Related Experiment Video
Updated: Mar 20, 2026

Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
Structure Elucidation of Poly-Faldaprevir: Polymer Backbone Solved Using Solid-State and Solution Nuclear Magnetic
Nina C Gonnella1, Carl A Busacca2, Li Zhang2
1Material and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877.
Abstract:
A large-scale synthesis of the hepatitis C virus drug Faldaprevir revealed precipitation of an unknown insoluble solid from methanol solutions of the drug substance. The unknown impurity was determined to be a polymer of Faldaprevir based on analytical methods that included size exclusion chromatography in combination with electrospray ionization mass spectrometry, solution nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization-time of flight, ultracentrifugation, elemental analysis, and sodium quantitation by atom absorption spectroscopy. Structure elucidation of the polymeric backbone was achieved using solid-state NMR cross-polarization/magic angle spinning (CP/MAS), cross polarization-polarization inversion, and heteronuclear correlation (HETCOR) experiments. The polymerization was found to occur at the vinyl cyclopropane via a likely free radical initiation mechanism. Full proton and carbon chemical shift assignments of the polymer were obtained using solution NMR spectroscopy. The polymer structure was corroborated with chemical synthesis of the polymer and solution NMR analysis.
More Related Videos
09:37Preparation of Fungal and Plant Materials for Structural Elucidation Using Dynamic Nuclear Polarization Solid-State NMR
Published on: February 12, 2019
12:47Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins
Published on: December 27, 2016
Related Concept Videos
Other Nuclides: 31P, 19F, 15N NMR
While fluorine-19 and phosphorous-31 have high natural abundances (100%) and positive gyromagnetic ratios, nitrogen-15 has a low natural abundance and a negative gyromagnetic ratio. However, nitrogen-15 is still preferred over nitrogen-14 (which has a...
NMR Spectroscopy of Aromatic Compounds
¹H NMR: Interpreting Distorted and Overlapping Signals
As Δν decreases and the signals move closer, the doublets appear increasingly distorted. The intensities of the inner lines increase at the cost of those of the outer lines as the signals are...
Nuclear Magnetic Resonance (NMR): Overview
NMR spectroscopy generates a spectrum where the characteristic absorption frequencies of the sample are...
¹H NMR: Complex Splitting
Splitting diagrams or splitting tree diagrams are routinely used to depict such complex couplings. While drawing splitting diagrams, the splitting with the larger coupling constant is usually applied...
NMR Spectroscopy Of Amines