Ab Initio Studies on the Structure and Properties of the Hydroxyl-Radical-Modified Adenine Derivatives in Different Tautomeric Forms

Abstract

The geometrical and electrical properties of four tautomers of 2-OH-adenine (2-OH-A) and 8-oxoadenine (8-oxo-A) and three tautomers of fapy-adenine (fapy-A) have been estimated on the basis of a 6-31G ab initio RHF method followed by single-point 6-3 1G** and MP2 calculations. The resulting relative stability of different tautomeric forms suggests that the most favorable in vacuum are the enol-amino forms of 2-OH-A, the keto-amino tautomer of 8-oxo-A, and the diamino form of fapy-A. After taking into account for the polarization functions and electron correlation contribution the energetical succession of the studied tautomers was not changed. The smaller contribution of the electron correlation was observed for the most stable tautomers and the highest for enol-imino isomers. The dipole moment strongly depends on the tautomeric form and has the lowest value for all enol-amino forms of adenine derivatives. The nonplanarity of all studied tautomers was noticed. The amino groups are nonsymmetrical pyramids with out of plane hydrogen atoms.For 2-OH-A and 8-oxo-A atom H62 is tumed above and atom &I below the ring plane. The opposite orientation is observed in the case of fapy-A. However, the 2-OH-A tautomers are characterized by a much smaller deviation from the strict planar structure then 8-oxo-A. The use of the prefix oxo for Cs-substituted adenine and hydroxyl for the derivative modified at the C2 position is justified by the most stable tautomeric forms.

An ab initio DFT Characteristics of Tautomeric Properties of Hydroxyl Radical Modified Nucleosides in Polar and Non-Polar Environments

“…However, in polar solution keto-amino tautomer (AA1) becomes dominant. This is in close correspondence to previously noticed observations [11,21].…”

“…Free radical adenosine analogs [11,12] have relatively simple tautomeric properties as it was demonstrated in Fig. 1.…”

“…There are evidences of direct correlation between levels of modified DNA bases and carcinogenesis, cancer and many non-cancerous diseases [4]. Despite of great efforts [5][6][7][8][9][10][11][12][13][14][15][16] made in the past still there are many open questions regarding fundamental properties of DNA modified bases. One of the first problems addressed to base analogues is their structure.…”

Molecular Perspective Review of Biochemical Role of Nucleobases Modified by Oxidative Stress

“…As it was presented in Fig. 1 AA adopts predominantly amino-enol form (AA1) in non-polar environment, while in the polar solution the keto-amino tautomer (AA2) is favoured [47,48]. The former isomer as less polar and dominates in the vapour state while the latter due to its higher polarity predominates if water field is present.…”

“…This is also the case for nucleosides and their free radical analogues [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60]. They can undergo reversible processes of migration of one or more double bonds and hydrogen atom(s) in so-called prototropic tautomerism [79,80].…”