Pyramidalization of the Carboxamide sp²-Center in Peptide Structures

A CSD search in the Cambridge Crystallographic Database for the substructure N-C_αH-C'(═O)-N gave 24,180 peptide structures for analysis of the pyramidalization of the sp²-hybridized carboxamide group C'(═O)NC_α, which had not been investigated before. The dependence of the pyramidalization θ = O-N-C'-C_α on the rotation angle ψ = O═C'-C_α-N about bond C'-C_α resulted in a curve with three maxima, three minima, and six zero-crossings. Surprisingly, the ψ/θ analysis of the individual amino acid building blocks showed that all of them exhibited similar curves, irrespective of their different R substituents. This unusual behavior is explained by a 3-fold short-range potential set up by the three covalent bonds, emanating from C_α. The tie-up of the rotation angle ψ and the pyramidalization θ in a rigid coupling is remarkable. In the 24,180 peptide structures, subjected to X-ray crystallography, there is no dynamics. For peptides in solution, the rotation/pyramidalization curve ψ/θ_av determines the degree of pyramidalization θ, when the rotation angle ψ runs through a full 360° circle. Density functional theory (DFT) calculations of alaninamide supported the analysis.