Study of the thermal processes in molecular crystals of peptides by means of NMR crystallography

Abstract

1D and 2D Very Fast Magic Angle Spinning (VF MAS) NMR experiments with sample rotation up to 55 kHz were applied to study both the dihydrate form of Tyr–(D)Ala–Phe–Gly (N-terminal sequence of opioid peptide dermorphin) and the anhydrous form, which was obtained by thermal treatment. Employing both homo-nuclear (1H–1H BABA, 13C–13C SHANGHAI) and hetero-nuclear 2D correlations (1H–13C and 1H–15N) with inverse detection, it was shown that removing water from the crystal lattice of this tetrapeptide does not destroy its subtle pseudo-cyclic structure, and its supramolecular array is preserved. The GIPAW method was employed to compute the geometry of the peptides and calculate the 13C σii principal elements of the NMR shielding tensor parameters and 1H isotropic NMR shifts. The theoretical values of 13C σii were compared with the experimental 13C δii chemical shift tensor values obtained by a 2D PASS experiment. The correlations 13C σii versus δii and 1H σiso versus δiso were used to evaluate the quality of the computational approach. With the new set of coordinates obtained by the GIPAW method, the crystal and molecular structure of the dehydrated Tyr–(D)Ala–Phe–Gly peptide that was obtained by thermal treatment was constructed. Methodology used in this project combining NMR measurements, analysis of X-ray powder diffraction data and advanced quantum mechanical calculations is known as NMR crystallography.