Structure of cationized arginine (Arg center dot M+, M = H, Li, Na, K, Rb,and Cs) in the gas phase: Further evidence for zwitterionic arginine

The gas-phase structures of cationized arginine, Arg . M+, M = Li, Na, K, R b, and Cs, were studied both by hybrid method density functional theory cal culations and experimentally using low-energy collisionally activated and t hermal radiative dissociation. Calculations at the B3LYP/LACVP++** level of theory show that the salt-bridge structures in which the arginine is a zwi tterion (protonated side chain, deprotonated C-terminus) become more stable than the charge-solvated structures with increasing metal ion size. The di fference in energy between the most stable charge-solvated structure and sa lt-bridge structure of Arg . M+ increases from -0.7 kcal/mol for Arg . Lito +3.3 kcal/mol for Arg . Cs+. The stabilities of the salt-bridge and char ge-solvated structures reverse between M = Li and Na. These calculations ar e in good agreement with the results of dissociation experiments. The low-e nergy dissociation pathways depend on the cation size. Arginine complexed w ith small cations (Li and Na) loses H2O, while arginine complexed with larg er cations (K, Rb, and Cs) loses NH3. Loss of H2O must come from a charge-s olvated ion, whereas the loss of NH3 can come from the protonated side chai n of a salt-bridge structure. The results of dissociation experiments using several cationized arginine derivatives are consistent with the existence of these two distinct structures. In particular, arginine methyl esters, wh ich cannot form salt bridges, dissociate by loss of methanol, analogous to loss of H2O from Arg . M+; no loss of NH3 is observed. Although dissociatio n experiments probe gas-phase structure indirectly, the observed fragmentat ion pathways are in good agreement with the calculated lowest energy isomer s. The combination of the results from experiment and theory provides stron g evidence that the structure of arginine-alkali metal ion complexes in the gas phase changes from a charge-solvated structure to a salt bridge struct ure as the size of the metal ion increases.