Isoguanine (2-oxo-6-aminoguanine, isoG) quintet and its cation (Na+ and K+) complexes have been investigated by density functional theory (DFT) in order to understand the formation and stability of the high-order self-pairing of isoG systems. The comparison of the relative stability of the quintet with that of the tetrad indicates preferential formation of the isoG tetrad in the absence of metal ions. This preference is governed by the entropy of the system as revealed in this study. The large interaction energy evaluated for complexes of cations with the isoG quintet suggests that metal ions are crucial for regulating the strand association. This study also provides direct evidence for the orbital interaction between K+ and the surrounding oxygen atoms in the tetrad and quintet complexes.