Solution-phase chemical shift anisotropy as a promising tool to probe intermolecular interactions and peptide bond geometry: A case study on ¹⁵N-labeled Nα-t-Boc-L-valine

Geometry-dependent chemical shift anisotropy (CSA_g) values of ¹H and ¹⁵N nuclei have been determined in solution for ¹⁵N-labeled, N^α-t-Boc-L-valine by measurements of CSA/dipole-dipole cross-correlated relaxation rates using longitudinal variants of the recently proposed one-dimensional cross-correlation experiments. We demonstrate that solvent dependence of the CSA_g is an invaluable tool for monitoring intermolecular H-bonding interactions. In addition, enhanced temperature dependence was observed for CSA_g, which indicates that the anisotropy of chemical shift is more sensitive to subtle changes in the electronic environment of the nucleus than the motionally averaged isotropic chemical shift. ¹⁵N CSA_g values have been determined in cyclosporin A at natural isotope abundance using the proposed ¹H-detected pulse schemes. A remarkable correlation was observed between the measured ¹⁵N CSA_g and the peptide ω angle, taken from the X-ray structure of cyclosporin A.