The Dependence of Geminal H-H Spin-Spin Coupling Constants on ϕ and Ψ Angles of Peptides in Solution

A theoretical study is presented of the conformational dependence of geminal H-H coupling constants in compounds which provide models for the peptide structure. Calculated results for Fermi contact coupling in TV-methylacetamide, N^α-acetylglycinamide, cyclo-(-Gly-Gly-), and a three-peptide fragment having a 7 turn are based on the finite perturbation theory (FPT) formulation in the semiempirical approximation of intermediate neglect of differential overlap (INDO). It is shown that the effect of the amide carbonyl is to produce a shift in the value of the geminal coupling constant to more negative values, depending on the value of the dihedral angle Ψ. However, the effect of the amide nitrogen is to shift the geminal coupling constants toward more positive values depending on the dihedral angle ϕ. Under the combined effects of the two groups, as in N^α-acetylglycinamide, the total variation of the coupling is calculated to be 8 Hz. Agreement of calculated and experimental values is quite satisfactory in those cases in which x-ray structural data for the molecules are known. Although polarity of the solvent is known to have an effect on geminal H-H coupling, the calculated results for the three-peptide fragment having a 7 turn suggests that intramolecular hydrogen bonding may not be an important factor. Based on these results, it is concluded that geminal H-H coupling constants can complement other NMR parameters as a probe of peptide structure in solution.