Comparison between protonation, lithiation, and argentination of 5-oxazolones: A study of a key intermediate in gas-phase peptide sequencing

Abstract

Molecular orbital calculations at B3LYP/6-31++G(d,p) are reported for bases 2-(aminomethyl)-5-oxazolone, 2-(aminomethyl)-4-methyl-5-oxazolone, 2-phenyl-5-oxazolone, and 2-phenyl-4 methyl-5-oxazolone and for the cations formed by protonation of these bases on their imino nitrogens. Structures and relative energies for isomers generated by protonation at each of the four heteroatoms of 2-(aminomethyl)-5-oxazolone are reported. Lithium and silver cations both add to 2-(aminomethyl)-5-oxazolone, but unlike the proton, they bind with two heteroatoms simultaneously. For both the lithiated and argentinated 2-(aminomethyl)-5-oxazolone cations the lowest energy isomers have the metal coordinated with the two nitrogen atoms. Proton affinities of these bases are in the range 217.0-221 kcal mol -1, with the methyl group at C4 increasing the proton affinity by ~3 kcal mol -1. Single-point calculations were performed at MP4(fc)/6-31 l++G(2df,p)//B3LYP/6-31++G-(d,p) for 2-(aminomethyl)-5-oxazolone, diketopiperazine, glycine, and alanine and their conjugate acids. The proton affinities from this level of theory are lower by as much as 2.7 kcal mol -1 than those calculated at B3LYP/6-31++G(d,p). Enthalpies of formation calculated at B3LYP/6-31++G(d,p) from isodesmic reactions for glycine, alanine, and their conjugate acids are all within l kcal mol -1 of the experimental values, but those calculated at MP4 deviate by as much as 4.8 kcal mol -1. Enthalpies of formation from atomization reactions at the MP4 level are in larger disagreement with experimental values. © 2000 American Chemical Society.