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Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
Understanding the molecular dynamics associated with polymorphic transitions of DL-norvaline with solid-state NMR
Pingping Ren1, Detlef Reichert, Qinghua He
1State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Wuhan, PR China.
The Journal of Physical Chemistry. B
|March 12, 2011
Summary
DL-Norvaline (NVA) exhibits two polymorphic transitions. Solid-state NMR reveals molecular motions, including side-chain dynamics, crucial for understanding these transitions in pharmaceutical intermediates.
Area of Science:
- Solid-state chemistry
- Materials science
- Pharmaceutical chemistry
Background:
- DL-Norvaline (NVA) is a key pharmaceutical intermediate.
- NVA undergoes two polymorphic transitions between 140 and 300 K.
- Understanding molecular dynamics during these transitions is essential.
Purpose of the Study:
- To comprehensively study the molecular motions of DL-Norvaline (NVA) across multiple time scales.
- To elucidate the relationship between molecular dynamics and polymorphic transitions in NVA.
- To provide insights into the mechanistic aspects of polymorphic transitions in linear side-chain amino acids.
Main Methods:
- Solid-state Nuclear Magnetic Resonance (NMR) spectroscopy.
- Cross-polarization magic-angle spinning ((13)C CPMAS) NMR.
- Proton and (13)C relaxation measurements.
- Dipolar and chemical shift experiments.
Main Results:
- (13)C CPMAS NMR identified at least three crystal modifications of NVA, indicating two polymorphic transitions.
- Relaxation studies revealed methyl and amino group reorientations.
- A distinct relaxation process, attributed to side-chain motions with activation energy of 16-21 kJ/mol, was observed after the second transition.
- No significant molecular motions were detected on the millisecond to second time scale (CODEX).
Conclusions:
- The study successfully characterized the molecular dynamics of DL-Norvaline (NVA) associated with its polymorphic transitions.
- Side-chain motions play a significant role in the second polymorphic transition of NVA.
- These findings contribute to a deeper mechanistic understanding of polymorphic transitions in aliphatic alpha-amino acids.
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