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Kuopio, Finland

Thiele H.,Bruker | McLeod G.,Bruker | Niemitz M.,PERCH Solutions Ltd | Kuhn T.,Bruker
Monatshefte fur Chemie

Abstract: The new complete molecular confidence (CMC) concept explores the synergies of the analytical techniques LC-MS and NMR to obtain an estimation of the purity, concentration, and identity of chemical compounds. The high mass accuracy of the MS and MS/MS data provided by the new generation of ESI-TOF and ESI-Q-TOF mass spectrometers provides an accurate determination of molecular weight, which is used specifically for the structural verification and purity determination of substances. The high separation of the isotope profile for both MS and MS/MS spectra affords further dimensions of information to achieve precise molecular formula determination. By performing a complete NMR spectral analysis, the automated consistency analysis routine provides a safe assessment of the consistency between molecular structure and 1H NMR spectrum. The routine returns the fully assigned spectrum and the accurate NMR parameters extracted from the experimental data. Absolute quantification of a series of samples can be automatically performed including the whole workflow from sample setup, automatic NMR measurements, analysis, and spread-sheet reporting. This allows determining mass contents, relative amounts of substances, and purity. The strategy is explored on a set of 96 different pyrrole derivates. Graphical Abstract: [Figure not available: see fulltext.] © 2011 Springer-Verlag. Source

Aranibar N.,Bristol Myers Squibb | Borys M.,Bristol Myers Squibb | Mackin N.A.,Bristol Myers Squibb | Ly V.,Bristol Myers Squibb | And 9 more authors.
Journal of Biomolecular NMR

NMR spectroscopy was used to evaluate growth media and the cellular metabolome in two systems of interest to biomedical research. The first of these was a Chinese hamster ovary cell line engineered to express a recombinant protein. Here, NMR spectroscopy and a quantum mechanical total line shape analysis were utilized to quantify 30 metabolites such as amino acids, Krebs cycle intermediates, activated sugars, cofactors, and others in both media and cell extracts. The impact of bioreactor scale and addition of anti-apoptotic agents to the media on the extracellular and intracellular metabolome indicated changes in metabolic pathways of energy utilization. These results shed light into culture parameters that can be manipulated to optimize growth and protein production. Second, metabolomic analysis was performed on the superfusion media in a common model used for drug metabolism and toxicology studies, in vitro liver slices. In this study, it is demonstrated that two of the 48 standard media components, choline and histidine are depleted at a faster rate than many other nutrients. Augmenting the starting media with extra choline and histidine improves the long-term liver slice viability as measured by higher tissues levels of lactate dehydrogenase (LDH), glutathione and ATP, as well as lower LDH levels in the media at time points out to 94 h after initiation of incubation. In both models, media components and cellular metabolites are measured over time and correlated with currently accepted endpoint measures. © 2011 Springer Science+Business Media B.V. Source

Pauli G.F.,University of Illinois at Chicago | Niemitz M.,PERCH Solutions Ltd | Bisson J.,University of Illinois at Chicago | Lodewyk M.W.,Butte College | And 12 more authors.
Journal of Organic Chemistry

The revision of the structure of the sesquiterpene aquatolide from a bicyclo[2.2.0]hexane to a bicyclo[2.1.1]hexane structure using compelling NMR data, X-ray crystallography, and the recent confirmation via full synthesis exemplify that the achievement of "structural correctness" depends on the completeness of the experimental evidence. Archived FIDs and newly acquired aquatolide spectra demonstrate that archiving and rigorous interpretation of 1D 1H NMR data may enhance the reproducibility of (bio)chemical research and curb the growing trend of structural misassignments. Despite being the most accessible NMR experiment, 1D 1H spectra encode a wealth of information about bonds and molecular geometry that may be fully mined by 1H iterative full spin analysis (HiFSA). Fully characterized 1D 1H spectra are unideterminant for a given structure. The corresponding FIDs may be readily submitted with publications and collected in databases. Proton NMR spectra are indispensable for structural characterization even in conjunction with 2D data. Quantum interaction and linkage tables (QuILTs) are introduced for a more intuitive visualization of 1D J-coupling relationships, NOESY correlations, and heteronuclear experiments. Overall, this study represents a significant contribution to best practices in NMR-based structural analysis and dereplication. © 2016 American Chemical Society. Source

