Adenine Tautomers:  Relative Stabilities, Ionization Energies, and Mismatch with Cytosine

Abstract

In this study, we have investigated 12 tautomers of the DNA base adenine at the BP86/TZ2P and BP86/QZ4P levels of density functional theory. The vertical and adiabatic ionization energies of all tautomers were determined as the difference in energy between the radical cation and the corresponding neutral system. Furthermore, an evaluation is made for the eigenvalue spectra calculated with the SAOP functional, which is shown to lead to substantial improvements for orbital energies compared to BP86. We have also explored the correlations between the Kohn-Sham orbitals of the different tautomers at the BP86/QZ4P and SAOP/QZ4P levels. Finally, we discuss implications of the existence of the tautomeric forms of adenine for the DNA replication.

Elementary Molecular Mechanisms of the Spontaneous Point Mutations in DNA: A Novel Quantum-Chemical Insight into the Classical Understanding

“…The intramolecular proton transfer schemes for isolated DNA bases are displayed in Figure 2. The MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) reaction barriers for the forward tautomerisation are 45.58 (Ade), 39.09 (Thy), 38.47 (Cyt) and 32.17 kcal/mol (Gua) and these values tightly correlate with the literature data (Basu et al, 2005;Brovarets' & Hovorun, 2010aDanilov et al, 2005;Fan et al, 2010;Fogarasi & Szalay, 2002;Fogarasi, 2008;Fonseca Guerra et al, 2006;Gorb & Leszczynski, 1998a, 1998bGorb et al, 2001;Gu & Leszczynski, 1999;Hanus et al, 2003Hanus et al, , 2004Kosenkov et al, 2009;Mejía-Mazariegos & Hernández-Trujillo, 2009;Saha et al, 2006). Very large kinetic barriers for intramolecular tautomerisation of all isolated DNA bases (above 32 kcal/mol) indicate that such tautomerisation will be very slow and this process may not occur readily in the isolated molecule.…”

“…In all of these studies, it was suggested that the 9H amino tautomer of Ade is the dominant contributor to the spectra. The experimental results agree closely with calculations at different levels of theory and consistently show the 9H amino tautomer to be the most stable one (Brovarets' & Hovorun, 2011b;Hanus et al, 2004;Fonseca Guerra et al, 2006;Kwiatkowski & Leszczynski, 1992;Norinder, 1987;Nowak et al, 1989bNowak et al, , 1991Nowak et al, , 1994aNowak et al, , 1994bNowak et al, , 1996Sabio et al, 1990;Saha et al, 2006;Sygula & Buda, 1983;Wiorkiewicz-Kuczera & Karplus, 1990).…”

“…Meanwhile, the mutagenic enol form of Gua (Gua*) can pair with Thy (Brovarets' & Hovorun, 2010d;Danilov et al, 2005;Mejía-Mazariegos & Hernández-Trujillo, 2009) instead of Cyt. Similarly, the mutagenic imino form of Cyt (Cyt*) pairs with Ade (Danilov et al, 2005;Fonseca Guerra et al, 2006) instead of Gua. Then, during replication, when the two strands separate the Thy and Ade bases of the anomalous Gua*·Thy and Ade·Cyt* base pairs would combine with Ade and Thy instead of Cyt and Gua, respectively.…”

“…Among all rare tautomers, only the imino tautomers of Cyt (Brown et al, 1989b;Dreyfus et al, 1976;Feyer et al, 2010;Szczesniak et al, 1988) and enol tautomers of Gua (Choi & Miller, 2006;Sheina et al, 1987;Plekan et al, 2009;Szczepaniak & Szczesniak, 1987) were experimentally detected. The lack of the experimental data on the rare tautomers of Ade (Brown et al, 1989a) and Thy can be explained by the high value of their relative energy (~12÷14 kcal/mol at 298.15 K) estimated by theoretical investigations (Basu et al, 2005;Brovarets' & Hovorun, 2010a;Fonseca Guerra et al, 2006;Mejía-Mazariegos & Hernández-Trujillo, 2009;Samijlenko et al, 2000Samijlenko et al, , 2004.…”

Supramolecular Structures and Tautomerism of Carboxylate Salts of Adenine and Pharmaceutically Relevant N6-Substituted Adenine

“…Furthermore, adenine can exist in different tautomeric forms with the most stable one being the 9H-amino tautomer ( Figure 1). [13][14][15] Protonation of the 9H-tautomer usually takes place at the N1 nitrogen. 11,[16][17][18][19][20] By contrast, while N 6 -benzyladenine 21 and kinetin 22 crystallize in the expected 9H-tautomeric form, the N3-protonated 7H-tautomer ( Figure 1) was observed in the crystal structures of their bromide, chloride and dihydrogenphosphate salts.…”