Understanding the Molecular Dynamics Associated with Polymorphic Transitions of DL-Norvaline with Solid-State NMR Methods

DL-Norvaline (NVA) is an important pharmaceutical intermediate and undergoes two polymorphic transitions between 140 and 300 K. To understand molecular dynamics of NVA accompanied with these transitions, we conducted a comprehensive study on its molecular motions at multiple time scales (10(-9)-1 s) with various solid-state NMR methods. C-13 CPMAS NMR spectra revealed four sets of clearly resolved signals for NVA, carbons corresponding to at least three crystal modifications with two polymorphic transitions. Proton and C-13 relaxation results showed that, apart from the reorientations of methyl and amino groups, NVA had another relaxation process following the second transition with the activation energy of 16-21 kJ/mol corresponding to the side-chain motions. This was further confirmed with the data from dipolar and chemical shift experiments. No motions were detected at CODEX time scale (ms-s). These results provide essential information for understanding the mechanistic aspects of the polymorphic transitions in aliphatic alpha-amino acids with linear side-chains.