Ab initio free energy calculations of guanidinium pairing in aqueous solution cofirmn
the counterintuitive conjecture that the like-charge ion pair is thermodynamically
stable. Transferring the guanidinium pair to the inside of a POPC lipid bilayer, like-
charge ion pairing is found to occur also inside the membrane defect. It is found to
contribute to the nonadditivity of ion transfer, thereby facilitating the presence of ions
inside the bilayer. The ect is quantified by free energy decomposition and compari-
son with ammonium ions, which do not form a stable pair. The presence of two charges
inside the center of the bilayer leads to the formation of a pore. Potential consequences
for cell penetrating peptides and ion conduction are drawn.