Metal-stabilized rare tautomers and mispairs of DNA bases: N6-metalated adenine and N4-metalated cytosine, theoretical and experimental views

Crystal structure studies indicate that metalation of the exocyclic amino g roup of cytosine and adenine nucleobases by Pt-II and Hg-II entities, respe ctively, induces protonation of a nucleobase ring nitrogen atom, and hence, causes a proton shift from an exocyclic to an endocyclic N atom. This meta l-assisted process thus leads to the generation of rare nucleobase tautomer s. In principle, such processes can lead to the stabilization of mispairs. The present study reports the first quantum chemical analysis of the metal- assisted tautomerization. The calculations clearly demonstrate that metalat ion of the exocyclic amino group of nucleobases significantly increases the protonation energy of the aromatic rings of nucleobases by about 30-34 kca l/mol for the Pt-II adduct and by about 10-14 kcal/mol for the Hg-II adduct . The calculations suggest that this kind of metalation could, besides the structural changes of DNA, significantly enhance the probability of formati on of mispairs in DNA. In the course of the study, we have realized a subst antial difference in terminology, which is used in computational chemistry and in bioinorganic chemistry to characterize the tautomerism of nucleobase s. The difference arises since nucleobases are studied in very different en vironments by quantum chemical and experimental bioinorganic methods. This point is clarified and discussed in detail because it is essential for futu re studies of metal-assisted tautomerism of nucleobases.