuth and three-dimensional (3D) lead based coordination polymers containing pyridine-2,5-dicarboxylate ligands (H(2)pydc) have been synthesized hydrothermally and characterized by single crystal X-ray diffraction. Bi(3)(μ(3)-O)(2)(pydc)(2)(Hpydc)(H(2)O)(2) (1), which crystallizes in the space group P1? (a = 8.7256(5) ?, b = 11.1217(7) ?, c = 14.0933(9) ?, α = 85.239(1)°, β = 98.582(1)°, γ = 71.106(1)°), has a 3D structure that contains Bi(6)O(4) clusters that connect into 2D sheets via linking ligands. The sheets form a 3D supramolecular structure via hydrogen bonding along the z-axis. Pb(pydc)(H(2)O) (2), which crystallizes in the space group P2(1)/c (a = 10.8343(14) ?, b = 11.2099(15) ?, c = 6.6573(9) ?, β = 90.697(2)°), contains 1D chains of corner-sharing distorted face capped trigonal prisms that are connected into a 3D framework via the pydc ligand. In addition, the ligands are hydrogen bonded to each other. Both 1 and 2 are single component "white" light emitting phosphors and are shown to exhibit "white" luminescence that covers a much wider spectral range than is observed for the as received H(2)pydc ligand.     

Biocompatible copper(I) catalysts for in vivo imaging of glycans

The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is the standard method for bioorthogonal conjugation. However, current Cu(I) catalyst formulations are toxic, hindering their use in living systems. Here we report that BTTES, a tris(triazolylmethyl)amine-based ligand for Cu(I), promotes the cycloaddition reaction rapidly in living systems without apparent toxicity. This catalyst allows, for the first time, noninvasive imaging of fucosylated glycans during zebrafish early embryogenesis. We microinjected embryos with alkyne-bearing GDP-fucose at the one-cell stage and detected the metabolically incorporated unnatural sugars using the biocompatible click chemistry. Labeled glycans could be imaged in the enveloping layer of zebrafish embryos between blastula and early larval stages. This new method paves the way for rapid, noninvasive imaging of biomolecules in living organisms.     

Redetermination of the X-ray structure of nitroxylcobalamin: base-on nitroxylcobalamin exhibits a remarkably long Co-N(dimethylbenzimidazole) bond distance

The X-ray structures of three new crystals of nitroxylcobalamin (NOCbl) have been determined. Unlike our earlier reported structure in which NOCbl was partially oxidized (L. Hannibal, C. A. Smith, D. W. Jacobsen and N. E. Brasch, Angew. Chem., Int. Ed. 2007, 46, 5140), the O atom of the nitroxyl ligand is located in a single position with a N=O bond distance of 1.12-1.14 ?, consistent with a double bond. The Co-N-O angle is in the 118.9-120.3 ? range. The α-axial Co-N(dimethylbenzimidazole) (Co-NB3) bond distance is a remarkable 2.32-2.35 ? in length, ~0.1 ? longer than that reported for all other cobalamin structures. The change in the Gibbs free energy for the base-on/base-off equilibrium now correlates extremely well with the Co-NB3 bond distance, as observed for other cobalamins.     

A top-down LC-FTICR MS-based strategy for characterizing oxidized calmodulin in activated macrophages

A liquid chromatography-mass spectrometry (LC-MS)-based approach for characterizing the degree of nitration and oxidation of intact calmodulin (CaM) has been used to resolve ～250 CaM oxiforms using only 500 ng of protein. The analysis was based on high-resolution data of the intact CaM isoforms obtained by Fourier-transform ion cyclotron resonance mass spectrometry (FTICR MS) coupled with an on-line reversed-phase LC separation. Tentative identifications of post-translational modifications (PTMs), such as oxidation or nitration, have been assigned by matching observed protein mass to a database containing all theoretically predicted oxidation products of CaM and verified through a combination of tryptic peptide information (generated from bottom-up analyses) and on-line collisionally induced dissociation (CID) tandem mass spectrometry (MS/MS) at the intact protein level. The reduction in abundance and diversity of oxidatively modified CaM (i.e., nitrated tyrosines and oxidized methionines) induced by macrophage activation has been explored and semiquantified for different oxidation degrees (i.e., no oxidation, moderate, and high oxidation). This work demonstrates the power of the top-down approach to identify and quantify hundreds of combinations of PTMs for single protein target such as CaM and implicate competing repair and peptidase activities to modulate cellular metabolism in response to oxidative stress.