title: 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.
authors: Department of Medicinal Chemistry & Pharmacognosy and Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors: José G
authors: JG
authors: Napolitano
authors: David C
authors: DC
authors: Lankin
authors: Tyler N
authors: TN
authors: Graf
authors: J Brent
authors: JB
authors: Friesen
authors: Shao-Nong
authors: SN
authors: Chen
authors: James B
authors: JB
authors: McAlpine
authors: Nicholas H
authors: NH
authors: Oberlies
authors: Guido F
authors: GF
authors: Pauli
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011522:Protons; D000077385:Silybin; D012838:Silymarin / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D011522:Protons; D012838:Silymarin; D000077385:Silybin; C075820:isosilybin