Molecular Orbital Calculations on the Protonation of Hydrogen-Bonded Formamide Chains. Implications for Peptides

Abstract

We report density functional studies of the protonation of H-bonded formamide chains containing up to 10 monomeric units. These chains contain H bonds that are similar to those in peptides and proteins. All structures considered were completely geometrically optimized at the B3LYP/D95** level of calculation. The proton affinities of the chains are greatest at the terminal CO oxygen atoms. They increase significantly with the length of the formamide chain from two to five formamides. Protonation of the terminal CO of chains containing five or more formamides results in the transfer of the NH proton of the terminal (protonated) monomer across the H bond to the adjacent formamide. Protonations at the NH2 termini of the formamide chains are generally unfavorable as they result in the rupture of the proximate H bond. The proton affinities at the CO's of formamide chains containing three or more monomers exceed that of the amino group of glycine, implying that peptides that contain such H-bonding chains might be preferentially protonated on a CO rather than a terminal amino group, in contrast to small oligopeptides where H-bonding chains do not form. The quasi-linear relationship between H-bond strength and length clearly does not hold for the protonated chains. The implications for studies on peptides are discussed.