Accurate prediction of proton chemical shifts. II. Peptide analogues

Proton chemical shifts of eight cyclic amide molecules were measured in DMSO and D 2 O solutions. The magnetic shieldings of the corresponding aliphatic, aromatic, and amide protons were calculated by Hartree‐Fock and DFT, using the 6‐311G**, 6‐311++G**, and TZVP basis sets. For aliphatic protons, all of these methods reproduce the experimental values in DMSO solutions excellently after linear regression. The Hartree‐Fock method tends to give slightly better agreement than DFT. The best performance is given by the HF/6‐311G** method, with an rms deviation of 0.068 ppm. The deviations from experimental chemical shifts in D 2 O solutions are only slightly larger than those in DMSO solutions. This suggests that we can use the calculated gas phase proton chemical shifts directly to predict experimental data in various solvents, including water. For amide protons, which exchange with water and form hydrogen bonds with DMSO, only modest agreement is obtained, as expected. The present studies confirm that the GIAO approach can reach high accuracy for the relative chemical shifts of aliphatic and aromatic protons at a low cost. Such calculations may provide constraints for the conformational analysis of proteins and other macromolecules. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 492–497, 2002; DOI 10.1002/jcc.10044