On the stability of amino acid zwitterions in the gas phase: The influenceof derivatization, proton affinity, and alkali ion addition

Collision cross sections have been measured for a series of N- and C-methyl ated glycines cationized by alkali ions using ion mobility methods. In all cases the measured cross sections are in excellent agreement with model str uctures obtained from a number of different theoretical approaches. Unfortu nately both charge solvation and zwitterion structures are predicted to hav e nearly identical cross sections. On the basis of a conformational search by molecular mechanics methods and density functional theory calculations a t the B3LYP/DZVP level it is found that the lowest energy forms of alkali c ationized glycine and alanine are charge solvation structures, whereas lowe st energy singly and doubly N-methylated glycines are salt bridges independ ent of metal ion. ol-Amino isobutyric acid forms a salt bridge when sodiate d and a charge solvation structure when rubidiated. In the most stable char ge solvation structures rubidium is bound to one or both carboxyl oxygens, while sodium is bound to both the N- and the C-terminus. The stability of s tilt bridge structures relative to charge solvation structures is found to be nearly proportional to the amino acid proton affinity (PA). For sodiated molecules a PA of >217 kcal/mol results in salt bridge formation, for rubi diated a PA of >219. Predictions are made for the structural preferences of all the common amino acids as a function of cationizing metal ion.