17O NMR Studies of the Solvation State of cis/trans Isomers of Amides and Model Protected Peptides

¹⁷O shielding constants have been utilized to investigate solvation differences of the cis/trans isomers ofN-methylformamide (NMF),N-ethylformamide (NEF), andtert-butylformamide (TBF) in a variety of solvents with particular emphasis on aqueous solution. Comparisons are also made with protected peptides of the formulas CH₃CO–YOH, CH₃CO–Y–NHR (Y = Pro, Sar), and CH₃CO–Y–Z–NHR (Y = Pro; Z =D-Ala) selectively enriched in¹⁷O at the acetyl oxygen atom. Hydration at the amide oxygen induces large and specific modifications of the¹⁷O shielding constants, which are practically the same for the cis and trans isomers of NMF, NEF, and the protected peptides. Fortert-butylformamide, the strong deshielding of the trans isomer compared to that of the cis isomer may be attributed to an out-of-plane (torsion-angle) deformation of the amide bond and/or a significant reduction of solvation of the trans isomer due to steric inhibition of the bulkytert-butyl group. Good linear correlation between δ(¹⁷O) of amides and δ(¹⁷O) of acetone was found for different solvents which have varying dielectric constants and solvation abilities. Sum-over-states calculations, within the solvaton model, underestimate effects of the dielectric constant of the medium on¹⁷O shielding, while finite-perturbation-theory calculations give good agreement with the experiment.