Interproton Coupling over Five Bonds 5J(H-Cα-C(O)-N-Cα-H) in the Peptide Moiety: The Importance of Specific Association Effects

Article abstract of DOI:10.1021/ja00376a009

An experimental and theoretical study is presented of the conformational and solvent dependencies of long-range H-H coupling constants ⁵J(H-C_α-C(O)-N-C_α-H) in compounds which model the peptide backbone.Molecular orbital results for Fermi contact coupling in cis- and trans-N-methylacetamides do not follow a conformational dependence of the homoallylic type; negative values are predicted for most out-of-plane orientations of the C_α-H bonds.In addition, the calculated values for ⁵C^cis_HH' and ⁵C^trans_HH' are of opposite signs in the planar conformation of cyclo-(Gly-Gly) and the boat conformation of cyclo-(Gly-Tyr).However, relative sign measurements show that these two coupling constants are of the same sign in cyclo-(Gly-Tyr), and that both are positive in cyclo-(Gly-Phgly).The inclusion of five water molecules in the MO calculations for cis-N-methylacetamide and ten water molecules in association with cyclo-(Gly-Gly) led to both positive ⁵J^cis_HH' and ⁵J^trans_HH'.As a consequence, any applicability of the empirical relationship of ⁵J(H-C_α-C(O-N-C_α-H) to φ and ψ angles in peptides does not have any theoretical basis in the molecular orbital theory for unhydrated amide bonds.