Stability and isomerization of complexes formed by metal ions and cytosine isomers in aqueous phase.

We present a systematic study of the stability of the formation of complexes produced by four metal ions (M+/2+) and 14 cytosine isomers (Cn). This work predicts theoretically that predominant product complexes are associated with higher-energy C4M+/2+ and C5M+/2+ rather than the most stable C1M+/2+. The prediction resolves successfully several experimental facts puzzling two research groups. Meanwhile, in-depth studies further reveal that direct isomerization of C1↔C4 is almost impossible, and also that the isomerization induced by either metalation or hydration, or by a combination of the two unfavorable. It is the single water molecule locating between the H1(−N1) and O2 of the cytosine that plays the dual roles of being a bridge and an activator that consequently improves the isomerization greatly. Moreover, the cooperation of divalent metal ion and such a monohydration actually leads to an energy-free C1←C4 isomerization in the gas phase. Henceforth, we are able to propose schemes inhibiting the free C1←C4 isomerization, based purely on extended hydration at the divalent metal ion.