Nam J.-W.,University of Illinois at Chicago | Phansalkar R.S.,University of Illinois at Chicago | Lankin D.C.,University of Illinois at Chicago | Bisson J.,University of Illinois at Chicago | And 8 more authors.
Journal of Organic Chemistry

The ability of certain oligomeric proanthocyanidins (OPACs) to enhance the biomechanical properties of dentin involves collagen cross-linking of the 1.3-4.5 nm wide space via protein-polyphenol interactions. A systematic interdisciplinary search for the bioactive principles of pine bark has yielded the trimeric PAC, ent-epicatechin-(4β'8)-epicatechin-(2β'O'7,4β'8)-catechin (3), representing the hitherto most potent single chemical entity capable of enhancing dentin stiffness. Building the case from two congeneric PAC dimers, a detailed structural analysis decoded the stereochemistry, spatial arrangement, and chemical properties of three dentin biomodifiers. Quantum-mechanics-driven 1H iterative full spin analysis (QM-HiFSA) of NMR spectra distinguished previously unrecognized details such as higher order J coupling and provided valuable information about 3D structure. Detection and quantification of H/D-exchange effects by QM-HiFSA identified C-8 and C-6 as (re)active sites, explain preferences in biosynthetic linkage, and suggest their involvement in dentin cross-linking activity. Mapping of these molecular properties underscored the significance of high δ precision in both 1H and 13C NMR spectroscopy. Occurring at low- to subppb levels, these newly characterized chemical shift differences in ppb are small but diagnostic measures of dynamic processes inherent to the OPAC pharmacophores and can help augment our understanding of nanometer-scale intermolecular interactions in biomodified dentin macromolecules. © 2015 American Chemical Society. Source

Pauli G.F.,University of Illinois at Chicago | Chen S.-N.,University of Illinois at Chicago | Lankin D.C.,University of Illinois at Chicago | Bisson J.,University of Illinois at Chicago | And 13 more authors.
Journal of Natural Products

The present study demonstrates the importance of adequate precision when reporting the λ and J parameters of frequency domain 1H NMR (HNMR) data. Using a variety of structural classes (terpenoids, phenolics, alkaloids) from different taxa (plants, cyanobacteria), this study develops rationales that explain the importance of enhanced precision in NMR spectroscopic analysis and rationalizes the need for reporting Δλ and ΔJ values at the 0.1-1 ppb and 10 mHz level, respectively. Spectral simulations paired with iteration are shown to be essential tools for complete spectral interpretation, adequate precision, and unambiguous HNMR-driven dereplication and metabolomic analysis. The broader applicability of the recommendation relates to the physicochemical properties of hydrogen ( 1H) and its ubiquity in organic molecules, making HNMR spectra an integral component of structure elucidation and verification. Regardless of origin or molecular weight, the HNMR spectrum of a compound can be very complex and encode a wealth of structural information that is often obscured by limited spectral dispersion and the occurrence of higher order effects. This altogether limits spectral interpretation, confines decoding of the underlying spin parameters, and explains the major challenge associated with the translation of HNMR spectra into tabulated information. On the other hand, the reproducibility of the spectral data set of any (new) chemical entity is essential for its structure elucidation and subsequent dereplication. Handling and documenting HNMR data with adequate precision is critical for establishing unequivocal links between chemical structure, analytical data, metabolomes, and biological activity. Using the full potential of HNMR spectra will facilitate the general reproducibility for future studies of bioactive chemicals, especially of compounds obtained from the diversity of terrestrial and marine organisms. © 2014 The American Chemical Society and American Society of Pharmacognosy. Source

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