Dataset Information

HiFSA fingerprinting applied to isomers with near-identical NMR spectra: the silybin/isosilybin case.

ABSTRACT: This study demonstrates how regio- and diastereo-isomers with near-identical NMR spectra can be distinguished and unambiguously assigned using quantum mechanical driven (1)H iterative Full Spin Analysis (HiFSA). The method is illustrated with four natural products, the flavonolignans silybin A, silybin B, isosilybin A, and isosilybin B, which exhibit extremely similar coupling patterns and chemical shift differences well below the commonly reported level of accuracy of 0.01 ppm. The HiFSA approach generated highly reproducible (1)H NMR fingerprints that enable distinction of all four isomers at (1)H frequencies from 300 to 900 MHz. Furthermore, it is demonstrated that the underlying numeric (1)H NMR profiles, combined with iterative computational analysis, allow parallel quantification of all four isomers, even in difficult to characterize reference materials and mixtures. The results shed new light on the historical challenges to the qualitative and quantitative analysis of these therapeutically relevant flavonolignans and open new opportunities to explore hidden diversity in the chemical space of organic molecules.

SUBMITTER: Napolitano JG

PROVIDER: S-EPMC3640553 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

HiFSA fingerprinting applied to isomers with near-identical NMR spectra: the silybin/isosilybin case.

Napolitano José G JG Lankin David C DC Graf Tyler N TN Friesen J Brent JB Chen Shao-Nong SN McAlpine James B JB Oberlies Nicholas H NH Pauli Guido F GF

The Journal of organic chemistry 20130305 7

This study demonstrates how regio- and diastereo-isomers with near-identical NMR spectra can be distinguished and unambiguously assigned using quantum mechanical driven (1)H iterative Full Spin Analysis (HiFSA). The method is illustrated with four natural products, the flavonolignans silybin A, silybin B, isosilybin A, and isosilybin B, which exhibit extremely similar coupling patterns and chemical shift differences well below the commonly reported level of accuracy of 0.01 ppm. The HiFSA approa ...[more]

PMID: 23461697

Similar Datasets

Project description:Precision medicine may significantly contribute to rapid disease diagnosis and targeted therapy, but relies on the availability of detailed, subject specific, clinical information. Proton nuclear magnetic resonance (¹H⁻NMR) spectroscopy of body fluids can extract individual metabolic fingerprints. Herein, we studied 64 patients admitted to the Florence main hospital emergency room with severe abdominal pain. A blood sample was drawn from each patient at admission, and the corresponding sera underwent ¹H⁻NMR metabolomics fingerprinting. Unsupervised Principal Component Analysis (PCA) analysis showed a significant discrimination between a group of patients with symptoms of upper abdominal pain and a second group consisting of patients with diffuse abdominal/intestinal pain. Prompted by this observation, supervised statistical analysis (Orthogonal Partial Least Squares⁻Discriminant Analysis (OPLS-DA)) showed a very good discrimination (>90%) between the two groups of symptoms. This is a surprising finding, given that neither of the two symptoms points directly to a specific disease among those studied here. Actually herein, upper abdominal pain may result from either symptomatic gallstones, cholecystitis, or pancreatitis, while diffuse abdominal/intestinal pain may result from either intestinal ischemia, strangulated obstruction, or mechanical obstruction. Although limited by the small number of samples from each of these six conditions, discrimination of these diseases was attempted. In the first symptom group, >70% discrimination accuracy was obtained among symptomatic gallstones, pancreatitis, and cholecystitis, while for the second symptom group >85% classification accuracy was obtained for intestinal ischemia, strangulated obstruction, and mechanical obstruction. No single metabolite stands up as a possible biomarker for any of these diseases, while the contribution of the whole ¹H⁻NMR serum fingerprint seems to be a promising candidate, to be confirmed on larger cohorts, as a first-line discriminator for these diseases.

Project description:BackgroundLophelia pertusa is a keystone cold-water coral species with a widespread distribution. Due to the lack of a mitochondrial marker variable enough for intraspecific analyses, the population structure of this species has only been studied using ITS and microsatellites so far. We therefore decided to sequence and compare complete mitochondrial genomes from two distant L. pertusa populations putatively isolated from each other (in the Barents Sea off Norway and in the Mediterranean Sea off Italy) in the hope of finding regions variable enough for population genetic and phylogeographic studies.ResultsThe mitogenomes of two L. pertusa individuals collected in the Mediterranean and Barents seas differed at only one position, which was a non-synonymous substitution, but comparison with another recently published L. pertusa mitochondrial genome sequence from Norway revealed 18 nucleotide differences. These included two synonymous and nine non-synonymous substitutions in protein-coding genes (dN/dS > 1): hence, the mitogenome of L. pertusa may be experiencing positive selection. To test for the presence of cryptic species, the mitochondrial control region and the nuclear ITS2 were sequenced for five individuals from each site: Italian and Norwegian populations turned out to share haplotypes of both markers, indicating that they belonged to the same species.ConclusionsL. pertusa corals collected 7,500 km apart shared identical nuclear ITS2 and near-identical mitogenomes, supporting the hypothesis of a recent connection between Lophelia reefs in the Mediterranean and in the Northern Atlantic. Multi-locus or population genomic approaches will be required to shed further light on the genetic connectivity between L. pertusa reefs across Europe; nevertheless, ITS2 and the mitochondrial control region may be useful markers for investigating the phylogeography and species boundaries of the keystone genus Lophelia across its worldwide area of distribution.

Dataset Information

HiFSA fingerprinting applied to isomers with near-identical NMR spectra: the silybin/isosilybin case.

Publications

HiFSA fingerprinting applied to isomers with near-identical NMR spectra: the silybin/isosilybin case.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets