The ground state for neutral, isolated molecules in the gas phase can be zwitterionic under appropriate conditions. Quantum chemical calculations show that increasing the basicity of the basic component of a zwitterion leads to enhanced stability for the charge-separated state, which can lead to a ground-state zwitterion. Density functional theory calculations show that methylation of the side chain of arginine is sufficient to induce a ground-state zwitterion. The results for the stepwise methylation of arginine are given, and clearly illustrate enhanced zwitterion stabilization with increasing basicity. In protonated systems, guanidinylation of the N-terminus of arginine yields a salt bridge or charge-stabilized zwitterion structure. The enhanced basicity of guanidino versus amino groups is responsible for the charge separation in this case, which is not observed to be the ground state for protonated arginine itself. These results indicate that charge separation can be favorable in the gas phase and are discussed in light of future experimental efforts.