Amino-imino tautomerism in derivatives of cytosine: Effect on hydrogen-bonding and stacking properties

The tautomeric preferences of cytosine and its derivatives substituted at p osition 5 (R = CH3, propynyl, Cl, and Br) have been analyzed both in the ga s phase and in aqueous solution by using a combination of state-of-the-art theoretical methods. It is found that 5- substitutions do not alter dramati cally the tautomeric preferences of cytosine in gas phase or aqueous soluti on. The Hoogsteen-type hydrogen-bonding and stacking properties of the imin o form of cytosine and its substituted derivatives are examined in light of the results determined by using ab initio quantum mechanical and density f unctional calculations. It is found that imino cytosines, and especially it s 5-propynyl and 5-Br derivatives show very good stacking in triplexes. The impact of the results in the design of new pyrimidines with ambiguous Hoog steen pairing ability for the stabilization of triple helices is discussed.