Gas-phase acidities of lysine homologues and proline analogs from the extended kinetic method

Abstract

The absolute gas-phase acidities (ΔHacid) for three lysine homologues (ornithine (Orn), 2,4-diaminobutanoic acid (Daba) and 2,3-diaminopropanoic acid (Dapa)) and 2 proline analogs (azetidine-2-carboxylic acid (Aze) and pipecolic acid (Pip)) were determined using the extended kinetic method in an electrospray ionization–triple quadrupole instrument. The gas-phase acidities of the three lysine homologues (1415±10, 1419±7, and 1418±8kJ/mol for Orn, Daba, and Dapa, respectively) are the same as that of lysine (1416±7kJ/mol) obtained from earlier studies within error limits. The two proline analogs are less acidic (1425±13 and 1432±11kJ/mol for Aze and Pip) than the lysine analogs, but have the same acidity as proline (1430±7kJ/mol). Experimental acidities are supported by density functional theory calculations at the B3LYP/6-311++G**//B3LYP/6-31+G* level, which give predictions for the acidities from an isodesmic reaction with acetic acid as the reference bases. Agreement between theory is excellent (within 5kJ/mol) for Daba, Dapa, Aze, and Pip. The computed acidity for Orn is 9kJ/mol higher than the measured acidity, but is still within the error limits. As the difference in acidities within the sets of analogs is smaller than the absolute error bars, relative acidities (ΔGacid) were obtained using kinetic method ratios with 3-OH-benzoic acid as the reference acid. Relative acidity (ΔGacid) orderings of Dapa>Lys>Daba>Orn and Pro>Pip>Aze were obtained.