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 σ_ii principal elements of the NMR shielding tensor parameters and ¹H isotropic NMR shifts. The theoretical values of ¹³C σ_ii were compared with the experimental ¹³C δ_ii chemical shift tensor values obtained by a 2D PASS experiment. The correlations ¹³C σ_ii versus δ_ii and ¹H σ_iso versus δ_iso 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.